79C3C34C52B45572883A05D425EB0F82
Medical Research Involving Children (2004)
https://mrc.ukri.org/documents/pdf/medical-research-involving-children/
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| Indicators in focus are typically shown highlighted in yellow; |
Peer Indicators (that share the same Vulnerability association) are shown highlighted in pink; |
"Outside" Indicators (those that do NOT share the same Vulnerability association) are shown highlighted in green; |
Trigger Words/Phrases are shown highlighted in gray. |
Link to Orphaned Trigger Words (Appendix (Indicator List, Indicator Peers, Trigger Words, Type/Vulnerability/Indicator Overlay)
Applicable Type / Vulnerability / Indicator Overlay for this Input
Political / criminal
Searching for indicator criminal:
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p.000035: wellbeing of the research participant. The assessment should draw on an appropriate range of expertise adequately
p.000035: reflecting professional and lay views, therefore a professional opinion should be sought for any research involving
p.000035: children. The ethics committee must be satisfied that dependent persons and vulnerable groups will not be subjected to
p.000035: undue influence.
p.000035: Whilst the Council of Europe protocol is a legal instrument, it has not so far been transposed into UK law. However,
p.000035: the Medicines for Human Use (Clinical Trials) Regulations 2004, which transpose Directive 2001/20/EC into UK law,
p.000035: require that an ethics committee considering a trial involving minors must receive advice on the relevant field of
p.000035: paediatric care.29, 30 A "minor" is defined as a person under the age of 16.
p.000035:
p.000035: 5.4 Children's safety in relation to researchers
p.000035: Any individual recruited by the MRC to work directly with children will undergo security screening, including criminal
p.000035: records review. This includes nurses, survey interviewers and some individuals involved in a clinically invasive
p.000035: capacity, eg, phlebotomists. The MRC expects its grant-holding institutions to do likewise.
p.000035: Security screening is complementary to other good recruitment practices and not a substitute for them. Staff involved
p.000035: in MRC's recruitment process are responsible for ensuring that standard checks are still made.
p.000035:
p.000035: 5.5 Specific situations
p.000035:
p.000035: 5.5.1 Research involving human material
p.000035: Please refer to the MRC guidance Human tissue and biological samples for use in research.12
p.000035: Further guidance will be issued when the Human Tissue Bill, and equivalent legislation in Scotland, become law.
p.000035: 5.5.2 The use of personal information
p.000035: Please refer to the MRC guidance Personal information in medical research.11
p.000035:
p.000035: 5.5.3 Research involving very young children
p.000035: A parent/guardian's informed consent is necessary for the involvement of babies in research. When a baby is seriously
p.000035: ill and a decision about treatment is required quickly, the pressure on parents is high and the difficulty of obtaining
p.000035: truly informed consent is recognised. The RCPCH provides detailed guidance relating to research involving babies.40
p.000035:
p.000035: 5.5.4 Emergency situations
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Political / political affiliation
Searching for indicator party:
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p.000033: his or her increasing ability to make decisions about complex and serious issues. It is helpful for researchers to
p.000033: produce child-friendly information in a form appropriate for the relevant age groups – this could make use of pictures
p.000033: or videos. More than one version may need to be produced
p.000033: if research covers a wide age range, such as eight-18 years. Where the research project lasts a number of years, the
p.000033: child and/or parent/guardian may need to be approached periodically to ensure they still consent to the child's
p.000033: involvement in research. For example, where a parent has consented to follow-up studies throughout the life of the
p.000033: child, the child must be given the opportunity to decide for himself/herself, once competent to do so, whether he or
p.000033: she wishes to continue his or her involvement.
p.000033:
p.000033: 5.2 Confidentiality
p.000033: Medical professionals have a duty of confidentiality to all patients including children. Legally competent children are
p.000033: entitled to expect that information about themselves will not be provided to a third party, including their
p.000033: parent/guardian, without their consent. However, it is important that wherever possible the parents/guardians are
p.000033: informed, and young people should be encouraged to involve them unless it is not in their best interests to do so. If
p.000033: competent children do not wish to involve their parents/guardians this should be respected. Disclosure can only be
p.000033: justified if there is reasonable cause to suspect that the child is suffering or is likely to suffer significant harm
p.000033: as a result of non-disclosure. Any decision to disclose confidential information to a third party must be relayed to
p.000033: the competent child before disclosure.
p.000033: To facilitate both the child's healthcare and longer term research, general practitioners (GPs) should be notified of
p.000033: all research on their paediatric patients. The consent form should request consent to inform and update GPs of the
p.000033: child's involvement. If a participant is likely to resist information being provided to parents/guardians and family
p.000033: practitioners because the research is of a sensitive
p.000033: nature, eg, investigating smoking habits or sexual health, advice should be sought from the Research Ethics Committee
p.000033: that assesses the protocol.
p.000033: Children who lack competence to consent to participate are nevertheless entitled to confidentiality. The researcher
p.000033: will have had to request the parent/guardian's consent to the child's involvement in research. Any intention to
p.000033: disclose information to anyone else should be discussed with both the parent/guardian and the child, taking into
p.000033: consideration whether disclosure to a third party is necessary in the interests of the child's health. Public health
p.000033: research may require the use of anonymous data without explicit consent – for detailed guidance on this researchers
p.000033: should consult the MRC guidance Personal information in medical research.11
p.000033: Researchers working with children have important responsibilities in relation to child protection. Where researchers
p.000033: have reasonable cause to suspect that a child is suffering or likely to suffer significant harm, they have a clear
p.000033: responsibility to liaise urgently with those responsible for the child's clinical care with a view to making a referral
p.000033: to social services. Again, a decision to disclose information should, wherever possible, be discussed with the child
p.000033: before disclosure, in terms appropriate to the child's capability to understand.
p.000033: All researchers need to be aware of relevant data protection legislation and the rights of the child (and their
p.000033: parents/guardians in some circumstances) to access their health records. Fuller guidance on confidentiality issues is
...
Political / vulnerable
Searching for indicator vulnerable:
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p.000007: in this age group and children may be given treatments that are potentially unsafe. In addition, progress on
p.000007: understanding adult diseases thought to have their origins in early life will be hampered, limiting the possibilities
p.000007: of preventive intervention.
p.000007: 3. What has limited research so far, and what are the challenges?
p.000007: Progress in research involving children has been limited primarily by:
p.000007:
p.000007: • Difficulty in reaching consensus about including children in research.
p.000007:
p.000007: • Methodological challenges.
p.000007:
p.000007: • Expense of developing new treatments.
p.000007:
p.000007: • Lack of legal enforcement for paediatric versions of drugs.
p.000007:
p.000007: 3.1 Difficulty in reaching consensus about including children in research
p.000007: Current ethical principles for conducting research involving children have evolved from the Nuremberg Code which
p.000007: emerged after the Second World War. The Code set out statements of moral, ethical and legal principles relating to
p.000007: research involving human subjects, and included a bar on research involving children. Research was seen as a potential
p.000007: harm from which vulnerable people should be protected. Later, in 1964, the Declaration of Helsinki, drawn up by the
p.000007: World Medical Association, advised that research involving minors could be carried out where "the research is necessary
p.000007: to promote the health of the population represented and this research cannot instead be performed on legally competent
p.000007: persons" and appropriate consent and assent had been obtained.
p.000007: Today, organisations such as the Council for International Organizations of Medical Sciences play a vital part in
p.000007: considering how these ethical principles can be effectively applied. While research may have associated risks, it can
p.000007: also offer potential benefits to all participants, including children. Changes in the way we regard children include a
p.000007: growing recognition of the importance of listening to children's views and wishes, and of their autonomy. This can be
p.000007: observed in
p.000007:
p.000008: 8
p.000008:
p.000009: 9
p.000009:
p.000009: MRC Ethics Guide: Medical research involving children
p.000009: MRC Ethics Guide: Medical research involving children
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
...
p.000013: longer uses these terms, setting out instead basic principles for all medical research and additional ones for research
p.000013: combined with medical care.
p.000013: The guidelines from the RCPCH published in 2000 likewise avoid drawing this distinction, highlighting instead the
p.000013: principles that research involving children is important for the benefit of all children, and that a research procedure
p.000013: which cannot directly benefit the child is not necessarily unethical if the findings might benefit future generations
p.000013: of children. Research where there is no benefit to the individual child participant would have to be of minimal risk.
p.000013: This is a major step forward in thinking. The expectation is that children can now begin to reap the benefits of
p.000013: research designed with children in mind.
p.000013: 4.3 Benefit, harm and risk
p.000013: In the past, the concern to protect children from the potential harms of research may have denied them potential
p.000013: benefits. To ensure that this vulnerable group are not exploited, the General Medical Council advises that it is
p.000013: important to assess carefully the potential benefits and harm to children at all stages of any research. As the
p.000013: benefits of research are not predictable, the researcher must be satisfied that the research is not contrary to the
p.000013: child participant's interests. The foreseeable risks should be kept as low as possible: the potential benefits from the
p.000013: development of treatments and furthering of knowledge must outweigh any foreseeable risks.22
p.000013:
p.000013: Risk - A potential harm; the characteristics of risk include the probability of its occurrence, as well as its
p.000013: magnitude and duration
p.000013:
p.000013: Risks may be estimated as minimal, low or high: i
p.000013:
p.000013: Minimal (the least possible) risk describes procedures such as questioning, observing, and measuring children, provided
p.000013: that procedures are carried out in a sensitive way, respecting the child's autonomy, and that consent has been given.
p.000013: Procedures with minimal risk include obtaining bodily fluids without invasive intervention, eg, taking saliva or urine
...
p.000033: 5.3 Ethics committee review
p.000033: The Council of Europe Protocol to the Convention on Human Rights and Biomedicine on Biomedical Research provides
p.000033: guidance regarding the role of the ethics committee in research.9 According to this guidance, every research project
p.000033: must be submitted for independent examination of its scientific merit, including assessment of the importance of the
p.000033: aim of research and ethical acceptability to an
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000035: 35
p.000035:
p.000035: MRC Ethics Guide: Medical research involving children
p.000035: MRC Ethics Guide: Medical research involving children
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: ethics committee. An examination of the ethical acceptability is necessary to protect the dignity, rights, safety and
p.000035: wellbeing of the research participant. The assessment should draw on an appropriate range of expertise adequately
p.000035: reflecting professional and lay views, therefore a professional opinion should be sought for any research involving
p.000035: children. The ethics committee must be satisfied that dependent persons and vulnerable groups will not be subjected to
p.000035: undue influence.
p.000035: Whilst the Council of Europe protocol is a legal instrument, it has not so far been transposed into UK law. However,
p.000035: the Medicines for Human Use (Clinical Trials) Regulations 2004, which transpose Directive 2001/20/EC into UK law,
p.000035: require that an ethics committee considering a trial involving minors must receive advice on the relevant field of
p.000035: paediatric care.29, 30 A "minor" is defined as a person under the age of 16.
p.000035:
p.000035: 5.4 Children's safety in relation to researchers
p.000035: Any individual recruited by the MRC to work directly with children will undergo security screening, including criminal
p.000035: records review. This includes nurses, survey interviewers and some individuals involved in a clinically invasive
p.000035: capacity, eg, phlebotomists. The MRC expects its grant-holding institutions to do likewise.
p.000035: Security screening is complementary to other good recruitment practices and not a substitute for them. Staff involved
p.000035: in MRC's recruitment process are responsible for ensuring that standard checks are still made.
p.000035:
p.000035: 5.5 Specific situations
p.000035:
p.000035: 5.5.1 Research involving human material
p.000035: Please refer to the MRC guidance Human tissue and biological samples for use in research.12
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Searching for indicator vulnerability:
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p.000017: participation in more than one trial or study might be potentially beneficial – both for participants and for the
p.000017: research. The potential benefits and risks of doing so would need to be carefully explored by all concerned, and
p.000017: clearly understood by the child and family.24
p.000017: Equipoise: this is when there is genuine uncertainty among those who have considered the issue, including patients,
p.000017: about the relative benefits and risks of treatments or tests being compared. A clinical trial cannot be ethical unless
p.000017: there is this genuine informed uncertainty among the expert medical community and in an informed competent
p.000017: patient/participant.
p.000017: 4.3.2 Minimising risk
p.000017: The National Academy of the Sciences provides guidance on how to minimise risk, summarised here: 25
p.000017:
p.000017: Minimising risk in research involving children
p.000017:
p.000017: • Is inclusion of children necessary to answer the scientific question posed by the research? What are the ages
p.000017: of the children to be included? Are any of the potential research harms age-dependent?
p.000017: • Will potential child participants be screened for known vulnerability to the risks associated with specific
p.000017: elements of the research?
p.000017: • What does the research require of children and their families? Is adherence to the research protocol a
p.000017: concern? If so, what are the risks of non-adherence?
p.000017: • Are all the procedures or interventions necessary to answer the research question? Can the investigators
p.000017: collect the required information using procedures that the child participants will undergo as part of their normal
p.000017: therapy or monitoring?
p.000017: • Have previous laboratory studies, animal research, studies with adults, or other data provided a sufficient
p.000017: basis for proceeding with research involving children?
p.000017: • Does the study follow principles of sound research design?
p.000017:
p.000017: • What are the theoretical risks involved with the research as proposed? Are data available to estimate the
p.000017: probability and magnitude of each risk as they relate to the categories of children to be included?
p.000017: • Have the investigators provided data on the frequency of adverse events for the procedures at the site in
p.000017: question? For example, sedation for research procedures.
p.000017: Continued...
p.000017:
p.000017:
p.000017:
p.000018: 18
p.000018:
p.000019: 19
p.000019:
p.000019: MRC Ethics Guide: Medical research involving children
...
Health / Cognitive Impairment
Searching for indicator cognitive:
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p.000009: Genetic disorders leading to severe disability or death are also rare.
p.000009:
p.000009: Even for more common conditions challenges arise. In asthma, for example, the diagnosis may be subjective, which poses
p.000009: problems in establishing the clear inclusion and exclusion criteria required for clinical trials. Standard outcome
p.000009: measures in adults include death and quality of life, but for many conditions different outcomes are more relevant.
p.000009: Measurements of these outcomes have been determined for use in adults specifically and may not be relevant for
p.000009: children. Quality of life measures can be used, but should be focused on the child or family and validated and tested
p.000009: for reliability and responsiveness to change before being used; such instruments have not always been available.
p.000009: It is therefore useful, and important, to consult children about outcome measures and other issues, when the research
p.000009: is being designed.
p.000009: When carrying out research on children, it is important to assess both the short- term and long-term outcomes. For
p.000009: example, early treatment of premature infants at high risk of chronic lung disease with steroid drugs reduces this
p.000009: risk, but long-term studies show an increased risk of cerebral palsy.16
p.000009: Investigations of cognitive, neurological and respiratory function can also pose challenges, eg, the inability of young
p.000009: children to understand and co-operate with the demands of complex tasks.
p.000009:
p.000009: 3.3 Expense of developing new treatments
p.000009: Because of the expense of developing a new treatment, commercially funded research understandably focuses on treatment
p.000009: options that are likely to be profitable. Pharmaceutical companies have traditionally been reluctant to invest in
p.000009: developing child-specific treatments or adapting existing medicines to meet the needs of children. The main reasons are
p.000009: that the market is often small and that long-term follow-up of adverse effects is often needed because the risks
p.000009: associated with paediatric treatments are generally higher.17
p.000009:
p.000009: 3.4 Weak licensing and regulation arrangements for paediatric versions of pharmaceuticals
p.000009: The National Audit Office recently reported that up to 90 per cent of medicines prescribed to children in hospitals
p.000009: were not licensed for that use.18 Consequently, there are potentially important public health benefits in improving
p.000009: the licensing of medicines and the testing of their safety for children. Currently in Europe there is no legal
p.000009: requirement for the necessary studies to be performed if the pharmaceutical company does not present the drug for use
...
Searching for indicator impaired:
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p.000007: While we have a responsibility to protect children, we also have an ethical obligation to ensure that they receive the
p.000007: best treatment. Like adults, they should be given the opportunity to benefit from the results of successful research.
p.000007: Children should therefore have the opportunity to participate while, of course, being protected from any hazards that
p.000007: involvement in the research project might bring. The MRC's research on childhood leukaemia shows how valuable this
p.000007: involvement can be. Most children diagnosed with leukaemia in the UK are entered into the MRC's trials, and in the last
p.000007: 40 years the survival rate for children with acute lymphoblastic leukaemia especially has greatly improved – from less
p.000007: than five per cent in 1962 to 80 per cent at present.13
p.000007:
p.000007: 2.1 What would be the consequences of not carrying out research on children?
p.000007: When research does not involve children, child-specific treatments for diseases are not developed and diseases with no
p.000007: close analogies in adults are not studied. This means that future generations of children miss the opportunity to
p.000007: benefit from the findings of that research. Progress in the clinical care of children will be impaired without research
p.000007: in this age group and children may be given treatments that are potentially unsafe. In addition, progress on
p.000007: understanding adult diseases thought to have their origins in early life will be hampered, limiting the possibilities
p.000007: of preventive intervention.
p.000007: 3. What has limited research so far, and what are the challenges?
p.000007: Progress in research involving children has been limited primarily by:
p.000007:
p.000007: • Difficulty in reaching consensus about including children in research.
p.000007:
p.000007: • Methodological challenges.
p.000007:
p.000007: • Expense of developing new treatments.
p.000007:
p.000007: • Lack of legal enforcement for paediatric versions of drugs.
p.000007:
p.000007: 3.1 Difficulty in reaching consensus about including children in research
p.000007: Current ethical principles for conducting research involving children have evolved from the Nuremberg Code which
p.000007: emerged after the Second World War. The Code set out statements of moral, ethical and legal principles relating to
p.000007: research involving human subjects, and included a bar on research involving children. Research was seen as a potential
...
Health / Drug Usage
Searching for indicator drug:
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p.000005: It is advisable to consider the risks of a particular research procedure in the context of the child's overall
p.000005: involvement in projects by different researchers.
p.000005: 2. Why do we need research involving children?
p.000005: Medical research involving children is essential for advancing child health and wellbeing. Often it is not sufficient,
p.000005: scientific, or ethical to carry out research with adults and apply the findings to children. This may be because:
p.000005: • The disease processes in children may differ from those in adults. Some childhood diseases have no close
p.000005: analogies in adults, therefore to understand these in any detail it is necessary to carry out research with children.
p.000005: • The physiology of children is different from that of adults, and the pharmacokinetics of many drugs will vary
p.000005: with the age of the child.Treatments designed specifically to meet the needs of children ensure that age-related
p.000005: differences in drug handling and/or effects are recognised, that the doses needed for efficacy are understood, and that
p.000005: any adverse effects can be avoided.
p.000005: • Many disorders can only be understood in the context of a child's growth and development. Examples include
p.000005: changes in the visual system following early squint, or the way the developing brain adapts to injury or damage in
p.000005: babies.
p.000005: • Children are not small adults. For the therapy to be effective, its delivery must suit their needs. Use of adult
p.000005: formulations is often not suitable, eg, many children find it easier to swallow a liquid formulation than a tablet.
p.000005: Research with children can also play a key part in increasing our understanding of some adult diseases that are thought
p.000005: to have their origins in early life. It enables the development of preventive intervention into the natural history of
p.000005: the disease. The findings of research involving children can therefore also be relevant for adults.
p.000005:
p.000005:
p.000005:
p.000005:
p.000006: 6
p.000006:
p.000007: 7
p.000007:
p.000007: MRC Ethics Guide: Medical research involving children
p.000007: MRC Ethics Guide: Medical research involving children
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
...
p.000009: children to understand and co-operate with the demands of complex tasks.
p.000009:
p.000009: 3.3 Expense of developing new treatments
p.000009: Because of the expense of developing a new treatment, commercially funded research understandably focuses on treatment
p.000009: options that are likely to be profitable. Pharmaceutical companies have traditionally been reluctant to invest in
p.000009: developing child-specific treatments or adapting existing medicines to meet the needs of children. The main reasons are
p.000009: that the market is often small and that long-term follow-up of adverse effects is often needed because the risks
p.000009: associated with paediatric treatments are generally higher.17
p.000009:
p.000009: 3.4 Weak licensing and regulation arrangements for paediatric versions of pharmaceuticals
p.000009: The National Audit Office recently reported that up to 90 per cent of medicines prescribed to children in hospitals
p.000009: were not licensed for that use.18 Consequently, there are potentially important public health benefits in improving
p.000009: the licensing of medicines and the testing of their safety for children. Currently in Europe there is no legal
p.000009: requirement for the necessary studies to be performed if the pharmaceutical company does not present the drug for use
p.000009: in children. However, the European Commission has proposed legislation on medicinal products for paediatric use. 17, 19
p.000009:
p.000009:
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000011: 11
p.000011:
p.000011: MRC Ethics Guide: Medical research involving children
p.000011: MRC Ethics Guide: Medical research involving children
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: This regulatory initiative takes its direction mainly from recent US legislation – the US Best Pharmaceuticals for
p.000011: Children Act 2002 and the related 'Pediatric Exclusivity' provision and 'Pediatric Rule'. The Pediatric Exclusivity
p.000011: provision grants an additional six months’ patent protection or market exclusivity to companies that voluntarily test
p.000011: the relevant drug on children, which has been generally well received. The Pediatric Rule demands that companies test
p.000011: their products on children under
p.000011: certain circumstances, including the likelihood of: usage for a substantial number of children, meaningful therapeutic
p.000011: benefits, risk to children in the absence of licensing and usage in different paediatric age groups.
p.000011: The European legislation will probably be finalised in 2006. Meanwhile, a co-ordinated UK strategy led by the Medicines
p.000011: and Healthcare products Regulatory Agency (MHRA) and the Department of Health aims to begin to address the issue and
p.000011: raise awareness in the pharmaceutical industry of the need to take action now to ensure that products are appropriately
p.000011: labelled and formulated for paediatric use.20 The resulting need for more research in paediatric pharmacology was
p.000011: highlighted in the Royal College of Paediatrics and Child Health (RCPCH) review Safer and Better Medicines for
p.000011: Children, which was commissioned by the MRC, the Department of Health and the Association of the British Pharmaceutical
p.000011: Industry. 21
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Searching for indicator influence:
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p.000021: information on the use of personal information in medical research is available from the MRC guidance Personal
p.000021: information in medical research.11
p.000021: Research linked to medical care in an emergency: the handling of this depends on whether the proposed study falls under
p.000021: the Clinical Trials Regulations. For further information please refer to 5.5.4.
p.000021:
p.000021: 5.1.3 Who can give consent, and who should you seek consent from?
p.000021: The law regarding the child's right to consent has developed differently in Scotland than in England, Wales and
p.000021: Northern Ireland – as outlined in 5.1.3a and 5.1.4a below. Generally, where children have sufficient understanding and
p.000021: intelligence to
p.000021: understand what is proposed, it is their consent and not that of their parent/guardian that is required by law.
p.000021: Ethically it is important to involve children as much as possible in decisions about their own health, wellbeing and
p.000021: healthcare. The United Nations Convention on the Rights of the Child states that the child has a right to be informed,
p.000021: to express a view and to influence a decision.27 Methods used to facilitate the consent process should be appropriate
p.000021: to the age and understanding of the child. The Department of Health provides very useful guidance on consent for both
p.000021: patients and clinicians, including guidance for children and for parents/guardians explaining what they have a right to
p.000021: expect.3
p.000021:
p.000021: 5.1.3.a Provision in law for children to consent
p.000021:
p.000021: England, Wales and Northern Ireland
p.000021: Where the Clinical Trial Regulations apply, a minor is defined as someone under the age of 16.
p.000021: Where the common law applies – all situations not covered by the Regulations – the law states that the age of majority
p.000021: is 18. Whilst not considered to have fully reached adulthood, young people between the age of 16 and 18 are presumed to
p.000021: be competent to give consent. No statute governs the rights of those under the age of 16 to give consent for medical
...
Searching for indicator substance:
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p.000041: presence of at least one witness and recorded in writing.”
p.000041:
p.000041: Confidentiality
p.000041: The duty of persons to whom personal information has been given not to share the information with any unauthorised
p.000041: person. For more information about what this involves in practice, see 5.2.
p.000041:
p.000041: Competence
p.000041: The ability of a person, given the necessary information, to understand the nature and the consequences of the proposed
p.000041: procedure or treatment, and to use that information to make a valid choice in accordance with their own fundamental
p.000041: values. Please refer to 5.1.4.
p.000041:
p.000041: Consent
p.000041: The voluntary agreement of an adult or competent child, based on adequate knowledge and understanding of relevant
p.000041: information, to participate in research. For further information please refer to Section 5.
p.000041:
p.000041: Family
p.000041: A group of individuals who together form a social structure; a family may or may not include biological relatives.
p.000041:
p.000041:
p.000041: Harm
p.000041: That which adversely affects the interests or welfare of an individual. This may be physical harm, discomfort, anxiety,
p.000041: pain, and psychological
p.000041:
p.000041: disturbance or social disadvantage (ostracism).
p.000041:
p.000041: Investigational medicinal product
p.000041: A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial,
p.000041: including products already with a marketing authorisation but used or assembled (formulated or packaged) in a way
p.000041: different from the authorised form, or when used for an unauthorised indication, or when used to gain further
p.000041: information about the authorised form.31
p.000041:
p.000041: Off-label
p.000041: Term used to describe a medicine used for an indication, dose, or route of administration outside the terms of the
p.000041: product licence.
p.000041:
p.000041: Parent/guardian
p.000041: The term "parent/guardian" is used in these guidelines to describe those with legal responsibility for the child. The
p.000041: Children Act 1989, the Children (Scotland) Act 1995 and the Children (Northern Ireland) Order 1995 set out who has
p.000041: parental responsibility in their respective jurisdictions. The Adoption and Children Act 2002 s111(2) has recently
p.000041: extended the definition of those with legal responsibility for the child to include unmarried fathers who have entered
p.000041: into a legally binding Parental Responsibility Agreement.42
...
Searching for indicator usage:
(return to top)
p.000009: requirement for the necessary studies to be performed if the pharmaceutical company does not present the drug for use
p.000009: in children. However, the European Commission has proposed legislation on medicinal products for paediatric use. 17, 19
p.000009:
p.000009:
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000011: 11
p.000011:
p.000011: MRC Ethics Guide: Medical research involving children
p.000011: MRC Ethics Guide: Medical research involving children
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: This regulatory initiative takes its direction mainly from recent US legislation – the US Best Pharmaceuticals for
p.000011: Children Act 2002 and the related 'Pediatric Exclusivity' provision and 'Pediatric Rule'. The Pediatric Exclusivity
p.000011: provision grants an additional six months’ patent protection or market exclusivity to companies that voluntarily test
p.000011: the relevant drug on children, which has been generally well received. The Pediatric Rule demands that companies test
p.000011: their products on children under
p.000011: certain circumstances, including the likelihood of: usage for a substantial number of children, meaningful therapeutic
p.000011: benefits, risk to children in the absence of licensing and usage in different paediatric age groups.
p.000011: The European legislation will probably be finalised in 2006. Meanwhile, a co-ordinated UK strategy led by the Medicines
p.000011: and Healthcare products Regulatory Agency (MHRA) and the Department of Health aims to begin to address the issue and
p.000011: raise awareness in the pharmaceutical industry of the need to take action now to ensure that products are appropriately
p.000011: labelled and formulated for paediatric use.20 The resulting need for more research in paediatric pharmacology was
p.000011: highlighted in the Royal College of Paediatrics and Child Health (RCPCH) review Safer and Better Medicines for
p.000011: Children, which was commissioned by the MRC, the Department of Health and the Association of the British Pharmaceutical
p.000011: Industry. 21
p.000011: In addition to the above constraints, the increased complexity of regulation for paediatric and adult clinical research
p.000011: has become more burdensome for clinicians and researchers.
p.000011: 4. The way forward – ethical considerations
p.000011: The following section outlines the key issues to consider when planning and conducting research involving children.
p.000011:
p.000011: 4.1 Does the research need to be carried out with children?
p.000011: Research involving children should only be carried out if it cannot feasibly be carried out on adults. Therefore the
p.000011: researcher needs to assess beforehand whether the same potential benefit for children could be derived from studies on
...
Health / HIV/AIDS
Searching for indicator HIV:
(return to top)
p.000041: On occasion it may be difficult for the researcher to determine who has legal responsibility for the child, and if
p.000041: necessary, further clarification should be sought from the child’s care giver or their GP.
p.000041:
p.000041:
p.000041: Risk
p.000041: A potential harm; the characteristics of risk include the probability of its occurrence, as well as its magnitude and
p.000041: duration. For more on assessment and minimising risk see 4.3.
p.000041:
p.000041: MRC Ethics Guide: Medical research involving children
p.000041: MRC Ethics Guide: Medical research involving children
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: 8. Other MRC ethics guidance
p.000041: The MRC produces a wide range of ethics guidance for researchers, which is available at www.mrc.ac.uk and includes the
p.000041: following:
p.000041: • MRC interim guidance on ethics of research involving human material derived from the nervous system (June 2003).
p.000041: • MRC policy on antiretroviral therapy (ART) for people infected with HIV and involved in AIDS research in
p.000041: developing countries – General guidance notes for consideration (2002).
p.000041: • MRC guidance on reviewing research proposals (2001).
p.000041:
p.000041: • Ethical conduct of research on the mentally incapacitated (1993) – to be revised following the introduction of
p.000041: English legislation. This guidance is no longer applicable in Scotland, following the introduction of the Adults with
p.000041: Incapacity (Scotland) Act 2000.
p.000041: • Good research practice (2000).
p.000041:
p.000041: • Personal information in medical research (2000) – also available as Executive Summary (2000). New guidance on
p.000041: Health and Social Care Act 2001: "Section 60" added – January 2003.
p.000041: • Human tissue and biological samples for use in research: operational and ethical guidelines (2001).
p.000041: • Policy and procedure for inquiring into allegations of scientific misconduct (1997).
p.000041: • Research involving human participants in developing societies: ethical guidelines for MRC-sponsored studies
p.000041: (2004).
p.000041: • Responsibility in the use of animals in medical research (1993).
p.000041:
p.000041: • The MRC's terms and conditions for research grants and training awards involving stem cells (2003).
p.000041: • Cluster randomised trials: Methodological and ethical considerations (2002).
p.000041:
p.000041: • MRC guidelines for good clinical practice in clinical trials (1998).
p.000041:
p.000041: • Health Technology Assessment in surgery (2003).
...
Health / Healthy People
Searching for indicator healthy volunteers:
(return to top)
p.000015:
p.000015:
p.000015:
p.000015:
p.000016: 16
p.000016:
p.000017: 17
p.000017:
p.000017: MRC Ethics Guide: Medical research involving children
p.000017: MRC Ethics Guide: Medical research involving children
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017: Careful consideration of consequences may be required to identify some risks or potential harm. For example, with
p.000017: research into serious genetic disorders that present in adult life, pre-symptomatic diagnosis in a child, while it may
p.000017: be beneficial, may also have harmful effects or implications which may affect the child's
p.000017: opportunities and freedom of choice.23
p.000017:
p.000017: Interim findings: as with adults, if evidence of harm emerges during the trial as a result of giving or withholding
p.000017: certain treatment, the interests of the child
p.000017: participants must be put before the requirements of the research. This must be taken into account by researchers and
p.000017: trial steering committees when deciding on 'stopping rules' for trials and in studies of new techniques.
p.000017: Child volunteers: healthy volunteers should be treated in the same way as other child participants. Please see 5.1.4
p.000017: for more information. It is ethical for a healthy child to participate in research as long as appropriate consent has
p.000017: been obtained, there is no more than minimal risk and the research is not against the child's interest.
p.000017: Participation in more than one research study: as with adults, there may be situations where it could be argued that
p.000017: participation in more than one trial or study might be potentially beneficial – both for participants and for the
p.000017: research. The potential benefits and risks of doing so would need to be carefully explored by all concerned, and
p.000017: clearly understood by the child and family.24
p.000017: Equipoise: this is when there is genuine uncertainty among those who have considered the issue, including patients,
p.000017: about the relative benefits and risks of treatments or tests being compared. A clinical trial cannot be ethical unless
p.000017: there is this genuine informed uncertainty among the expert medical community and in an informed competent
p.000017: patient/participant.
p.000017: 4.3.2 Minimising risk
p.000017: The National Academy of the Sciences provides guidance on how to minimise risk, summarised here: 25
p.000017:
...
Searching for indicator volunteers:
(return to top)
p.000015:
p.000015:
p.000015:
p.000015:
p.000016: 16
p.000016:
p.000017: 17
p.000017:
p.000017: MRC Ethics Guide: Medical research involving children
p.000017: MRC Ethics Guide: Medical research involving children
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017: Careful consideration of consequences may be required to identify some risks or potential harm. For example, with
p.000017: research into serious genetic disorders that present in adult life, pre-symptomatic diagnosis in a child, while it may
p.000017: be beneficial, may also have harmful effects or implications which may affect the child's
p.000017: opportunities and freedom of choice.23
p.000017:
p.000017: Interim findings: as with adults, if evidence of harm emerges during the trial as a result of giving or withholding
p.000017: certain treatment, the interests of the child
p.000017: participants must be put before the requirements of the research. This must be taken into account by researchers and
p.000017: trial steering committees when deciding on 'stopping rules' for trials and in studies of new techniques.
p.000017: Child volunteers: healthy volunteers should be treated in the same way as other child participants. Please see 5.1.4
p.000017: for more information. It is ethical for a healthy child to participate in research as long as appropriate consent has
p.000017: been obtained, there is no more than minimal risk and the research is not against the child's interest.
p.000017: Participation in more than one research study: as with adults, there may be situations where it could be argued that
p.000017: participation in more than one trial or study might be potentially beneficial – both for participants and for the
p.000017: research. The potential benefits and risks of doing so would need to be carefully explored by all concerned, and
p.000017: clearly understood by the child and family.24
p.000017: Equipoise: this is when there is genuine uncertainty among those who have considered the issue, including patients,
p.000017: about the relative benefits and risks of treatments or tests being compared. A clinical trial cannot be ethical unless
p.000017: there is this genuine informed uncertainty among the expert medical community and in an informed competent
p.000017: patient/participant.
p.000017: 4.3.2 Minimising risk
p.000017: The National Academy of the Sciences provides guidance on how to minimise risk, summarised here: 25
p.000017:
...
Health / Mentally Disabled
Searching for indicator mentally:
(return to top)
p.000041:
p.000041:
p.000041: Risk
p.000041: A potential harm; the characteristics of risk include the probability of its occurrence, as well as its magnitude and
p.000041: duration. For more on assessment and minimising risk see 4.3.
p.000041:
p.000041: MRC Ethics Guide: Medical research involving children
p.000041: MRC Ethics Guide: Medical research involving children
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: 8. Other MRC ethics guidance
p.000041: The MRC produces a wide range of ethics guidance for researchers, which is available at www.mrc.ac.uk and includes the
p.000041: following:
p.000041: • MRC interim guidance on ethics of research involving human material derived from the nervous system (June 2003).
p.000041: • MRC policy on antiretroviral therapy (ART) for people infected with HIV and involved in AIDS research in
p.000041: developing countries – General guidance notes for consideration (2002).
p.000041: • MRC guidance on reviewing research proposals (2001).
p.000041:
p.000041: • Ethical conduct of research on the mentally incapacitated (1993) – to be revised following the introduction of
p.000041: English legislation. This guidance is no longer applicable in Scotland, following the introduction of the Adults with
p.000041: Incapacity (Scotland) Act 2000.
p.000041: • Good research practice (2000).
p.000041:
p.000041: • Personal information in medical research (2000) – also available as Executive Summary (2000). New guidance on
p.000041: Health and Social Care Act 2001: "Section 60" added – January 2003.
p.000041: • Human tissue and biological samples for use in research: operational and ethical guidelines (2001).
p.000041: • Policy and procedure for inquiring into allegations of scientific misconduct (1997).
p.000041: • Research involving human participants in developing societies: ethical guidelines for MRC-sponsored studies
p.000041: (2004).
p.000041: • Responsibility in the use of animals in medical research (1993).
p.000041:
p.000041: • The MRC's terms and conditions for research grants and training awards involving stem cells (2003).
p.000041: • Cluster randomised trials: Methodological and ethical considerations (2002).
p.000041:
p.000041: • MRC guidelines for good clinical practice in clinical trials (1998).
p.000041:
p.000041: • Health Technology Assessment in surgery (2003).
p.000041:
p.000041:
p.000041: Additional guidance available by post includes:
p.000041:
p.000041: • Principles in the assessment and conduct of medical research and publicising results (1995).
p.000041:
p.000041:
p.000041:
p.000044: 44
p.000044:
p.000045: 45
p.000045:
...
Searching for indicator disability:
(return to top)
p.000009: MRC Ethics Guide: Medical research involving children
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: attitudes towards research involving children. Earlier research tended to be on children, with children regarded as
p.000009: subjects of the research. Increasingly, research is conducted with children, who are involved as active participants.
p.000009:
p.000009: 3.2 Methodological challenges
p.000009: Smyth and Weindling describe how the emergence of evidence-based healthcare has led to a greater awareness of the need
p.000009: to evaluate critically what is already known before making recommendations for clinical practice or embarking on
p.000009: further research.14 Studies have shown that in comparison to research on adults, research questions relevant to the
p.000009: health of children may not have been addressed at all, or only by small, poorly designed studies.15
p.000009: Particular methodological challenges occur in research involving children. Childhood forms of many chronic diseases,
p.000009: eg, juvenile chronic arthritis, are uncommon and this may lead to difficulties in gaining statistical power to detect
p.000009: an effective treatment.
p.000009: Genetic disorders leading to severe disability or death are also rare.
p.000009:
p.000009: Even for more common conditions challenges arise. In asthma, for example, the diagnosis may be subjective, which poses
p.000009: problems in establishing the clear inclusion and exclusion criteria required for clinical trials. Standard outcome
p.000009: measures in adults include death and quality of life, but for many conditions different outcomes are more relevant.
p.000009: Measurements of these outcomes have been determined for use in adults specifically and may not be relevant for
p.000009: children. Quality of life measures can be used, but should be focused on the child or family and validated and tested
p.000009: for reliability and responsiveness to change before being used; such instruments have not always been available.
p.000009: It is therefore useful, and important, to consult children about outcome measures and other issues, when the research
p.000009: is being designed.
p.000009: When carrying out research on children, it is important to assess both the short- term and long-term outcomes. For
p.000009: example, early treatment of premature infants at high risk of chronic lung disease with steroid drugs reduces this
p.000009: risk, but long-term studies show an increased risk of cerebral palsy.16
p.000009: Investigations of cognitive, neurological and respiratory function can also pose challenges, eg, the inability of young
...
p.000037: unable to do so. This could be the doctor primarily responsible for the person’s treatment (if not involved in the
p.000037: trial) or, if they are not available, a person nominated by the healthcare provider.41
p.000037:
p.000037: 5.5.5 Including minority groups – equality in research
p.000037: As with adults it is important to include minority groups in research involving children to ensure that they as a group
p.000037: receive a share of the potential benefits of research.
p.000037: Researchers should be sensitive to cultural issues and particularly to participants' specific concerns and values. For
p.000037: example, whether acceptance of research is necessary from someone in the extended cultural group as well as the
p.000037: immediate family, or whether participants undertake religious fasts that may affect when they can take medicines.
p.000037: When seeking consent where the child or parent needs an interpreter, an independent interpreter is preferable to a
p.000037: family member.
p.000037: Where the child has a disability, particular care should be taken to ensure that information is provided in a suitable
p.000037: form. Specialist colleagues may be able to act as
p.000037: facilitators or advocates where the child has particular needs. Children with specific impairments such as learning
p.000037: difficulties should not be excluded from participating in research, but equally should not be over-researched because
p.000037: of their condition.
p.000037:
p.000037: 5.5.6 Research in developing countries
p.000037: Please refer to MRC guidance on Research involving human participants in developing societies.
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000039: 39
p.000039:
p.000039: MRC Ethics Guide: Medical research involving children
p.000039: MRC Ethics Guide: Medical research involving children
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: 6. Summary
p.000039: Children should be included in medical research only if:
p.000039:
p.000039: • The relevant knowledge cannot be gained through research with adults.
p.000039:
p.000039: • It is approved by the appropriate Research Ethics Committee/s.
p.000039:
...
Health / Motherhood/Family
Searching for indicator family:
(return to top)
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005: • The purpose of the research is to obtain knowledge relevant to the health, wellbeing or healthcare needs of
p.000005: children.
p.000005: • Researchers can only involve competent children if they have obtained their informed consent beforehand.
p.000005: • A child's refusal to participate or continue in research should always be respected.
p.000005: • If a child becomes upset by a procedure, researchers must accept this as a valid refusal.
p.000005: • Researchers should involve parents/guardians in the decision to participate wherever possible, and in all cases
p.000005: where the child is not yet competent. Exceptional circumstances where this is not possible are discussed in 5.5.4.
p.000005: • Researchers should attempt to avoid any pressures that might lead the child to volunteer for research or that
p.000005: might lead parents to volunteer their children, in the expectation of direct benefit (whether therapeutic or
p.000005: financial).
p.000005: • Research involves partnership with the child and/or family, who should be kept informed and consent to separate
p.000005: stages of the project. Obtaining consent is a continuing process, rather than a one-off occurrence. Children and their
p.000005: families are likely to appreciate some recognition of their role in this partnership, such as a certificate of
p.000005: participation.
p.000005: • Researchers must take account of the cumulative medical, emotional, social and psychological consequences of the
p.000005: child being involved in research. Children with certain conditions may be exposed to a sequence of research projects.
p.000005: It is advisable to consider the risks of a particular research procedure in the context of the child's overall
p.000005: involvement in projects by different researchers.
p.000005: 2. Why do we need research involving children?
p.000005: Medical research involving children is essential for advancing child health and wellbeing. Often it is not sufficient,
p.000005: scientific, or ethical to carry out research with adults and apply the findings to children. This may be because:
p.000005: • The disease processes in children may differ from those in adults. Some childhood diseases have no close
...
p.000009:
p.000009: 3.2 Methodological challenges
p.000009: Smyth and Weindling describe how the emergence of evidence-based healthcare has led to a greater awareness of the need
p.000009: to evaluate critically what is already known before making recommendations for clinical practice or embarking on
p.000009: further research.14 Studies have shown that in comparison to research on adults, research questions relevant to the
p.000009: health of children may not have been addressed at all, or only by small, poorly designed studies.15
p.000009: Particular methodological challenges occur in research involving children. Childhood forms of many chronic diseases,
p.000009: eg, juvenile chronic arthritis, are uncommon and this may lead to difficulties in gaining statistical power to detect
p.000009: an effective treatment.
p.000009: Genetic disorders leading to severe disability or death are also rare.
p.000009:
p.000009: Even for more common conditions challenges arise. In asthma, for example, the diagnosis may be subjective, which poses
p.000009: problems in establishing the clear inclusion and exclusion criteria required for clinical trials. Standard outcome
p.000009: measures in adults include death and quality of life, but for many conditions different outcomes are more relevant.
p.000009: Measurements of these outcomes have been determined for use in adults specifically and may not be relevant for
p.000009: children. Quality of life measures can be used, but should be focused on the child or family and validated and tested
p.000009: for reliability and responsiveness to change before being used; such instruments have not always been available.
p.000009: It is therefore useful, and important, to consult children about outcome measures and other issues, when the research
p.000009: is being designed.
p.000009: When carrying out research on children, it is important to assess both the short- term and long-term outcomes. For
p.000009: example, early treatment of premature infants at high risk of chronic lung disease with steroid drugs reduces this
p.000009: risk, but long-term studies show an increased risk of cerebral palsy.16
p.000009: Investigations of cognitive, neurological and respiratory function can also pose challenges, eg, the inability of young
p.000009: children to understand and co-operate with the demands of complex tasks.
p.000009:
p.000009: 3.3 Expense of developing new treatments
p.000009: Because of the expense of developing a new treatment, commercially funded research understandably focuses on treatment
p.000009: options that are likely to be profitable. Pharmaceutical companies have traditionally been reluctant to invest in
...
p.000017: opportunities and freedom of choice.23
p.000017:
p.000017: Interim findings: as with adults, if evidence of harm emerges during the trial as a result of giving or withholding
p.000017: certain treatment, the interests of the child
p.000017: participants must be put before the requirements of the research. This must be taken into account by researchers and
p.000017: trial steering committees when deciding on 'stopping rules' for trials and in studies of new techniques.
p.000017: Child volunteers: healthy volunteers should be treated in the same way as other child participants. Please see 5.1.4
p.000017: for more information. It is ethical for a healthy child to participate in research as long as appropriate consent has
p.000017: been obtained, there is no more than minimal risk and the research is not against the child's interest.
p.000017: Participation in more than one research study: as with adults, there may be situations where it could be argued that
p.000017: participation in more than one trial or study might be potentially beneficial – both for participants and for the
p.000017: research. The potential benefits and risks of doing so would need to be carefully explored by all concerned, and
p.000017: clearly understood by the child and family.24
p.000017: Equipoise: this is when there is genuine uncertainty among those who have considered the issue, including patients,
p.000017: about the relative benefits and risks of treatments or tests being compared. A clinical trial cannot be ethical unless
p.000017: there is this genuine informed uncertainty among the expert medical community and in an informed competent
p.000017: patient/participant.
p.000017: 4.3.2 Minimising risk
p.000017: The National Academy of the Sciences provides guidance on how to minimise risk, summarised here: 25
p.000017:
p.000017: Minimising risk in research involving children
p.000017:
p.000017: • Is inclusion of children necessary to answer the scientific question posed by the research? What are the ages
p.000017: of the children to be included? Are any of the potential research harms age-dependent?
p.000017: • Will potential child participants be screened for known vulnerability to the risks associated with specific
p.000017: elements of the research?
p.000017: • What does the research require of children and their families? Is adherence to the research protocol a
p.000017: concern? If so, what are the risks of non-adherence?
p.000017: • Are all the procedures or interventions necessary to answer the research question? Can the investigators
...
p.000025: to understand and weigh up options. It can be influenced by the way information is presented – many children will be
p.000025: competent if information is presented in an appropriate way and they are
p.000025: supported through the decision-making process. The Central Office for Research Ethics Committees (COREC) provides a
p.000025: useful template for designing patient information sheets and seeking assent/consent from children and young people.33 A
p.000025: child's ability to consent develops as he or she learns to make increasingly complex and serious decisions, which can
p.000025: be experience and/or age-related.
p.000025: For people to be able to have the capacity to take a particular decision they must be able to: 34
p.000025: • Comprehend and retain information material to the decision, especially the consequences of having or not having
p.000025: any intervention.
p.000025: • Use and weigh this information in a decision-making process.
p.000025:
p.000025: • Reach and communicate a decision.
p.000025:
p.000025: Even if the child is competent, it is still normally good practice to involve the family in the decision-making
p.000025: process. It is particularly desirable to obtain parental consent for younger children or for procedures that carry any
p.000025: risk or discomfort.
p.000025: If the competent child specifically asks for the family not to be involved in the decision-making process and they
p.000025: cannot be persuaded otherwise, their privacy should be respected.
p.000025: For further information please see 5.2.
p.000025:
p.000025:
p.000025:
p.000025: ii Extract from MHRA Description of the Medicines for Human Use (Clinical Trials) Regulations 2004.32
p.000025:
p.000025:
p.000026: 26
p.000026:
p.000027: 27
p.000027:
p.000027: MRC Ethics Guide: Medical research involving children
p.000027: MRC Ethics Guide: Medical research involving children
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027: 5.1.4.a Children unable to consent to involvement, and parental consent
p.000027: If the child is deemed incompetent to consent to participate in research, then he or she should normally not
p.000027: participate without the consent of a person with parental responsibility. A person with parental responsibility may
p.000027: legally consent to treatment on an incompetent child's behalf. If the child is able to give assent to decisions about
...
p.000033: parent/guardian, without their consent. However, it is important that wherever possible the parents/guardians are
p.000033: informed, and young people should be encouraged to involve them unless it is not in their best interests to do so. If
p.000033: competent children do not wish to involve their parents/guardians this should be respected. Disclosure can only be
p.000033: justified if there is reasonable cause to suspect that the child is suffering or is likely to suffer significant harm
p.000033: as a result of non-disclosure. Any decision to disclose confidential information to a third party must be relayed to
p.000033: the competent child before disclosure.
p.000033: To facilitate both the child's healthcare and longer term research, general practitioners (GPs) should be notified of
p.000033: all research on their paediatric patients. The consent form should request consent to inform and update GPs of the
p.000033: child's involvement. If a participant is likely to resist information being provided to parents/guardians and family
p.000033: practitioners because the research is of a sensitive
p.000033: nature, eg, investigating smoking habits or sexual health, advice should be sought from the Research Ethics Committee
p.000033: that assesses the protocol.
p.000033: Children who lack competence to consent to participate are nevertheless entitled to confidentiality. The researcher
p.000033: will have had to request the parent/guardian's consent to the child's involvement in research. Any intention to
p.000033: disclose information to anyone else should be discussed with both the parent/guardian and the child, taking into
p.000033: consideration whether disclosure to a third party is necessary in the interests of the child's health. Public health
p.000033: research may require the use of anonymous data without explicit consent – for detailed guidance on this researchers
p.000033: should consult the MRC guidance Personal information in medical research.11
p.000033: Researchers working with children have important responsibilities in relation to child protection. Where researchers
...
p.000037: Under the Clinical Trial Regulations, consent must be given on behalf of a minor prior to participation in a trial of
p.000037: an investigational medicinal product in all circumstances; there is currently no exception for emergency situations.
p.000037: However, it is possible for someone other than a parent to give consent as a “legal representative”, if the parent is
p.000037: unable to do so. This could be the doctor primarily responsible for the person’s treatment (if not involved in the
p.000037: trial) or, if they are not available, a person nominated by the healthcare provider.41
p.000037:
p.000037: 5.5.5 Including minority groups – equality in research
p.000037: As with adults it is important to include minority groups in research involving children to ensure that they as a group
p.000037: receive a share of the potential benefits of research.
p.000037: Researchers should be sensitive to cultural issues and particularly to participants' specific concerns and values. For
p.000037: example, whether acceptance of research is necessary from someone in the extended cultural group as well as the
p.000037: immediate family, or whether participants undertake religious fasts that may affect when they can take medicines.
p.000037: When seeking consent where the child or parent needs an interpreter, an independent interpreter is preferable to a
p.000037: family member.
p.000037: Where the child has a disability, particular care should be taken to ensure that information is provided in a suitable
p.000037: form. Specialist colleagues may be able to act as
p.000037: facilitators or advocates where the child has particular needs. Children with specific impairments such as learning
p.000037: difficulties should not be excluded from participating in research, but equally should not be over-researched because
p.000037: of their condition.
p.000037:
p.000037: 5.5.6 Research in developing countries
p.000037: Please refer to MRC guidance on Research involving human participants in developing societies.
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000039: 39
p.000039:
p.000039: MRC Ethics Guide: Medical research involving children
p.000039: MRC Ethics Guide: Medical research involving children
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: 6. Summary
p.000039: Children should be included in medical research only if:
p.000039:
p.000039: • The relevant knowledge cannot be gained through research with adults.
p.000039:
p.000039: • It is approved by the appropriate Research Ethics Committee/s.
p.000039:
...
p.000039: decision –
p.000039: (a) is given freely after that person is informed of the nature, significance, implications and risks of the trial;
p.000039: and
p.000039:
p.000039:
p.000040: 40
p.000040:
p.000041: 41
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: (b) either –
p.000041: (i) is evidenced in writing, dated and signed, or otherwise marked, by that person so as to indicate his consent, or
p.000041: (ii) If the person is unable to sign or to mark a document so as to indicate his consent, is given orally in the
p.000041: presence of at least one witness and recorded in writing.”
p.000041:
p.000041: Confidentiality
p.000041: The duty of persons to whom personal information has been given not to share the information with any unauthorised
p.000041: person. For more information about what this involves in practice, see 5.2.
p.000041:
p.000041: Competence
p.000041: The ability of a person, given the necessary information, to understand the nature and the consequences of the proposed
p.000041: procedure or treatment, and to use that information to make a valid choice in accordance with their own fundamental
p.000041: values. Please refer to 5.1.4.
p.000041:
p.000041: Consent
p.000041: The voluntary agreement of an adult or competent child, based on adequate knowledge and understanding of relevant
p.000041: information, to participate in research. For further information please refer to Section 5.
p.000041:
p.000041: Family
p.000041: A group of individuals who together form a social structure; a family may or may not include biological relatives.
p.000041:
p.000041:
p.000041: Harm
p.000041: That which adversely affects the interests or welfare of an individual. This may be physical harm, discomfort, anxiety,
p.000041: pain, and psychological
p.000041:
p.000041: disturbance or social disadvantage (ostracism).
p.000041:
p.000041: Investigational medicinal product
p.000041: A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial,
p.000041: including products already with a marketing authorisation but used or assembled (formulated or packaged) in a way
p.000041: different from the authorised form, or when used for an unauthorised indication, or when used to gain further
p.000041: information about the authorised form.31
p.000041:
p.000041: Off-label
p.000041: Term used to describe a medicine used for an indication, dose, or route of administration outside the terms of the
p.000041: product licence.
p.000041:
p.000041: Parent/guardian
p.000041: The term "parent/guardian" is used in these guidelines to describe those with legal responsibility for the child. The
p.000041: Children Act 1989, the Children (Scotland) Act 1995 and the Children (Northern Ireland) Order 1995 set out who has
...
Health / Physically Disabled
Searching for indicator illness:
(return to top)
p.000025: MRC Ethics Guide: Medical research involving children
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025: Key provisions for the protection of minors within the Medicines for Human Use (Clinical Trials) Regulations 2004
p.000025: (Regulation 15 and Part 4 of Schedule 1) – extract from MHRA adviceii
p.000025:
p.000025: The Regulations provide additional protection for a minor (a person under the age of
p.000025: 16) who is a candidate for a clinical trial.They require, among other provisions, that:
p.000025:
p.000025: • an ethics committee considering the trial must receive advice on the relevant field of paediatric care; and
p.000025: • a person with parental responsibility or a legal representative must give informed consent and may withdraw the
p.000025: young person at any time; and, in relation to the minor himself:
p.000025: • staff with experience with young persons must inform him/her of the risks and benefits of the trial according to
p.000025: his capacity to understand;
p.000025: • the investigator must consider his or her explicit wish to refuse to participate or to be withdrawn from the
p.000025: trial at any time;
p.000025: • the clinical trial relate directly to an illness from which he or she suffers or that can only be carried out on
p.000025: minors; and
p.000025: • the trial must aim to provide some direct benefit for the group of patients involved.
p.000025: 5.1.4 Assessing the competence of a child to consent
p.000025: While normally increasing with age, competence is considered not to depend primarily on age, but rather on the ability
p.000025: to understand and weigh up options. It can be influenced by the way information is presented – many children will be
p.000025: competent if information is presented in an appropriate way and they are
p.000025: supported through the decision-making process. The Central Office for Research Ethics Committees (COREC) provides a
p.000025: useful template for designing patient information sheets and seeking assent/consent from children and young people.33 A
p.000025: child's ability to consent develops as he or she learns to make increasingly complex and serious decisions, which can
p.000025: be experience and/or age-related.
p.000025: For people to be able to have the capacity to take a particular decision they must be able to: 34
p.000025: • Comprehend and retain information material to the decision, especially the consequences of having or not having
...
Health / Pregnant
Searching for indicator pregnant:
(return to top)
p.000045: 18. National Audit Office Report (HC 255 2002-2003). Safety, quality, efficacy: regulating medicines in the UK.
p.000045: London: the Stationery Office, 2003.
p.000045: 19. Smith Robert N. 2000. Meeting report – A European conference on clinical research in children: ethical,
p.000045: scientific and regulatory issues. Section: "Research, the rights of the child and legal considerations in paediatric
p.000045: clinical research". International Journal of Pharmaceutical Medicine; reprinted from: Archives of Disease in Childhood
p.000045: 16:15-29.
p.000045: 20. Medicines and Healthcare products Regulatory Agency/Department of Health: Strategy on Medicines for Children,
p.000045: July 2004. http://medicines.mhra.gov.uk/ourwork/licensingmeds/children/paediatricstrategydoc.pdf
p.000045: 21. Safer and Better Medicines for Children – Developing the Clinical and Research Base of Paediatric
p.000045: Pharmacology in the United Kingdom. Royal College of Paediatrics and Child Health Review (commissioned by the MRC, the
p.000045: Department of Health, and the Association of the British Pharmaceutical Industry), May 2004.
p.000045: 22. Research: the role and responsibilities of doctors. London: General Medical Council, 2002.
p.000045: 23. Testing for late onset genetic disorders. London: British Paediatric Association, 1996.
p.000045: 24. Brocklehurst P. 1997. "Randomised controlled trials in perinatal medicine: 2. Recruitment of a pregnant woman
p.000045: or her newborn child into more than one trial." British Journal of Obstetrics and Gynaecology 104 (7):765-7.
p.000045: 25. Ethical Conduct of Clinical Research Involving Children.The National Academy of the Sciences USA, 2004.
p.000045: 26. The Medicines for Human Use (Clinical Trials) Regulations. 2004.
p.000045: www.legislation.hmso.gov.uk/si/si2004/20041031.htm
p.000045:
p.000045: 27. UN Convention on the Rights of the Child. General Assembly resolution 44/25 of 20 November 1989, entry into
p.000045: force 2 September 1990 in accordance with article 49. www.childrenslawcentre.org/UNCRC_hearing.htm
p.000045: 28. Gillick v West Norfolk and Wisbech. London: House of Lords, Gillick v West Norfolk and Wisbech AHA (1986) AC
p.000045: 112, [1985] 3 WLR 830, [1985] 3 AII ER 402, HL
p.000045: 29. Age of Majority (Scotland) Act 1969 s 1.
p.000045: 30. Age of Legal Capacity (Scotland) Act 1991. (c. 50)
p.000045: 31. Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of
p.000045: the laws, regulations and administrative provisions of the Member States relating to the implementation of good
p.000045: clinical practice in the conduct of clinical trials on medicinal products for human use.
p.000045: http://europa.eu.int/eur-lex/pri/en/oj/dat/2001/l_121/l_12120010501en00340044.pdf
p.000045:
p.000045:
p.000045:
p.000046: 46
p.000046:
p.000047: 47
p.000047:
p.000047:
p.000047:
...
Health / ill
Searching for indicator ill:
(return to top)
p.000035:
p.000035: 5.4 Children's safety in relation to researchers
p.000035: Any individual recruited by the MRC to work directly with children will undergo security screening, including criminal
p.000035: records review. This includes nurses, survey interviewers and some individuals involved in a clinically invasive
p.000035: capacity, eg, phlebotomists. The MRC expects its grant-holding institutions to do likewise.
p.000035: Security screening is complementary to other good recruitment practices and not a substitute for them. Staff involved
p.000035: in MRC's recruitment process are responsible for ensuring that standard checks are still made.
p.000035:
p.000035: 5.5 Specific situations
p.000035:
p.000035: 5.5.1 Research involving human material
p.000035: Please refer to the MRC guidance Human tissue and biological samples for use in research.12
p.000035: Further guidance will be issued when the Human Tissue Bill, and equivalent legislation in Scotland, become law.
p.000035: 5.5.2 The use of personal information
p.000035: Please refer to the MRC guidance Personal information in medical research.11
p.000035:
p.000035: 5.5.3 Research involving very young children
p.000035: A parent/guardian's informed consent is necessary for the involvement of babies in research. When a baby is seriously
p.000035: ill and a decision about treatment is required quickly, the pressure on parents is high and the difficulty of obtaining
p.000035: truly informed consent is recognised. The RCPCH provides detailed guidance relating to research involving babies.40
p.000035:
p.000035: 5.5.4 Emergency situations
p.000035: Under common law, provided that the specific approval of a research ethics committee has been obtained for the project
p.000035: overall, it is ethical to carry out research involving children on occasions of extreme urgency without obtaining prior
p.000035: consent. However, there is a lack of clarity in the law about this if the research does not have the potential to
p.000035: benefit the child in question. If in doubt, it would be advisable to seek legal advice in potentially contentious
p.000035: circumstances.
p.000035: Research involving children in an emergency situation may be needed when treatment is available only as part of a
p.000035: research programme. Ethically, if the research does not have the potential to produce results of direct benefit to the
p.000035: individual participant, the Council of Europe recommends that it should only be carried out if it has the aim of
p.000035: contributing or improving understanding of the individual's condition so that it could ultimately confer benefit upon
...
Health / patients in emergency situations
Searching for indicator emergency situation:
(return to top)
p.000035: 5.5.2 The use of personal information
p.000035: Please refer to the MRC guidance Personal information in medical research.11
p.000035:
p.000035: 5.5.3 Research involving very young children
p.000035: A parent/guardian's informed consent is necessary for the involvement of babies in research. When a baby is seriously
p.000035: ill and a decision about treatment is required quickly, the pressure on parents is high and the difficulty of obtaining
p.000035: truly informed consent is recognised. The RCPCH provides detailed guidance relating to research involving babies.40
p.000035:
p.000035: 5.5.4 Emergency situations
p.000035: Under common law, provided that the specific approval of a research ethics committee has been obtained for the project
p.000035: overall, it is ethical to carry out research involving children on occasions of extreme urgency without obtaining prior
p.000035: consent. However, there is a lack of clarity in the law about this if the research does not have the potential to
p.000035: benefit the child in question. If in doubt, it would be advisable to seek legal advice in potentially contentious
p.000035: circumstances.
p.000035: Research involving children in an emergency situation may be needed when treatment is available only as part of a
p.000035: research programme. Ethically, if the research does not have the potential to produce results of direct benefit to the
p.000035: individual participant, the Council of Europe recommends that it should only be carried out if it has the aim of
p.000035: contributing or improving understanding of the individual's condition so that it could ultimately confer benefit upon
p.000035: the patient or others with the same condition, and that it entails only minimal risk.9
p.000035: Research involving children in emergency situations should be carried out only where research of comparable
p.000035: effectiveness cannot be carried out on persons in non- emergency situations. The parents and child must be informed
p.000035: about the research as
p.000035:
p.000036: 36
p.000036:
p.000037: 37
p.000037:
p.000037: MRC Ethics Guide: Medical research involving children
p.000037: MRC Ethics Guide: Medical research involving children
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037: soon as possible afterwards and their consent for future involvement sought. It must be made clear that the child (or
...
Health / stem cells
Searching for indicator stem cells:
(return to top)
p.000041: • MRC policy on antiretroviral therapy (ART) for people infected with HIV and involved in AIDS research in
p.000041: developing countries – General guidance notes for consideration (2002).
p.000041: • MRC guidance on reviewing research proposals (2001).
p.000041:
p.000041: • Ethical conduct of research on the mentally incapacitated (1993) – to be revised following the introduction of
p.000041: English legislation. This guidance is no longer applicable in Scotland, following the introduction of the Adults with
p.000041: Incapacity (Scotland) Act 2000.
p.000041: • Good research practice (2000).
p.000041:
p.000041: • Personal information in medical research (2000) – also available as Executive Summary (2000). New guidance on
p.000041: Health and Social Care Act 2001: "Section 60" added – January 2003.
p.000041: • Human tissue and biological samples for use in research: operational and ethical guidelines (2001).
p.000041: • Policy and procedure for inquiring into allegations of scientific misconduct (1997).
p.000041: • Research involving human participants in developing societies: ethical guidelines for MRC-sponsored studies
p.000041: (2004).
p.000041: • Responsibility in the use of animals in medical research (1993).
p.000041:
p.000041: • The MRC's terms and conditions for research grants and training awards involving stem cells (2003).
p.000041: • Cluster randomised trials: Methodological and ethical considerations (2002).
p.000041:
p.000041: • MRC guidelines for good clinical practice in clinical trials (1998).
p.000041:
p.000041: • Health Technology Assessment in surgery (2003).
p.000041:
p.000041:
p.000041: Additional guidance available by post includes:
p.000041:
p.000041: • Principles in the assessment and conduct of medical research and publicising results (1995).
p.000041:
p.000041:
p.000041:
p.000044: 44
p.000044:
p.000045: 45
p.000045:
p.000045: MRC Ethics Guide: Medical research involving children
p.000045: MRC Ethics Guide: Medical research involving children
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045: 9. References
p.000045: 1. The ethical conduct of research on children. London: Medical Research Council (MRC), 1991.
p.000045: 2. Royal College of Paediatrics and Child Health: Ethics Advisory Committee. 2002. "Guidelines for the ethical
p.000045: conduct of medical research involving children". Reprinted from Archives of Disease in Childhood 82 (2): 177-182.
p.000045: 3. Department of Health: Consent guidance webpages. www.dh.gov.uk/PolicyAndGuidance/
p.000045: HealthAndSocialCareTopics/Consent/ConsentGeneralInformation/fs/en
...
Health / visual impairment
Searching for indicator blind:
(return to top)
p.000029: • Exert no pressure on families.
p.000029: • Give them as much time as possible (a few days for a major study, if at all possible) to consider whether to take
p.000029: part in the project.
p.000029: • Encourage families to discuss the project with – for example – their relatives, primary health carers – or an
p.000029: independent counsellor where available.
p.000029: • Tell them that they may refuse to take part, or may withdraw at any time even if they have signed a consent form.
p.000029: • Say that they need not give a reason for withdrawing (although their reason may help the researchers and other
p.000029: children in the study).
p.000029: • Assure them that the child patient's treatment will not be prejudiced by withdrawal from research.
p.000029: • Encourage parents/guardians to stay with the child during procedures.
p.000029: • Respond to families' questions, anxiety or distress throughout the study.
p.000029:
p.000029: For consent to be informed researchers must discuss with families:
p.000029:
p.000029: • The purpose of the research.
p.000029: • Whether the child stands to benefit directly and if so how; the difference between research and treatment.
p.000029: • The meaning of relevant research terms and any implications of consent (eg, placebo, randomised double-blind
p.000029: trial).
p.000029: • The nature of each procedure, how often and for how long each may occur.
p.000029: • The potential benefits and harms (both immediate and long-term).
p.000029: • The name of a researcher whom they can contact with their enquiries.
p.000029: • The name of the doctor directly responsible for the child's care.
p.000029: • How the child can withdraw from the project.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: Researchers must also:
p.000029:
p.000029: • Willingly explain and answer questions throughout the project.
p.000029: • Ensure that other staff caring for child subjects know about the research, and can also explain it if necessary.
p.000029: • Give clearly written patient information leaflets setting out all relevant information for families to keep
p.000029: (guidance on this can be found on the COREC website 33).
p.000029: • Report the results of research to the families involved wherever possible.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000030: 30
p.000030:
p.000031: 31
p.000031:
p.000031: MRC Ethics Guide: Medical research involving children
p.000031: MRC Ethics Guide: Medical research involving children
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 5.1.6 Seeking consent – a summaryiii
p.000031:
...
Social / Access to Social Goods
Searching for indicator access:
(return to top)
p.000019: assessments specified in the protocol and recognise potential risks and adverse outcomes? Does the research team have
p.000019: appropriate skills and expertise in caring for children of the ages included in the study?
p.000019: • Will research be performed in a setting that is 'friendly' to children of the ages included in the study? Is
p.000019: the setting appropriate for the physical, clinical, psychological and emotional needs of those age groups?
p.000019: • For research that involves more than minimal risk, does the research protocol have an adequate plan for
p.000019: monitoring the safety of the child participants? Does the monitoring plan provide for the inclusion of professionals
p.000019: with the appropriate expertise in paediatrics?
p.000019: • If the protocol presents the risk of a physical or psychological emergency, is the research setting equipped
p.000019: to respond? Are plans for responding to an emergency specified in the protocol?
p.000019: • What are the stopping rules or 'endpoints' for early discontinuation of the research on the basis of strong
p.000019: findings about harms or benefits? Are they specific and appropriate?
p.000019: • What happens to the data once they are collected? Where are research records stored, and who has access to
p.000019: them? What are the practices and procedures for maintaining the short-term and long-term confidentiality of the data?
p.000019: 5. Children, ethics and the law
p.000019:
p.000019: 5.1 Consent
p.000019:
p.000019: 5.1.1 What is valid consent?
p.000019:
p.000019: Consent – The voluntary agreement of an adult or competent child, based on adequate knowledge and understanding of
p.000019: relevant information, to participate in research
p.000019:
p.000019: Consent is legally valid and professionally acceptable only where the participants (or their parental guardian) are
p.000019: competent to give consent, have been properly informed, and have agreed without coercion.22
p.000019:
p.000019:
p.000019: In the UK, there are now two legal systems running in parallel.The common law applies to research not involving the
p.000019: Clinical Trials Regulations. As of May 2004, the Medicines for Human Use (Clinical Trials) Regulations apply to
p.000019: research involving investigational medicinal products (see Glossary). Researchers need to familiarise themselves with
p.000019: the Regulations.26
p.000019:
p.000019: 5.1.2 When should consent be sought, and who should seek consent?
...
p.000033: research may require the use of anonymous data without explicit consent – for detailed guidance on this researchers
p.000033: should consult the MRC guidance Personal information in medical research.11
p.000033: Researchers working with children have important responsibilities in relation to child protection. Where researchers
p.000033: have reasonable cause to suspect that a child is suffering or likely to suffer significant harm, they have a clear
p.000033: responsibility to liaise urgently with those responsible for the child's clinical care with a view to making a referral
p.000033: to social services. Again, a decision to disclose information should, wherever possible, be discussed with the child
p.000033: before disclosure, in terms appropriate to the child's capability to understand.
p.000033: All researchers need to be aware of relevant data protection legislation and the rights of the child (and their
p.000033: parents/guardians in some circumstances) to access their health records. Fuller guidance on confidentiality issues is
p.000033: available from the Department of Health, the British Medical Association and the General Medical Council.3, 4, 39
p.000033:
p.000033: 5.3 Ethics committee review
p.000033: The Council of Europe Protocol to the Convention on Human Rights and Biomedicine on Biomedical Research provides
p.000033: guidance regarding the role of the ethics committee in research.9 According to this guidance, every research project
p.000033: must be submitted for independent examination of its scientific merit, including assessment of the importance of the
p.000033: aim of research and ethical acceptability to an
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000035: 35
p.000035:
p.000035: MRC Ethics Guide: Medical research involving children
p.000035: MRC Ethics Guide: Medical research involving children
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: ethics committee. An examination of the ethical acceptability is necessary to protect the dignity, rights, safety and
p.000035: wellbeing of the research participant. The assessment should draw on an appropriate range of expertise adequately
p.000035: reflecting professional and lay views, therefore a professional opinion should be sought for any research involving
...
Social / Age
Searching for indicator age:
(return to top)
p.000005: families are likely to appreciate some recognition of their role in this partnership, such as a certificate of
p.000005: participation.
p.000005: • Researchers must take account of the cumulative medical, emotional, social and psychological consequences of the
p.000005: child being involved in research. Children with certain conditions may be exposed to a sequence of research projects.
p.000005: It is advisable to consider the risks of a particular research procedure in the context of the child's overall
p.000005: involvement in projects by different researchers.
p.000005: 2. Why do we need research involving children?
p.000005: Medical research involving children is essential for advancing child health and wellbeing. Often it is not sufficient,
p.000005: scientific, or ethical to carry out research with adults and apply the findings to children. This may be because:
p.000005: • The disease processes in children may differ from those in adults. Some childhood diseases have no close
p.000005: analogies in adults, therefore to understand these in any detail it is necessary to carry out research with children.
p.000005: • The physiology of children is different from that of adults, and the pharmacokinetics of many drugs will vary
p.000005: with the age of the child.Treatments designed specifically to meet the needs of children ensure that age-related
p.000005: differences in drug handling and/or effects are recognised, that the doses needed for efficacy are understood, and that
p.000005: any adverse effects can be avoided.
p.000005: • Many disorders can only be understood in the context of a child's growth and development. Examples include
p.000005: changes in the visual system following early squint, or the way the developing brain adapts to injury or damage in
p.000005: babies.
p.000005: • Children are not small adults. For the therapy to be effective, its delivery must suit their needs. Use of adult
p.000005: formulations is often not suitable, eg, many children find it easier to swallow a liquid formulation than a tablet.
p.000005: Research with children can also play a key part in increasing our understanding of some adult diseases that are thought
p.000005: to have their origins in early life. It enables the development of preventive intervention into the natural history of
p.000005: the disease. The findings of research involving children can therefore also be relevant for adults.
p.000005:
p.000005:
p.000005:
p.000005:
p.000006: 6
p.000006:
p.000007: 7
p.000007:
p.000007: MRC Ethics Guide: Medical research involving children
p.000007: MRC Ethics Guide: Medical research involving children
p.000007:
p.000007:
...
p.000007: best treatment. Like adults, they should be given the opportunity to benefit from the results of successful research.
p.000007: Children should therefore have the opportunity to participate while, of course, being protected from any hazards that
p.000007: involvement in the research project might bring. The MRC's research on childhood leukaemia shows how valuable this
p.000007: involvement can be. Most children diagnosed with leukaemia in the UK are entered into the MRC's trials, and in the last
p.000007: 40 years the survival rate for children with acute lymphoblastic leukaemia especially has greatly improved – from less
p.000007: than five per cent in 1962 to 80 per cent at present.13
p.000007:
p.000007: 2.1 What would be the consequences of not carrying out research on children?
p.000007: When research does not involve children, child-specific treatments for diseases are not developed and diseases with no
p.000007: close analogies in adults are not studied. This means that future generations of children miss the opportunity to
p.000007: benefit from the findings of that research. Progress in the clinical care of children will be impaired without research
p.000007: in this age group and children may be given treatments that are potentially unsafe. In addition, progress on
p.000007: understanding adult diseases thought to have their origins in early life will be hampered, limiting the possibilities
p.000007: of preventive intervention.
p.000007: 3. What has limited research so far, and what are the challenges?
p.000007: Progress in research involving children has been limited primarily by:
p.000007:
p.000007: • Difficulty in reaching consensus about including children in research.
p.000007:
p.000007: • Methodological challenges.
p.000007:
p.000007: • Expense of developing new treatments.
p.000007:
p.000007: • Lack of legal enforcement for paediatric versions of drugs.
p.000007:
p.000007: 3.1 Difficulty in reaching consensus about including children in research
p.000007: Current ethical principles for conducting research involving children have evolved from the Nuremberg Code which
p.000007: emerged after the Second World War. The Code set out statements of moral, ethical and legal principles relating to
p.000007: research involving human subjects, and included a bar on research involving children. Research was seen as a potential
p.000007: harm from which vulnerable people should be protected. Later, in 1964, the Declaration of Helsinki, drawn up by the
...
p.000009:
p.000009:
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000011: 11
p.000011:
p.000011: MRC Ethics Guide: Medical research involving children
p.000011: MRC Ethics Guide: Medical research involving children
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: This regulatory initiative takes its direction mainly from recent US legislation – the US Best Pharmaceuticals for
p.000011: Children Act 2002 and the related 'Pediatric Exclusivity' provision and 'Pediatric Rule'. The Pediatric Exclusivity
p.000011: provision grants an additional six months’ patent protection or market exclusivity to companies that voluntarily test
p.000011: the relevant drug on children, which has been generally well received. The Pediatric Rule demands that companies test
p.000011: their products on children under
p.000011: certain circumstances, including the likelihood of: usage for a substantial number of children, meaningful therapeutic
p.000011: benefits, risk to children in the absence of licensing and usage in different paediatric age groups.
p.000011: The European legislation will probably be finalised in 2006. Meanwhile, a co-ordinated UK strategy led by the Medicines
p.000011: and Healthcare products Regulatory Agency (MHRA) and the Department of Health aims to begin to address the issue and
p.000011: raise awareness in the pharmaceutical industry of the need to take action now to ensure that products are appropriately
p.000011: labelled and formulated for paediatric use.20 The resulting need for more research in paediatric pharmacology was
p.000011: highlighted in the Royal College of Paediatrics and Child Health (RCPCH) review Safer and Better Medicines for
p.000011: Children, which was commissioned by the MRC, the Department of Health and the Association of the British Pharmaceutical
p.000011: Industry. 21
p.000011: In addition to the above constraints, the increased complexity of regulation for paediatric and adult clinical research
p.000011: has become more burdensome for clinicians and researchers.
p.000011: 4. The way forward – ethical considerations
p.000011: The following section outlines the key issues to consider when planning and conducting research involving children.
p.000011:
p.000011: 4.1 Does the research need to be carried out with children?
p.000011: Research involving children should only be carried out if it cannot feasibly be carried out on adults. Therefore the
p.000011: researcher needs to assess beforehand whether the same potential benefit for children could be derived from studies on
p.000011: adults, which involves asking the following questions:
...
p.000011: child health?
p.000011: • Are the relevant pharmacokinetics of the treatment option being studied already known in adults? Is it expected
p.000011: that the pharmacokinetics for children and adults will differ? Is there a need to test this?
p.000011: • Is the adult-style therapy shown or believed to be unpalatable or difficult to administer to children? Has the
p.000011: therapy previously been developed for adults and not tolerated by children?
p.000011: • Is the adult disease believed to have its origins in early life? Will studies involving children shed light on
p.000011: the disease and its natural history and increase understanding of the possibilities of prevention?
p.000011: If the answer to any of these questions is yes, children may ethically be involved in this research, and may benefit
p.000011: from it.
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000013: 13
p.000013:
p.000013: MRC Ethics Guide: Medical research involving children
p.000013: MRC Ethics Guide: Medical research involving children
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013: When a choice of age groups is possible, older children should be involved in preference to younger ones, although some
p.000013: research questions are specific to younger children and babies.2
p.000013:
p.000013: 4.2 Use of terms 'therapeutic' and 'non-therapeutic' research
p.000013: The distinction drawn previously between therapeutic and non-therapeutic research is now regarded by many as unhelpful
p.000013: and potentially misleading. For example, clinical trials that involve medicines include both therapeutic elements – the
p.000013: medicine being given – and non-therapeutic ones – the taking of a blood sample.
p.000013: Moreover, the term therapeutic can cause confusion if it raises hopes of success whereas the outcome of the research
p.000013: may not provide a treatment that benefits the individual participant. Indeed, some 'therapeutic' research has been
p.000013: considered to be more hazardous than 'non-therapeutic' research. Consequently, the Declaration of Helsinki (2000) no
p.000013: longer uses these terms, setting out instead basic principles for all medical research and additional ones for research
p.000013: combined with medical care.
p.000013: The guidelines from the RCPCH published in 2000 likewise avoid drawing this distinction, highlighting instead the
p.000013: principles that research involving children is important for the benefit of all children, and that a research procedure
p.000013: which cannot directly benefit the child is not necessarily unethical if the findings might benefit future generations
...
p.000017: Participation in more than one research study: as with adults, there may be situations where it could be argued that
p.000017: participation in more than one trial or study might be potentially beneficial – both for participants and for the
p.000017: research. The potential benefits and risks of doing so would need to be carefully explored by all concerned, and
p.000017: clearly understood by the child and family.24
p.000017: Equipoise: this is when there is genuine uncertainty among those who have considered the issue, including patients,
p.000017: about the relative benefits and risks of treatments or tests being compared. A clinical trial cannot be ethical unless
p.000017: there is this genuine informed uncertainty among the expert medical community and in an informed competent
p.000017: patient/participant.
p.000017: 4.3.2 Minimising risk
p.000017: The National Academy of the Sciences provides guidance on how to minimise risk, summarised here: 25
p.000017:
p.000017: Minimising risk in research involving children
p.000017:
p.000017: • Is inclusion of children necessary to answer the scientific question posed by the research? What are the ages
p.000017: of the children to be included? Are any of the potential research harms age-dependent?
p.000017: • Will potential child participants be screened for known vulnerability to the risks associated with specific
p.000017: elements of the research?
p.000017: • What does the research require of children and their families? Is adherence to the research protocol a
p.000017: concern? If so, what are the risks of non-adherence?
p.000017: • Are all the procedures or interventions necessary to answer the research question? Can the investigators
p.000017: collect the required information using procedures that the child participants will undergo as part of their normal
p.000017: therapy or monitoring?
p.000017: • Have previous laboratory studies, animal research, studies with adults, or other data provided a sufficient
p.000017: basis for proceeding with research involving children?
p.000017: • Does the study follow principles of sound research design?
p.000017:
p.000017: • What are the theoretical risks involved with the research as proposed? Are data available to estimate the
p.000017: probability and magnitude of each risk as they relate to the categories of children to be included?
p.000017: • Have the investigators provided data on the frequency of adverse events for the procedures at the site in
p.000017: question? For example, sedation for research procedures.
p.000017: Continued...
p.000017:
p.000017:
p.000017:
p.000018: 18
p.000018:
p.000019: 19
p.000019:
p.000019: MRC Ethics Guide: Medical research involving children
p.000019: MRC Ethics Guide: Medical research involving children
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019: Minimising risk in research involving children - Continued
p.000019:
p.000019: • Are the investigators and other members of the research team qualified to perform each of the procedures or
p.000019: assessments specified in the protocol and recognise potential risks and adverse outcomes? Does the research team have
p.000019: appropriate skills and expertise in caring for children of the ages included in the study?
p.000019: • Will research be performed in a setting that is 'friendly' to children of the ages included in the study? Is
p.000019: the setting appropriate for the physical, clinical, psychological and emotional needs of those age groups?
p.000019: • For research that involves more than minimal risk, does the research protocol have an adequate plan for
p.000019: monitoring the safety of the child participants? Does the monitoring plan provide for the inclusion of professionals
p.000019: with the appropriate expertise in paediatrics?
p.000019: • If the protocol presents the risk of a physical or psychological emergency, is the research setting equipped
p.000019: to respond? Are plans for responding to an emergency specified in the protocol?
p.000019: • What are the stopping rules or 'endpoints' for early discontinuation of the research on the basis of strong
p.000019: findings about harms or benefits? Are they specific and appropriate?
p.000019: • What happens to the data once they are collected? Where are research records stored, and who has access to
p.000019: them? What are the practices and procedures for maintaining the short-term and long-term confidentiality of the data?
p.000019: 5. Children, ethics and the law
p.000019:
p.000019: 5.1 Consent
p.000019:
p.000019: 5.1.1 What is valid consent?
p.000019:
p.000019: Consent – The voluntary agreement of an adult or competent child, based on adequate knowledge and understanding of
...
p.000021: information in medical research.11
p.000021: Research linked to medical care in an emergency: the handling of this depends on whether the proposed study falls under
p.000021: the Clinical Trials Regulations. For further information please refer to 5.5.4.
p.000021:
p.000021: 5.1.3 Who can give consent, and who should you seek consent from?
p.000021: The law regarding the child's right to consent has developed differently in Scotland than in England, Wales and
p.000021: Northern Ireland – as outlined in 5.1.3a and 5.1.4a below. Generally, where children have sufficient understanding and
p.000021: intelligence to
p.000021: understand what is proposed, it is their consent and not that of their parent/guardian that is required by law.
p.000021: Ethically it is important to involve children as much as possible in decisions about their own health, wellbeing and
p.000021: healthcare. The United Nations Convention on the Rights of the Child states that the child has a right to be informed,
p.000021: to express a view and to influence a decision.27 Methods used to facilitate the consent process should be appropriate
p.000021: to the age and understanding of the child. The Department of Health provides very useful guidance on consent for both
p.000021: patients and clinicians, including guidance for children and for parents/guardians explaining what they have a right to
p.000021: expect.3
p.000021:
p.000021: 5.1.3.a Provision in law for children to consent
p.000021:
p.000021: England, Wales and Northern Ireland
p.000021: Where the Clinical Trial Regulations apply, a minor is defined as someone under the age of 16.
p.000021: Where the common law applies – all situations not covered by the Regulations – the law states that the age of majority
p.000021: is 18. Whilst not considered to have fully reached adulthood, young people between the age of 16 and 18 are presumed to
p.000021: be competent to give consent. No statute governs the rights of those under the age of 16 to give consent for medical
p.000021: treatment or research. However, case law provides the example of the Gillick case with respect to treatment.28 This
p.000021: case determined that where a young person has sufficient understanding and intelligence to understand fully what is
p.000021: proposed, and use and weigh this information in reaching a decision, he or she can give consent to treatment and
p.000021: consent from parents is not legally necessary – although parental involvement should always be encouraged. The term
p.000021: "Gillick competent" is used to describe a young person's ability to make a decision regarding consent.
p.000021:
p.000021:
p.000022: 22
p.000022:
p.000023: 23
p.000023:
p.000023: MRC Ethics Guide: Medical research involving children
p.000023: MRC Ethics Guide: Medical research involving children
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023: In the absence of case law dealing specifically with research, the Gillick principles might reasonably be applied
p.000023: here, although the threshold for understanding will vary according to the complexity of the research. However there is
p.000023: continuing uncertainty about the application of these principles to research in general and, in the case of law covered
p.000023: by the Clinical Trials Regulations, it will be those Regulations that apply and not the Gillick case law.
p.000023:
p.000023: Scotland
p.000023: As in England, Wales and Northern Ireland, where the Clinical Trials Regulations apply, a minor is defined as someone
p.000023: under the age of 16.
p.000023: Also as in England, Wales and Northern Ireland, in Scotland a person reaches majority at the age of 18.29 However,
p.000023: Scottish statute makes legal provision for young people, where they are considered to be competent, to consent to
p.000023: medical procedures or treatment. Under Scottish statute young people aged 16 and above are presumed to be competent to
p.000023: give consent until proven otherwise, having legal capacity to enter into any transaction, which includes "…the giving
p.000023: by a person of any consent having legal effect." 30
p.000023: Young people under the age of 16 can also give legally binding consent to participate in medical research as long as
p.000023: they are believed by the medical
p.000023: practitioner to be competent: "…a person under the age of 16 years shall have legal capacity to consent on his own
p.000023: behalf to any surgical, medical or dental procedure or treatment where in the opinion of a qualified medical
p.000023: practitioner attending him, he is capable of understanding the nature and possible consequences of the procedure or
p.000023: treatment." 30 Interpretation of Scottish law has been that a young person's competency allows them to refuse as well
p.000023: as consent to treatment.
p.000023: It is not entirely clear whether this Scottish statute covers consent to participate in research, but as discussed
p.000023: above, in the absence of law dealing specifically with research, the principles of Scottish law relating to consent to
p.000023: procedures and
p.000023: treatment might reasonably be applied. At the same time, it is vital to recognise that the threshold for understanding
p.000023: will relate to the complexity of the research being undertaken.
p.000023:
p.000023: Additional protection for children participating in clinical trials
p.000023: The Medicines for Human Use (Clinical Trials) Regulations 2004 have been law since they came into force on 1 May 2004
p.000023: and regulate trials in the UK.26 These regulations transpose European Union Directive 2001/20/EC into UK law.31 The
p.000023: Regulations offer additional protection for a minor (a person under the age of 16 years) who is being considered for a
p.000023: clinical trial. This additional protection comes at a time when more children are expected to be asked to participate
p.000023: in clinical trials, as part of an international initiative to provide medicines for children that are fully licensed
p.000023: (see 3.4 for more information). The regulations specify that for a minor
p.000023: to participate in a clinical trial, a person with parental responsibility or a legal representative must give informed
p.000023: consent and may withdraw the young person at any time.
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000025: 25
p.000025:
p.000025: MRC Ethics Guide: Medical research involving children
p.000025: MRC Ethics Guide: Medical research involving children
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025: Key provisions for the protection of minors within the Medicines for Human Use (Clinical Trials) Regulations 2004
p.000025: (Regulation 15 and Part 4 of Schedule 1) – extract from MHRA adviceii
p.000025:
p.000025: The Regulations provide additional protection for a minor (a person under the age of
p.000025: 16) who is a candidate for a clinical trial.They require, among other provisions, that:
p.000025:
p.000025: • an ethics committee considering the trial must receive advice on the relevant field of paediatric care; and
p.000025: • a person with parental responsibility or a legal representative must give informed consent and may withdraw the
p.000025: young person at any time; and, in relation to the minor himself:
p.000025: • staff with experience with young persons must inform him/her of the risks and benefits of the trial according to
p.000025: his capacity to understand;
p.000025: • the investigator must consider his or her explicit wish to refuse to participate or to be withdrawn from the
p.000025: trial at any time;
p.000025: • the clinical trial relate directly to an illness from which he or she suffers or that can only be carried out on
p.000025: minors; and
p.000025: • the trial must aim to provide some direct benefit for the group of patients involved.
p.000025: 5.1.4 Assessing the competence of a child to consent
p.000025: While normally increasing with age, competence is considered not to depend primarily on age, but rather on the ability
p.000025: to understand and weigh up options. It can be influenced by the way information is presented – many children will be
p.000025: competent if information is presented in an appropriate way and they are
p.000025: supported through the decision-making process. The Central Office for Research Ethics Committees (COREC) provides a
p.000025: useful template for designing patient information sheets and seeking assent/consent from children and young people.33 A
p.000025: child's ability to consent develops as he or she learns to make increasingly complex and serious decisions, which can
p.000025: be experience and/or age-related.
p.000025: For people to be able to have the capacity to take a particular decision they must be able to: 34
p.000025: • Comprehend and retain information material to the decision, especially the consequences of having or not having
p.000025: any intervention.
p.000025: • Use and weigh this information in a decision-making process.
p.000025:
p.000025: • Reach and communicate a decision.
p.000025:
p.000025: Even if the child is competent, it is still normally good practice to involve the family in the decision-making
p.000025: process. It is particularly desirable to obtain parental consent for younger children or for procedures that carry any
p.000025: risk or discomfort.
p.000025: If the competent child specifically asks for the family not to be involved in the decision-making process and they
p.000025: cannot be persuaded otherwise, their privacy should be respected.
p.000025: For further information please see 5.2.
p.000025:
p.000025:
p.000025:
p.000025: ii Extract from MHRA Description of the Medicines for Human Use (Clinical Trials) Regulations 2004.32
p.000025:
p.000025:
p.000026: 26
p.000026:
p.000027: 27
p.000027:
p.000027: MRC Ethics Guide: Medical research involving children
...
p.000027: participate without the consent of a person with parental responsibility. A person with parental responsibility may
p.000027: legally consent to treatment on an incompetent child's behalf. If the child is able to give assent to decisions about
p.000027: participation in research, the investigator must obtain that assent in addition to the consent of the legally
p.000027: authorised representative. If the child does not assent, this should be respected.
p.000027: Legally, the researcher need only obtain consent from one person with parental responsibility. However, it is good
p.000027: practice and in the best interests of the child to involve others close to the child – for example, a second parent –
p.000027: in the decision- making process. Where opinions are strongly divided and agreement cannot be reached, it would be
p.000027: advisable to exclude the child from the research study unless a treatment option is only available as part of that
p.000027: programme. In such a case, every effort should be made to overcome the disagreement without a decision having to be
p.000027: referred to the courts.
p.000027: If the parents are themselves under 16 years of age, they will only be able to give valid consent on behalf of their
p.000027: child if they are competent to take the decision in question.
p.000027: Parents/guardians can consent to research procedures that offer potential benefit to the child. If the research is
p.000027: thought not to offer potential benefit to the child, parents/guardians can still consent provided the risks are
p.000027: sufficiently small to mean that research can be reasonably said not to go against the child's interests.
p.000027: Guidance on the law regarding parental consent is available from the BMA.4 A summary of country-specific differences
p.000027: follows:
p.000027: England,Wales and Northern Ireland
p.000027: The Children Act 1989 and The Children Act (Northern Ireland) Order 1995 make provision for parental rights in respect
p.000027: of their child, including the right to give consent to medical treatment.35, 36 Case law shows that a person with
p.000027: parental responsibility or the court can overrule a competent child's decision to refuse potentially beneficial
p.000027: treatment if it is felt to be in the best interests of the child or young person.
p.000027:
p.000027: Scotland
p.000027: The Children (Scotland) Act 1995 37 makes provision for cases where a young person aged under 16 is not competent to
p.000027: give legally valid consent. Parental rights enabling parents to carry out parental responsibilities include
p.000027: "safeguarding and promoting the child's health, welfare and development, providing direction and guidance to the child
p.000027: in a manner appropriate to the stage of the child's development and acting as the child's legal representative." Most
p.000027: of these last until the young person is 16 years old or shows competency to make their own decisions. Interestingly, in
p.000027: this Act it is stated that a child of 12 years or more should be presumed to be of sufficient age and maturity to form
p.000027: a view. The parental responsibility to provide guidance continues until the young person is 18. Case law suggests that
p.000027: a parent cannot overrule the decision of a competent child; however this has not yet been added to statute.
p.000027: The Adults with Incapacity (Scotland) Act 2000 38 covers the treatment and welfare of people over the age of 16 who
p.000027: are unable to give consent.
p.000027: In the absence of case law dealing specifically with research, the principles applying to medical treatment in England,
p.000027: Wales, Scotland and Northern Ireland might reasonably be applied to research.
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000029: 29
p.000029:
p.000029: MRC Ethics Guide: Medical research involving children
p.000029: MRC Ethics Guide: Medical research involving children
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: 5.1.4.b Seeking legal advice
p.000029: Researchers should seek legal advice if in any doubt regarding authority to proceed.
p.000029:
p.000029: 5.1.5 How best to seek consent
p.000029: The RCPCH provides guidance on how best to seek consent: 2
p.000029:
p.000029:
p.000029: For consent to be freely given researchers must:
p.000029:
p.000029: • Offer families no financial inducement although expenses should be paid.
p.000029: • Exert no pressure on families.
p.000029: • Give them as much time as possible (a few days for a major study, if at all possible) to consider whether to take
p.000029: part in the project.
p.000029: • Encourage families to discuss the project with – for example – their relatives, primary health carers – or an
p.000029: independent counsellor where available.
...
p.000031: continuing with investigational treatment
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Parent can overule child's objections.
p.000031: Research can go ahead
p.000031:
p.000031: iii Flow chart based on text from Council for International Organizations of
p.000031: Medical Sciences International ethical guidelines for biomedical research involving human subjects.5
p.000032: 32
p.000032: YES
p.000032: consents and parents assent
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033: MRC Ethics Guide: Medical research involving children
p.000033: MRC Ethics Guide: Medical research involving children
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: Seeking consent is not a single response but a process. The child should be provided with information appropriate to
p.000033: his or her increasing ability to make decisions about complex and serious issues. It is helpful for researchers to
p.000033: produce child-friendly information in a form appropriate for the relevant age groups – this could make use of pictures
p.000033: or videos. More than one version may need to be produced
p.000033: if research covers a wide age range, such as eight-18 years. Where the research project lasts a number of years, the
p.000033: child and/or parent/guardian may need to be approached periodically to ensure they still consent to the child's
p.000033: involvement in research. For example, where a parent has consented to follow-up studies throughout the life of the
p.000033: child, the child must be given the opportunity to decide for himself/herself, once competent to do so, whether he or
p.000033: she wishes to continue his or her involvement.
p.000033:
p.000033: 5.2 Confidentiality
p.000033: Medical professionals have a duty of confidentiality to all patients including children. Legally competent children are
p.000033: entitled to expect that information about themselves will not be provided to a third party, including their
p.000033: parent/guardian, without their consent. However, it is important that wherever possible the parents/guardians are
p.000033: informed, and young people should be encouraged to involve them unless it is not in their best interests to do so. If
...
p.000035: MRC Ethics Guide: Medical research involving children
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: ethics committee. An examination of the ethical acceptability is necessary to protect the dignity, rights, safety and
p.000035: wellbeing of the research participant. The assessment should draw on an appropriate range of expertise adequately
p.000035: reflecting professional and lay views, therefore a professional opinion should be sought for any research involving
p.000035: children. The ethics committee must be satisfied that dependent persons and vulnerable groups will not be subjected to
p.000035: undue influence.
p.000035: Whilst the Council of Europe protocol is a legal instrument, it has not so far been transposed into UK law. However,
p.000035: the Medicines for Human Use (Clinical Trials) Regulations 2004, which transpose Directive 2001/20/EC into UK law,
p.000035: require that an ethics committee considering a trial involving minors must receive advice on the relevant field of
p.000035: paediatric care.29, 30 A "minor" is defined as a person under the age of 16.
p.000035:
p.000035: 5.4 Children's safety in relation to researchers
p.000035: Any individual recruited by the MRC to work directly with children will undergo security screening, including criminal
p.000035: records review. This includes nurses, survey interviewers and some individuals involved in a clinically invasive
p.000035: capacity, eg, phlebotomists. The MRC expects its grant-holding institutions to do likewise.
p.000035: Security screening is complementary to other good recruitment practices and not a substitute for them. Staff involved
p.000035: in MRC's recruitment process are responsible for ensuring that standard checks are still made.
p.000035:
p.000035: 5.5 Specific situations
p.000035:
p.000035: 5.5.1 Research involving human material
p.000035: Please refer to the MRC guidance Human tissue and biological samples for use in research.12
p.000035: Further guidance will be issued when the Human Tissue Bill, and equivalent legislation in Scotland, become law.
p.000035: 5.5.2 The use of personal information
p.000035: Please refer to the MRC guidance Personal information in medical research.11
p.000035:
p.000035: 5.5.3 Research involving very young children
p.000035: A parent/guardian's informed consent is necessary for the involvement of babies in research. When a baby is seriously
...
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: 6. Summary
p.000039: Children should be included in medical research only if:
p.000039:
p.000039: • The relevant knowledge cannot be gained through research with adults.
p.000039:
p.000039: • It is approved by the appropriate Research Ethics Committee/s.
p.000039:
p.000039: • Either the participant has given consent where competent, or consent has been given on his or her behalf by a
p.000039: parent or guardian and the participant does not object or appear to object in either words or actions. iv
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: iv See 5.5.4 for guidance on emergency situations, when this might not be possible.
p.000039: 7. Glossary
p.000039: The definitions provided here apply as they are used in the above guidelines.
p.000039:
p.000039: Assent
p.000039: A child's affirmative agreement to participate. Failure to object should not be construed as assent.
p.000039: Burden of disease
p.000039: The impact of disease on the individual and on society due to loss of duration and quality of life. Measures include
p.000039: (i) 'morbidity burden', ie, the prevalence of a condition, the range of its severity and the age distribution of the
p.000039: population suffering from the condition, and (ii) the financial burden to society in meeting the obligation to support
p.000039: the individual; for example, in terms of net public expenditure on health services and on social services.
p.000039: Child
p.000039: In the UK, a person under the age of 18. "Young person" is a term often used to describe older children in this age
p.000039: group. The competence of children to consent is discussed in Section 5.
p.000039: Clinical Trials Regulations
p.000039: The Medicines for Human Use (Clinical Trials) Regulations apply to research involving investigational medicinal
p.000039: products (see below). In such studies, informed consent is strictly defined as follows and only consent meeting this
p.000039: definition will suffice:
p.000039: “A person gives informed consent to take part, or that a subject is to take part, in a clinical trial only if his
p.000039: decision –
p.000039: (a) is given freely after that person is informed of the nature, significance, implications and risks of the trial;
p.000039: and
p.000039:
p.000039:
p.000040: 40
p.000040:
p.000041: 41
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: (b) either –
p.000041: (i) is evidenced in writing, dated and signed, or otherwise marked, by that person so as to indicate his consent, or
p.000041: (ii) If the person is unable to sign or to mark a document so as to indicate his consent, is given orally in the
p.000041: presence of at least one witness and recorded in writing.”
p.000041:
p.000041: Confidentiality
p.000041: The duty of persons to whom personal information has been given not to share the information with any unauthorised
p.000041: person. For more information about what this involves in practice, see 5.2.
p.000041:
p.000041: Competence
...
p.000045: Pharmacology in the United Kingdom. Royal College of Paediatrics and Child Health Review (commissioned by the MRC, the
p.000045: Department of Health, and the Association of the British Pharmaceutical Industry), May 2004.
p.000045: 22. Research: the role and responsibilities of doctors. London: General Medical Council, 2002.
p.000045: 23. Testing for late onset genetic disorders. London: British Paediatric Association, 1996.
p.000045: 24. Brocklehurst P. 1997. "Randomised controlled trials in perinatal medicine: 2. Recruitment of a pregnant woman
p.000045: or her newborn child into more than one trial." British Journal of Obstetrics and Gynaecology 104 (7):765-7.
p.000045: 25. Ethical Conduct of Clinical Research Involving Children.The National Academy of the Sciences USA, 2004.
p.000045: 26. The Medicines for Human Use (Clinical Trials) Regulations. 2004.
p.000045: www.legislation.hmso.gov.uk/si/si2004/20041031.htm
p.000045:
p.000045: 27. UN Convention on the Rights of the Child. General Assembly resolution 44/25 of 20 November 1989, entry into
p.000045: force 2 September 1990 in accordance with article 49. www.childrenslawcentre.org/UNCRC_hearing.htm
p.000045: 28. Gillick v West Norfolk and Wisbech. London: House of Lords, Gillick v West Norfolk and Wisbech AHA (1986) AC
p.000045: 112, [1985] 3 WLR 830, [1985] 3 AII ER 402, HL
p.000045: 29. Age of Majority (Scotland) Act 1969 s 1.
p.000045: 30. Age of Legal Capacity (Scotland) Act 1991. (c. 50)
p.000045: 31. Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of
p.000045: the laws, regulations and administrative provisions of the Member States relating to the implementation of good
p.000045: clinical practice in the conduct of clinical trials on medicinal products for human use.
p.000045: http://europa.eu.int/eur-lex/pri/en/oj/dat/2001/l_121/l_12120010501en00340044.pdf
p.000045:
p.000045:
p.000045:
p.000046: 46
p.000046:
p.000047: 47
p.000047:
p.000047:
p.000047:
p.000047: MRC Ethics Guide: Medical research involving children
p.000047:
p.000047:
p.000047:
p.000047:
p.000047:
p.000047: 32. Medicines and Healthcare products Regulatory Agency: Description of the Medicines for Human Use (Clinical
p.000047: Trials) Regulations 2004. http://medicines.mhra.gov.uk/ourwork/licensingmeds/types/ctdregs_shortdesc.pdf
p.000047: 33. Central Office for Research Ethics Committees. www.corec.org.uk
p.000047: 34. Seeking Consent:Working with children. Department of Health, 2001. www.dh.gov.uk/PublicationsAndStatistics/
p.000047: Publications/PublicationsPolicyAndGuidance/PublicationsPolicyAndGuidanceArticle/fs/en?CONTENT_ ID=4007005&chk=xFifXP
p.000047: 35. Children Act 1989 (c. 41). www.hmso.gov.uk
p.000047: 36. Children Act (Northern Ireland) Order 1995. www.northernireland-legislation.hmso.gov.uk
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p.002004: children or begin in childhood have never been greater.
p.002004: The Medical Research Council (MRC) believes that research involving children should be supported, encouraged, and
p.002004: conducted in an ethical manner. We want to ensure that research participants, their parents and the general public can
p.002004: be confident that medical researchers work ethically with children.
p.002004: We recognise that while many other organisations have published guidance on medical research involving children, this
p.002004: is a vital area in which we must provide support and guidance to MRC researchers.The previous MRC guidance The ethical
p.002004: conduct of research on children1 (1991) has been replaced by the following updated guidelines. They outline the
p.002004: practical, ethical and legal issues that researchers need to consider when carrying out studies involving children. Our
p.002004: aim has been to set out general principles that can be applied in most situations rather than to cover every possible
p.002004: eventuality. The guidelines are intended to be concise and easily readable, and include a glossary defining some of the
p.002004: key terms used (see Section 7).
p.002004: We refer to guidance from The Royal College of Paediatrics and Child Health,2 the
p.002004: Department of Health3 and British Medical Association4 throughout this document. These organisations can all provide
p.002004: further useful information.
p.002004: This guide complements guidance on other research-related topics produced by the MRC, all of which is available at the
p.002004: MRC website, www.mrc.ac.uk. Any changes to MRC guidance are highlighted on the site as they arise.
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.000001: 1
p.000001:
p.000001: MRC Ethics Guide: Medical research involving children
p.000001: MRC Ethics Guide: Medical research involving children
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Contents
p.000001: 1. Introduction 4
p.000001: 1.1 Purpose 4
p.000001: 1.2 General ethical principles 5
p.000001: 1.3 Summary of key ethical principles relating to research
p.000001: involving children 5
p.000001: 2. Why do we need research involving children? 7
...
p.000001: 4.3 Benefit, harm and risk 15
p.000001: 4.3.1 Other considerations 17
p.000001: 4.3.2 Minimising risk 19
p.000001: 5. Children, ethics and the law 21
p.000001: 5.1 Consent 21
p.000001: 5.1.1 What is valid consent? 21
p.000001: 5.1.2 When should consent be sought, and who should seek consent? 21
p.000001: 5.1.3 Who can give consent, and who should you seek consent from? 22
p.000001: 5.1.3.a Provision in law for children to consent 23
p.000001: 5.1.4 Assessing the competence of a child to consent 27
p.000001: 5.1.4.a Children unable to consent to involvement, and parental consent 28
p.000001: 5.1.4.b Seeking legal advice
p.000030: 30
p.000030: 5.1.5 How best to seek consent 30
p.000030: 5.1.6 Seeking consent – a summary 32
p.000030: 5.2 Confidentiality 34
p.000030: 5.3 Ethics committee review 35
p.000030: 5.4 Children's safety in relation to researchers 36
p.000030: 5.5 Specific situations 36
p.000030: 5.5.1 Research involving human material 36
p.000030: 5.5.2 The use of personal information 37
p.000030: 5.5.3 Research involving very young children 37
...
p.000003: defend their interests – they may not have the capacity to give consent.
p.000003: The following principles should guide all MRC-funded research involving children: 4, 5
p.000003:
p.000003: • Research should only include children where the relevant knowledge cannot by obtained by research in adults (for
p.000003: guidance, see 4.1)
p.000003:
p.000003:
p.000004: 4
p.000004:
p.000005: 5
p.000005:
p.000005: MRC Ethics Guide: Medical research involving children
p.000005: MRC Ethics Guide: Medical research involving children
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005: • The purpose of the research is to obtain knowledge relevant to the health, wellbeing or healthcare needs of
p.000005: children.
p.000005: • Researchers can only involve competent children if they have obtained their informed consent beforehand.
p.000005: • A child's refusal to participate or continue in research should always be respected.
p.000005: • If a child becomes upset by a procedure, researchers must accept this as a valid refusal.
p.000005: • Researchers should involve parents/guardians in the decision to participate wherever possible, and in all cases
p.000005: where the child is not yet competent. Exceptional circumstances where this is not possible are discussed in 5.5.4.
p.000005: • Researchers should attempt to avoid any pressures that might lead the child to volunteer for research or that
p.000005: might lead parents to volunteer their children, in the expectation of direct benefit (whether therapeutic or
p.000005: financial).
p.000005: • Research involves partnership with the child and/or family, who should be kept informed and consent to separate
p.000005: stages of the project. Obtaining consent is a continuing process, rather than a one-off occurrence. Children and their
p.000005: families are likely to appreciate some recognition of their role in this partnership, such as a certificate of
p.000005: participation.
p.000005: • Researchers must take account of the cumulative medical, emotional, social and psychological consequences of the
p.000005: child being involved in research. Children with certain conditions may be exposed to a sequence of research projects.
p.000005: It is advisable to consider the risks of a particular research procedure in the context of the child's overall
p.000005: involvement in projects by different researchers.
p.000005: 2. Why do we need research involving children?
p.000005: Medical research involving children is essential for advancing child health and wellbeing. Often it is not sufficient,
p.000005: scientific, or ethical to carry out research with adults and apply the findings to children. This may be because:
p.000005: • The disease processes in children may differ from those in adults. Some childhood diseases have no close
p.000005: analogies in adults, therefore to understand these in any detail it is necessary to carry out research with children.
p.000005: • The physiology of children is different from that of adults, and the pharmacokinetics of many drugs will vary
p.000005: with the age of the child.Treatments designed specifically to meet the needs of children ensure that age-related
p.000005: differences in drug handling and/or effects are recognised, that the doses needed for efficacy are understood, and that
p.000005: any adverse effects can be avoided.
p.000005: • Many disorders can only be understood in the context of a child's growth and development. Examples include
p.000005: changes in the visual system following early squint, or the way the developing brain adapts to injury or damage in
p.000005: babies.
p.000005: • Children are not small adults. For the therapy to be effective, its delivery must suit their needs. Use of adult
p.000005: formulations is often not suitable, eg, many children find it easier to swallow a liquid formulation than a tablet.
p.000005: Research with children can also play a key part in increasing our understanding of some adult diseases that are thought
p.000005: to have their origins in early life. It enables the development of preventive intervention into the natural history of
p.000005: the disease. The findings of research involving children can therefore also be relevant for adults.
p.000005:
p.000005:
p.000005:
p.000005:
p.000006: 6
p.000006:
p.000007: 7
p.000007:
p.000007: MRC Ethics Guide: Medical research involving children
p.000007: MRC Ethics Guide: Medical research involving children
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
...
p.000007: While we have a responsibility to protect children, we also have an ethical obligation to ensure that they receive the
p.000007: best treatment. Like adults, they should be given the opportunity to benefit from the results of successful research.
p.000007: Children should therefore have the opportunity to participate while, of course, being protected from any hazards that
p.000007: involvement in the research project might bring. The MRC's research on childhood leukaemia shows how valuable this
p.000007: involvement can be. Most children diagnosed with leukaemia in the UK are entered into the MRC's trials, and in the last
p.000007: 40 years the survival rate for children with acute lymphoblastic leukaemia especially has greatly improved – from less
p.000007: than five per cent in 1962 to 80 per cent at present.13
p.000007:
p.000007: 2.1 What would be the consequences of not carrying out research on children?
p.000007: When research does not involve children, child-specific treatments for diseases are not developed and diseases with no
p.000007: close analogies in adults are not studied. This means that future generations of children miss the opportunity to
p.000007: benefit from the findings of that research. Progress in the clinical care of children will be impaired without research
p.000007: in this age group and children may be given treatments that are potentially unsafe. In addition, progress on
p.000007: understanding adult diseases thought to have their origins in early life will be hampered, limiting the possibilities
p.000007: of preventive intervention.
p.000007: 3. What has limited research so far, and what are the challenges?
p.000007: Progress in research involving children has been limited primarily by:
p.000007:
p.000007: • Difficulty in reaching consensus about including children in research.
p.000007:
p.000007: • Methodological challenges.
p.000007:
p.000007: • Expense of developing new treatments.
p.000007:
p.000007: • Lack of legal enforcement for paediatric versions of drugs.
p.000007:
...
p.000009:
p.000009: 3.2 Methodological challenges
p.000009: Smyth and Weindling describe how the emergence of evidence-based healthcare has led to a greater awareness of the need
p.000009: to evaluate critically what is already known before making recommendations for clinical practice or embarking on
p.000009: further research.14 Studies have shown that in comparison to research on adults, research questions relevant to the
p.000009: health of children may not have been addressed at all, or only by small, poorly designed studies.15
p.000009: Particular methodological challenges occur in research involving children. Childhood forms of many chronic diseases,
p.000009: eg, juvenile chronic arthritis, are uncommon and this may lead to difficulties in gaining statistical power to detect
p.000009: an effective treatment.
p.000009: Genetic disorders leading to severe disability or death are also rare.
p.000009:
p.000009: Even for more common conditions challenges arise. In asthma, for example, the diagnosis may be subjective, which poses
p.000009: problems in establishing the clear inclusion and exclusion criteria required for clinical trials. Standard outcome
p.000009: measures in adults include death and quality of life, but for many conditions different outcomes are more relevant.
p.000009: Measurements of these outcomes have been determined for use in adults specifically and may not be relevant for
p.000009: children. Quality of life measures can be used, but should be focused on the child or family and validated and tested
p.000009: for reliability and responsiveness to change before being used; such instruments have not always been available.
p.000009: It is therefore useful, and important, to consult children about outcome measures and other issues, when the research
p.000009: is being designed.
p.000009: When carrying out research on children, it is important to assess both the short- term and long-term outcomes. For
p.000009: example, early treatment of premature infants at high risk of chronic lung disease with steroid drugs reduces this
p.000009: risk, but long-term studies show an increased risk of cerebral palsy.16
p.000009: Investigations of cognitive, neurological and respiratory function can also pose challenges, eg, the inability of young
p.000009: children to understand and co-operate with the demands of complex tasks.
p.000009:
p.000009: 3.3 Expense of developing new treatments
p.000009: Because of the expense of developing a new treatment, commercially funded research understandably focuses on treatment
p.000009: options that are likely to be profitable. Pharmaceutical companies have traditionally been reluctant to invest in
p.000009: developing child-specific treatments or adapting existing medicines to meet the needs of children. The main reasons are
p.000009: that the market is often small and that long-term follow-up of adverse effects is often needed because the risks
p.000009: associated with paediatric treatments are generally higher.17
p.000009:
p.000009: 3.4 Weak licensing and regulation arrangements for paediatric versions of pharmaceuticals
p.000009: The National Audit Office recently reported that up to 90 per cent of medicines prescribed to children in hospitals
p.000009: were not licensed for that use.18 Consequently, there are potentially important public health benefits in improving
p.000009: the licensing of medicines and the testing of their safety for children. Currently in Europe there is no legal
p.000009: requirement for the necessary studies to be performed if the pharmaceutical company does not present the drug for use
p.000009: in children. However, the European Commission has proposed legislation on medicinal products for paediatric use. 17, 19
p.000009:
p.000009:
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000011: 11
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p.000011: MRC Ethics Guide: Medical research involving children
...
p.000011: provision grants an additional six months’ patent protection or market exclusivity to companies that voluntarily test
p.000011: the relevant drug on children, which has been generally well received. The Pediatric Rule demands that companies test
p.000011: their products on children under
p.000011: certain circumstances, including the likelihood of: usage for a substantial number of children, meaningful therapeutic
p.000011: benefits, risk to children in the absence of licensing and usage in different paediatric age groups.
p.000011: The European legislation will probably be finalised in 2006. Meanwhile, a co-ordinated UK strategy led by the Medicines
p.000011: and Healthcare products Regulatory Agency (MHRA) and the Department of Health aims to begin to address the issue and
p.000011: raise awareness in the pharmaceutical industry of the need to take action now to ensure that products are appropriately
p.000011: labelled and formulated for paediatric use.20 The resulting need for more research in paediatric pharmacology was
p.000011: highlighted in the Royal College of Paediatrics and Child Health (RCPCH) review Safer and Better Medicines for
p.000011: Children, which was commissioned by the MRC, the Department of Health and the Association of the British Pharmaceutical
p.000011: Industry. 21
p.000011: In addition to the above constraints, the increased complexity of regulation for paediatric and adult clinical research
p.000011: has become more burdensome for clinicians and researchers.
p.000011: 4. The way forward – ethical considerations
p.000011: The following section outlines the key issues to consider when planning and conducting research involving children.
p.000011:
p.000011: 4.1 Does the research need to be carried out with children?
p.000011: Research involving children should only be carried out if it cannot feasibly be carried out on adults. Therefore the
p.000011: researcher needs to assess beforehand whether the same potential benefit for children could be derived from studies on
p.000011: adults, which involves asking the following questions:
p.000011: • Is the disease specific to children, with no close analogy in adults? For example, juvenile rheumatoid arthritis
p.000011: or Kawasaki's disease.
p.000011: • Will the study increase understanding of the children's development and/or wellbeing with the aim of improving
p.000011: child health?
p.000011: • Are the relevant pharmacokinetics of the treatment option being studied already known in adults? Is it expected
p.000011: that the pharmacokinetics for children and adults will differ? Is there a need to test this?
p.000011: • Is the adult-style therapy shown or believed to be unpalatable or difficult to administer to children? Has the
p.000011: therapy previously been developed for adults and not tolerated by children?
p.000011: • Is the adult disease believed to have its origins in early life? Will studies involving children shed light on
p.000011: the disease and its natural history and increase understanding of the possibilities of prevention?
p.000011: If the answer to any of these questions is yes, children may ethically be involved in this research, and may benefit
p.000011: from it.
p.000011:
p.000011:
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p.000012: 12
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p.000013: 13
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p.000013:
p.000013:
...
p.000013: research questions are specific to younger children and babies.2
p.000013:
p.000013: 4.2 Use of terms 'therapeutic' and 'non-therapeutic' research
p.000013: The distinction drawn previously between therapeutic and non-therapeutic research is now regarded by many as unhelpful
p.000013: and potentially misleading. For example, clinical trials that involve medicines include both therapeutic elements – the
p.000013: medicine being given – and non-therapeutic ones – the taking of a blood sample.
p.000013: Moreover, the term therapeutic can cause confusion if it raises hopes of success whereas the outcome of the research
p.000013: may not provide a treatment that benefits the individual participant. Indeed, some 'therapeutic' research has been
p.000013: considered to be more hazardous than 'non-therapeutic' research. Consequently, the Declaration of Helsinki (2000) no
p.000013: longer uses these terms, setting out instead basic principles for all medical research and additional ones for research
p.000013: combined with medical care.
p.000013: The guidelines from the RCPCH published in 2000 likewise avoid drawing this distinction, highlighting instead the
p.000013: principles that research involving children is important for the benefit of all children, and that a research procedure
p.000013: which cannot directly benefit the child is not necessarily unethical if the findings might benefit future generations
p.000013: of children. Research where there is no benefit to the individual child participant would have to be of minimal risk.
p.000013: This is a major step forward in thinking. The expectation is that children can now begin to reap the benefits of
p.000013: research designed with children in mind.
p.000013: 4.3 Benefit, harm and risk
p.000013: In the past, the concern to protect children from the potential harms of research may have denied them potential
p.000013: benefits. To ensure that this vulnerable group are not exploited, the General Medical Council advises that it is
p.000013: important to assess carefully the potential benefits and harm to children at all stages of any research. As the
p.000013: benefits of research are not predictable, the researcher must be satisfied that the research is not contrary to the
p.000013: child participant's interests. The foreseeable risks should be kept as low as possible: the potential benefits from the
p.000013: development of treatments and furthering of knowledge must outweigh any foreseeable risks.22
p.000013:
p.000013: Risk - A potential harm; the characteristics of risk include the probability of its occurrence, as well as its
p.000013: magnitude and duration
p.000013:
p.000013: Risks may be estimated as minimal, low or high: i
p.000013:
p.000013: Minimal (the least possible) risk describes procedures such as questioning, observing, and measuring children, provided
p.000013: that procedures are carried out in a sensitive way, respecting the child's autonomy, and that consent has been given.
p.000013: Procedures with minimal risk include obtaining bodily fluids without invasive intervention, eg, taking saliva or urine
p.000013: samples. It is expected that research of minimal risk would not result in more than a very slight and temporary
p.000013: negative impact on the health of the person concerned.
p.000013: Low risk describes procedures that might cause no more than brief pain or tenderness, small bruises or scars, or very
p.000013: slight, temporary distress; eg, a blood test.
p.000013: High risk procedures such as lung or liver biopsy, arterial or lumbar puncture, and cardiac catheterisation are not
p.000013: justified for research purposes alone with children. They should be carried out only when research is combined with
p.000013: diagnosis or treatment intended to benefit the child concerned.
p.000013:
p.000013:
p.000013: i Adapted from RCPCH guidance and Council of Europe guidance.
p.000013:
p.000014: 14
p.000014:
p.000015: 15
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p.000015: MRC Ethics Guide: Medical research involving children
p.000015: MRC Ethics Guide: Medical research involving children
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015: Research in which children are submitted to more than minimal risk with only slight, uncertain, or no benefit to
p.000015: themselves requires serious ethical consideration.
p.000015: The RCPCH advises that assessment of potential benefits and harms includes considering the following: 2
p.000015:
p.000015: Assessing potential benefit for the participant and children as a whole
p.000015:
p.000015: Magnitude – How severe is the condition that the research aims to alleviate and how common is it? How is the knowledge
p.000015: gained likely to be used?
p.000015: Probability – How likely is the research to achieve its aims?
p.000015:
p.000015: Beneficiaries – Is the research intended to benefit the child participants, and/or other children?
p.000015: Resources – Will potential benefits be limited because the treatment is very expensive, or difficult to deliver?
p.000015: Types of intervention – Might a new treatment or procedure replace one that is more invasive?
p.000015: Timing – Might benefits be brief or long-lasting, immediate or not evident until years later?
p.000015:
p.000015: Equity – Should a wider range of children be offered the potential benefits of participating in the research?
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015: 4.3.1
p.000015:
p.000015: Assessing potential harms to the participant
p.000015:
p.000015: Magnitude – How severe may the harms associated with the research procedures be? Probability – How likely are the harms
p.000015: to occur?
p.000015: Types of intervention – How invasive or intrusive is the research? (Psychosocial research should be assessed as
p.000015: carefully as physical research.)
p.000015: Timing – Might adverse effects be brief or long-lasting, immediate or not evident until years later?
p.000015: Equity – Are a few children who already have many medical problems drawn into too many projects simply because they are
p.000015: available?
p.000015:
p.000015:
p.000015: Other considerations
p.000015: The assessment of risk must be carried out by all involved in the research – the children where possible, the
p.000015: parents/guardians, the researchers and clinicians concerned and the research ethics committees. This assessment
p.000015: includes reviewing personal circumstances: generalisation can be controversial as children's responses vary, can be
p.000015: unpredictable, and alter as children develop; a procedure that does not bother one child can arouse severe distress in
p.000015: another. For example, many children fear needles. For them, low rather than minimal risk could be incurred by
p.000015: injections and venepuncture. However, the procedure may be made more acceptable with careful explanation of the
p.000015: effectiveness of local anaesthetic cream and an understanding of the reason for the venepuncture – so that the child
p.000015: may choose to proceed. Researchers sometimes underestimate high risk of pain if the effects are brief, whereas the
p.000015: child or parents may consider that the severe transient pain is not justified by the hoped-for benefit.
p.000015:
p.000015:
p.000015:
p.000015:
p.000016: 16
p.000016:
p.000017: 17
p.000017:
p.000017: MRC Ethics Guide: Medical research involving children
p.000017: MRC Ethics Guide: Medical research involving children
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017: Careful consideration of consequences may be required to identify some risks or potential harm. For example, with
p.000017: research into serious genetic disorders that present in adult life, pre-symptomatic diagnosis in a child, while it may
p.000017: be beneficial, may also have harmful effects or implications which may affect the child's
p.000017: opportunities and freedom of choice.23
p.000017:
p.000017: Interim findings: as with adults, if evidence of harm emerges during the trial as a result of giving or withholding
p.000017: certain treatment, the interests of the child
p.000017: participants must be put before the requirements of the research. This must be taken into account by researchers and
p.000017: trial steering committees when deciding on 'stopping rules' for trials and in studies of new techniques.
p.000017: Child volunteers: healthy volunteers should be treated in the same way as other child participants. Please see 5.1.4
p.000017: for more information. It is ethical for a healthy child to participate in research as long as appropriate consent has
p.000017: been obtained, there is no more than minimal risk and the research is not against the child's interest.
p.000017: Participation in more than one research study: as with adults, there may be situations where it could be argued that
p.000017: participation in more than one trial or study might be potentially beneficial – both for participants and for the
p.000017: research. The potential benefits and risks of doing so would need to be carefully explored by all concerned, and
p.000017: clearly understood by the child and family.24
p.000017: Equipoise: this is when there is genuine uncertainty among those who have considered the issue, including patients,
p.000017: about the relative benefits and risks of treatments or tests being compared. A clinical trial cannot be ethical unless
p.000017: there is this genuine informed uncertainty among the expert medical community and in an informed competent
p.000017: patient/participant.
p.000017: 4.3.2 Minimising risk
p.000017: The National Academy of the Sciences provides guidance on how to minimise risk, summarised here: 25
p.000017:
p.000017: Minimising risk in research involving children
p.000017:
p.000017: • Is inclusion of children necessary to answer the scientific question posed by the research? What are the ages
p.000017: of the children to be included? Are any of the potential research harms age-dependent?
p.000017: • Will potential child participants be screened for known vulnerability to the risks associated with specific
p.000017: elements of the research?
p.000017: • What does the research require of children and their families? Is adherence to the research protocol a
p.000017: concern? If so, what are the risks of non-adherence?
p.000017: • Are all the procedures or interventions necessary to answer the research question? Can the investigators
p.000017: collect the required information using procedures that the child participants will undergo as part of their normal
p.000017: therapy or monitoring?
p.000017: • Have previous laboratory studies, animal research, studies with adults, or other data provided a sufficient
p.000017: basis for proceeding with research involving children?
p.000017: • Does the study follow principles of sound research design?
p.000017:
p.000017: • What are the theoretical risks involved with the research as proposed? Are data available to estimate the
p.000017: probability and magnitude of each risk as they relate to the categories of children to be included?
p.000017: • Have the investigators provided data on the frequency of adverse events for the procedures at the site in
p.000017: question? For example, sedation for research procedures.
p.000017: Continued...
p.000017:
p.000017:
p.000017:
p.000018: 18
p.000018:
p.000019: 19
p.000019:
p.000019: MRC Ethics Guide: Medical research involving children
p.000019: MRC Ethics Guide: Medical research involving children
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019: Minimising risk in research involving children - Continued
p.000019:
p.000019: • Are the investigators and other members of the research team qualified to perform each of the procedures or
p.000019: assessments specified in the protocol and recognise potential risks and adverse outcomes? Does the research team have
p.000019: appropriate skills and expertise in caring for children of the ages included in the study?
p.000019: • Will research be performed in a setting that is 'friendly' to children of the ages included in the study? Is
p.000019: the setting appropriate for the physical, clinical, psychological and emotional needs of those age groups?
p.000019: • For research that involves more than minimal risk, does the research protocol have an adequate plan for
p.000019: monitoring the safety of the child participants? Does the monitoring plan provide for the inclusion of professionals
p.000019: with the appropriate expertise in paediatrics?
p.000019: • If the protocol presents the risk of a physical or psychological emergency, is the research setting equipped
p.000019: to respond? Are plans for responding to an emergency specified in the protocol?
p.000019: • What are the stopping rules or 'endpoints' for early discontinuation of the research on the basis of strong
p.000019: findings about harms or benefits? Are they specific and appropriate?
p.000019: • What happens to the data once they are collected? Where are research records stored, and who has access to
p.000019: them? What are the practices and procedures for maintaining the short-term and long-term confidentiality of the data?
p.000019: 5. Children, ethics and the law
p.000019:
p.000019: 5.1 Consent
p.000019:
p.000019: 5.1.1 What is valid consent?
p.000019:
p.000019: Consent – The voluntary agreement of an adult or competent child, based on adequate knowledge and understanding of
p.000019: relevant information, to participate in research
p.000019:
p.000019: Consent is legally valid and professionally acceptable only where the participants (or their parental guardian) are
p.000019: competent to give consent, have been properly informed, and have agreed without coercion.22
p.000019:
p.000019:
p.000019: In the UK, there are now two legal systems running in parallel.The common law applies to research not involving the
p.000019: Clinical Trials Regulations. As of May 2004, the Medicines for Human Use (Clinical Trials) Regulations apply to
p.000019: research involving investigational medicinal products (see Glossary). Researchers need to familiarise themselves with
p.000019: the Regulations.26
p.000019:
p.000019: 5.1.2 When should consent be sought, and who should seek consent?
p.000019: Research with children must normally only be carried out with the consent of the parent/guardian and/or child depending
p.000019: on the competence of the child. A summary of what is required in different circumstances is given below and in the flow
p.000019: diagram in 5.1.6. The physical integrity of children is protected by law and unless they or their parent/guardian
p.000019: agrees, it is not lawful to do anything that involves touching them.
p.000019: Consent should be sought before a child is examined, treated, cared for or involved in research. The clinician
p.000019: responsible for the child's treatment needs to ensure that
p.000019:
p.000020: 20
p.000020:
p.000021: 21
p.000021:
p.000021: MRC Ethics Guide: Medical research involving children
p.000021: MRC Ethics Guide: Medical research involving children
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: processes are in place and adhered to that ensure that the child and/or parent/guardian have given their informed
p.000021: consent. However the task of seeking consent can be delegated to another suitably trained and qualified health
p.000021: professional who understands the procedure(s) for which consent is being sought.
p.000021: As indicated in 5.1.5, the process of obtaining consent entails far more than a signature on paper. Verbal informed
p.000021: consent can be as valid as written consent for research, unless the Clinical Trials Regulations apply. It is vital that
p.000021: the person seeking consent records in writing that it has been given verbally. It may nevertheless be useful to obtain
p.000021: a signature from the participant or parent where this seems appropriate. It is important to note that under the
p.000021: Clinical Trials Regulations, verbal consent is not valid. The consent must be in writing unless the person giving
p.000021: consent is unable to write or otherwise mark the consent document.
p.000021: Informed consent is only one possible result of the informed choice process; the other possible result is the informed
p.000021: choice not to participate.
p.000021: Possible exceptions – Some research based on observation, on information collated from notes and tests already
p.000021: performed for therapeutic purposes, and public health research may be permissible without consent.2 Further
p.000021: information on the use of personal information in medical research is available from the MRC guidance Personal
p.000021: information in medical research.11
p.000021: Research linked to medical care in an emergency: the handling of this depends on whether the proposed study falls under
p.000021: the Clinical Trials Regulations. For further information please refer to 5.5.4.
p.000021:
p.000021: 5.1.3 Who can give consent, and who should you seek consent from?
p.000021: The law regarding the child's right to consent has developed differently in Scotland than in England, Wales and
p.000021: Northern Ireland – as outlined in 5.1.3a and 5.1.4a below. Generally, where children have sufficient understanding and
p.000021: intelligence to
p.000021: understand what is proposed, it is their consent and not that of their parent/guardian that is required by law.
p.000021: Ethically it is important to involve children as much as possible in decisions about their own health, wellbeing and
p.000021: healthcare. The United Nations Convention on the Rights of the Child states that the child has a right to be informed,
p.000021: to express a view and to influence a decision.27 Methods used to facilitate the consent process should be appropriate
p.000021: to the age and understanding of the child. The Department of Health provides very useful guidance on consent for both
p.000021: patients and clinicians, including guidance for children and for parents/guardians explaining what they have a right to
p.000021: expect.3
p.000021:
p.000021: 5.1.3.a Provision in law for children to consent
p.000021:
p.000021: England, Wales and Northern Ireland
p.000021: Where the Clinical Trial Regulations apply, a minor is defined as someone under the age of 16.
p.000021: Where the common law applies – all situations not covered by the Regulations – the law states that the age of majority
p.000021: is 18. Whilst not considered to have fully reached adulthood, young people between the age of 16 and 18 are presumed to
p.000021: be competent to give consent. No statute governs the rights of those under the age of 16 to give consent for medical
p.000021: treatment or research. However, case law provides the example of the Gillick case with respect to treatment.28 This
p.000021: case determined that where a young person has sufficient understanding and intelligence to understand fully what is
...
p.000025:
p.000025: Key provisions for the protection of minors within the Medicines for Human Use (Clinical Trials) Regulations 2004
p.000025: (Regulation 15 and Part 4 of Schedule 1) – extract from MHRA adviceii
p.000025:
p.000025: The Regulations provide additional protection for a minor (a person under the age of
p.000025: 16) who is a candidate for a clinical trial.They require, among other provisions, that:
p.000025:
p.000025: • an ethics committee considering the trial must receive advice on the relevant field of paediatric care; and
p.000025: • a person with parental responsibility or a legal representative must give informed consent and may withdraw the
p.000025: young person at any time; and, in relation to the minor himself:
p.000025: • staff with experience with young persons must inform him/her of the risks and benefits of the trial according to
p.000025: his capacity to understand;
p.000025: • the investigator must consider his or her explicit wish to refuse to participate or to be withdrawn from the
p.000025: trial at any time;
p.000025: • the clinical trial relate directly to an illness from which he or she suffers or that can only be carried out on
p.000025: minors; and
p.000025: • the trial must aim to provide some direct benefit for the group of patients involved.
p.000025: 5.1.4 Assessing the competence of a child to consent
p.000025: While normally increasing with age, competence is considered not to depend primarily on age, but rather on the ability
p.000025: to understand and weigh up options. It can be influenced by the way information is presented – many children will be
p.000025: competent if information is presented in an appropriate way and they are
p.000025: supported through the decision-making process. The Central Office for Research Ethics Committees (COREC) provides a
p.000025: useful template for designing patient information sheets and seeking assent/consent from children and young people.33 A
p.000025: child's ability to consent develops as he or she learns to make increasingly complex and serious decisions, which can
p.000025: be experience and/or age-related.
p.000025: For people to be able to have the capacity to take a particular decision they must be able to: 34
p.000025: • Comprehend and retain information material to the decision, especially the consequences of having or not having
p.000025: any intervention.
p.000025: • Use and weigh this information in a decision-making process.
p.000025:
p.000025: • Reach and communicate a decision.
p.000025:
p.000025: Even if the child is competent, it is still normally good practice to involve the family in the decision-making
p.000025: process. It is particularly desirable to obtain parental consent for younger children or for procedures that carry any
p.000025: risk or discomfort.
p.000025: If the competent child specifically asks for the family not to be involved in the decision-making process and they
p.000025: cannot be persuaded otherwise, their privacy should be respected.
p.000025: For further information please see 5.2.
p.000025:
p.000025:
p.000025:
p.000025: ii Extract from MHRA Description of the Medicines for Human Use (Clinical Trials) Regulations 2004.32
p.000025:
p.000025:
p.000026: 26
p.000026:
p.000027: 27
p.000027:
p.000027: MRC Ethics Guide: Medical research involving children
p.000027: MRC Ethics Guide: Medical research involving children
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027: 5.1.4.a Children unable to consent to involvement, and parental consent
p.000027: If the child is deemed incompetent to consent to participate in research, then he or she should normally not
p.000027: participate without the consent of a person with parental responsibility. A person with parental responsibility may
p.000027: legally consent to treatment on an incompetent child's behalf. If the child is able to give assent to decisions about
p.000027: participation in research, the investigator must obtain that assent in addition to the consent of the legally
p.000027: authorised representative. If the child does not assent, this should be respected.
p.000027: Legally, the researcher need only obtain consent from one person with parental responsibility. However, it is good
p.000027: practice and in the best interests of the child to involve others close to the child – for example, a second parent –
p.000027: in the decision- making process. Where opinions are strongly divided and agreement cannot be reached, it would be
p.000027: advisable to exclude the child from the research study unless a treatment option is only available as part of that
p.000027: programme. In such a case, every effort should be made to overcome the disagreement without a decision having to be
p.000027: referred to the courts.
p.000027: If the parents are themselves under 16 years of age, they will only be able to give valid consent on behalf of their
p.000027: child if they are competent to take the decision in question.
p.000027: Parents/guardians can consent to research procedures that offer potential benefit to the child. If the research is
p.000027: thought not to offer potential benefit to the child, parents/guardians can still consent provided the risks are
p.000027: sufficiently small to mean that research can be reasonably said not to go against the child's interests.
p.000027: Guidance on the law regarding parental consent is available from the BMA.4 A summary of country-specific differences
p.000027: follows:
p.000027: England,Wales and Northern Ireland
p.000027: The Children Act 1989 and The Children Act (Northern Ireland) Order 1995 make provision for parental rights in respect
p.000027: of their child, including the right to give consent to medical treatment.35, 36 Case law shows that a person with
p.000027: parental responsibility or the court can overrule a competent child's decision to refuse potentially beneficial
p.000027: treatment if it is felt to be in the best interests of the child or young person.
p.000027:
p.000027: Scotland
p.000027: The Children (Scotland) Act 1995 37 makes provision for cases where a young person aged under 16 is not competent to
p.000027: give legally valid consent. Parental rights enabling parents to carry out parental responsibilities include
p.000027: "safeguarding and promoting the child's health, welfare and development, providing direction and guidance to the child
p.000027: in a manner appropriate to the stage of the child's development and acting as the child's legal representative." Most
p.000027: of these last until the young person is 16 years old or shows competency to make their own decisions. Interestingly, in
p.000027: this Act it is stated that a child of 12 years or more should be presumed to be of sufficient age and maturity to form
p.000027: a view. The parental responsibility to provide guidance continues until the young person is 18. Case law suggests that
p.000027: a parent cannot overrule the decision of a competent child; however this has not yet been added to statute.
p.000027: The Adults with Incapacity (Scotland) Act 2000 38 covers the treatment and welfare of people over the age of 16 who
p.000027: are unable to give consent.
p.000027: In the absence of case law dealing specifically with research, the principles applying to medical treatment in England,
p.000027: Wales, Scotland and Northern Ireland might reasonably be applied to research.
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000029: 29
p.000029:
p.000029: MRC Ethics Guide: Medical research involving children
p.000029: MRC Ethics Guide: Medical research involving children
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: 5.1.4.b Seeking legal advice
p.000029: Researchers should seek legal advice if in any doubt regarding authority to proceed.
p.000029:
p.000029: 5.1.5 How best to seek consent
p.000029: The RCPCH provides guidance on how best to seek consent: 2
p.000029:
p.000029:
p.000029: For consent to be freely given researchers must:
p.000029:
p.000029: • Offer families no financial inducement although expenses should be paid.
p.000029: • Exert no pressure on families.
p.000029: • Give them as much time as possible (a few days for a major study, if at all possible) to consider whether to take
p.000029: part in the project.
p.000029: • Encourage families to discuss the project with – for example – their relatives, primary health carers – or an
p.000029: independent counsellor where available.
p.000029: • Tell them that they may refuse to take part, or may withdraw at any time even if they have signed a consent form.
p.000029: • Say that they need not give a reason for withdrawing (although their reason may help the researchers and other
p.000029: children in the study).
p.000029: • Assure them that the child patient's treatment will not be prejudiced by withdrawal from research.
p.000029: • Encourage parents/guardians to stay with the child during procedures.
p.000029: • Respond to families' questions, anxiety or distress throughout the study.
p.000029:
p.000029: For consent to be informed researchers must discuss with families:
p.000029:
p.000029: • The purpose of the research.
p.000029: • Whether the child stands to benefit directly and if so how; the difference between research and treatment.
p.000029: • The meaning of relevant research terms and any implications of consent (eg, placebo, randomised double-blind
p.000029: trial).
p.000029: • The nature of each procedure, how often and for how long each may occur.
p.000029: • The potential benefits and harms (both immediate and long-term).
p.000029: • The name of a researcher whom they can contact with their enquiries.
p.000029: • The name of the doctor directly responsible for the child's care.
p.000029: • How the child can withdraw from the project.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: Researchers must also:
p.000029:
p.000029: • Willingly explain and answer questions throughout the project.
p.000029: • Ensure that other staff caring for child subjects know about the research, and can also explain it if necessary.
p.000029: • Give clearly written patient information leaflets setting out all relevant information for families to keep
p.000029: (guidance on this can be found on the COREC website 33).
p.000029: • Report the results of research to the families involved wherever possible.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000030: 30
p.000030:
p.000031: 31
p.000031:
p.000031: MRC Ethics Guide: Medical research involving children
p.000031: MRC Ethics Guide: Medical research involving children
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 5.1.6 Seeking consent – a summaryiii
p.000031:
p.000031: If research is linked to medical care, it is justifiable in an emergency to start treatment prior to consent being
p.000031: obtained **
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Do the parents consent to the participation of
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: YES NO
p.000031:
p.000031: Is emergency treatment required where treatment is available only as part of a research programme?
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Research cannot go ahead. Parental consent MUST be obtained
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Research can go ahead Research cannot go ahead
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Research can go ahead with parental consent
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Even if the parents have given their consent, the deliberate objection of the child should be
p.000031: * In England, Wales and Northern Ireland parents may overule the child's decision if it is felt to be in the best
p.000031: interests of the child.
p.000031: ** Where parents refuse to give their consent, the courts can overrule if it is felt to be in the best interests of
p.000031: the child.
p.000031: *** The researcher must obtain the permission of the parent/guardian in accordance with local laws or established
p.000031: procedures eg, in the UK participation of a minor in a clinical trial requires parental consent under The Medicines for
p.000031: Human Use (Clinical Trials) Regulations (2004).
p.000031:
p.000031: NO their child in the
p.000031: research?
p.000031: Does the child
p.000031: NO actively object?
p.000031: respected
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Is the child believed to
p.000031: be competent to consent to the proposed treatment?
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: YES
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Does the competent child consent to participation?
p.000031:
p.000031: YES
p.000031:
p.000031: Does the child assent? ie, knowingly agree
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031: The child's opinion should be respected. Research should not go ahead *
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Is the child happy to involve the parents?
p.000031:
p.000031: YES
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031: Research can go ahead, the child has assented and parents’ consent obtained
p.000031:
p.000031:
p.000031:
p.000031: The child should be persuaded to involve the parents. Research can go ahead, as the child is competent ***
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Do the parents assent to the participation of their child in the research?
p.000031:
p.000031: Does the child need treatment that is not available outside the context of the research, does the investigation show
p.000031: promise of therapeutic benefit and is there no acceptable alternative therapy?
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031: The competent child's consent is sufficient – research could go ahead. However, if parents do not assent it may be
p.000031: unwise
p.000031: to proceed
p.000031:
p.000031:
p.000031: Research can go ahead. Competent child
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Do the parents wish their child to participate in the research project despite the child's objection?
p.000031:
p.000031: YES
p.000031:
p.000031: Research cannot go ahead. Parental consent must be obtained to proceed. The matter can be referred to the courts **
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Is the child very young or immature?
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: If the child is older or closer to being
p.000031: able to consent actively, seek the specific approval of the relevant Research Ethics Committees before initiating and
p.000031: continuing with investigational treatment
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Parent can overule child's objections.
p.000031: Research can go ahead
p.000031:
p.000031: iii Flow chart based on text from Council for International Organizations of
p.000031: Medical Sciences International ethical guidelines for biomedical research involving human subjects.5
p.000032: 32
p.000032: YES
p.000032: consents and parents assent
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033: MRC Ethics Guide: Medical research involving children
p.000033: MRC Ethics Guide: Medical research involving children
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: Seeking consent is not a single response but a process. The child should be provided with information appropriate to
p.000033: his or her increasing ability to make decisions about complex and serious issues. It is helpful for researchers to
p.000033: produce child-friendly information in a form appropriate for the relevant age groups – this could make use of pictures
p.000033: or videos. More than one version may need to be produced
p.000033: if research covers a wide age range, such as eight-18 years. Where the research project lasts a number of years, the
p.000033: child and/or parent/guardian may need to be approached periodically to ensure they still consent to the child's
p.000033: involvement in research. For example, where a parent has consented to follow-up studies throughout the life of the
p.000033: child, the child must be given the opportunity to decide for himself/herself, once competent to do so, whether he or
p.000033: she wishes to continue his or her involvement.
p.000033:
p.000033: 5.2 Confidentiality
p.000033: Medical professionals have a duty of confidentiality to all patients including children. Legally competent children are
p.000033: entitled to expect that information about themselves will not be provided to a third party, including their
p.000033: parent/guardian, without their consent. However, it is important that wherever possible the parents/guardians are
p.000033: informed, and young people should be encouraged to involve them unless it is not in their best interests to do so. If
p.000033: competent children do not wish to involve their parents/guardians this should be respected. Disclosure can only be
p.000033: justified if there is reasonable cause to suspect that the child is suffering or is likely to suffer significant harm
p.000033: as a result of non-disclosure. Any decision to disclose confidential information to a third party must be relayed to
p.000033: the competent child before disclosure.
p.000033: To facilitate both the child's healthcare and longer term research, general practitioners (GPs) should be notified of
p.000033: all research on their paediatric patients. The consent form should request consent to inform and update GPs of the
p.000033: child's involvement. If a participant is likely to resist information being provided to parents/guardians and family
p.000033: practitioners because the research is of a sensitive
p.000033: nature, eg, investigating smoking habits or sexual health, advice should be sought from the Research Ethics Committee
p.000033: that assesses the protocol.
p.000033: Children who lack competence to consent to participate are nevertheless entitled to confidentiality. The researcher
p.000033: will have had to request the parent/guardian's consent to the child's involvement in research. Any intention to
p.000033: disclose information to anyone else should be discussed with both the parent/guardian and the child, taking into
p.000033: consideration whether disclosure to a third party is necessary in the interests of the child's health. Public health
p.000033: research may require the use of anonymous data without explicit consent – for detailed guidance on this researchers
p.000033: should consult the MRC guidance Personal information in medical research.11
p.000033: Researchers working with children have important responsibilities in relation to child protection. Where researchers
p.000033: have reasonable cause to suspect that a child is suffering or likely to suffer significant harm, they have a clear
p.000033: responsibility to liaise urgently with those responsible for the child's clinical care with a view to making a referral
p.000033: to social services. Again, a decision to disclose information should, wherever possible, be discussed with the child
p.000033: before disclosure, in terms appropriate to the child's capability to understand.
p.000033: All researchers need to be aware of relevant data protection legislation and the rights of the child (and their
p.000033: parents/guardians in some circumstances) to access their health records. Fuller guidance on confidentiality issues is
p.000033: available from the Department of Health, the British Medical Association and the General Medical Council.3, 4, 39
p.000033:
p.000033: 5.3 Ethics committee review
p.000033: The Council of Europe Protocol to the Convention on Human Rights and Biomedicine on Biomedical Research provides
p.000033: guidance regarding the role of the ethics committee in research.9 According to this guidance, every research project
p.000033: must be submitted for independent examination of its scientific merit, including assessment of the importance of the
p.000033: aim of research and ethical acceptability to an
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000035: 35
p.000035:
p.000035: MRC Ethics Guide: Medical research involving children
p.000035: MRC Ethics Guide: Medical research involving children
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: ethics committee. An examination of the ethical acceptability is necessary to protect the dignity, rights, safety and
p.000035: wellbeing of the research participant. The assessment should draw on an appropriate range of expertise adequately
...
p.000035: Further guidance will be issued when the Human Tissue Bill, and equivalent legislation in Scotland, become law.
p.000035: 5.5.2 The use of personal information
p.000035: Please refer to the MRC guidance Personal information in medical research.11
p.000035:
p.000035: 5.5.3 Research involving very young children
p.000035: A parent/guardian's informed consent is necessary for the involvement of babies in research. When a baby is seriously
p.000035: ill and a decision about treatment is required quickly, the pressure on parents is high and the difficulty of obtaining
p.000035: truly informed consent is recognised. The RCPCH provides detailed guidance relating to research involving babies.40
p.000035:
p.000035: 5.5.4 Emergency situations
p.000035: Under common law, provided that the specific approval of a research ethics committee has been obtained for the project
p.000035: overall, it is ethical to carry out research involving children on occasions of extreme urgency without obtaining prior
p.000035: consent. However, there is a lack of clarity in the law about this if the research does not have the potential to
p.000035: benefit the child in question. If in doubt, it would be advisable to seek legal advice in potentially contentious
p.000035: circumstances.
p.000035: Research involving children in an emergency situation may be needed when treatment is available only as part of a
p.000035: research programme. Ethically, if the research does not have the potential to produce results of direct benefit to the
p.000035: individual participant, the Council of Europe recommends that it should only be carried out if it has the aim of
p.000035: contributing or improving understanding of the individual's condition so that it could ultimately confer benefit upon
p.000035: the patient or others with the same condition, and that it entails only minimal risk.9
p.000035: Research involving children in emergency situations should be carried out only where research of comparable
p.000035: effectiveness cannot be carried out on persons in non- emergency situations. The parents and child must be informed
p.000035: about the research as
p.000035:
p.000036: 36
p.000036:
p.000037: 37
p.000037:
p.000037: MRC Ethics Guide: Medical research involving children
p.000037: MRC Ethics Guide: Medical research involving children
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037: soon as possible afterwards and their consent for future involvement sought. It must be made clear that the child (or
p.000037: parent on behalf of a child not yet competent) can withdraw from the study at any point.
p.000037: The Council of Europe provide further guidance on research in emergency clinical situations.9
p.000037: Under the Clinical Trial Regulations, consent must be given on behalf of a minor prior to participation in a trial of
p.000037: an investigational medicinal product in all circumstances; there is currently no exception for emergency situations.
p.000037: However, it is possible for someone other than a parent to give consent as a “legal representative”, if the parent is
p.000037: unable to do so. This could be the doctor primarily responsible for the person’s treatment (if not involved in the
p.000037: trial) or, if they are not available, a person nominated by the healthcare provider.41
p.000037:
p.000037: 5.5.5 Including minority groups – equality in research
p.000037: As with adults it is important to include minority groups in research involving children to ensure that they as a group
p.000037: receive a share of the potential benefits of research.
p.000037: Researchers should be sensitive to cultural issues and particularly to participants' specific concerns and values. For
p.000037: example, whether acceptance of research is necessary from someone in the extended cultural group as well as the
p.000037: immediate family, or whether participants undertake religious fasts that may affect when they can take medicines.
p.000037: When seeking consent where the child or parent needs an interpreter, an independent interpreter is preferable to a
p.000037: family member.
p.000037: Where the child has a disability, particular care should be taken to ensure that information is provided in a suitable
p.000037: form. Specialist colleagues may be able to act as
p.000037: facilitators or advocates where the child has particular needs. Children with specific impairments such as learning
p.000037: difficulties should not be excluded from participating in research, but equally should not be over-researched because
p.000037: of their condition.
p.000037:
p.000037: 5.5.6 Research in developing countries
p.000037: Please refer to MRC guidance on Research involving human participants in developing societies.
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000039: 39
p.000039:
p.000039: MRC Ethics Guide: Medical research involving children
p.000039: MRC Ethics Guide: Medical research involving children
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: 6. Summary
p.000039: Children should be included in medical research only if:
p.000039:
p.000039: • The relevant knowledge cannot be gained through research with adults.
p.000039:
p.000039: • It is approved by the appropriate Research Ethics Committee/s.
p.000039:
p.000039: • Either the participant has given consent where competent, or consent has been given on his or her behalf by a
p.000039: parent or guardian and the participant does not object or appear to object in either words or actions. iv
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: iv See 5.5.4 for guidance on emergency situations, when this might not be possible.
p.000039: 7. Glossary
p.000039: The definitions provided here apply as they are used in the above guidelines.
p.000039:
p.000039: Assent
p.000039: A child's affirmative agreement to participate. Failure to object should not be construed as assent.
p.000039: Burden of disease
p.000039: The impact of disease on the individual and on society due to loss of duration and quality of life. Measures include
p.000039: (i) 'morbidity burden', ie, the prevalence of a condition, the range of its severity and the age distribution of the
p.000039: population suffering from the condition, and (ii) the financial burden to society in meeting the obligation to support
p.000039: the individual; for example, in terms of net public expenditure on health services and on social services.
p.000039: Child
p.000039: In the UK, a person under the age of 18. "Young person" is a term often used to describe older children in this age
p.000039: group. The competence of children to consent is discussed in Section 5.
p.000039: Clinical Trials Regulations
p.000039: The Medicines for Human Use (Clinical Trials) Regulations apply to research involving investigational medicinal
p.000039: products (see below). In such studies, informed consent is strictly defined as follows and only consent meeting this
p.000039: definition will suffice:
p.000039: “A person gives informed consent to take part, or that a subject is to take part, in a clinical trial only if his
p.000039: decision –
p.000039: (a) is given freely after that person is informed of the nature, significance, implications and risks of the trial;
p.000039: and
p.000039:
p.000039:
p.000040: 40
p.000040:
p.000041: 41
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: (b) either –
p.000041: (i) is evidenced in writing, dated and signed, or otherwise marked, by that person so as to indicate his consent, or
p.000041: (ii) If the person is unable to sign or to mark a document so as to indicate his consent, is given orally in the
p.000041: presence of at least one witness and recorded in writing.”
p.000041:
p.000041: Confidentiality
p.000041: The duty of persons to whom personal information has been given not to share the information with any unauthorised
p.000041: person. For more information about what this involves in practice, see 5.2.
p.000041:
p.000041: Competence
p.000041: The ability of a person, given the necessary information, to understand the nature and the consequences of the proposed
p.000041: procedure or treatment, and to use that information to make a valid choice in accordance with their own fundamental
p.000041: values. Please refer to 5.1.4.
p.000041:
p.000041: Consent
p.000041: The voluntary agreement of an adult or competent child, based on adequate knowledge and understanding of relevant
p.000041: information, to participate in research. For further information please refer to Section 5.
p.000041:
p.000041: Family
p.000041: A group of individuals who together form a social structure; a family may or may not include biological relatives.
p.000041:
p.000041:
p.000041: Harm
p.000041: That which adversely affects the interests or welfare of an individual. This may be physical harm, discomfort, anxiety,
p.000041: pain, and psychological
p.000041:
p.000041: disturbance or social disadvantage (ostracism).
p.000041:
p.000041: Investigational medicinal product
p.000041: A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial,
p.000041: including products already with a marketing authorisation but used or assembled (formulated or packaged) in a way
p.000041: different from the authorised form, or when used for an unauthorised indication, or when used to gain further
p.000041: information about the authorised form.31
p.000041:
p.000041: Off-label
p.000041: Term used to describe a medicine used for an indication, dose, or route of administration outside the terms of the
p.000041: product licence.
p.000041:
p.000041: Parent/guardian
p.000041: The term "parent/guardian" is used in these guidelines to describe those with legal responsibility for the child. The
p.000041: Children Act 1989, the Children (Scotland) Act 1995 and the Children (Northern Ireland) Order 1995 set out who has
p.000041: parental responsibility in their respective jurisdictions. The Adoption and Children Act 2002 s111(2) has recently
p.000041: extended the definition of those with legal responsibility for the child to include unmarried fathers who have entered
p.000041: into a legally binding Parental Responsibility Agreement.42
p.000041: The MRC is aware that some children will not be resident with both or either of their parents.
p.000041: On occasion it may be difficult for the researcher to determine who has legal responsibility for the child, and if
p.000041: necessary, further clarification should be sought from the child’s care giver or their GP.
p.000041:
p.000041:
p.000041: Risk
p.000041: A potential harm; the characteristics of risk include the probability of its occurrence, as well as its magnitude and
p.000041: duration. For more on assessment and minimising risk see 4.3.
p.000041:
p.000041: MRC Ethics Guide: Medical research involving children
p.000041: MRC Ethics Guide: Medical research involving children
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: 8. Other MRC ethics guidance
p.000041: The MRC produces a wide range of ethics guidance for researchers, which is available at www.mrc.ac.uk and includes the
p.000041: following:
p.000041: • MRC interim guidance on ethics of research involving human material derived from the nervous system (June 2003).
p.000041: • MRC policy on antiretroviral therapy (ART) for people infected with HIV and involved in AIDS research in
p.000041: developing countries – General guidance notes for consideration (2002).
p.000041: • MRC guidance on reviewing research proposals (2001).
p.000041:
...
p.000041: • Research involving human participants in developing societies: ethical guidelines for MRC-sponsored studies
p.000041: (2004).
p.000041: • Responsibility in the use of animals in medical research (1993).
p.000041:
p.000041: • The MRC's terms and conditions for research grants and training awards involving stem cells (2003).
p.000041: • Cluster randomised trials: Methodological and ethical considerations (2002).
p.000041:
p.000041: • MRC guidelines for good clinical practice in clinical trials (1998).
p.000041:
p.000041: • Health Technology Assessment in surgery (2003).
p.000041:
p.000041:
p.000041: Additional guidance available by post includes:
p.000041:
p.000041: • Principles in the assessment and conduct of medical research and publicising results (1995).
p.000041:
p.000041:
p.000041:
p.000044: 44
p.000044:
p.000045: 45
p.000045:
p.000045: MRC Ethics Guide: Medical research involving children
p.000045: MRC Ethics Guide: Medical research involving children
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045: 9. References
p.000045: 1. The ethical conduct of research on children. London: Medical Research Council (MRC), 1991.
p.000045: 2. Royal College of Paediatrics and Child Health: Ethics Advisory Committee. 2002. "Guidelines for the ethical
p.000045: conduct of medical research involving children". Reprinted from Archives of Disease in Childhood 82 (2): 177-182.
p.000045: 3. Department of Health: Consent guidance webpages. www.dh.gov.uk/PolicyAndGuidance/
p.000045: HealthAndSocialCareTopics/Consent/ConsentGeneralInformation/fs/en
p.000045: 4. Consent, rights and choices in healthcare for children and young people. London: British Medical
p.000045: Association, 2001.
p.000045: 5. International ethical guidelines for biomedical research involving human subjects. Geneva: Council for
p.000045: International Organizations of Medical Sciences, 2002.
p.000045: 6. Declaration of Helsinki: ethical principles for medical research involving human subjects. Amended by the
p.000045: 52nd World Medical Association (WMA) General Assembly. Ferney-Voltaire:WMA, 2000.
p.000045: 7. International Guidelines for ethical review of epidemiological studies. Geneva: Council for International
p.000045: Organizations of Medical Sciences, 1991.
p.000045: 8. MRC guidelines for good clinical practice in clinical trials. London: MRC, 1998.
p.000045: 9. Additional protocol to the Convention on Human Rights and Biomedicine on Biomedical Research. Strasbourg:
p.000045: Council of Europe, 2004.
...
p.000045: 13. Office for National Statistics. www.statistics.gov.uk/children/downloads/child_cancer.pdf
p.000045: 14. Smyth R.L.,Weindling A.M. 1999. "Research in children: ethical and scientific aspects". Lancet 354 (suppl
p.000045: II): 21-24.
p.000045: 15. Campbell H., Surry S.A.M., Royle E.M. 1998. "A review of randomised controlled trials published in Archives
p.000045: of Disease in Childhood from 1982-96." Archives of Disease in Childhood 79: 192-197.
p.000045: 16. Halliday H.L., Ehrenkranz R.A., Doyle L.W. 2004. "Early postnatal (<96 hours) corticosteroids for preventing
p.000045: chronic lung disease in preterm infants" (Cochrane Review). In: The Cochrane Library, Issue 2. Chichester, UK: John
p.000045: Wiley & Sons, Ltd.
p.000045: 17. Better Medicines for Children: proposed regulatory actions on paediatrics medicinal products. European
p.000045: Commission (EC) consultation document. Addendum to ref 18. Brussels: EC, 2002.
p.000045: http://pharmacos.eudra.org/F2/pharmacos/docs/Doc2002/feb/cd_pediatrics_en.pdf
p.000045: 18. National Audit Office Report (HC 255 2002-2003). Safety, quality, efficacy: regulating medicines in the UK.
p.000045: London: the Stationery Office, 2003.
p.000045: 19. Smith Robert N. 2000. Meeting report – A European conference on clinical research in children: ethical,
p.000045: scientific and regulatory issues. Section: "Research, the rights of the child and legal considerations in paediatric
p.000045: clinical research". International Journal of Pharmaceutical Medicine; reprinted from: Archives of Disease in Childhood
p.000045: 16:15-29.
p.000045: 20. Medicines and Healthcare products Regulatory Agency/Department of Health: Strategy on Medicines for Children,
p.000045: July 2004. http://medicines.mhra.gov.uk/ourwork/licensingmeds/children/paediatricstrategydoc.pdf
p.000045: 21. Safer and Better Medicines for Children – Developing the Clinical and Research Base of Paediatric
p.000045: Pharmacology in the United Kingdom. Royal College of Paediatrics and Child Health Review (commissioned by the MRC, the
p.000045: Department of Health, and the Association of the British Pharmaceutical Industry), May 2004.
p.000045: 22. Research: the role and responsibilities of doctors. London: General Medical Council, 2002.
p.000045: 23. Testing for late onset genetic disorders. London: British Paediatric Association, 1996.
p.000045: 24. Brocklehurst P. 1997. "Randomised controlled trials in perinatal medicine: 2. Recruitment of a pregnant woman
p.000045: or her newborn child into more than one trial." British Journal of Obstetrics and Gynaecology 104 (7):765-7.
p.000045: 25. Ethical Conduct of Clinical Research Involving Children.The National Academy of the Sciences USA, 2004.
p.000045: 26. The Medicines for Human Use (Clinical Trials) Regulations. 2004.
p.000045: www.legislation.hmso.gov.uk/si/si2004/20041031.htm
p.000045:
p.000045: 27. UN Convention on the Rights of the Child. General Assembly resolution 44/25 of 20 November 1989, entry into
p.000045: force 2 September 1990 in accordance with article 49. www.childrenslawcentre.org/UNCRC_hearing.htm
p.000045: 28. Gillick v West Norfolk and Wisbech. London: House of Lords, Gillick v West Norfolk and Wisbech AHA (1986) AC
p.000045: 112, [1985] 3 WLR 830, [1985] 3 AII ER 402, HL
p.000045: 29. Age of Majority (Scotland) Act 1969 s 1.
p.000045: 30. Age of Legal Capacity (Scotland) Act 1991. (c. 50)
p.000045: 31. Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of
p.000045: the laws, regulations and administrative provisions of the Member States relating to the implementation of good
p.000045: clinical practice in the conduct of clinical trials on medicinal products for human use.
p.000045: http://europa.eu.int/eur-lex/pri/en/oj/dat/2001/l_121/l_12120010501en00340044.pdf
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p.000047: 47
p.000047:
p.000047:
p.000047:
p.000047: MRC Ethics Guide: Medical research involving children
p.000047:
p.000047:
p.000047:
p.000047:
p.000047:
p.000047: 32. Medicines and Healthcare products Regulatory Agency: Description of the Medicines for Human Use (Clinical
p.000047: Trials) Regulations 2004. http://medicines.mhra.gov.uk/ourwork/licensingmeds/types/ctdregs_shortdesc.pdf
p.000047: 33. Central Office for Research Ethics Committees. www.corec.org.uk
p.000047: 34. Seeking Consent:Working with children. Department of Health, 2001. www.dh.gov.uk/PublicationsAndStatistics/
p.000047: Publications/PublicationsPolicyAndGuidance/PublicationsPolicyAndGuidanceArticle/fs/en?CONTENT_ ID=4007005&chk=xFifXP
p.000047: 35. Children Act 1989 (c. 41). www.hmso.gov.uk
p.000047: 36. Children Act (Northern Ireland) Order 1995. www.northernireland-legislation.hmso.gov.uk
p.000047: 37. Children (Scotland) Act 1995. www.hmso.gov.uk
p.000047: 38. Adults with incapacity (Scotland) Act 2000. www.scotland-legislation.hmso.gov.uk
p.000047: 39. Confidentiality: protecting and providing information. London: General Medical Council, 2004.
p.000047: 40. Guidance safeguarding informed parental involvement in clinical research involving newborn babies and
p.000047: infants. London: Royal College of Paediatrics and Child Health, 1999.
p.000047: 41. Department of Health/MRC: Clinical Trials Toolkit. 2004. www.ct-toolkit.ac.uk
p.000047: 42. The Adoption and Children Act 2002. www.hmso.gov.uk/acts/acts2002/20020038.htm
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p.000047: Medical Research Council
p.000047: 20 Park Crescent London W1B 1AL
p.000047: Tel: 020 7636 5422 Fax: 020 7436 6179
p.000048: 48
p.000048: www.mrc.ac.uk
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p.002004: MRC Ethics Guide: Medical research involving children
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p.002004:
p.002004:
p.002004: Foreword
p.002004: Medical research involving children is important for the benefit of all children. It leads to innovations in healthcare
p.002004: that can substantially improve their health and quality of life.
p.002004: Furthermore, the scientific opportunities for developing better methods of preventing and treating diseases that affect
p.002004: children or begin in childhood have never been greater.
p.002004: The Medical Research Council (MRC) believes that research involving children should be supported, encouraged, and
p.002004: conducted in an ethical manner. We want to ensure that research participants, their parents and the general public can
p.002004: be confident that medical researchers work ethically with children.
p.002004: We recognise that while many other organisations have published guidance on medical research involving children, this
p.002004: is a vital area in which we must provide support and guidance to MRC researchers.The previous MRC guidance The ethical
p.002004: conduct of research on children1 (1991) has been replaced by the following updated guidelines. They outline the
p.002004: practical, ethical and legal issues that researchers need to consider when carrying out studies involving children. Our
p.002004: aim has been to set out general principles that can be applied in most situations rather than to cover every possible
p.002004: eventuality. The guidelines are intended to be concise and easily readable, and include a glossary defining some of the
p.002004: key terms used (see Section 7).
p.002004: We refer to guidance from The Royal College of Paediatrics and Child Health,2 the
p.002004: Department of Health3 and British Medical Association4 throughout this document. These organisations can all provide
p.002004: further useful information.
p.002004: This guide complements guidance on other research-related topics produced by the MRC, all of which is available at the
p.002004: MRC website, www.mrc.ac.uk. Any changes to MRC guidance are highlighted on the site as they arise.
p.002004:
p.002004:
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p.000001: MRC Ethics Guide: Medical research involving children
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p.000001:
p.000001:
p.000001: Contents
p.000001: 1. Introduction 4
p.000001: 1.1 Purpose 4
p.000001: 1.2 General ethical principles 5
p.000001: 1.3 Summary of key ethical principles relating to research
p.000001: involving children 5
p.000001: 2. Why do we need research involving children? 7
p.000001: 2.1 What would be the consequences of not carrying
p.000001: out research on children? 8
p.000001: 3. What has limited research so far, and what are
p.000001: the challenges? 9
p.000001: 3.1 Difficulty in reaching consensus about including
p.000001: children in research 9
p.000001: 3.2 Methodological challenges 10
p.000001: 3.3 Expense of developing new treatments 11
p.000001: 3.4 Weak licensing and regulation arrangements for
p.000001: paediatric versions of pharmaceuticals 11
p.000001: 4. The way forward – ethical considerations 13
p.000001: 4.1 Does the research need to be carried out with children? 13
p.000001: 4.2 Use of terms 'therapeutic' and 'non-therapeutic' research 14
p.000001: 4.3 Benefit, harm and risk 15
p.000001: 4.3.1 Other considerations 17
p.000001: 4.3.2 Minimising risk 19
p.000001: 5. Children, ethics and the law 21
p.000001: 5.1 Consent 21
p.000001: 5.1.1 What is valid consent? 21
p.000001: 5.1.2 When should consent be sought, and who should seek consent? 21
p.000001: 5.1.3 Who can give consent, and who should you seek consent from? 22
p.000001: 5.1.3.a Provision in law for children to consent 23
p.000001: 5.1.4 Assessing the competence of a child to consent 27
p.000001: 5.1.4.a Children unable to consent to involvement, and parental consent 28
p.000001: 5.1.4.b Seeking legal advice
p.000030: 30
p.000030: 5.1.5 How best to seek consent 30
p.000030: 5.1.6 Seeking consent – a summary 32
p.000030: 5.2 Confidentiality 34
p.000030: 5.3 Ethics committee review 35
p.000030: 5.4 Children's safety in relation to researchers 36
p.000030: 5.5 Specific situations 36
p.000030: 5.5.1 Research involving human material 36
p.000030: 5.5.2 The use of personal information 37
p.000030: 5.5.3 Research involving very young children 37
p.000030: 5.5.4 Emergency situations 37
p.000030: 5.5.5 Including minority groups – equality in research 38
p.000030: 5.5.6 Research in developing countries 39
p.000030: 6. Summary 40
p.000030: 7. Glossary 41
p.000030: 8. Other MRC ethics guidance 44
p.000030: 9. References 46
p.000002: 2
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p.000003: MRC Ethics Guide: Medical research involving children
p.000003: MRC Ethics Guide: Medical research involving children
p.000003:
p.000003:
p.000003:
p.000003: 1. Introduction
p.000003: 1.1 Purpose
p.000003: These guidelines are designed to be of use to researchers preparing proposals for MRC support for research involving
p.000003: children, and to those planning, undertaking or collaborating in such research. They will also be helpful to other
p.000003: researchers, and to doctors and other health professionals whose patients may be involved in research, to ethics
p.000003: committees, to others reviewing or supervising research, and to the public.
p.000003: The guidelines take into account recent publications by leading organisations and professional bodies, which are
p.000003: referred to throughout. They should be read in conjunction with MRC guidance on different aspects of good practice in
p.000003: research with adults (listed in Section 8), the principles of which are also relevant to paediatric research.
p.000003:
p.000003:
p.000003:
p.000003:
p.000003: 1.2 General ethical principles
p.000003: The MRC is committed to the highest ethical standards in medical research. The fundamental principles underpinning
p.000003: research on human beings and information relating to them have been elaborated and refined in various national and
p.000003: international guidelines: 5-12
p.000003: • Participants' interests must prevail over those of science and society, where there is conflict.
p.000003: • The research must have potential to generate scientific understanding that may be a basis for improvements in
p.000003: human health and wellbeing.
p.000003: • There must be an acceptable balance of risk and benefit for participants.
p.000003:
p.000003: • Researchers can only proceed if they have obtained voluntary informed consent from the participant to
p.000003: participate in research (special safeguards apply when this is not possible).
p.000003: • An appropriate independent research ethics committee must review and approve the research proposal.
p.000003:
p.000003: 1.3 Summary of key ethical principles relating to research involving children
p.000003: Children require special protection because they are less likely than adults to be able to express their needs or
p.000003: defend their interests – they may not have the capacity to give consent.
p.000003: The following principles should guide all MRC-funded research involving children: 4, 5
p.000003:
p.000003: • Research should only include children where the relevant knowledge cannot by obtained by research in adults (for
p.000003: guidance, see 4.1)
p.000003:
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p.000004:
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p.000005: • The purpose of the research is to obtain knowledge relevant to the health, wellbeing or healthcare needs of
p.000005: children.
p.000005: • Researchers can only involve competent children if they have obtained their informed consent beforehand.
p.000005: • A child's refusal to participate or continue in research should always be respected.
p.000005: • If a child becomes upset by a procedure, researchers must accept this as a valid refusal.
p.000005: • Researchers should involve parents/guardians in the decision to participate wherever possible, and in all cases
p.000005: where the child is not yet competent. Exceptional circumstances where this is not possible are discussed in 5.5.4.
p.000005: • Researchers should attempt to avoid any pressures that might lead the child to volunteer for research or that
p.000005: might lead parents to volunteer their children, in the expectation of direct benefit (whether therapeutic or
p.000005: financial).
p.000005: • Research involves partnership with the child and/or family, who should be kept informed and consent to separate
p.000005: stages of the project. Obtaining consent is a continuing process, rather than a one-off occurrence. Children and their
p.000005: families are likely to appreciate some recognition of their role in this partnership, such as a certificate of
p.000005: participation.
p.000005: • Researchers must take account of the cumulative medical, emotional, social and psychological consequences of the
p.000005: child being involved in research. Children with certain conditions may be exposed to a sequence of research projects.
p.000005: It is advisable to consider the risks of a particular research procedure in the context of the child's overall
p.000005: involvement in projects by different researchers.
p.000005: 2. Why do we need research involving children?
p.000005: Medical research involving children is essential for advancing child health and wellbeing. Often it is not sufficient,
p.000005: scientific, or ethical to carry out research with adults and apply the findings to children. This may be because:
p.000005: • The disease processes in children may differ from those in adults. Some childhood diseases have no close
p.000005: analogies in adults, therefore to understand these in any detail it is necessary to carry out research with children.
p.000005: • The physiology of children is different from that of adults, and the pharmacokinetics of many drugs will vary
p.000005: with the age of the child.Treatments designed specifically to meet the needs of children ensure that age-related
p.000005: differences in drug handling and/or effects are recognised, that the doses needed for efficacy are understood, and that
p.000005: any adverse effects can be avoided.
p.000005: • Many disorders can only be understood in the context of a child's growth and development. Examples include
p.000005: changes in the visual system following early squint, or the way the developing brain adapts to injury or damage in
p.000005: babies.
p.000005: • Children are not small adults. For the therapy to be effective, its delivery must suit their needs. Use of adult
p.000005: formulations is often not suitable, eg, many children find it easier to swallow a liquid formulation than a tablet.
p.000005: Research with children can also play a key part in increasing our understanding of some adult diseases that are thought
p.000005: to have their origins in early life. It enables the development of preventive intervention into the natural history of
p.000005: the disease. The findings of research involving children can therefore also be relevant for adults.
p.000005:
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p.000007: Research promoting the health of children can include investigation of: 2
p.000007:
p.000007: • Normal childhood development.
p.000007:
p.000007: • Origins and causes of disease.
p.000007:
p.000007: • Means of promoting health.
p.000007:
p.000007: • Means of preventing, diagnosing, assessing and treating disease.
p.000007:
p.000007: • Whether the beneficial results of research conducted in adults can be applied to children.
p.000007: While we have a responsibility to protect children, we also have an ethical obligation to ensure that they receive the
p.000007: best treatment. Like adults, they should be given the opportunity to benefit from the results of successful research.
p.000007: Children should therefore have the opportunity to participate while, of course, being protected from any hazards that
p.000007: involvement in the research project might bring. The MRC's research on childhood leukaemia shows how valuable this
p.000007: involvement can be. Most children diagnosed with leukaemia in the UK are entered into the MRC's trials, and in the last
p.000007: 40 years the survival rate for children with acute lymphoblastic leukaemia especially has greatly improved – from less
p.000007: than five per cent in 1962 to 80 per cent at present.13
p.000007:
p.000007: 2.1 What would be the consequences of not carrying out research on children?
p.000007: When research does not involve children, child-specific treatments for diseases are not developed and diseases with no
p.000007: close analogies in adults are not studied. This means that future generations of children miss the opportunity to
p.000007: benefit from the findings of that research. Progress in the clinical care of children will be impaired without research
p.000007: in this age group and children may be given treatments that are potentially unsafe. In addition, progress on
p.000007: understanding adult diseases thought to have their origins in early life will be hampered, limiting the possibilities
p.000007: of preventive intervention.
p.000007: 3. What has limited research so far, and what are the challenges?
p.000007: Progress in research involving children has been limited primarily by:
p.000007:
p.000007: • Difficulty in reaching consensus about including children in research.
p.000007:
p.000007: • Methodological challenges.
p.000007:
p.000007: • Expense of developing new treatments.
p.000007:
p.000007: • Lack of legal enforcement for paediatric versions of drugs.
p.000007:
p.000007: 3.1 Difficulty in reaching consensus about including children in research
p.000007: Current ethical principles for conducting research involving children have evolved from the Nuremberg Code which
p.000007: emerged after the Second World War. The Code set out statements of moral, ethical and legal principles relating to
p.000007: research involving human subjects, and included a bar on research involving children. Research was seen as a potential
p.000007: harm from which vulnerable people should be protected. Later, in 1964, the Declaration of Helsinki, drawn up by the
p.000007: World Medical Association, advised that research involving minors could be carried out where "the research is necessary
p.000007: to promote the health of the population represented and this research cannot instead be performed on legally competent
p.000007: persons" and appropriate consent and assent had been obtained.
p.000007: Today, organisations such as the Council for International Organizations of Medical Sciences play a vital part in
p.000007: considering how these ethical principles can be effectively applied. While research may have associated risks, it can
p.000007: also offer potential benefits to all participants, including children. Changes in the way we regard children include a
p.000007: growing recognition of the importance of listening to children's views and wishes, and of their autonomy. This can be
p.000007: observed in
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p.000009:
p.000009:
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p.000009:
p.000009:
p.000009:
p.000009: attitudes towards research involving children. Earlier research tended to be on children, with children regarded as
p.000009: subjects of the research. Increasingly, research is conducted with children, who are involved as active participants.
p.000009:
p.000009: 3.2 Methodological challenges
p.000009: Smyth and Weindling describe how the emergence of evidence-based healthcare has led to a greater awareness of the need
p.000009: to evaluate critically what is already known before making recommendations for clinical practice or embarking on
p.000009: further research.14 Studies have shown that in comparison to research on adults, research questions relevant to the
p.000009: health of children may not have been addressed at all, or only by small, poorly designed studies.15
p.000009: Particular methodological challenges occur in research involving children. Childhood forms of many chronic diseases,
p.000009: eg, juvenile chronic arthritis, are uncommon and this may lead to difficulties in gaining statistical power to detect
p.000009: an effective treatment.
p.000009: Genetic disorders leading to severe disability or death are also rare.
p.000009:
p.000009: Even for more common conditions challenges arise. In asthma, for example, the diagnosis may be subjective, which poses
p.000009: problems in establishing the clear inclusion and exclusion criteria required for clinical trials. Standard outcome
p.000009: measures in adults include death and quality of life, but for many conditions different outcomes are more relevant.
p.000009: Measurements of these outcomes have been determined for use in adults specifically and may not be relevant for
p.000009: children. Quality of life measures can be used, but should be focused on the child or family and validated and tested
p.000009: for reliability and responsiveness to change before being used; such instruments have not always been available.
p.000009: It is therefore useful, and important, to consult children about outcome measures and other issues, when the research
p.000009: is being designed.
p.000009: When carrying out research on children, it is important to assess both the short- term and long-term outcomes. For
p.000009: example, early treatment of premature infants at high risk of chronic lung disease with steroid drugs reduces this
p.000009: risk, but long-term studies show an increased risk of cerebral palsy.16
p.000009: Investigations of cognitive, neurological and respiratory function can also pose challenges, eg, the inability of young
p.000009: children to understand and co-operate with the demands of complex tasks.
p.000009:
p.000009: 3.3 Expense of developing new treatments
p.000009: Because of the expense of developing a new treatment, commercially funded research understandably focuses on treatment
p.000009: options that are likely to be profitable. Pharmaceutical companies have traditionally been reluctant to invest in
p.000009: developing child-specific treatments or adapting existing medicines to meet the needs of children. The main reasons are
p.000009: that the market is often small and that long-term follow-up of adverse effects is often needed because the risks
p.000009: associated with paediatric treatments are generally higher.17
p.000009:
p.000009: 3.4 Weak licensing and regulation arrangements for paediatric versions of pharmaceuticals
p.000009: The National Audit Office recently reported that up to 90 per cent of medicines prescribed to children in hospitals
p.000009: were not licensed for that use.18 Consequently, there are potentially important public health benefits in improving
p.000009: the licensing of medicines and the testing of their safety for children. Currently in Europe there is no legal
p.000009: requirement for the necessary studies to be performed if the pharmaceutical company does not present the drug for use
p.000009: in children. However, the European Commission has proposed legislation on medicinal products for paediatric use. 17, 19
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p.000011: This regulatory initiative takes its direction mainly from recent US legislation – the US Best Pharmaceuticals for
p.000011: Children Act 2002 and the related 'Pediatric Exclusivity' provision and 'Pediatric Rule'. The Pediatric Exclusivity
p.000011: provision grants an additional six months’ patent protection or market exclusivity to companies that voluntarily test
p.000011: the relevant drug on children, which has been generally well received. The Pediatric Rule demands that companies test
p.000011: their products on children under
p.000011: certain circumstances, including the likelihood of: usage for a substantial number of children, meaningful therapeutic
p.000011: benefits, risk to children in the absence of licensing and usage in different paediatric age groups.
p.000011: The European legislation will probably be finalised in 2006. Meanwhile, a co-ordinated UK strategy led by the Medicines
p.000011: and Healthcare products Regulatory Agency (MHRA) and the Department of Health aims to begin to address the issue and
p.000011: raise awareness in the pharmaceutical industry of the need to take action now to ensure that products are appropriately
p.000011: labelled and formulated for paediatric use.20 The resulting need for more research in paediatric pharmacology was
p.000011: highlighted in the Royal College of Paediatrics and Child Health (RCPCH) review Safer and Better Medicines for
p.000011: Children, which was commissioned by the MRC, the Department of Health and the Association of the British Pharmaceutical
p.000011: Industry. 21
p.000011: In addition to the above constraints, the increased complexity of regulation for paediatric and adult clinical research
p.000011: has become more burdensome for clinicians and researchers.
p.000011: 4. The way forward – ethical considerations
p.000011: The following section outlines the key issues to consider when planning and conducting research involving children.
p.000011:
p.000011: 4.1 Does the research need to be carried out with children?
p.000011: Research involving children should only be carried out if it cannot feasibly be carried out on adults. Therefore the
p.000011: researcher needs to assess beforehand whether the same potential benefit for children could be derived from studies on
p.000011: adults, which involves asking the following questions:
p.000011: • Is the disease specific to children, with no close analogy in adults? For example, juvenile rheumatoid arthritis
p.000011: or Kawasaki's disease.
p.000011: • Will the study increase understanding of the children's development and/or wellbeing with the aim of improving
p.000011: child health?
p.000011: • Are the relevant pharmacokinetics of the treatment option being studied already known in adults? Is it expected
p.000011: that the pharmacokinetics for children and adults will differ? Is there a need to test this?
p.000011: • Is the adult-style therapy shown or believed to be unpalatable or difficult to administer to children? Has the
p.000011: therapy previously been developed for adults and not tolerated by children?
p.000011: • Is the adult disease believed to have its origins in early life? Will studies involving children shed light on
p.000011: the disease and its natural history and increase understanding of the possibilities of prevention?
p.000011: If the answer to any of these questions is yes, children may ethically be involved in this research, and may benefit
p.000011: from it.
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p.000013: When a choice of age groups is possible, older children should be involved in preference to younger ones, although some
p.000013: research questions are specific to younger children and babies.2
p.000013:
p.000013: 4.2 Use of terms 'therapeutic' and 'non-therapeutic' research
p.000013: The distinction drawn previously between therapeutic and non-therapeutic research is now regarded by many as unhelpful
p.000013: and potentially misleading. For example, clinical trials that involve medicines include both therapeutic elements – the
p.000013: medicine being given – and non-therapeutic ones – the taking of a blood sample.
p.000013: Moreover, the term therapeutic can cause confusion if it raises hopes of success whereas the outcome of the research
p.000013: may not provide a treatment that benefits the individual participant. Indeed, some 'therapeutic' research has been
p.000013: considered to be more hazardous than 'non-therapeutic' research. Consequently, the Declaration of Helsinki (2000) no
p.000013: longer uses these terms, setting out instead basic principles for all medical research and additional ones for research
p.000013: combined with medical care.
p.000013: The guidelines from the RCPCH published in 2000 likewise avoid drawing this distinction, highlighting instead the
p.000013: principles that research involving children is important for the benefit of all children, and that a research procedure
p.000013: which cannot directly benefit the child is not necessarily unethical if the findings might benefit future generations
p.000013: of children. Research where there is no benefit to the individual child participant would have to be of minimal risk.
p.000013: This is a major step forward in thinking. The expectation is that children can now begin to reap the benefits of
p.000013: research designed with children in mind.
p.000013: 4.3 Benefit, harm and risk
p.000013: In the past, the concern to protect children from the potential harms of research may have denied them potential
p.000013: benefits. To ensure that this vulnerable group are not exploited, the General Medical Council advises that it is
p.000013: important to assess carefully the potential benefits and harm to children at all stages of any research. As the
p.000013: benefits of research are not predictable, the researcher must be satisfied that the research is not contrary to the
p.000013: child participant's interests. The foreseeable risks should be kept as low as possible: the potential benefits from the
p.000013: development of treatments and furthering of knowledge must outweigh any foreseeable risks.22
p.000013:
p.000013: Risk - A potential harm; the characteristics of risk include the probability of its occurrence, as well as its
p.000013: magnitude and duration
p.000013:
p.000013: Risks may be estimated as minimal, low or high: i
p.000013:
p.000013: Minimal (the least possible) risk describes procedures such as questioning, observing, and measuring children, provided
p.000013: that procedures are carried out in a sensitive way, respecting the child's autonomy, and that consent has been given.
p.000013: Procedures with minimal risk include obtaining bodily fluids without invasive intervention, eg, taking saliva or urine
p.000013: samples. It is expected that research of minimal risk would not result in more than a very slight and temporary
p.000013: negative impact on the health of the person concerned.
p.000013: Low risk describes procedures that might cause no more than brief pain or tenderness, small bruises or scars, or very
p.000013: slight, temporary distress; eg, a blood test.
p.000013: High risk procedures such as lung or liver biopsy, arterial or lumbar puncture, and cardiac catheterisation are not
p.000013: justified for research purposes alone with children. They should be carried out only when research is combined with
p.000013: diagnosis or treatment intended to benefit the child concerned.
p.000013:
p.000013:
p.000013: i Adapted from RCPCH guidance and Council of Europe guidance.
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p.000015: Research in which children are submitted to more than minimal risk with only slight, uncertain, or no benefit to
p.000015: themselves requires serious ethical consideration.
p.000015: The RCPCH advises that assessment of potential benefits and harms includes considering the following: 2
p.000015:
p.000015: Assessing potential benefit for the participant and children as a whole
p.000015:
p.000015: Magnitude – How severe is the condition that the research aims to alleviate and how common is it? How is the knowledge
p.000015: gained likely to be used?
p.000015: Probability – How likely is the research to achieve its aims?
p.000015:
p.000015: Beneficiaries – Is the research intended to benefit the child participants, and/or other children?
p.000015: Resources – Will potential benefits be limited because the treatment is very expensive, or difficult to deliver?
p.000015: Types of intervention – Might a new treatment or procedure replace one that is more invasive?
p.000015: Timing – Might benefits be brief or long-lasting, immediate or not evident until years later?
p.000015:
p.000015: Equity – Should a wider range of children be offered the potential benefits of participating in the research?
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p.000015: 4.3.1
p.000015:
p.000015: Assessing potential harms to the participant
p.000015:
p.000015: Magnitude – How severe may the harms associated with the research procedures be? Probability – How likely are the harms
p.000015: to occur?
p.000015: Types of intervention – How invasive or intrusive is the research? (Psychosocial research should be assessed as
p.000015: carefully as physical research.)
p.000015: Timing – Might adverse effects be brief or long-lasting, immediate or not evident until years later?
p.000015: Equity – Are a few children who already have many medical problems drawn into too many projects simply because they are
p.000015: available?
p.000015:
p.000015:
p.000015: Other considerations
p.000015: The assessment of risk must be carried out by all involved in the research – the children where possible, the
p.000015: parents/guardians, the researchers and clinicians concerned and the research ethics committees. This assessment
p.000015: includes reviewing personal circumstances: generalisation can be controversial as children's responses vary, can be
p.000015: unpredictable, and alter as children develop; a procedure that does not bother one child can arouse severe distress in
p.000015: another. For example, many children fear needles. For them, low rather than minimal risk could be incurred by
p.000015: injections and venepuncture. However, the procedure may be made more acceptable with careful explanation of the
p.000015: effectiveness of local anaesthetic cream and an understanding of the reason for the venepuncture – so that the child
p.000015: may choose to proceed. Researchers sometimes underestimate high risk of pain if the effects are brief, whereas the
p.000015: child or parents may consider that the severe transient pain is not justified by the hoped-for benefit.
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p.000017:
p.000017: MRC Ethics Guide: Medical research involving children
p.000017: MRC Ethics Guide: Medical research involving children
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017: Careful consideration of consequences may be required to identify some risks or potential harm. For example, with
p.000017: research into serious genetic disorders that present in adult life, pre-symptomatic diagnosis in a child, while it may
p.000017: be beneficial, may also have harmful effects or implications which may affect the child's
p.000017: opportunities and freedom of choice.23
p.000017:
p.000017: Interim findings: as with adults, if evidence of harm emerges during the trial as a result of giving or withholding
p.000017: certain treatment, the interests of the child
p.000017: participants must be put before the requirements of the research. This must be taken into account by researchers and
p.000017: trial steering committees when deciding on 'stopping rules' for trials and in studies of new techniques.
p.000017: Child volunteers: healthy volunteers should be treated in the same way as other child participants. Please see 5.1.4
p.000017: for more information. It is ethical for a healthy child to participate in research as long as appropriate consent has
p.000017: been obtained, there is no more than minimal risk and the research is not against the child's interest.
p.000017: Participation in more than one research study: as with adults, there may be situations where it could be argued that
p.000017: participation in more than one trial or study might be potentially beneficial – both for participants and for the
p.000017: research. The potential benefits and risks of doing so would need to be carefully explored by all concerned, and
p.000017: clearly understood by the child and family.24
p.000017: Equipoise: this is when there is genuine uncertainty among those who have considered the issue, including patients,
p.000017: about the relative benefits and risks of treatments or tests being compared. A clinical trial cannot be ethical unless
p.000017: there is this genuine informed uncertainty among the expert medical community and in an informed competent
p.000017: patient/participant.
p.000017: 4.3.2 Minimising risk
p.000017: The National Academy of the Sciences provides guidance on how to minimise risk, summarised here: 25
p.000017:
p.000017: Minimising risk in research involving children
p.000017:
p.000017: • Is inclusion of children necessary to answer the scientific question posed by the research? What are the ages
p.000017: of the children to be included? Are any of the potential research harms age-dependent?
p.000017: • Will potential child participants be screened for known vulnerability to the risks associated with specific
p.000017: elements of the research?
p.000017: • What does the research require of children and their families? Is adherence to the research protocol a
p.000017: concern? If so, what are the risks of non-adherence?
p.000017: • Are all the procedures or interventions necessary to answer the research question? Can the investigators
p.000017: collect the required information using procedures that the child participants will undergo as part of their normal
p.000017: therapy or monitoring?
p.000017: • Have previous laboratory studies, animal research, studies with adults, or other data provided a sufficient
p.000017: basis for proceeding with research involving children?
p.000017: • Does the study follow principles of sound research design?
p.000017:
p.000017: • What are the theoretical risks involved with the research as proposed? Are data available to estimate the
p.000017: probability and magnitude of each risk as they relate to the categories of children to be included?
p.000017: • Have the investigators provided data on the frequency of adverse events for the procedures at the site in
p.000017: question? For example, sedation for research procedures.
p.000017: Continued...
p.000017:
p.000017:
p.000017:
p.000018: 18
p.000018:
p.000019: 19
p.000019:
p.000019: MRC Ethics Guide: Medical research involving children
p.000019: MRC Ethics Guide: Medical research involving children
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019: Minimising risk in research involving children - Continued
p.000019:
p.000019: • Are the investigators and other members of the research team qualified to perform each of the procedures or
p.000019: assessments specified in the protocol and recognise potential risks and adverse outcomes? Does the research team have
p.000019: appropriate skills and expertise in caring for children of the ages included in the study?
p.000019: • Will research be performed in a setting that is 'friendly' to children of the ages included in the study? Is
p.000019: the setting appropriate for the physical, clinical, psychological and emotional needs of those age groups?
p.000019: • For research that involves more than minimal risk, does the research protocol have an adequate plan for
p.000019: monitoring the safety of the child participants? Does the monitoring plan provide for the inclusion of professionals
p.000019: with the appropriate expertise in paediatrics?
p.000019: • If the protocol presents the risk of a physical or psychological emergency, is the research setting equipped
p.000019: to respond? Are plans for responding to an emergency specified in the protocol?
p.000019: • What are the stopping rules or 'endpoints' for early discontinuation of the research on the basis of strong
p.000019: findings about harms or benefits? Are they specific and appropriate?
p.000019: • What happens to the data once they are collected? Where are research records stored, and who has access to
p.000019: them? What are the practices and procedures for maintaining the short-term and long-term confidentiality of the data?
p.000019: 5. Children, ethics and the law
p.000019:
p.000019: 5.1 Consent
p.000019:
p.000019: 5.1.1 What is valid consent?
p.000019:
p.000019: Consent – The voluntary agreement of an adult or competent child, based on adequate knowledge and understanding of
p.000019: relevant information, to participate in research
p.000019:
p.000019: Consent is legally valid and professionally acceptable only where the participants (or their parental guardian) are
p.000019: competent to give consent, have been properly informed, and have agreed without coercion.22
p.000019:
p.000019:
p.000019: In the UK, there are now two legal systems running in parallel.The common law applies to research not involving the
p.000019: Clinical Trials Regulations. As of May 2004, the Medicines for Human Use (Clinical Trials) Regulations apply to
p.000019: research involving investigational medicinal products (see Glossary). Researchers need to familiarise themselves with
p.000019: the Regulations.26
p.000019:
p.000019: 5.1.2 When should consent be sought, and who should seek consent?
p.000019: Research with children must normally only be carried out with the consent of the parent/guardian and/or child depending
p.000019: on the competence of the child. A summary of what is required in different circumstances is given below and in the flow
p.000019: diagram in 5.1.6. The physical integrity of children is protected by law and unless they or their parent/guardian
p.000019: agrees, it is not lawful to do anything that involves touching them.
p.000019: Consent should be sought before a child is examined, treated, cared for or involved in research. The clinician
p.000019: responsible for the child's treatment needs to ensure that
p.000019:
p.000020: 20
p.000020:
p.000021: 21
p.000021:
p.000021: MRC Ethics Guide: Medical research involving children
p.000021: MRC Ethics Guide: Medical research involving children
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: processes are in place and adhered to that ensure that the child and/or parent/guardian have given their informed
p.000021: consent. However the task of seeking consent can be delegated to another suitably trained and qualified health
p.000021: professional who understands the procedure(s) for which consent is being sought.
p.000021: As indicated in 5.1.5, the process of obtaining consent entails far more than a signature on paper. Verbal informed
p.000021: consent can be as valid as written consent for research, unless the Clinical Trials Regulations apply. It is vital that
p.000021: the person seeking consent records in writing that it has been given verbally. It may nevertheless be useful to obtain
p.000021: a signature from the participant or parent where this seems appropriate. It is important to note that under the
p.000021: Clinical Trials Regulations, verbal consent is not valid. The consent must be in writing unless the person giving
p.000021: consent is unable to write or otherwise mark the consent document.
p.000021: Informed consent is only one possible result of the informed choice process; the other possible result is the informed
p.000021: choice not to participate.
p.000021: Possible exceptions – Some research based on observation, on information collated from notes and tests already
p.000021: performed for therapeutic purposes, and public health research may be permissible without consent.2 Further
p.000021: information on the use of personal information in medical research is available from the MRC guidance Personal
p.000021: information in medical research.11
p.000021: Research linked to medical care in an emergency: the handling of this depends on whether the proposed study falls under
p.000021: the Clinical Trials Regulations. For further information please refer to 5.5.4.
p.000021:
p.000021: 5.1.3 Who can give consent, and who should you seek consent from?
p.000021: The law regarding the child's right to consent has developed differently in Scotland than in England, Wales and
p.000021: Northern Ireland – as outlined in 5.1.3a and 5.1.4a below. Generally, where children have sufficient understanding and
p.000021: intelligence to
p.000021: understand what is proposed, it is their consent and not that of their parent/guardian that is required by law.
p.000021: Ethically it is important to involve children as much as possible in decisions about their own health, wellbeing and
p.000021: healthcare. The United Nations Convention on the Rights of the Child states that the child has a right to be informed,
p.000021: to express a view and to influence a decision.27 Methods used to facilitate the consent process should be appropriate
p.000021: to the age and understanding of the child. The Department of Health provides very useful guidance on consent for both
p.000021: patients and clinicians, including guidance for children and for parents/guardians explaining what they have a right to
p.000021: expect.3
p.000021:
p.000021: 5.1.3.a Provision in law for children to consent
p.000021:
p.000021: England, Wales and Northern Ireland
p.000021: Where the Clinical Trial Regulations apply, a minor is defined as someone under the age of 16.
p.000021: Where the common law applies – all situations not covered by the Regulations – the law states that the age of majority
p.000021: is 18. Whilst not considered to have fully reached adulthood, young people between the age of 16 and 18 are presumed to
p.000021: be competent to give consent. No statute governs the rights of those under the age of 16 to give consent for medical
p.000021: treatment or research. However, case law provides the example of the Gillick case with respect to treatment.28 This
p.000021: case determined that where a young person has sufficient understanding and intelligence to understand fully what is
p.000021: proposed, and use and weigh this information in reaching a decision, he or she can give consent to treatment and
p.000021: consent from parents is not legally necessary – although parental involvement should always be encouraged. The term
p.000021: "Gillick competent" is used to describe a young person's ability to make a decision regarding consent.
p.000021:
p.000021:
p.000022: 22
p.000022:
p.000023: 23
p.000023:
p.000023: MRC Ethics Guide: Medical research involving children
p.000023: MRC Ethics Guide: Medical research involving children
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023: In the absence of case law dealing specifically with research, the Gillick principles might reasonably be applied
p.000023: here, although the threshold for understanding will vary according to the complexity of the research. However there is
p.000023: continuing uncertainty about the application of these principles to research in general and, in the case of law covered
p.000023: by the Clinical Trials Regulations, it will be those Regulations that apply and not the Gillick case law.
p.000023:
p.000023: Scotland
p.000023: As in England, Wales and Northern Ireland, where the Clinical Trials Regulations apply, a minor is defined as someone
p.000023: under the age of 16.
p.000023: Also as in England, Wales and Northern Ireland, in Scotland a person reaches majority at the age of 18.29 However,
p.000023: Scottish statute makes legal provision for young people, where they are considered to be competent, to consent to
p.000023: medical procedures or treatment. Under Scottish statute young people aged 16 and above are presumed to be competent to
p.000023: give consent until proven otherwise, having legal capacity to enter into any transaction, which includes "…the giving
p.000023: by a person of any consent having legal effect." 30
p.000023: Young people under the age of 16 can also give legally binding consent to participate in medical research as long as
p.000023: they are believed by the medical
p.000023: practitioner to be competent: "…a person under the age of 16 years shall have legal capacity to consent on his own
p.000023: behalf to any surgical, medical or dental procedure or treatment where in the opinion of a qualified medical
p.000023: practitioner attending him, he is capable of understanding the nature and possible consequences of the procedure or
p.000023: treatment." 30 Interpretation of Scottish law has been that a young person's competency allows them to refuse as well
p.000023: as consent to treatment.
p.000023: It is not entirely clear whether this Scottish statute covers consent to participate in research, but as discussed
p.000023: above, in the absence of law dealing specifically with research, the principles of Scottish law relating to consent to
p.000023: procedures and
p.000023: treatment might reasonably be applied. At the same time, it is vital to recognise that the threshold for understanding
p.000023: will relate to the complexity of the research being undertaken.
p.000023:
p.000023: Additional protection for children participating in clinical trials
p.000023: The Medicines for Human Use (Clinical Trials) Regulations 2004 have been law since they came into force on 1 May 2004
p.000023: and regulate trials in the UK.26 These regulations transpose European Union Directive 2001/20/EC into UK law.31 The
p.000023: Regulations offer additional protection for a minor (a person under the age of 16 years) who is being considered for a
p.000023: clinical trial. This additional protection comes at a time when more children are expected to be asked to participate
p.000023: in clinical trials, as part of an international initiative to provide medicines for children that are fully licensed
p.000023: (see 3.4 for more information). The regulations specify that for a minor
p.000023: to participate in a clinical trial, a person with parental responsibility or a legal representative must give informed
p.000023: consent and may withdraw the young person at any time.
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000025: 25
p.000025:
p.000025: MRC Ethics Guide: Medical research involving children
p.000025: MRC Ethics Guide: Medical research involving children
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025: Key provisions for the protection of minors within the Medicines for Human Use (Clinical Trials) Regulations 2004
p.000025: (Regulation 15 and Part 4 of Schedule 1) – extract from MHRA adviceii
p.000025:
p.000025: The Regulations provide additional protection for a minor (a person under the age of
p.000025: 16) who is a candidate for a clinical trial.They require, among other provisions, that:
p.000025:
p.000025: • an ethics committee considering the trial must receive advice on the relevant field of paediatric care; and
p.000025: • a person with parental responsibility or a legal representative must give informed consent and may withdraw the
p.000025: young person at any time; and, in relation to the minor himself:
p.000025: • staff with experience with young persons must inform him/her of the risks and benefits of the trial according to
p.000025: his capacity to understand;
p.000025: • the investigator must consider his or her explicit wish to refuse to participate or to be withdrawn from the
p.000025: trial at any time;
p.000025: • the clinical trial relate directly to an illness from which he or she suffers or that can only be carried out on
p.000025: minors; and
p.000025: • the trial must aim to provide some direct benefit for the group of patients involved.
p.000025: 5.1.4 Assessing the competence of a child to consent
p.000025: While normally increasing with age, competence is considered not to depend primarily on age, but rather on the ability
p.000025: to understand and weigh up options. It can be influenced by the way information is presented – many children will be
p.000025: competent if information is presented in an appropriate way and they are
p.000025: supported through the decision-making process. The Central Office for Research Ethics Committees (COREC) provides a
p.000025: useful template for designing patient information sheets and seeking assent/consent from children and young people.33 A
p.000025: child's ability to consent develops as he or she learns to make increasingly complex and serious decisions, which can
p.000025: be experience and/or age-related.
p.000025: For people to be able to have the capacity to take a particular decision they must be able to: 34
p.000025: • Comprehend and retain information material to the decision, especially the consequences of having or not having
p.000025: any intervention.
p.000025: • Use and weigh this information in a decision-making process.
p.000025:
p.000025: • Reach and communicate a decision.
p.000025:
p.000025: Even if the child is competent, it is still normally good practice to involve the family in the decision-making
p.000025: process. It is particularly desirable to obtain parental consent for younger children or for procedures that carry any
p.000025: risk or discomfort.
p.000025: If the competent child specifically asks for the family not to be involved in the decision-making process and they
p.000025: cannot be persuaded otherwise, their privacy should be respected.
p.000025: For further information please see 5.2.
p.000025:
p.000025:
p.000025:
p.000025: ii Extract from MHRA Description of the Medicines for Human Use (Clinical Trials) Regulations 2004.32
p.000025:
p.000025:
p.000026: 26
p.000026:
p.000027: 27
p.000027:
p.000027: MRC Ethics Guide: Medical research involving children
p.000027: MRC Ethics Guide: Medical research involving children
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027: 5.1.4.a Children unable to consent to involvement, and parental consent
p.000027: If the child is deemed incompetent to consent to participate in research, then he or she should normally not
p.000027: participate without the consent of a person with parental responsibility. A person with parental responsibility may
p.000027: legally consent to treatment on an incompetent child's behalf. If the child is able to give assent to decisions about
p.000027: participation in research, the investigator must obtain that assent in addition to the consent of the legally
p.000027: authorised representative. If the child does not assent, this should be respected.
p.000027: Legally, the researcher need only obtain consent from one person with parental responsibility. However, it is good
...
p.000027: programme. In such a case, every effort should be made to overcome the disagreement without a decision having to be
p.000027: referred to the courts.
p.000027: If the parents are themselves under 16 years of age, they will only be able to give valid consent on behalf of their
p.000027: child if they are competent to take the decision in question.
p.000027: Parents/guardians can consent to research procedures that offer potential benefit to the child. If the research is
p.000027: thought not to offer potential benefit to the child, parents/guardians can still consent provided the risks are
p.000027: sufficiently small to mean that research can be reasonably said not to go against the child's interests.
p.000027: Guidance on the law regarding parental consent is available from the BMA.4 A summary of country-specific differences
p.000027: follows:
p.000027: England,Wales and Northern Ireland
p.000027: The Children Act 1989 and The Children Act (Northern Ireland) Order 1995 make provision for parental rights in respect
p.000027: of their child, including the right to give consent to medical treatment.35, 36 Case law shows that a person with
p.000027: parental responsibility or the court can overrule a competent child's decision to refuse potentially beneficial
p.000027: treatment if it is felt to be in the best interests of the child or young person.
p.000027:
p.000027: Scotland
p.000027: The Children (Scotland) Act 1995 37 makes provision for cases where a young person aged under 16 is not competent to
p.000027: give legally valid consent. Parental rights enabling parents to carry out parental responsibilities include
p.000027: "safeguarding and promoting the child's health, welfare and development, providing direction and guidance to the child
p.000027: in a manner appropriate to the stage of the child's development and acting as the child's legal representative." Most
p.000027: of these last until the young person is 16 years old or shows competency to make their own decisions. Interestingly, in
p.000027: this Act it is stated that a child of 12 years or more should be presumed to be of sufficient age and maturity to form
p.000027: a view. The parental responsibility to provide guidance continues until the young person is 18. Case law suggests that
p.000027: a parent cannot overrule the decision of a competent child; however this has not yet been added to statute.
p.000027: The Adults with Incapacity (Scotland) Act 2000 38 covers the treatment and welfare of people over the age of 16 who
p.000027: are unable to give consent.
p.000027: In the absence of case law dealing specifically with research, the principles applying to medical treatment in England,
p.000027: Wales, Scotland and Northern Ireland might reasonably be applied to research.
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000029: 29
p.000029:
p.000029: MRC Ethics Guide: Medical research involving children
p.000029: MRC Ethics Guide: Medical research involving children
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: 5.1.4.b Seeking legal advice
p.000029: Researchers should seek legal advice if in any doubt regarding authority to proceed.
p.000029:
p.000029: 5.1.5 How best to seek consent
p.000029: The RCPCH provides guidance on how best to seek consent: 2
p.000029:
p.000029:
p.000029: For consent to be freely given researchers must:
p.000029:
p.000029: • Offer families no financial inducement although expenses should be paid.
p.000029: • Exert no pressure on families.
p.000029: • Give them as much time as possible (a few days for a major study, if at all possible) to consider whether to take
p.000029: part in the project.
p.000029: • Encourage families to discuss the project with – for example – their relatives, primary health carers – or an
p.000029: independent counsellor where available.
p.000029: • Tell them that they may refuse to take part, or may withdraw at any time even if they have signed a consent form.
p.000029: • Say that they need not give a reason for withdrawing (although their reason may help the researchers and other
p.000029: children in the study).
p.000029: • Assure them that the child patient's treatment will not be prejudiced by withdrawal from research.
p.000029: • Encourage parents/guardians to stay with the child during procedures.
p.000029: • Respond to families' questions, anxiety or distress throughout the study.
p.000029:
p.000029: For consent to be informed researchers must discuss with families:
p.000029:
p.000029: • The purpose of the research.
p.000029: • Whether the child stands to benefit directly and if so how; the difference between research and treatment.
p.000029: • The meaning of relevant research terms and any implications of consent (eg, placebo, randomised double-blind
p.000029: trial).
p.000029: • The nature of each procedure, how often and for how long each may occur.
p.000029: • The potential benefits and harms (both immediate and long-term).
p.000029: • The name of a researcher whom they can contact with their enquiries.
p.000029: • The name of the doctor directly responsible for the child's care.
p.000029: • How the child can withdraw from the project.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: Researchers must also:
p.000029:
p.000029: • Willingly explain and answer questions throughout the project.
p.000029: • Ensure that other staff caring for child subjects know about the research, and can also explain it if necessary.
p.000029: • Give clearly written patient information leaflets setting out all relevant information for families to keep
p.000029: (guidance on this can be found on the COREC website 33).
p.000029: • Report the results of research to the families involved wherever possible.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000030: 30
p.000030:
p.000031: 31
p.000031:
p.000031: MRC Ethics Guide: Medical research involving children
p.000031: MRC Ethics Guide: Medical research involving children
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 5.1.6 Seeking consent – a summaryiii
p.000031:
p.000031: If research is linked to medical care, it is justifiable in an emergency to start treatment prior to consent being
p.000031: obtained **
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Do the parents consent to the participation of
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: YES NO
p.000031:
p.000031: Is emergency treatment required where treatment is available only as part of a research programme?
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Research cannot go ahead. Parental consent MUST be obtained
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Research can go ahead Research cannot go ahead
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Research can go ahead with parental consent
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
...
p.000031:
p.000031: YES
p.000031:
p.000031: Research cannot go ahead. Parental consent must be obtained to proceed. The matter can be referred to the courts **
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Is the child very young or immature?
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: If the child is older or closer to being
p.000031: able to consent actively, seek the specific approval of the relevant Research Ethics Committees before initiating and
p.000031: continuing with investigational treatment
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Parent can overule child's objections.
p.000031: Research can go ahead
p.000031:
p.000031: iii Flow chart based on text from Council for International Organizations of
p.000031: Medical Sciences International ethical guidelines for biomedical research involving human subjects.5
p.000032: 32
p.000032: YES
p.000032: consents and parents assent
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033: MRC Ethics Guide: Medical research involving children
p.000033: MRC Ethics Guide: Medical research involving children
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: Seeking consent is not a single response but a process. The child should be provided with information appropriate to
p.000033: his or her increasing ability to make decisions about complex and serious issues. It is helpful for researchers to
p.000033: produce child-friendly information in a form appropriate for the relevant age groups – this could make use of pictures
p.000033: or videos. More than one version may need to be produced
p.000033: if research covers a wide age range, such as eight-18 years. Where the research project lasts a number of years, the
p.000033: child and/or parent/guardian may need to be approached periodically to ensure they still consent to the child's
p.000033: involvement in research. For example, where a parent has consented to follow-up studies throughout the life of the
p.000033: child, the child must be given the opportunity to decide for himself/herself, once competent to do so, whether he or
p.000033: she wishes to continue his or her involvement.
p.000033:
p.000033: 5.2 Confidentiality
p.000033: Medical professionals have a duty of confidentiality to all patients including children. Legally competent children are
p.000033: entitled to expect that information about themselves will not be provided to a third party, including their
p.000033: parent/guardian, without their consent. However, it is important that wherever possible the parents/guardians are
p.000033: informed, and young people should be encouraged to involve them unless it is not in their best interests to do so. If
p.000033: competent children do not wish to involve their parents/guardians this should be respected. Disclosure can only be
p.000033: justified if there is reasonable cause to suspect that the child is suffering or is likely to suffer significant harm
p.000033: as a result of non-disclosure. Any decision to disclose confidential information to a third party must be relayed to
p.000033: the competent child before disclosure.
p.000033: To facilitate both the child's healthcare and longer term research, general practitioners (GPs) should be notified of
p.000033: all research on their paediatric patients. The consent form should request consent to inform and update GPs of the
p.000033: child's involvement. If a participant is likely to resist information being provided to parents/guardians and family
p.000033: practitioners because the research is of a sensitive
p.000033: nature, eg, investigating smoking habits or sexual health, advice should be sought from the Research Ethics Committee
p.000033: that assesses the protocol.
p.000033: Children who lack competence to consent to participate are nevertheless entitled to confidentiality. The researcher
p.000033: will have had to request the parent/guardian's consent to the child's involvement in research. Any intention to
p.000033: disclose information to anyone else should be discussed with both the parent/guardian and the child, taking into
p.000033: consideration whether disclosure to a third party is necessary in the interests of the child's health. Public health
p.000033: research may require the use of anonymous data without explicit consent – for detailed guidance on this researchers
p.000033: should consult the MRC guidance Personal information in medical research.11
p.000033: Researchers working with children have important responsibilities in relation to child protection. Where researchers
p.000033: have reasonable cause to suspect that a child is suffering or likely to suffer significant harm, they have a clear
p.000033: responsibility to liaise urgently with those responsible for the child's clinical care with a view to making a referral
p.000033: to social services. Again, a decision to disclose information should, wherever possible, be discussed with the child
p.000033: before disclosure, in terms appropriate to the child's capability to understand.
p.000033: All researchers need to be aware of relevant data protection legislation and the rights of the child (and their
p.000033: parents/guardians in some circumstances) to access their health records. Fuller guidance on confidentiality issues is
p.000033: available from the Department of Health, the British Medical Association and the General Medical Council.3, 4, 39
p.000033:
p.000033: 5.3 Ethics committee review
p.000033: The Council of Europe Protocol to the Convention on Human Rights and Biomedicine on Biomedical Research provides
p.000033: guidance regarding the role of the ethics committee in research.9 According to this guidance, every research project
p.000033: must be submitted for independent examination of its scientific merit, including assessment of the importance of the
p.000033: aim of research and ethical acceptability to an
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000035: 35
p.000035:
p.000035: MRC Ethics Guide: Medical research involving children
p.000035: MRC Ethics Guide: Medical research involving children
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: ethics committee. An examination of the ethical acceptability is necessary to protect the dignity, rights, safety and
p.000035: wellbeing of the research participant. The assessment should draw on an appropriate range of expertise adequately
p.000035: reflecting professional and lay views, therefore a professional opinion should be sought for any research involving
p.000035: children. The ethics committee must be satisfied that dependent persons and vulnerable groups will not be subjected to
p.000035: undue influence.
p.000035: Whilst the Council of Europe protocol is a legal instrument, it has not so far been transposed into UK law. However,
p.000035: the Medicines for Human Use (Clinical Trials) Regulations 2004, which transpose Directive 2001/20/EC into UK law,
p.000035: require that an ethics committee considering a trial involving minors must receive advice on the relevant field of
p.000035: paediatric care.29, 30 A "minor" is defined as a person under the age of 16.
p.000035:
p.000035: 5.4 Children's safety in relation to researchers
p.000035: Any individual recruited by the MRC to work directly with children will undergo security screening, including criminal
p.000035: records review. This includes nurses, survey interviewers and some individuals involved in a clinically invasive
p.000035: capacity, eg, phlebotomists. The MRC expects its grant-holding institutions to do likewise.
p.000035: Security screening is complementary to other good recruitment practices and not a substitute for them. Staff involved
p.000035: in MRC's recruitment process are responsible for ensuring that standard checks are still made.
p.000035:
p.000035: 5.5 Specific situations
p.000035:
p.000035: 5.5.1 Research involving human material
p.000035: Please refer to the MRC guidance Human tissue and biological samples for use in research.12
p.000035: Further guidance will be issued when the Human Tissue Bill, and equivalent legislation in Scotland, become law.
p.000035: 5.5.2 The use of personal information
p.000035: Please refer to the MRC guidance Personal information in medical research.11
p.000035:
p.000035: 5.5.3 Research involving very young children
p.000035: A parent/guardian's informed consent is necessary for the involvement of babies in research. When a baby is seriously
p.000035: ill and a decision about treatment is required quickly, the pressure on parents is high and the difficulty of obtaining
p.000035: truly informed consent is recognised. The RCPCH provides detailed guidance relating to research involving babies.40
p.000035:
p.000035: 5.5.4 Emergency situations
p.000035: Under common law, provided that the specific approval of a research ethics committee has been obtained for the project
p.000035: overall, it is ethical to carry out research involving children on occasions of extreme urgency without obtaining prior
p.000035: consent. However, there is a lack of clarity in the law about this if the research does not have the potential to
p.000035: benefit the child in question. If in doubt, it would be advisable to seek legal advice in potentially contentious
p.000035: circumstances.
p.000035: Research involving children in an emergency situation may be needed when treatment is available only as part of a
p.000035: research programme. Ethically, if the research does not have the potential to produce results of direct benefit to the
p.000035: individual participant, the Council of Europe recommends that it should only be carried out if it has the aim of
p.000035: contributing or improving understanding of the individual's condition so that it could ultimately confer benefit upon
p.000035: the patient or others with the same condition, and that it entails only minimal risk.9
p.000035: Research involving children in emergency situations should be carried out only where research of comparable
p.000035: effectiveness cannot be carried out on persons in non- emergency situations. The parents and child must be informed
p.000035: about the research as
p.000035:
p.000036: 36
p.000036:
p.000037: 37
p.000037:
p.000037: MRC Ethics Guide: Medical research involving children
p.000037: MRC Ethics Guide: Medical research involving children
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037: soon as possible afterwards and their consent for future involvement sought. It must be made clear that the child (or
p.000037: parent on behalf of a child not yet competent) can withdraw from the study at any point.
p.000037: The Council of Europe provide further guidance on research in emergency clinical situations.9
p.000037: Under the Clinical Trial Regulations, consent must be given on behalf of a minor prior to participation in a trial of
p.000037: an investigational medicinal product in all circumstances; there is currently no exception for emergency situations.
p.000037: However, it is possible for someone other than a parent to give consent as a “legal representative”, if the parent is
p.000037: unable to do so. This could be the doctor primarily responsible for the person’s treatment (if not involved in the
p.000037: trial) or, if they are not available, a person nominated by the healthcare provider.41
p.000037:
p.000037: 5.5.5 Including minority groups – equality in research
p.000037: As with adults it is important to include minority groups in research involving children to ensure that they as a group
p.000037: receive a share of the potential benefits of research.
p.000037: Researchers should be sensitive to cultural issues and particularly to participants' specific concerns and values. For
p.000037: example, whether acceptance of research is necessary from someone in the extended cultural group as well as the
p.000037: immediate family, or whether participants undertake religious fasts that may affect when they can take medicines.
p.000037: When seeking consent where the child or parent needs an interpreter, an independent interpreter is preferable to a
p.000037: family member.
p.000037: Where the child has a disability, particular care should be taken to ensure that information is provided in a suitable
p.000037: form. Specialist colleagues may be able to act as
p.000037: facilitators or advocates where the child has particular needs. Children with specific impairments such as learning
p.000037: difficulties should not be excluded from participating in research, but equally should not be over-researched because
p.000037: of their condition.
p.000037:
p.000037: 5.5.6 Research in developing countries
p.000037: Please refer to MRC guidance on Research involving human participants in developing societies.
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000039: 39
p.000039:
p.000039: MRC Ethics Guide: Medical research involving children
p.000039: MRC Ethics Guide: Medical research involving children
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: 6. Summary
p.000039: Children should be included in medical research only if:
p.000039:
p.000039: • The relevant knowledge cannot be gained through research with adults.
p.000039:
p.000039: • It is approved by the appropriate Research Ethics Committee/s.
p.000039:
p.000039: • Either the participant has given consent where competent, or consent has been given on his or her behalf by a
p.000039: parent or guardian and the participant does not object or appear to object in either words or actions. iv
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: iv See 5.5.4 for guidance on emergency situations, when this might not be possible.
p.000039: 7. Glossary
p.000039: The definitions provided here apply as they are used in the above guidelines.
p.000039:
p.000039: Assent
p.000039: A child's affirmative agreement to participate. Failure to object should not be construed as assent.
p.000039: Burden of disease
p.000039: The impact of disease on the individual and on society due to loss of duration and quality of life. Measures include
p.000039: (i) 'morbidity burden', ie, the prevalence of a condition, the range of its severity and the age distribution of the
p.000039: population suffering from the condition, and (ii) the financial burden to society in meeting the obligation to support
p.000039: the individual; for example, in terms of net public expenditure on health services and on social services.
p.000039: Child
p.000039: In the UK, a person under the age of 18. "Young person" is a term often used to describe older children in this age
p.000039: group. The competence of children to consent is discussed in Section 5.
p.000039: Clinical Trials Regulations
p.000039: The Medicines for Human Use (Clinical Trials) Regulations apply to research involving investigational medicinal
p.000039: products (see below). In such studies, informed consent is strictly defined as follows and only consent meeting this
p.000039: definition will suffice:
p.000039: “A person gives informed consent to take part, or that a subject is to take part, in a clinical trial only if his
p.000039: decision –
p.000039: (a) is given freely after that person is informed of the nature, significance, implications and risks of the trial;
p.000039: and
p.000039:
p.000039:
p.000040: 40
p.000040:
p.000041: 41
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: (b) either –
p.000041: (i) is evidenced in writing, dated and signed, or otherwise marked, by that person so as to indicate his consent, or
p.000041: (ii) If the person is unable to sign or to mark a document so as to indicate his consent, is given orally in the
p.000041: presence of at least one witness and recorded in writing.”
p.000041:
p.000041: Confidentiality
p.000041: The duty of persons to whom personal information has been given not to share the information with any unauthorised
p.000041: person. For more information about what this involves in practice, see 5.2.
p.000041:
p.000041: Competence
p.000041: The ability of a person, given the necessary information, to understand the nature and the consequences of the proposed
...
p.000041:
p.000041: Family
p.000041: A group of individuals who together form a social structure; a family may or may not include biological relatives.
p.000041:
p.000041:
p.000041: Harm
p.000041: That which adversely affects the interests or welfare of an individual. This may be physical harm, discomfort, anxiety,
p.000041: pain, and psychological
p.000041:
p.000041: disturbance or social disadvantage (ostracism).
p.000041:
p.000041: Investigational medicinal product
p.000041: A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial,
p.000041: including products already with a marketing authorisation but used or assembled (formulated or packaged) in a way
p.000041: different from the authorised form, or when used for an unauthorised indication, or when used to gain further
p.000041: information about the authorised form.31
p.000041:
p.000041: Off-label
p.000041: Term used to describe a medicine used for an indication, dose, or route of administration outside the terms of the
p.000041: product licence.
p.000041:
p.000041: Parent/guardian
p.000041: The term "parent/guardian" is used in these guidelines to describe those with legal responsibility for the child. The
p.000041: Children Act 1989, the Children (Scotland) Act 1995 and the Children (Northern Ireland) Order 1995 set out who has
p.000041: parental responsibility in their respective jurisdictions. The Adoption and Children Act 2002 s111(2) has recently
p.000041: extended the definition of those with legal responsibility for the child to include unmarried fathers who have entered
p.000041: into a legally binding Parental Responsibility Agreement.42
p.000041: The MRC is aware that some children will not be resident with both or either of their parents.
p.000041: On occasion it may be difficult for the researcher to determine who has legal responsibility for the child, and if
p.000041: necessary, further clarification should be sought from the child’s care giver or their GP.
p.000041:
p.000041:
p.000041: Risk
p.000041: A potential harm; the characteristics of risk include the probability of its occurrence, as well as its magnitude and
p.000041: duration. For more on assessment and minimising risk see 4.3.
p.000041:
p.000041: MRC Ethics Guide: Medical research involving children
p.000041: MRC Ethics Guide: Medical research involving children
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: 8. Other MRC ethics guidance
p.000041: The MRC produces a wide range of ethics guidance for researchers, which is available at www.mrc.ac.uk and includes the
p.000041: following:
p.000041: • MRC interim guidance on ethics of research involving human material derived from the nervous system (June 2003).
p.000041: • MRC policy on antiretroviral therapy (ART) for people infected with HIV and involved in AIDS research in
p.000041: developing countries – General guidance notes for consideration (2002).
p.000041: • MRC guidance on reviewing research proposals (2001).
p.000041:
p.000041: • Ethical conduct of research on the mentally incapacitated (1993) – to be revised following the introduction of
p.000041: English legislation. This guidance is no longer applicable in Scotland, following the introduction of the Adults with
p.000041: Incapacity (Scotland) Act 2000.
p.000041: • Good research practice (2000).
p.000041:
p.000041: • Personal information in medical research (2000) – also available as Executive Summary (2000). New guidance on
p.000041: Health and Social Care Act 2001: "Section 60" added – January 2003.
p.000041: • Human tissue and biological samples for use in research: operational and ethical guidelines (2001).
p.000041: • Policy and procedure for inquiring into allegations of scientific misconduct (1997).
p.000041: • Research involving human participants in developing societies: ethical guidelines for MRC-sponsored studies
p.000041: (2004).
p.000041: • Responsibility in the use of animals in medical research (1993).
p.000041:
p.000041: • The MRC's terms and conditions for research grants and training awards involving stem cells (2003).
p.000041: • Cluster randomised trials: Methodological and ethical considerations (2002).
p.000041:
p.000041: • MRC guidelines for good clinical practice in clinical trials (1998).
p.000041:
p.000041: • Health Technology Assessment in surgery (2003).
p.000041:
p.000041:
p.000041: Additional guidance available by post includes:
p.000041:
p.000041: • Principles in the assessment and conduct of medical research and publicising results (1995).
p.000041:
p.000041:
p.000041:
p.000044: 44
p.000044:
p.000045: 45
p.000045:
p.000045: MRC Ethics Guide: Medical research involving children
p.000045: MRC Ethics Guide: Medical research involving children
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045: 9. References
p.000045: 1. The ethical conduct of research on children. London: Medical Research Council (MRC), 1991.
p.000045: 2. Royal College of Paediatrics and Child Health: Ethics Advisory Committee. 2002. "Guidelines for the ethical
p.000045: conduct of medical research involving children". Reprinted from Archives of Disease in Childhood 82 (2): 177-182.
p.000045: 3. Department of Health: Consent guidance webpages. www.dh.gov.uk/PolicyAndGuidance/
p.000045: HealthAndSocialCareTopics/Consent/ConsentGeneralInformation/fs/en
p.000045: 4. Consent, rights and choices in healthcare for children and young people. London: British Medical
p.000045: Association, 2001.
p.000045: 5. International ethical guidelines for biomedical research involving human subjects. Geneva: Council for
p.000045: International Organizations of Medical Sciences, 2002.
p.000045: 6. Declaration of Helsinki: ethical principles for medical research involving human subjects. Amended by the
p.000045: 52nd World Medical Association (WMA) General Assembly. Ferney-Voltaire:WMA, 2000.
p.000045: 7. International Guidelines for ethical review of epidemiological studies. Geneva: Council for International
p.000045: Organizations of Medical Sciences, 1991.
p.000045: 8. MRC guidelines for good clinical practice in clinical trials. London: MRC, 1998.
p.000045: 9. Additional protocol to the Convention on Human Rights and Biomedicine on Biomedical Research. Strasbourg:
p.000045: Council of Europe, 2004.
p.000045: 10. Declaration of professional ethics.Voorburg: International Statistical Institute, 1985.
p.000045: www.cbs.nl/isi/ethics.htm
p.000045: 11. Personal information in medical research. London: MRC, 2000.
p.000045: 12. Human tissue and biological samples for use in research: operational and ethical guidelines. London: MRC,
p.000045: 2001.
p.000045: 13. Stiller C., Quinn M., Rowan S. 2004. "Childhood cancer". In: The health of children and young people, chapter
p.000045: 13. Office for National Statistics. www.statistics.gov.uk/children/downloads/child_cancer.pdf
p.000045: 14. Smyth R.L.,Weindling A.M. 1999. "Research in children: ethical and scientific aspects". Lancet 354 (suppl
p.000045: II): 21-24.
p.000045: 15. Campbell H., Surry S.A.M., Royle E.M. 1998. "A review of randomised controlled trials published in Archives
p.000045: of Disease in Childhood from 1982-96." Archives of Disease in Childhood 79: 192-197.
p.000045: 16. Halliday H.L., Ehrenkranz R.A., Doyle L.W. 2004. "Early postnatal (<96 hours) corticosteroids for preventing
p.000045: chronic lung disease in preterm infants" (Cochrane Review). In: The Cochrane Library, Issue 2. Chichester, UK: John
p.000045: Wiley & Sons, Ltd.
p.000045: 17. Better Medicines for Children: proposed regulatory actions on paediatrics medicinal products. European
p.000045: Commission (EC) consultation document. Addendum to ref 18. Brussels: EC, 2002.
p.000045: http://pharmacos.eudra.org/F2/pharmacos/docs/Doc2002/feb/cd_pediatrics_en.pdf
p.000045: 18. National Audit Office Report (HC 255 2002-2003). Safety, quality, efficacy: regulating medicines in the UK.
p.000045: London: the Stationery Office, 2003.
p.000045: 19. Smith Robert N. 2000. Meeting report – A European conference on clinical research in children: ethical,
p.000045: scientific and regulatory issues. Section: "Research, the rights of the child and legal considerations in paediatric
p.000045: clinical research". International Journal of Pharmaceutical Medicine; reprinted from: Archives of Disease in Childhood
p.000045: 16:15-29.
p.000045: 20. Medicines and Healthcare products Regulatory Agency/Department of Health: Strategy on Medicines for Children,
p.000045: July 2004. http://medicines.mhra.gov.uk/ourwork/licensingmeds/children/paediatricstrategydoc.pdf
p.000045: 21. Safer and Better Medicines for Children – Developing the Clinical and Research Base of Paediatric
p.000045: Pharmacology in the United Kingdom. Royal College of Paediatrics and Child Health Review (commissioned by the MRC, the
p.000045: Department of Health, and the Association of the British Pharmaceutical Industry), May 2004.
p.000045: 22. Research: the role and responsibilities of doctors. London: General Medical Council, 2002.
p.000045: 23. Testing for late onset genetic disorders. London: British Paediatric Association, 1996.
p.000045: 24. Brocklehurst P. 1997. "Randomised controlled trials in perinatal medicine: 2. Recruitment of a pregnant woman
p.000045: or her newborn child into more than one trial." British Journal of Obstetrics and Gynaecology 104 (7):765-7.
p.000045: 25. Ethical Conduct of Clinical Research Involving Children.The National Academy of the Sciences USA, 2004.
p.000045: 26. The Medicines for Human Use (Clinical Trials) Regulations. 2004.
p.000045: www.legislation.hmso.gov.uk/si/si2004/20041031.htm
p.000045:
p.000045: 27. UN Convention on the Rights of the Child. General Assembly resolution 44/25 of 20 November 1989, entry into
p.000045: force 2 September 1990 in accordance with article 49. www.childrenslawcentre.org/UNCRC_hearing.htm
p.000045: 28. Gillick v West Norfolk and Wisbech. London: House of Lords, Gillick v West Norfolk and Wisbech AHA (1986) AC
p.000045: 112, [1985] 3 WLR 830, [1985] 3 AII ER 402, HL
p.000045: 29. Age of Majority (Scotland) Act 1969 s 1.
p.000045: 30. Age of Legal Capacity (Scotland) Act 1991. (c. 50)
p.000045: 31. Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of
p.000045: the laws, regulations and administrative provisions of the Member States relating to the implementation of good
p.000045: clinical practice in the conduct of clinical trials on medicinal products for human use.
p.000045: http://europa.eu.int/eur-lex/pri/en/oj/dat/2001/l_121/l_12120010501en00340044.pdf
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p.000047: 47
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p.000047:
p.000047:
p.000047: MRC Ethics Guide: Medical research involving children
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p.000047:
p.000047:
p.000047:
p.000047:
p.000047: 32. Medicines and Healthcare products Regulatory Agency: Description of the Medicines for Human Use (Clinical
p.000047: Trials) Regulations 2004. http://medicines.mhra.gov.uk/ourwork/licensingmeds/types/ctdregs_shortdesc.pdf
p.000047: 33. Central Office for Research Ethics Committees. www.corec.org.uk
p.000047: 34. Seeking Consent:Working with children. Department of Health, 2001. www.dh.gov.uk/PublicationsAndStatistics/
p.000047: Publications/PublicationsPolicyAndGuidance/PublicationsPolicyAndGuidanceArticle/fs/en?CONTENT_ ID=4007005&chk=xFifXP
p.000047: 35. Children Act 1989 (c. 41). www.hmso.gov.uk
p.000047: 36. Children Act (Northern Ireland) Order 1995. www.northernireland-legislation.hmso.gov.uk
p.000047: 37. Children (Scotland) Act 1995. www.hmso.gov.uk
p.000047: 38. Adults with incapacity (Scotland) Act 2000. www.scotland-legislation.hmso.gov.uk
p.000047: 39. Confidentiality: protecting and providing information. London: General Medical Council, 2004.
p.000047: 40. Guidance safeguarding informed parental involvement in clinical research involving newborn babies and
p.000047: infants. London: Royal College of Paediatrics and Child Health, 1999.
p.000047: 41. Department of Health/MRC: Clinical Trials Toolkit. 2004. www.ct-toolkit.ac.uk
p.000047: 42. The Adoption and Children Act 2002. www.hmso.gov.uk/acts/acts2002/20020038.htm
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p.000047: Medical Research Council
p.000047: 20 Park Crescent London W1B 1AL
p.000047: Tel: 020 7636 5422 Fax: 020 7436 6179
p.000048: 48
p.000048: www.mrc.ac.uk
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Social / Fathers
Searching for indicator fathers:
(return to top)
p.000041:
p.000041: disturbance or social disadvantage (ostracism).
p.000041:
p.000041: Investigational medicinal product
p.000041: A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial,
p.000041: including products already with a marketing authorisation but used or assembled (formulated or packaged) in a way
p.000041: different from the authorised form, or when used for an unauthorised indication, or when used to gain further
p.000041: information about the authorised form.31
p.000041:
p.000041: Off-label
p.000041: Term used to describe a medicine used for an indication, dose, or route of administration outside the terms of the
p.000041: product licence.
p.000041:
p.000041: Parent/guardian
p.000041: The term "parent/guardian" is used in these guidelines to describe those with legal responsibility for the child. The
p.000041: Children Act 1989, the Children (Scotland) Act 1995 and the Children (Northern Ireland) Order 1995 set out who has
p.000041: parental responsibility in their respective jurisdictions. The Adoption and Children Act 2002 s111(2) has recently
p.000041: extended the definition of those with legal responsibility for the child to include unmarried fathers who have entered
p.000041: into a legally binding Parental Responsibility Agreement.42
p.000041: The MRC is aware that some children will not be resident with both or either of their parents.
p.000041: On occasion it may be difficult for the researcher to determine who has legal responsibility for the child, and if
p.000041: necessary, further clarification should be sought from the child’s care giver or their GP.
p.000041:
p.000041:
p.000041: Risk
p.000041: A potential harm; the characteristics of risk include the probability of its occurrence, as well as its magnitude and
p.000041: duration. For more on assessment and minimising risk see 4.3.
p.000041:
p.000041: MRC Ethics Guide: Medical research involving children
p.000041: MRC Ethics Guide: Medical research involving children
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: 8. Other MRC ethics guidance
p.000041: The MRC produces a wide range of ethics guidance for researchers, which is available at www.mrc.ac.uk and includes the
p.000041: following:
...
Social / Marital Status
Searching for indicator single:
(return to top)
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Is the child very young or immature?
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: If the child is older or closer to being
p.000031: able to consent actively, seek the specific approval of the relevant Research Ethics Committees before initiating and
p.000031: continuing with investigational treatment
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Parent can overule child's objections.
p.000031: Research can go ahead
p.000031:
p.000031: iii Flow chart based on text from Council for International Organizations of
p.000031: Medical Sciences International ethical guidelines for biomedical research involving human subjects.5
p.000032: 32
p.000032: YES
p.000032: consents and parents assent
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033: MRC Ethics Guide: Medical research involving children
p.000033: MRC Ethics Guide: Medical research involving children
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: Seeking consent is not a single response but a process. The child should be provided with information appropriate to
p.000033: his or her increasing ability to make decisions about complex and serious issues. It is helpful for researchers to
p.000033: produce child-friendly information in a form appropriate for the relevant age groups – this could make use of pictures
p.000033: or videos. More than one version may need to be produced
p.000033: if research covers a wide age range, such as eight-18 years. Where the research project lasts a number of years, the
p.000033: child and/or parent/guardian may need to be approached periodically to ensure they still consent to the child's
p.000033: involvement in research. For example, where a parent has consented to follow-up studies throughout the life of the
p.000033: child, the child must be given the opportunity to decide for himself/herself, once competent to do so, whether he or
p.000033: she wishes to continue his or her involvement.
p.000033:
p.000033: 5.2 Confidentiality
p.000033: Medical professionals have a duty of confidentiality to all patients including children. Legally competent children are
...
Searching for indicator unmarried:
(return to top)
p.000041: pain, and psychological
p.000041:
p.000041: disturbance or social disadvantage (ostracism).
p.000041:
p.000041: Investigational medicinal product
p.000041: A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial,
p.000041: including products already with a marketing authorisation but used or assembled (formulated or packaged) in a way
p.000041: different from the authorised form, or when used for an unauthorised indication, or when used to gain further
p.000041: information about the authorised form.31
p.000041:
p.000041: Off-label
p.000041: Term used to describe a medicine used for an indication, dose, or route of administration outside the terms of the
p.000041: product licence.
p.000041:
p.000041: Parent/guardian
p.000041: The term "parent/guardian" is used in these guidelines to describe those with legal responsibility for the child. The
p.000041: Children Act 1989, the Children (Scotland) Act 1995 and the Children (Northern Ireland) Order 1995 set out who has
p.000041: parental responsibility in their respective jurisdictions. The Adoption and Children Act 2002 s111(2) has recently
p.000041: extended the definition of those with legal responsibility for the child to include unmarried fathers who have entered
p.000041: into a legally binding Parental Responsibility Agreement.42
p.000041: The MRC is aware that some children will not be resident with both or either of their parents.
p.000041: On occasion it may be difficult for the researcher to determine who has legal responsibility for the child, and if
p.000041: necessary, further clarification should be sought from the child’s care giver or their GP.
p.000041:
p.000041:
p.000041: Risk
p.000041: A potential harm; the characteristics of risk include the probability of its occurrence, as well as its magnitude and
p.000041: duration. For more on assessment and minimising risk see 4.3.
p.000041:
p.000041: MRC Ethics Guide: Medical research involving children
p.000041: MRC Ethics Guide: Medical research involving children
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: 8. Other MRC ethics guidance
p.000041: The MRC produces a wide range of ethics guidance for researchers, which is available at www.mrc.ac.uk and includes the
p.000041: following:
...
Social / Racial Minority
Searching for indicator minority:
(return to top)
p.000001: 5.1.4.a Children unable to consent to involvement, and parental consent 28
p.000001: 5.1.4.b Seeking legal advice
p.000030: 30
p.000030: 5.1.5 How best to seek consent 30
p.000030: 5.1.6 Seeking consent – a summary 32
p.000030: 5.2 Confidentiality 34
p.000030: 5.3 Ethics committee review 35
p.000030: 5.4 Children's safety in relation to researchers 36
p.000030: 5.5 Specific situations 36
p.000030: 5.5.1 Research involving human material 36
p.000030: 5.5.2 The use of personal information 37
p.000030: 5.5.3 Research involving very young children 37
p.000030: 5.5.4 Emergency situations 37
p.000030: 5.5.5 Including minority groups – equality in research 38
p.000030: 5.5.6 Research in developing countries 39
p.000030: 6. Summary 40
p.000030: 7. Glossary 41
p.000030: 8. Other MRC ethics guidance 44
p.000030: 9. References 46
p.000002: 2
p.000002:
p.000003: 3
p.000003:
p.000003: MRC Ethics Guide: Medical research involving children
p.000003: MRC Ethics Guide: Medical research involving children
p.000003:
p.000003:
p.000003:
p.000003: 1. Introduction
p.000003: 1.1 Purpose
p.000003: These guidelines are designed to be of use to researchers preparing proposals for MRC support for research involving
p.000003: children, and to those planning, undertaking or collaborating in such research. They will also be helpful to other
p.000003: researchers, and to doctors and other health professionals whose patients may be involved in research, to ethics
p.000003: committees, to others reviewing or supervising research, and to the public.
p.000003: The guidelines take into account recent publications by leading organisations and professional bodies, which are
...
p.000037: MRC Ethics Guide: Medical research involving children
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037: soon as possible afterwards and their consent for future involvement sought. It must be made clear that the child (or
p.000037: parent on behalf of a child not yet competent) can withdraw from the study at any point.
p.000037: The Council of Europe provide further guidance on research in emergency clinical situations.9
p.000037: Under the Clinical Trial Regulations, consent must be given on behalf of a minor prior to participation in a trial of
p.000037: an investigational medicinal product in all circumstances; there is currently no exception for emergency situations.
p.000037: However, it is possible for someone other than a parent to give consent as a “legal representative”, if the parent is
p.000037: unable to do so. This could be the doctor primarily responsible for the person’s treatment (if not involved in the
p.000037: trial) or, if they are not available, a person nominated by the healthcare provider.41
p.000037:
p.000037: 5.5.5 Including minority groups – equality in research
p.000037: As with adults it is important to include minority groups in research involving children to ensure that they as a group
p.000037: receive a share of the potential benefits of research.
p.000037: Researchers should be sensitive to cultural issues and particularly to participants' specific concerns and values. For
p.000037: example, whether acceptance of research is necessary from someone in the extended cultural group as well as the
p.000037: immediate family, or whether participants undertake religious fasts that may affect when they can take medicines.
p.000037: When seeking consent where the child or parent needs an interpreter, an independent interpreter is preferable to a
p.000037: family member.
p.000037: Where the child has a disability, particular care should be taken to ensure that information is provided in a suitable
p.000037: form. Specialist colleagues may be able to act as
p.000037: facilitators or advocates where the child has particular needs. Children with specific impairments such as learning
p.000037: difficulties should not be excluded from participating in research, but equally should not be over-researched because
p.000037: of their condition.
p.000037:
...
Social / Religion
Searching for indicator religious:
(return to top)
p.000037: an investigational medicinal product in all circumstances; there is currently no exception for emergency situations.
p.000037: However, it is possible for someone other than a parent to give consent as a “legal representative”, if the parent is
p.000037: unable to do so. This could be the doctor primarily responsible for the person’s treatment (if not involved in the
p.000037: trial) or, if they are not available, a person nominated by the healthcare provider.41
p.000037:
p.000037: 5.5.5 Including minority groups – equality in research
p.000037: As with adults it is important to include minority groups in research involving children to ensure that they as a group
p.000037: receive a share of the potential benefits of research.
p.000037: Researchers should be sensitive to cultural issues and particularly to participants' specific concerns and values. For
p.000037: example, whether acceptance of research is necessary from someone in the extended cultural group as well as the
p.000037: immediate family, or whether participants undertake religious fasts that may affect when they can take medicines.
p.000037: When seeking consent where the child or parent needs an interpreter, an independent interpreter is preferable to a
p.000037: family member.
p.000037: Where the child has a disability, particular care should be taken to ensure that information is provided in a suitable
p.000037: form. Specialist colleagues may be able to act as
p.000037: facilitators or advocates where the child has particular needs. Children with specific impairments such as learning
p.000037: difficulties should not be excluded from participating in research, but equally should not be over-researched because
p.000037: of their condition.
p.000037:
p.000037: 5.5.6 Research in developing countries
p.000037: Please refer to MRC guidance on Research involving human participants in developing societies.
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000039: 39
p.000039:
p.000039: MRC Ethics Guide: Medical research involving children
p.000039: MRC Ethics Guide: Medical research involving children
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: 6. Summary
...
Social / Trade Union Membership
Searching for indicator union:
(return to top)
p.000023: they are believed by the medical
p.000023: practitioner to be competent: "…a person under the age of 16 years shall have legal capacity to consent on his own
p.000023: behalf to any surgical, medical or dental procedure or treatment where in the opinion of a qualified medical
p.000023: practitioner attending him, he is capable of understanding the nature and possible consequences of the procedure or
p.000023: treatment." 30 Interpretation of Scottish law has been that a young person's competency allows them to refuse as well
p.000023: as consent to treatment.
p.000023: It is not entirely clear whether this Scottish statute covers consent to participate in research, but as discussed
p.000023: above, in the absence of law dealing specifically with research, the principles of Scottish law relating to consent to
p.000023: procedures and
p.000023: treatment might reasonably be applied. At the same time, it is vital to recognise that the threshold for understanding
p.000023: will relate to the complexity of the research being undertaken.
p.000023:
p.000023: Additional protection for children participating in clinical trials
p.000023: The Medicines for Human Use (Clinical Trials) Regulations 2004 have been law since they came into force on 1 May 2004
p.000023: and regulate trials in the UK.26 These regulations transpose European Union Directive 2001/20/EC into UK law.31 The
p.000023: Regulations offer additional protection for a minor (a person under the age of 16 years) who is being considered for a
p.000023: clinical trial. This additional protection comes at a time when more children are expected to be asked to participate
p.000023: in clinical trials, as part of an international initiative to provide medicines for children that are fully licensed
p.000023: (see 3.4 for more information). The regulations specify that for a minor
p.000023: to participate in a clinical trial, a person with parental responsibility or a legal representative must give informed
p.000023: consent and may withdraw the young person at any time.
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000025: 25
p.000025:
p.000025: MRC Ethics Guide: Medical research involving children
p.000025: MRC Ethics Guide: Medical research involving children
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025: Key provisions for the protection of minors within the Medicines for Human Use (Clinical Trials) Regulations 2004
p.000025: (Regulation 15 and Part 4 of Schedule 1) – extract from MHRA adviceii
p.000025:
...
Social / Youth/Minors
Searching for indicator minor:
(return to top)
p.000021: intelligence to
p.000021: understand what is proposed, it is their consent and not that of their parent/guardian that is required by law.
p.000021: Ethically it is important to involve children as much as possible in decisions about their own health, wellbeing and
p.000021: healthcare. The United Nations Convention on the Rights of the Child states that the child has a right to be informed,
p.000021: to express a view and to influence a decision.27 Methods used to facilitate the consent process should be appropriate
p.000021: to the age and understanding of the child. The Department of Health provides very useful guidance on consent for both
p.000021: patients and clinicians, including guidance for children and for parents/guardians explaining what they have a right to
p.000021: expect.3
p.000021:
p.000021: 5.1.3.a Provision in law for children to consent
p.000021:
p.000021: England, Wales and Northern Ireland
p.000021: Where the Clinical Trial Regulations apply, a minor is defined as someone under the age of 16.
p.000021: Where the common law applies – all situations not covered by the Regulations – the law states that the age of majority
p.000021: is 18. Whilst not considered to have fully reached adulthood, young people between the age of 16 and 18 are presumed to
p.000021: be competent to give consent. No statute governs the rights of those under the age of 16 to give consent for medical
p.000021: treatment or research. However, case law provides the example of the Gillick case with respect to treatment.28 This
p.000021: case determined that where a young person has sufficient understanding and intelligence to understand fully what is
p.000021: proposed, and use and weigh this information in reaching a decision, he or she can give consent to treatment and
p.000021: consent from parents is not legally necessary – although parental involvement should always be encouraged. The term
p.000021: "Gillick competent" is used to describe a young person's ability to make a decision regarding consent.
p.000021:
p.000021:
p.000022: 22
p.000022:
p.000023: 23
p.000023:
p.000023: MRC Ethics Guide: Medical research involving children
p.000023: MRC Ethics Guide: Medical research involving children
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023: In the absence of case law dealing specifically with research, the Gillick principles might reasonably be applied
p.000023: here, although the threshold for understanding will vary according to the complexity of the research. However there is
p.000023: continuing uncertainty about the application of these principles to research in general and, in the case of law covered
p.000023: by the Clinical Trials Regulations, it will be those Regulations that apply and not the Gillick case law.
p.000023:
p.000023: Scotland
p.000023: As in England, Wales and Northern Ireland, where the Clinical Trials Regulations apply, a minor is defined as someone
p.000023: under the age of 16.
p.000023: Also as in England, Wales and Northern Ireland, in Scotland a person reaches majority at the age of 18.29 However,
p.000023: Scottish statute makes legal provision for young people, where they are considered to be competent, to consent to
p.000023: medical procedures or treatment. Under Scottish statute young people aged 16 and above are presumed to be competent to
p.000023: give consent until proven otherwise, having legal capacity to enter into any transaction, which includes "…the giving
p.000023: by a person of any consent having legal effect." 30
p.000023: Young people under the age of 16 can also give legally binding consent to participate in medical research as long as
p.000023: they are believed by the medical
p.000023: practitioner to be competent: "…a person under the age of 16 years shall have legal capacity to consent on his own
p.000023: behalf to any surgical, medical or dental procedure or treatment where in the opinion of a qualified medical
p.000023: practitioner attending him, he is capable of understanding the nature and possible consequences of the procedure or
p.000023: treatment." 30 Interpretation of Scottish law has been that a young person's competency allows them to refuse as well
p.000023: as consent to treatment.
p.000023: It is not entirely clear whether this Scottish statute covers consent to participate in research, but as discussed
p.000023: above, in the absence of law dealing specifically with research, the principles of Scottish law relating to consent to
p.000023: procedures and
p.000023: treatment might reasonably be applied. At the same time, it is vital to recognise that the threshold for understanding
p.000023: will relate to the complexity of the research being undertaken.
p.000023:
p.000023: Additional protection for children participating in clinical trials
p.000023: The Medicines for Human Use (Clinical Trials) Regulations 2004 have been law since they came into force on 1 May 2004
p.000023: and regulate trials in the UK.26 These regulations transpose European Union Directive 2001/20/EC into UK law.31 The
p.000023: Regulations offer additional protection for a minor (a person under the age of 16 years) who is being considered for a
p.000023: clinical trial. This additional protection comes at a time when more children are expected to be asked to participate
p.000023: in clinical trials, as part of an international initiative to provide medicines for children that are fully licensed
p.000023: (see 3.4 for more information). The regulations specify that for a minor
p.000023: to participate in a clinical trial, a person with parental responsibility or a legal representative must give informed
p.000023: consent and may withdraw the young person at any time.
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000025: 25
p.000025:
p.000025: MRC Ethics Guide: Medical research involving children
p.000025: MRC Ethics Guide: Medical research involving children
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025: Key provisions for the protection of minors within the Medicines for Human Use (Clinical Trials) Regulations 2004
p.000025: (Regulation 15 and Part 4 of Schedule 1) – extract from MHRA adviceii
p.000025:
p.000025: The Regulations provide additional protection for a minor (a person under the age of
p.000025: 16) who is a candidate for a clinical trial.They require, among other provisions, that:
p.000025:
p.000025: • an ethics committee considering the trial must receive advice on the relevant field of paediatric care; and
p.000025: • a person with parental responsibility or a legal representative must give informed consent and may withdraw the
p.000025: young person at any time; and, in relation to the minor himself:
p.000025: • staff with experience with young persons must inform him/her of the risks and benefits of the trial according to
p.000025: his capacity to understand;
p.000025: • the investigator must consider his or her explicit wish to refuse to participate or to be withdrawn from the
p.000025: trial at any time;
p.000025: • the clinical trial relate directly to an illness from which he or she suffers or that can only be carried out on
p.000025: minors; and
p.000025: • the trial must aim to provide some direct benefit for the group of patients involved.
p.000025: 5.1.4 Assessing the competence of a child to consent
p.000025: While normally increasing with age, competence is considered not to depend primarily on age, but rather on the ability
p.000025: to understand and weigh up options. It can be influenced by the way information is presented – many children will be
p.000025: competent if information is presented in an appropriate way and they are
p.000025: supported through the decision-making process. The Central Office for Research Ethics Committees (COREC) provides a
p.000025: useful template for designing patient information sheets and seeking assent/consent from children and young people.33 A
...
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Research cannot go ahead. Parental consent MUST be obtained
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Research can go ahead Research cannot go ahead
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Research can go ahead with parental consent
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Even if the parents have given their consent, the deliberate objection of the child should be
p.000031: * In England, Wales and Northern Ireland parents may overule the child's decision if it is felt to be in the best
p.000031: interests of the child.
p.000031: ** Where parents refuse to give their consent, the courts can overrule if it is felt to be in the best interests of
p.000031: the child.
p.000031: *** The researcher must obtain the permission of the parent/guardian in accordance with local laws or established
p.000031: procedures eg, in the UK participation of a minor in a clinical trial requires parental consent under The Medicines for
p.000031: Human Use (Clinical Trials) Regulations (2004).
p.000031:
p.000031: NO their child in the
p.000031: research?
p.000031: Does the child
p.000031: NO actively object?
p.000031: respected
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Is the child believed to
p.000031: be competent to consent to the proposed treatment?
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: YES
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Does the competent child consent to participation?
p.000031:
p.000031: YES
p.000031:
p.000031: Does the child assent? ie, knowingly agree
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031: The child's opinion should be respected. Research should not go ahead *
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Is the child happy to involve the parents?
p.000031:
p.000031: YES
p.000031:
p.000031: YES
p.000031:
p.000031:
...
p.000035:
p.000035: MRC Ethics Guide: Medical research involving children
p.000035: MRC Ethics Guide: Medical research involving children
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: ethics committee. An examination of the ethical acceptability is necessary to protect the dignity, rights, safety and
p.000035: wellbeing of the research participant. The assessment should draw on an appropriate range of expertise adequately
p.000035: reflecting professional and lay views, therefore a professional opinion should be sought for any research involving
p.000035: children. The ethics committee must be satisfied that dependent persons and vulnerable groups will not be subjected to
p.000035: undue influence.
p.000035: Whilst the Council of Europe protocol is a legal instrument, it has not so far been transposed into UK law. However,
p.000035: the Medicines for Human Use (Clinical Trials) Regulations 2004, which transpose Directive 2001/20/EC into UK law,
p.000035: require that an ethics committee considering a trial involving minors must receive advice on the relevant field of
p.000035: paediatric care.29, 30 A "minor" is defined as a person under the age of 16.
p.000035:
p.000035: 5.4 Children's safety in relation to researchers
p.000035: Any individual recruited by the MRC to work directly with children will undergo security screening, including criminal
p.000035: records review. This includes nurses, survey interviewers and some individuals involved in a clinically invasive
p.000035: capacity, eg, phlebotomists. The MRC expects its grant-holding institutions to do likewise.
p.000035: Security screening is complementary to other good recruitment practices and not a substitute for them. Staff involved
p.000035: in MRC's recruitment process are responsible for ensuring that standard checks are still made.
p.000035:
p.000035: 5.5 Specific situations
p.000035:
p.000035: 5.5.1 Research involving human material
p.000035: Please refer to the MRC guidance Human tissue and biological samples for use in research.12
p.000035: Further guidance will be issued when the Human Tissue Bill, and equivalent legislation in Scotland, become law.
p.000035: 5.5.2 The use of personal information
p.000035: Please refer to the MRC guidance Personal information in medical research.11
p.000035:
p.000035: 5.5.3 Research involving very young children
p.000035: A parent/guardian's informed consent is necessary for the involvement of babies in research. When a baby is seriously
...
p.000035: Research involving children in emergency situations should be carried out only where research of comparable
p.000035: effectiveness cannot be carried out on persons in non- emergency situations. The parents and child must be informed
p.000035: about the research as
p.000035:
p.000036: 36
p.000036:
p.000037: 37
p.000037:
p.000037: MRC Ethics Guide: Medical research involving children
p.000037: MRC Ethics Guide: Medical research involving children
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037: soon as possible afterwards and their consent for future involvement sought. It must be made clear that the child (or
p.000037: parent on behalf of a child not yet competent) can withdraw from the study at any point.
p.000037: The Council of Europe provide further guidance on research in emergency clinical situations.9
p.000037: Under the Clinical Trial Regulations, consent must be given on behalf of a minor prior to participation in a trial of
p.000037: an investigational medicinal product in all circumstances; there is currently no exception for emergency situations.
p.000037: However, it is possible for someone other than a parent to give consent as a “legal representative”, if the parent is
p.000037: unable to do so. This could be the doctor primarily responsible for the person’s treatment (if not involved in the
p.000037: trial) or, if they are not available, a person nominated by the healthcare provider.41
p.000037:
p.000037: 5.5.5 Including minority groups – equality in research
p.000037: As with adults it is important to include minority groups in research involving children to ensure that they as a group
p.000037: receive a share of the potential benefits of research.
p.000037: Researchers should be sensitive to cultural issues and particularly to participants' specific concerns and values. For
p.000037: example, whether acceptance of research is necessary from someone in the extended cultural group as well as the
p.000037: immediate family, or whether participants undertake religious fasts that may affect when they can take medicines.
...
Social / parents
Searching for indicator parent:
(return to top)
p.000019:
p.000019: 5.1 Consent
p.000019:
p.000019: 5.1.1 What is valid consent?
p.000019:
p.000019: Consent – The voluntary agreement of an adult or competent child, based on adequate knowledge and understanding of
p.000019: relevant information, to participate in research
p.000019:
p.000019: Consent is legally valid and professionally acceptable only where the participants (or their parental guardian) are
p.000019: competent to give consent, have been properly informed, and have agreed without coercion.22
p.000019:
p.000019:
p.000019: In the UK, there are now two legal systems running in parallel.The common law applies to research not involving the
p.000019: Clinical Trials Regulations. As of May 2004, the Medicines for Human Use (Clinical Trials) Regulations apply to
p.000019: research involving investigational medicinal products (see Glossary). Researchers need to familiarise themselves with
p.000019: the Regulations.26
p.000019:
p.000019: 5.1.2 When should consent be sought, and who should seek consent?
p.000019: Research with children must normally only be carried out with the consent of the parent/guardian and/or child depending
p.000019: on the competence of the child. A summary of what is required in different circumstances is given below and in the flow
p.000019: diagram in 5.1.6. The physical integrity of children is protected by law and unless they or their parent/guardian
p.000019: agrees, it is not lawful to do anything that involves touching them.
p.000019: Consent should be sought before a child is examined, treated, cared for or involved in research. The clinician
p.000019: responsible for the child's treatment needs to ensure that
p.000019:
p.000020: 20
p.000020:
p.000021: 21
p.000021:
p.000021: MRC Ethics Guide: Medical research involving children
p.000021: MRC Ethics Guide: Medical research involving children
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: processes are in place and adhered to that ensure that the child and/or parent/guardian have given their informed
p.000021: consent. However the task of seeking consent can be delegated to another suitably trained and qualified health
p.000021: professional who understands the procedure(s) for which consent is being sought.
p.000021: As indicated in 5.1.5, the process of obtaining consent entails far more than a signature on paper. Verbal informed
p.000021: consent can be as valid as written consent for research, unless the Clinical Trials Regulations apply. It is vital that
p.000021: the person seeking consent records in writing that it has been given verbally. It may nevertheless be useful to obtain
p.000021: a signature from the participant or parent where this seems appropriate. It is important to note that under the
p.000021: Clinical Trials Regulations, verbal consent is not valid. The consent must be in writing unless the person giving
p.000021: consent is unable to write or otherwise mark the consent document.
p.000021: Informed consent is only one possible result of the informed choice process; the other possible result is the informed
p.000021: choice not to participate.
p.000021: Possible exceptions – Some research based on observation, on information collated from notes and tests already
p.000021: performed for therapeutic purposes, and public health research may be permissible without consent.2 Further
p.000021: information on the use of personal information in medical research is available from the MRC guidance Personal
p.000021: information in medical research.11
p.000021: Research linked to medical care in an emergency: the handling of this depends on whether the proposed study falls under
p.000021: the Clinical Trials Regulations. For further information please refer to 5.5.4.
p.000021:
p.000021: 5.1.3 Who can give consent, and who should you seek consent from?
p.000021: The law regarding the child's right to consent has developed differently in Scotland than in England, Wales and
p.000021: Northern Ireland – as outlined in 5.1.3a and 5.1.4a below. Generally, where children have sufficient understanding and
p.000021: intelligence to
p.000021: understand what is proposed, it is their consent and not that of their parent/guardian that is required by law.
p.000021: Ethically it is important to involve children as much as possible in decisions about their own health, wellbeing and
p.000021: healthcare. The United Nations Convention on the Rights of the Child states that the child has a right to be informed,
p.000021: to express a view and to influence a decision.27 Methods used to facilitate the consent process should be appropriate
p.000021: to the age and understanding of the child. The Department of Health provides very useful guidance on consent for both
p.000021: patients and clinicians, including guidance for children and for parents/guardians explaining what they have a right to
p.000021: expect.3
p.000021:
p.000021: 5.1.3.a Provision in law for children to consent
p.000021:
p.000021: England, Wales and Northern Ireland
p.000021: Where the Clinical Trial Regulations apply, a minor is defined as someone under the age of 16.
...
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027: 5.1.4.a Children unable to consent to involvement, and parental consent
p.000027: If the child is deemed incompetent to consent to participate in research, then he or she should normally not
p.000027: participate without the consent of a person with parental responsibility. A person with parental responsibility may
p.000027: legally consent to treatment on an incompetent child's behalf. If the child is able to give assent to decisions about
p.000027: participation in research, the investigator must obtain that assent in addition to the consent of the legally
p.000027: authorised representative. If the child does not assent, this should be respected.
p.000027: Legally, the researcher need only obtain consent from one person with parental responsibility. However, it is good
p.000027: practice and in the best interests of the child to involve others close to the child – for example, a second parent –
p.000027: in the decision- making process. Where opinions are strongly divided and agreement cannot be reached, it would be
p.000027: advisable to exclude the child from the research study unless a treatment option is only available as part of that
p.000027: programme. In such a case, every effort should be made to overcome the disagreement without a decision having to be
p.000027: referred to the courts.
p.000027: If the parents are themselves under 16 years of age, they will only be able to give valid consent on behalf of their
p.000027: child if they are competent to take the decision in question.
p.000027: Parents/guardians can consent to research procedures that offer potential benefit to the child. If the research is
p.000027: thought not to offer potential benefit to the child, parents/guardians can still consent provided the risks are
p.000027: sufficiently small to mean that research can be reasonably said not to go against the child's interests.
...
p.000027: parental responsibility or the court can overrule a competent child's decision to refuse potentially beneficial
p.000027: treatment if it is felt to be in the best interests of the child or young person.
p.000027:
p.000027: Scotland
p.000027: The Children (Scotland) Act 1995 37 makes provision for cases where a young person aged under 16 is not competent to
p.000027: give legally valid consent. Parental rights enabling parents to carry out parental responsibilities include
p.000027: "safeguarding and promoting the child's health, welfare and development, providing direction and guidance to the child
p.000027: in a manner appropriate to the stage of the child's development and acting as the child's legal representative." Most
p.000027: of these last until the young person is 16 years old or shows competency to make their own decisions. Interestingly, in
p.000027: this Act it is stated that a child of 12 years or more should be presumed to be of sufficient age and maturity to form
p.000027: a view. The parental responsibility to provide guidance continues until the young person is 18. Case law suggests that
p.000027: a parent cannot overrule the decision of a competent child; however this has not yet been added to statute.
p.000027: The Adults with Incapacity (Scotland) Act 2000 38 covers the treatment and welfare of people over the age of 16 who
p.000027: are unable to give consent.
p.000027: In the absence of case law dealing specifically with research, the principles applying to medical treatment in England,
p.000027: Wales, Scotland and Northern Ireland might reasonably be applied to research.
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000029: 29
p.000029:
p.000029: MRC Ethics Guide: Medical research involving children
p.000029: MRC Ethics Guide: Medical research involving children
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: 5.1.4.b Seeking legal advice
p.000029: Researchers should seek legal advice if in any doubt regarding authority to proceed.
p.000029:
p.000029: 5.1.5 How best to seek consent
p.000029: The RCPCH provides guidance on how best to seek consent: 2
p.000029:
p.000029:
p.000029: For consent to be freely given researchers must:
p.000029:
...
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Research cannot go ahead. Parental consent MUST be obtained
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Research can go ahead Research cannot go ahead
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Research can go ahead with parental consent
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Even if the parents have given their consent, the deliberate objection of the child should be
p.000031: * In England, Wales and Northern Ireland parents may overule the child's decision if it is felt to be in the best
p.000031: interests of the child.
p.000031: ** Where parents refuse to give their consent, the courts can overrule if it is felt to be in the best interests of
p.000031: the child.
p.000031: *** The researcher must obtain the permission of the parent/guardian in accordance with local laws or established
p.000031: procedures eg, in the UK participation of a minor in a clinical trial requires parental consent under The Medicines for
p.000031: Human Use (Clinical Trials) Regulations (2004).
p.000031:
p.000031: NO their child in the
p.000031: research?
p.000031: Does the child
p.000031: NO actively object?
p.000031: respected
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Is the child believed to
p.000031: be competent to consent to the proposed treatment?
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: YES
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Does the competent child consent to participation?
p.000031:
p.000031: YES
p.000031:
p.000031: Does the child assent? ie, knowingly agree
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031: The child's opinion should be respected. Research should not go ahead *
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
...
p.000031: unwise
p.000031: to proceed
p.000031:
p.000031:
p.000031: Research can go ahead. Competent child
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Do the parents wish their child to participate in the research project despite the child's objection?
p.000031:
p.000031: YES
p.000031:
p.000031: Research cannot go ahead. Parental consent must be obtained to proceed. The matter can be referred to the courts **
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Is the child very young or immature?
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: If the child is older or closer to being
p.000031: able to consent actively, seek the specific approval of the relevant Research Ethics Committees before initiating and
p.000031: continuing with investigational treatment
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Parent can overule child's objections.
p.000031: Research can go ahead
p.000031:
p.000031: iii Flow chart based on text from Council for International Organizations of
p.000031: Medical Sciences International ethical guidelines for biomedical research involving human subjects.5
p.000032: 32
p.000032: YES
p.000032: consents and parents assent
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033: MRC Ethics Guide: Medical research involving children
p.000033: MRC Ethics Guide: Medical research involving children
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: Seeking consent is not a single response but a process. The child should be provided with information appropriate to
p.000033: his or her increasing ability to make decisions about complex and serious issues. It is helpful for researchers to
p.000033: produce child-friendly information in a form appropriate for the relevant age groups – this could make use of pictures
p.000033: or videos. More than one version may need to be produced
p.000033: if research covers a wide age range, such as eight-18 years. Where the research project lasts a number of years, the
p.000033: child and/or parent/guardian may need to be approached periodically to ensure they still consent to the child's
p.000033: involvement in research. For example, where a parent has consented to follow-up studies throughout the life of the
p.000033: child, the child must be given the opportunity to decide for himself/herself, once competent to do so, whether he or
p.000033: she wishes to continue his or her involvement.
p.000033:
p.000033: 5.2 Confidentiality
p.000033: Medical professionals have a duty of confidentiality to all patients including children. Legally competent children are
p.000033: entitled to expect that information about themselves will not be provided to a third party, including their
p.000033: parent/guardian, without their consent. However, it is important that wherever possible the parents/guardians are
p.000033: informed, and young people should be encouraged to involve them unless it is not in their best interests to do so. If
p.000033: competent children do not wish to involve their parents/guardians this should be respected. Disclosure can only be
p.000033: justified if there is reasonable cause to suspect that the child is suffering or is likely to suffer significant harm
p.000033: as a result of non-disclosure. Any decision to disclose confidential information to a third party must be relayed to
p.000033: the competent child before disclosure.
p.000033: To facilitate both the child's healthcare and longer term research, general practitioners (GPs) should be notified of
p.000033: all research on their paediatric patients. The consent form should request consent to inform and update GPs of the
p.000033: child's involvement. If a participant is likely to resist information being provided to parents/guardians and family
p.000033: practitioners because the research is of a sensitive
p.000033: nature, eg, investigating smoking habits or sexual health, advice should be sought from the Research Ethics Committee
p.000033: that assesses the protocol.
p.000033: Children who lack competence to consent to participate are nevertheless entitled to confidentiality. The researcher
p.000033: will have had to request the parent/guardian's consent to the child's involvement in research. Any intention to
p.000033: disclose information to anyone else should be discussed with both the parent/guardian and the child, taking into
p.000033: consideration whether disclosure to a third party is necessary in the interests of the child's health. Public health
p.000033: research may require the use of anonymous data without explicit consent – for detailed guidance on this researchers
p.000033: should consult the MRC guidance Personal information in medical research.11
p.000033: Researchers working with children have important responsibilities in relation to child protection. Where researchers
p.000033: have reasonable cause to suspect that a child is suffering or likely to suffer significant harm, they have a clear
p.000033: responsibility to liaise urgently with those responsible for the child's clinical care with a view to making a referral
p.000033: to social services. Again, a decision to disclose information should, wherever possible, be discussed with the child
p.000033: before disclosure, in terms appropriate to the child's capability to understand.
p.000033: All researchers need to be aware of relevant data protection legislation and the rights of the child (and their
...
p.000035: require that an ethics committee considering a trial involving minors must receive advice on the relevant field of
p.000035: paediatric care.29, 30 A "minor" is defined as a person under the age of 16.
p.000035:
p.000035: 5.4 Children's safety in relation to researchers
p.000035: Any individual recruited by the MRC to work directly with children will undergo security screening, including criminal
p.000035: records review. This includes nurses, survey interviewers and some individuals involved in a clinically invasive
p.000035: capacity, eg, phlebotomists. The MRC expects its grant-holding institutions to do likewise.
p.000035: Security screening is complementary to other good recruitment practices and not a substitute for them. Staff involved
p.000035: in MRC's recruitment process are responsible for ensuring that standard checks are still made.
p.000035:
p.000035: 5.5 Specific situations
p.000035:
p.000035: 5.5.1 Research involving human material
p.000035: Please refer to the MRC guidance Human tissue and biological samples for use in research.12
p.000035: Further guidance will be issued when the Human Tissue Bill, and equivalent legislation in Scotland, become law.
p.000035: 5.5.2 The use of personal information
p.000035: Please refer to the MRC guidance Personal information in medical research.11
p.000035:
p.000035: 5.5.3 Research involving very young children
p.000035: A parent/guardian's informed consent is necessary for the involvement of babies in research. When a baby is seriously
p.000035: ill and a decision about treatment is required quickly, the pressure on parents is high and the difficulty of obtaining
p.000035: truly informed consent is recognised. The RCPCH provides detailed guidance relating to research involving babies.40
p.000035:
p.000035: 5.5.4 Emergency situations
p.000035: Under common law, provided that the specific approval of a research ethics committee has been obtained for the project
p.000035: overall, it is ethical to carry out research involving children on occasions of extreme urgency without obtaining prior
p.000035: consent. However, there is a lack of clarity in the law about this if the research does not have the potential to
p.000035: benefit the child in question. If in doubt, it would be advisable to seek legal advice in potentially contentious
p.000035: circumstances.
p.000035: Research involving children in an emergency situation may be needed when treatment is available only as part of a
p.000035: research programme. Ethically, if the research does not have the potential to produce results of direct benefit to the
p.000035: individual participant, the Council of Europe recommends that it should only be carried out if it has the aim of
p.000035: contributing or improving understanding of the individual's condition so that it could ultimately confer benefit upon
p.000035: the patient or others with the same condition, and that it entails only minimal risk.9
p.000035: Research involving children in emergency situations should be carried out only where research of comparable
p.000035: effectiveness cannot be carried out on persons in non- emergency situations. The parents and child must be informed
p.000035: about the research as
p.000035:
p.000036: 36
p.000036:
p.000037: 37
p.000037:
p.000037: MRC Ethics Guide: Medical research involving children
p.000037: MRC Ethics Guide: Medical research involving children
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037: soon as possible afterwards and their consent for future involvement sought. It must be made clear that the child (or
p.000037: parent on behalf of a child not yet competent) can withdraw from the study at any point.
p.000037: The Council of Europe provide further guidance on research in emergency clinical situations.9
p.000037: Under the Clinical Trial Regulations, consent must be given on behalf of a minor prior to participation in a trial of
p.000037: an investigational medicinal product in all circumstances; there is currently no exception for emergency situations.
p.000037: However, it is possible for someone other than a parent to give consent as a “legal representative”, if the parent is
p.000037: unable to do so. This could be the doctor primarily responsible for the person’s treatment (if not involved in the
p.000037: trial) or, if they are not available, a person nominated by the healthcare provider.41
p.000037:
p.000037: 5.5.5 Including minority groups – equality in research
p.000037: As with adults it is important to include minority groups in research involving children to ensure that they as a group
p.000037: receive a share of the potential benefits of research.
p.000037: Researchers should be sensitive to cultural issues and particularly to participants' specific concerns and values. For
p.000037: example, whether acceptance of research is necessary from someone in the extended cultural group as well as the
p.000037: immediate family, or whether participants undertake religious fasts that may affect when they can take medicines.
p.000037: When seeking consent where the child or parent needs an interpreter, an independent interpreter is preferable to a
p.000037: family member.
p.000037: Where the child has a disability, particular care should be taken to ensure that information is provided in a suitable
p.000037: form. Specialist colleagues may be able to act as
p.000037: facilitators or advocates where the child has particular needs. Children with specific impairments such as learning
p.000037: difficulties should not be excluded from participating in research, but equally should not be over-researched because
p.000037: of their condition.
p.000037:
p.000037: 5.5.6 Research in developing countries
p.000037: Please refer to MRC guidance on Research involving human participants in developing societies.
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000039: 39
p.000039:
p.000039: MRC Ethics Guide: Medical research involving children
p.000039: MRC Ethics Guide: Medical research involving children
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: 6. Summary
p.000039: Children should be included in medical research only if:
p.000039:
p.000039: • The relevant knowledge cannot be gained through research with adults.
p.000039:
p.000039: • It is approved by the appropriate Research Ethics Committee/s.
p.000039:
p.000039: • Either the participant has given consent where competent, or consent has been given on his or her behalf by a
p.000039: parent or guardian and the participant does not object or appear to object in either words or actions. iv
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: iv See 5.5.4 for guidance on emergency situations, when this might not be possible.
p.000039: 7. Glossary
p.000039: The definitions provided here apply as they are used in the above guidelines.
p.000039:
p.000039: Assent
p.000039: A child's affirmative agreement to participate. Failure to object should not be construed as assent.
p.000039: Burden of disease
p.000039: The impact of disease on the individual and on society due to loss of duration and quality of life. Measures include
p.000039: (i) 'morbidity burden', ie, the prevalence of a condition, the range of its severity and the age distribution of the
p.000039: population suffering from the condition, and (ii) the financial burden to society in meeting the obligation to support
p.000039: the individual; for example, in terms of net public expenditure on health services and on social services.
p.000039: Child
p.000039: In the UK, a person under the age of 18. "Young person" is a term often used to describe older children in this age
...
p.000041:
p.000041: Consent
p.000041: The voluntary agreement of an adult or competent child, based on adequate knowledge and understanding of relevant
p.000041: information, to participate in research. For further information please refer to Section 5.
p.000041:
p.000041: Family
p.000041: A group of individuals who together form a social structure; a family may or may not include biological relatives.
p.000041:
p.000041:
p.000041: Harm
p.000041: That which adversely affects the interests or welfare of an individual. This may be physical harm, discomfort, anxiety,
p.000041: pain, and psychological
p.000041:
p.000041: disturbance or social disadvantage (ostracism).
p.000041:
p.000041: Investigational medicinal product
p.000041: A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial,
p.000041: including products already with a marketing authorisation but used or assembled (formulated or packaged) in a way
p.000041: different from the authorised form, or when used for an unauthorised indication, or when used to gain further
p.000041: information about the authorised form.31
p.000041:
p.000041: Off-label
p.000041: Term used to describe a medicine used for an indication, dose, or route of administration outside the terms of the
p.000041: product licence.
p.000041:
p.000041: Parent/guardian
p.000041: The term "parent/guardian" is used in these guidelines to describe those with legal responsibility for the child. The
p.000041: Children Act 1989, the Children (Scotland) Act 1995 and the Children (Northern Ireland) Order 1995 set out who has
p.000041: parental responsibility in their respective jurisdictions. The Adoption and Children Act 2002 s111(2) has recently
p.000041: extended the definition of those with legal responsibility for the child to include unmarried fathers who have entered
p.000041: into a legally binding Parental Responsibility Agreement.42
p.000041: The MRC is aware that some children will not be resident with both or either of their parents.
p.000041: On occasion it may be difficult for the researcher to determine who has legal responsibility for the child, and if
p.000041: necessary, further clarification should be sought from the child’s care giver or their GP.
p.000041:
p.000041:
p.000041: Risk
p.000041: A potential harm; the characteristics of risk include the probability of its occurrence, as well as its magnitude and
...
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p.002004: MRC Ethics Guide
p.002004: Medical research involving children
p.002004:
p.002004: 2004
p.002004:
p.002004:
p.002004:
p.002004: MRC Ethics Guide: Medical research involving children
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004: Foreword
p.002004: Medical research involving children is important for the benefit of all children. It leads to innovations in healthcare
p.002004: that can substantially improve their health and quality of life.
p.002004: Furthermore, the scientific opportunities for developing better methods of preventing and treating diseases that affect
p.002004: children or begin in childhood have never been greater.
p.002004: The Medical Research Council (MRC) believes that research involving children should be supported, encouraged, and
p.002004: conducted in an ethical manner. We want to ensure that research participants, their parents and the general public can
p.002004: be confident that medical researchers work ethically with children.
p.002004: We recognise that while many other organisations have published guidance on medical research involving children, this
p.002004: is a vital area in which we must provide support and guidance to MRC researchers.The previous MRC guidance The ethical
p.002004: conduct of research on children1 (1991) has been replaced by the following updated guidelines. They outline the
p.002004: practical, ethical and legal issues that researchers need to consider when carrying out studies involving children. Our
p.002004: aim has been to set out general principles that can be applied in most situations rather than to cover every possible
p.002004: eventuality. The guidelines are intended to be concise and easily readable, and include a glossary defining some of the
p.002004: key terms used (see Section 7).
p.002004: We refer to guidance from The Royal College of Paediatrics and Child Health,2 the
p.002004: Department of Health3 and British Medical Association4 throughout this document. These organisations can all provide
p.002004: further useful information.
p.002004: This guide complements guidance on other research-related topics produced by the MRC, all of which is available at the
p.002004: MRC website, www.mrc.ac.uk. Any changes to MRC guidance are highlighted on the site as they arise.
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.000001: 1
p.000001:
p.000001: MRC Ethics Guide: Medical research involving children
...
p.000003: defend their interests – they may not have the capacity to give consent.
p.000003: The following principles should guide all MRC-funded research involving children: 4, 5
p.000003:
p.000003: • Research should only include children where the relevant knowledge cannot by obtained by research in adults (for
p.000003: guidance, see 4.1)
p.000003:
p.000003:
p.000004: 4
p.000004:
p.000005: 5
p.000005:
p.000005: MRC Ethics Guide: Medical research involving children
p.000005: MRC Ethics Guide: Medical research involving children
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005: • The purpose of the research is to obtain knowledge relevant to the health, wellbeing or healthcare needs of
p.000005: children.
p.000005: • Researchers can only involve competent children if they have obtained their informed consent beforehand.
p.000005: • A child's refusal to participate or continue in research should always be respected.
p.000005: • If a child becomes upset by a procedure, researchers must accept this as a valid refusal.
p.000005: • Researchers should involve parents/guardians in the decision to participate wherever possible, and in all cases
p.000005: where the child is not yet competent. Exceptional circumstances where this is not possible are discussed in 5.5.4.
p.000005: • Researchers should attempt to avoid any pressures that might lead the child to volunteer for research or that
p.000005: might lead parents to volunteer their children, in the expectation of direct benefit (whether therapeutic or
p.000005: financial).
p.000005: • Research involves partnership with the child and/or family, who should be kept informed and consent to separate
p.000005: stages of the project. Obtaining consent is a continuing process, rather than a one-off occurrence. Children and their
p.000005: families are likely to appreciate some recognition of their role in this partnership, such as a certificate of
p.000005: participation.
p.000005: • Researchers must take account of the cumulative medical, emotional, social and psychological consequences of the
p.000005: child being involved in research. Children with certain conditions may be exposed to a sequence of research projects.
p.000005: It is advisable to consider the risks of a particular research procedure in the context of the child's overall
p.000005: involvement in projects by different researchers.
p.000005: 2. Why do we need research involving children?
p.000005: Medical research involving children is essential for advancing child health and wellbeing. Often it is not sufficient,
...
p.000015: Resources – Will potential benefits be limited because the treatment is very expensive, or difficult to deliver?
p.000015: Types of intervention – Might a new treatment or procedure replace one that is more invasive?
p.000015: Timing – Might benefits be brief or long-lasting, immediate or not evident until years later?
p.000015:
p.000015: Equity – Should a wider range of children be offered the potential benefits of participating in the research?
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015: 4.3.1
p.000015:
p.000015: Assessing potential harms to the participant
p.000015:
p.000015: Magnitude – How severe may the harms associated with the research procedures be? Probability – How likely are the harms
p.000015: to occur?
p.000015: Types of intervention – How invasive or intrusive is the research? (Psychosocial research should be assessed as
p.000015: carefully as physical research.)
p.000015: Timing – Might adverse effects be brief or long-lasting, immediate or not evident until years later?
p.000015: Equity – Are a few children who already have many medical problems drawn into too many projects simply because they are
p.000015: available?
p.000015:
p.000015:
p.000015: Other considerations
p.000015: The assessment of risk must be carried out by all involved in the research – the children where possible, the
p.000015: parents/guardians, the researchers and clinicians concerned and the research ethics committees. This assessment
p.000015: includes reviewing personal circumstances: generalisation can be controversial as children's responses vary, can be
p.000015: unpredictable, and alter as children develop; a procedure that does not bother one child can arouse severe distress in
p.000015: another. For example, many children fear needles. For them, low rather than minimal risk could be incurred by
p.000015: injections and venepuncture. However, the procedure may be made more acceptable with careful explanation of the
p.000015: effectiveness of local anaesthetic cream and an understanding of the reason for the venepuncture – so that the child
p.000015: may choose to proceed. Researchers sometimes underestimate high risk of pain if the effects are brief, whereas the
p.000015: child or parents may consider that the severe transient pain is not justified by the hoped-for benefit.
p.000015:
p.000015:
p.000015:
p.000015:
p.000016: 16
p.000016:
p.000017: 17
p.000017:
p.000017: MRC Ethics Guide: Medical research involving children
p.000017: MRC Ethics Guide: Medical research involving children
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017: Careful consideration of consequences may be required to identify some risks or potential harm. For example, with
p.000017: research into serious genetic disorders that present in adult life, pre-symptomatic diagnosis in a child, while it may
p.000017: be beneficial, may also have harmful effects or implications which may affect the child's
p.000017: opportunities and freedom of choice.23
p.000017:
p.000017: Interim findings: as with adults, if evidence of harm emerges during the trial as a result of giving or withholding
p.000017: certain treatment, the interests of the child
p.000017: participants must be put before the requirements of the research. This must be taken into account by researchers and
p.000017: trial steering committees when deciding on 'stopping rules' for trials and in studies of new techniques.
...
p.000021: The law regarding the child's right to consent has developed differently in Scotland than in England, Wales and
p.000021: Northern Ireland – as outlined in 5.1.3a and 5.1.4a below. Generally, where children have sufficient understanding and
p.000021: intelligence to
p.000021: understand what is proposed, it is their consent and not that of their parent/guardian that is required by law.
p.000021: Ethically it is important to involve children as much as possible in decisions about their own health, wellbeing and
p.000021: healthcare. The United Nations Convention on the Rights of the Child states that the child has a right to be informed,
p.000021: to express a view and to influence a decision.27 Methods used to facilitate the consent process should be appropriate
p.000021: to the age and understanding of the child. The Department of Health provides very useful guidance on consent for both
p.000021: patients and clinicians, including guidance for children and for parents/guardians explaining what they have a right to
p.000021: expect.3
p.000021:
p.000021: 5.1.3.a Provision in law for children to consent
p.000021:
p.000021: England, Wales and Northern Ireland
p.000021: Where the Clinical Trial Regulations apply, a minor is defined as someone under the age of 16.
p.000021: Where the common law applies – all situations not covered by the Regulations – the law states that the age of majority
p.000021: is 18. Whilst not considered to have fully reached adulthood, young people between the age of 16 and 18 are presumed to
p.000021: be competent to give consent. No statute governs the rights of those under the age of 16 to give consent for medical
p.000021: treatment or research. However, case law provides the example of the Gillick case with respect to treatment.28 This
p.000021: case determined that where a young person has sufficient understanding and intelligence to understand fully what is
p.000021: proposed, and use and weigh this information in reaching a decision, he or she can give consent to treatment and
p.000021: consent from parents is not legally necessary – although parental involvement should always be encouraged. The term
p.000021: "Gillick competent" is used to describe a young person's ability to make a decision regarding consent.
p.000021:
p.000021:
p.000022: 22
p.000022:
p.000023: 23
p.000023:
p.000023: MRC Ethics Guide: Medical research involving children
p.000023: MRC Ethics Guide: Medical research involving children
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023: In the absence of case law dealing specifically with research, the Gillick principles might reasonably be applied
p.000023: here, although the threshold for understanding will vary according to the complexity of the research. However there is
p.000023: continuing uncertainty about the application of these principles to research in general and, in the case of law covered
p.000023: by the Clinical Trials Regulations, it will be those Regulations that apply and not the Gillick case law.
p.000023:
p.000023: Scotland
p.000023: As in England, Wales and Northern Ireland, where the Clinical Trials Regulations apply, a minor is defined as someone
p.000023: under the age of 16.
p.000023: Also as in England, Wales and Northern Ireland, in Scotland a person reaches majority at the age of 18.29 However,
p.000023: Scottish statute makes legal provision for young people, where they are considered to be competent, to consent to
...
p.000027: participate without the consent of a person with parental responsibility. A person with parental responsibility may
p.000027: legally consent to treatment on an incompetent child's behalf. If the child is able to give assent to decisions about
p.000027: participation in research, the investigator must obtain that assent in addition to the consent of the legally
p.000027: authorised representative. If the child does not assent, this should be respected.
p.000027: Legally, the researcher need only obtain consent from one person with parental responsibility. However, it is good
p.000027: practice and in the best interests of the child to involve others close to the child – for example, a second parent –
p.000027: in the decision- making process. Where opinions are strongly divided and agreement cannot be reached, it would be
p.000027: advisable to exclude the child from the research study unless a treatment option is only available as part of that
p.000027: programme. In such a case, every effort should be made to overcome the disagreement without a decision having to be
p.000027: referred to the courts.
p.000027: If the parents are themselves under 16 years of age, they will only be able to give valid consent on behalf of their
p.000027: child if they are competent to take the decision in question.
p.000027: Parents/guardians can consent to research procedures that offer potential benefit to the child. If the research is
p.000027: thought not to offer potential benefit to the child, parents/guardians can still consent provided the risks are
p.000027: sufficiently small to mean that research can be reasonably said not to go against the child's interests.
p.000027: Guidance on the law regarding parental consent is available from the BMA.4 A summary of country-specific differences
p.000027: follows:
p.000027: England,Wales and Northern Ireland
p.000027: The Children Act 1989 and The Children Act (Northern Ireland) Order 1995 make provision for parental rights in respect
p.000027: of their child, including the right to give consent to medical treatment.35, 36 Case law shows that a person with
p.000027: parental responsibility or the court can overrule a competent child's decision to refuse potentially beneficial
p.000027: treatment if it is felt to be in the best interests of the child or young person.
p.000027:
p.000027: Scotland
p.000027: The Children (Scotland) Act 1995 37 makes provision for cases where a young person aged under 16 is not competent to
p.000027: give legally valid consent. Parental rights enabling parents to carry out parental responsibilities include
p.000027: "safeguarding and promoting the child's health, welfare and development, providing direction and guidance to the child
p.000027: in a manner appropriate to the stage of the child's development and acting as the child's legal representative." Most
p.000027: of these last until the young person is 16 years old or shows competency to make their own decisions. Interestingly, in
p.000027: this Act it is stated that a child of 12 years or more should be presumed to be of sufficient age and maturity to form
p.000027: a view. The parental responsibility to provide guidance continues until the young person is 18. Case law suggests that
p.000027: a parent cannot overrule the decision of a competent child; however this has not yet been added to statute.
p.000027: The Adults with Incapacity (Scotland) Act 2000 38 covers the treatment and welfare of people over the age of 16 who
p.000027: are unable to give consent.
p.000027: In the absence of case law dealing specifically with research, the principles applying to medical treatment in England,
...
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: 5.1.4.b Seeking legal advice
p.000029: Researchers should seek legal advice if in any doubt regarding authority to proceed.
p.000029:
p.000029: 5.1.5 How best to seek consent
p.000029: The RCPCH provides guidance on how best to seek consent: 2
p.000029:
p.000029:
p.000029: For consent to be freely given researchers must:
p.000029:
p.000029: • Offer families no financial inducement although expenses should be paid.
p.000029: • Exert no pressure on families.
p.000029: • Give them as much time as possible (a few days for a major study, if at all possible) to consider whether to take
p.000029: part in the project.
p.000029: • Encourage families to discuss the project with – for example – their relatives, primary health carers – or an
p.000029: independent counsellor where available.
p.000029: • Tell them that they may refuse to take part, or may withdraw at any time even if they have signed a consent form.
p.000029: • Say that they need not give a reason for withdrawing (although their reason may help the researchers and other
p.000029: children in the study).
p.000029: • Assure them that the child patient's treatment will not be prejudiced by withdrawal from research.
p.000029: • Encourage parents/guardians to stay with the child during procedures.
p.000029: • Respond to families' questions, anxiety or distress throughout the study.
p.000029:
p.000029: For consent to be informed researchers must discuss with families:
p.000029:
p.000029: • The purpose of the research.
p.000029: • Whether the child stands to benefit directly and if so how; the difference between research and treatment.
p.000029: • The meaning of relevant research terms and any implications of consent (eg, placebo, randomised double-blind
p.000029: trial).
p.000029: • The nature of each procedure, how often and for how long each may occur.
p.000029: • The potential benefits and harms (both immediate and long-term).
p.000029: • The name of a researcher whom they can contact with their enquiries.
p.000029: • The name of the doctor directly responsible for the child's care.
p.000029: • How the child can withdraw from the project.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: Researchers must also:
p.000029:
p.000029: • Willingly explain and answer questions throughout the project.
p.000029: • Ensure that other staff caring for child subjects know about the research, and can also explain it if necessary.
p.000029: • Give clearly written patient information leaflets setting out all relevant information for families to keep
p.000029: (guidance on this can be found on the COREC website 33).
p.000029: • Report the results of research to the families involved wherever possible.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000030: 30
p.000030:
p.000031: 31
p.000031:
p.000031: MRC Ethics Guide: Medical research involving children
p.000031: MRC Ethics Guide: Medical research involving children
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 5.1.6 Seeking consent – a summaryiii
p.000031:
p.000031: If research is linked to medical care, it is justifiable in an emergency to start treatment prior to consent being
p.000031: obtained **
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Do the parents consent to the participation of
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: YES NO
p.000031:
p.000031: Is emergency treatment required where treatment is available only as part of a research programme?
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Research cannot go ahead. Parental consent MUST be obtained
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Research can go ahead Research cannot go ahead
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Research can go ahead with parental consent
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Even if the parents have given their consent, the deliberate objection of the child should be
p.000031: * In England, Wales and Northern Ireland parents may overule the child's decision if it is felt to be in the best
p.000031: interests of the child.
p.000031: ** Where parents refuse to give their consent, the courts can overrule if it is felt to be in the best interests of
p.000031: the child.
p.000031: *** The researcher must obtain the permission of the parent/guardian in accordance with local laws or established
p.000031: procedures eg, in the UK participation of a minor in a clinical trial requires parental consent under The Medicines for
p.000031: Human Use (Clinical Trials) Regulations (2004).
p.000031:
p.000031: NO their child in the
p.000031: research?
p.000031: Does the child
p.000031: NO actively object?
p.000031: respected
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Is the child believed to
p.000031: be competent to consent to the proposed treatment?
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: YES
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Does the competent child consent to participation?
p.000031:
p.000031: YES
p.000031:
p.000031: Does the child assent? ie, knowingly agree
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031: The child's opinion should be respected. Research should not go ahead *
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Is the child happy to involve the parents?
p.000031:
p.000031: YES
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031: Research can go ahead, the child has assented and parents’ consent obtained
p.000031:
p.000031:
p.000031:
p.000031: The child should be persuaded to involve the parents. Research can go ahead, as the child is competent ***
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Do the parents assent to the participation of their child in the research?
p.000031:
p.000031: Does the child need treatment that is not available outside the context of the research, does the investigation show
p.000031: promise of therapeutic benefit and is there no acceptable alternative therapy?
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031: The competent child's consent is sufficient – research could go ahead. However, if parents do not assent it may be
p.000031: unwise
p.000031: to proceed
p.000031:
p.000031:
p.000031: Research can go ahead. Competent child
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Do the parents wish their child to participate in the research project despite the child's objection?
p.000031:
p.000031: YES
p.000031:
p.000031: Research cannot go ahead. Parental consent must be obtained to proceed. The matter can be referred to the courts **
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Is the child very young or immature?
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: If the child is older or closer to being
p.000031: able to consent actively, seek the specific approval of the relevant Research Ethics Committees before initiating and
p.000031: continuing with investigational treatment
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Parent can overule child's objections.
p.000031: Research can go ahead
p.000031:
p.000031: iii Flow chart based on text from Council for International Organizations of
p.000031: Medical Sciences International ethical guidelines for biomedical research involving human subjects.5
p.000032: 32
p.000032: YES
p.000032: consents and parents assent
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033: MRC Ethics Guide: Medical research involving children
p.000033: MRC Ethics Guide: Medical research involving children
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: Seeking consent is not a single response but a process. The child should be provided with information appropriate to
p.000033: his or her increasing ability to make decisions about complex and serious issues. It is helpful for researchers to
p.000033: produce child-friendly information in a form appropriate for the relevant age groups – this could make use of pictures
p.000033: or videos. More than one version may need to be produced
p.000033: if research covers a wide age range, such as eight-18 years. Where the research project lasts a number of years, the
p.000033: child and/or parent/guardian may need to be approached periodically to ensure they still consent to the child's
p.000033: involvement in research. For example, where a parent has consented to follow-up studies throughout the life of the
p.000033: child, the child must be given the opportunity to decide for himself/herself, once competent to do so, whether he or
p.000033: she wishes to continue his or her involvement.
p.000033:
p.000033: 5.2 Confidentiality
p.000033: Medical professionals have a duty of confidentiality to all patients including children. Legally competent children are
p.000033: entitled to expect that information about themselves will not be provided to a third party, including their
p.000033: parent/guardian, without their consent. However, it is important that wherever possible the parents/guardians are
p.000033: informed, and young people should be encouraged to involve them unless it is not in their best interests to do so. If
p.000033: competent children do not wish to involve their parents/guardians this should be respected. Disclosure can only be
p.000033: justified if there is reasonable cause to suspect that the child is suffering or is likely to suffer significant harm
p.000033: as a result of non-disclosure. Any decision to disclose confidential information to a third party must be relayed to
p.000033: the competent child before disclosure.
p.000033: To facilitate both the child's healthcare and longer term research, general practitioners (GPs) should be notified of
p.000033: all research on their paediatric patients. The consent form should request consent to inform and update GPs of the
p.000033: child's involvement. If a participant is likely to resist information being provided to parents/guardians and family
p.000033: practitioners because the research is of a sensitive
p.000033: nature, eg, investigating smoking habits or sexual health, advice should be sought from the Research Ethics Committee
p.000033: that assesses the protocol.
p.000033: Children who lack competence to consent to participate are nevertheless entitled to confidentiality. The researcher
p.000033: will have had to request the parent/guardian's consent to the child's involvement in research. Any intention to
p.000033: disclose information to anyone else should be discussed with both the parent/guardian and the child, taking into
p.000033: consideration whether disclosure to a third party is necessary in the interests of the child's health. Public health
p.000033: research may require the use of anonymous data without explicit consent – for detailed guidance on this researchers
p.000033: should consult the MRC guidance Personal information in medical research.11
p.000033: Researchers working with children have important responsibilities in relation to child protection. Where researchers
p.000033: have reasonable cause to suspect that a child is suffering or likely to suffer significant harm, they have a clear
p.000033: responsibility to liaise urgently with those responsible for the child's clinical care with a view to making a referral
p.000033: to social services. Again, a decision to disclose information should, wherever possible, be discussed with the child
p.000033: before disclosure, in terms appropriate to the child's capability to understand.
p.000033: All researchers need to be aware of relevant data protection legislation and the rights of the child (and their
p.000033: parents/guardians in some circumstances) to access their health records. Fuller guidance on confidentiality issues is
p.000033: available from the Department of Health, the British Medical Association and the General Medical Council.3, 4, 39
p.000033:
p.000033: 5.3 Ethics committee review
p.000033: The Council of Europe Protocol to the Convention on Human Rights and Biomedicine on Biomedical Research provides
p.000033: guidance regarding the role of the ethics committee in research.9 According to this guidance, every research project
p.000033: must be submitted for independent examination of its scientific merit, including assessment of the importance of the
p.000033: aim of research and ethical acceptability to an
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000035: 35
p.000035:
p.000035: MRC Ethics Guide: Medical research involving children
p.000035: MRC Ethics Guide: Medical research involving children
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: ethics committee. An examination of the ethical acceptability is necessary to protect the dignity, rights, safety and
p.000035: wellbeing of the research participant. The assessment should draw on an appropriate range of expertise adequately
p.000035: reflecting professional and lay views, therefore a professional opinion should be sought for any research involving
...
p.000035: Any individual recruited by the MRC to work directly with children will undergo security screening, including criminal
p.000035: records review. This includes nurses, survey interviewers and some individuals involved in a clinically invasive
p.000035: capacity, eg, phlebotomists. The MRC expects its grant-holding institutions to do likewise.
p.000035: Security screening is complementary to other good recruitment practices and not a substitute for them. Staff involved
p.000035: in MRC's recruitment process are responsible for ensuring that standard checks are still made.
p.000035:
p.000035: 5.5 Specific situations
p.000035:
p.000035: 5.5.1 Research involving human material
p.000035: Please refer to the MRC guidance Human tissue and biological samples for use in research.12
p.000035: Further guidance will be issued when the Human Tissue Bill, and equivalent legislation in Scotland, become law.
p.000035: 5.5.2 The use of personal information
p.000035: Please refer to the MRC guidance Personal information in medical research.11
p.000035:
p.000035: 5.5.3 Research involving very young children
p.000035: A parent/guardian's informed consent is necessary for the involvement of babies in research. When a baby is seriously
p.000035: ill and a decision about treatment is required quickly, the pressure on parents is high and the difficulty of obtaining
p.000035: truly informed consent is recognised. The RCPCH provides detailed guidance relating to research involving babies.40
p.000035:
p.000035: 5.5.4 Emergency situations
p.000035: Under common law, provided that the specific approval of a research ethics committee has been obtained for the project
p.000035: overall, it is ethical to carry out research involving children on occasions of extreme urgency without obtaining prior
p.000035: consent. However, there is a lack of clarity in the law about this if the research does not have the potential to
p.000035: benefit the child in question. If in doubt, it would be advisable to seek legal advice in potentially contentious
p.000035: circumstances.
p.000035: Research involving children in an emergency situation may be needed when treatment is available only as part of a
p.000035: research programme. Ethically, if the research does not have the potential to produce results of direct benefit to the
p.000035: individual participant, the Council of Europe recommends that it should only be carried out if it has the aim of
p.000035: contributing or improving understanding of the individual's condition so that it could ultimately confer benefit upon
p.000035: the patient or others with the same condition, and that it entails only minimal risk.9
p.000035: Research involving children in emergency situations should be carried out only where research of comparable
p.000035: effectiveness cannot be carried out on persons in non- emergency situations. The parents and child must be informed
p.000035: about the research as
p.000035:
p.000036: 36
p.000036:
p.000037: 37
p.000037:
p.000037: MRC Ethics Guide: Medical research involving children
p.000037: MRC Ethics Guide: Medical research involving children
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037: soon as possible afterwards and their consent for future involvement sought. It must be made clear that the child (or
p.000037: parent on behalf of a child not yet competent) can withdraw from the study at any point.
p.000037: The Council of Europe provide further guidance on research in emergency clinical situations.9
p.000037: Under the Clinical Trial Regulations, consent must be given on behalf of a minor prior to participation in a trial of
p.000037: an investigational medicinal product in all circumstances; there is currently no exception for emergency situations.
...
p.000041: different from the authorised form, or when used for an unauthorised indication, or when used to gain further
p.000041: information about the authorised form.31
p.000041:
p.000041: Off-label
p.000041: Term used to describe a medicine used for an indication, dose, or route of administration outside the terms of the
p.000041: product licence.
p.000041:
p.000041: Parent/guardian
p.000041: The term "parent/guardian" is used in these guidelines to describe those with legal responsibility for the child. The
p.000041: Children Act 1989, the Children (Scotland) Act 1995 and the Children (Northern Ireland) Order 1995 set out who has
p.000041: parental responsibility in their respective jurisdictions. The Adoption and Children Act 2002 s111(2) has recently
p.000041: extended the definition of those with legal responsibility for the child to include unmarried fathers who have entered
p.000041: into a legally binding Parental Responsibility Agreement.42
p.000041: The MRC is aware that some children will not be resident with both or either of their parents.
p.000041: On occasion it may be difficult for the researcher to determine who has legal responsibility for the child, and if
p.000041: necessary, further clarification should be sought from the child’s care giver or their GP.
p.000041:
p.000041:
p.000041: Risk
p.000041: A potential harm; the characteristics of risk include the probability of its occurrence, as well as its magnitude and
p.000041: duration. For more on assessment and minimising risk see 4.3.
p.000041:
p.000041: MRC Ethics Guide: Medical research involving children
p.000041: MRC Ethics Guide: Medical research involving children
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: 8. Other MRC ethics guidance
p.000041: The MRC produces a wide range of ethics guidance for researchers, which is available at www.mrc.ac.uk and includes the
p.000041: following:
p.000041: • MRC interim guidance on ethics of research involving human material derived from the nervous system (June 2003).
p.000041: • MRC policy on antiretroviral therapy (ART) for people infected with HIV and involved in AIDS research in
...
Social / philosophical differences/differences of opinion
Searching for indicator opinion:
(return to top)
p.000023:
p.000023: Scotland
p.000023: As in England, Wales and Northern Ireland, where the Clinical Trials Regulations apply, a minor is defined as someone
p.000023: under the age of 16.
p.000023: Also as in England, Wales and Northern Ireland, in Scotland a person reaches majority at the age of 18.29 However,
p.000023: Scottish statute makes legal provision for young people, where they are considered to be competent, to consent to
p.000023: medical procedures or treatment. Under Scottish statute young people aged 16 and above are presumed to be competent to
p.000023: give consent until proven otherwise, having legal capacity to enter into any transaction, which includes "…the giving
p.000023: by a person of any consent having legal effect." 30
p.000023: Young people under the age of 16 can also give legally binding consent to participate in medical research as long as
p.000023: they are believed by the medical
p.000023: practitioner to be competent: "…a person under the age of 16 years shall have legal capacity to consent on his own
p.000023: behalf to any surgical, medical or dental procedure or treatment where in the opinion of a qualified medical
p.000023: practitioner attending him, he is capable of understanding the nature and possible consequences of the procedure or
p.000023: treatment." 30 Interpretation of Scottish law has been that a young person's competency allows them to refuse as well
p.000023: as consent to treatment.
p.000023: It is not entirely clear whether this Scottish statute covers consent to participate in research, but as discussed
p.000023: above, in the absence of law dealing specifically with research, the principles of Scottish law relating to consent to
p.000023: procedures and
p.000023: treatment might reasonably be applied. At the same time, it is vital to recognise that the threshold for understanding
p.000023: will relate to the complexity of the research being undertaken.
p.000023:
p.000023: Additional protection for children participating in clinical trials
p.000023: The Medicines for Human Use (Clinical Trials) Regulations 2004 have been law since they came into force on 1 May 2004
p.000023: and regulate trials in the UK.26 These regulations transpose European Union Directive 2001/20/EC into UK law.31 The
p.000023: Regulations offer additional protection for a minor (a person under the age of 16 years) who is being considered for a
...
p.000031: the child.
p.000031: *** The researcher must obtain the permission of the parent/guardian in accordance with local laws or established
p.000031: procedures eg, in the UK participation of a minor in a clinical trial requires parental consent under The Medicines for
p.000031: Human Use (Clinical Trials) Regulations (2004).
p.000031:
p.000031: NO their child in the
p.000031: research?
p.000031: Does the child
p.000031: NO actively object?
p.000031: respected
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Is the child believed to
p.000031: be competent to consent to the proposed treatment?
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: YES
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Does the competent child consent to participation?
p.000031:
p.000031: YES
p.000031:
p.000031: Does the child assent? ie, knowingly agree
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031: The child's opinion should be respected. Research should not go ahead *
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Is the child happy to involve the parents?
p.000031:
p.000031: YES
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031: Research can go ahead, the child has assented and parents’ consent obtained
p.000031:
p.000031:
p.000031:
p.000031: The child should be persuaded to involve the parents. Research can go ahead, as the child is competent ***
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Do the parents assent to the participation of their child in the research?
p.000031:
p.000031: Does the child need treatment that is not available outside the context of the research, does the investigation show
p.000031: promise of therapeutic benefit and is there no acceptable alternative therapy?
p.000031:
p.000031: YES
p.000031:
p.000031:
p.000031: The competent child's consent is sufficient – research could go ahead. However, if parents do not assent it may be
p.000031: unwise
p.000031: to proceed
p.000031:
p.000031:
...
p.000033: available from the Department of Health, the British Medical Association and the General Medical Council.3, 4, 39
p.000033:
p.000033: 5.3 Ethics committee review
p.000033: The Council of Europe Protocol to the Convention on Human Rights and Biomedicine on Biomedical Research provides
p.000033: guidance regarding the role of the ethics committee in research.9 According to this guidance, every research project
p.000033: must be submitted for independent examination of its scientific merit, including assessment of the importance of the
p.000033: aim of research and ethical acceptability to an
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000035: 35
p.000035:
p.000035: MRC Ethics Guide: Medical research involving children
p.000035: MRC Ethics Guide: Medical research involving children
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: ethics committee. An examination of the ethical acceptability is necessary to protect the dignity, rights, safety and
p.000035: wellbeing of the research participant. The assessment should draw on an appropriate range of expertise adequately
p.000035: reflecting professional and lay views, therefore a professional opinion should be sought for any research involving
p.000035: children. The ethics committee must be satisfied that dependent persons and vulnerable groups will not be subjected to
p.000035: undue influence.
p.000035: Whilst the Council of Europe protocol is a legal instrument, it has not so far been transposed into UK law. However,
p.000035: the Medicines for Human Use (Clinical Trials) Regulations 2004, which transpose Directive 2001/20/EC into UK law,
p.000035: require that an ethics committee considering a trial involving minors must receive advice on the relevant field of
p.000035: paediatric care.29, 30 A "minor" is defined as a person under the age of 16.
p.000035:
p.000035: 5.4 Children's safety in relation to researchers
p.000035: Any individual recruited by the MRC to work directly with children will undergo security screening, including criminal
p.000035: records review. This includes nurses, survey interviewers and some individuals involved in a clinically invasive
p.000035: capacity, eg, phlebotomists. The MRC expects its grant-holding institutions to do likewise.
p.000035: Security screening is complementary to other good recruitment practices and not a substitute for them. Staff involved
...
General/Other / Dependent
Searching for indicator dependent:
(return to top)
p.000017: Participation in more than one research study: as with adults, there may be situations where it could be argued that
p.000017: participation in more than one trial or study might be potentially beneficial – both for participants and for the
p.000017: research. The potential benefits and risks of doing so would need to be carefully explored by all concerned, and
p.000017: clearly understood by the child and family.24
p.000017: Equipoise: this is when there is genuine uncertainty among those who have considered the issue, including patients,
p.000017: about the relative benefits and risks of treatments or tests being compared. A clinical trial cannot be ethical unless
p.000017: there is this genuine informed uncertainty among the expert medical community and in an informed competent
p.000017: patient/participant.
p.000017: 4.3.2 Minimising risk
p.000017: The National Academy of the Sciences provides guidance on how to minimise risk, summarised here: 25
p.000017:
p.000017: Minimising risk in research involving children
p.000017:
p.000017: • Is inclusion of children necessary to answer the scientific question posed by the research? What are the ages
p.000017: of the children to be included? Are any of the potential research harms age-dependent?
p.000017: • Will potential child participants be screened for known vulnerability to the risks associated with specific
p.000017: elements of the research?
p.000017: • What does the research require of children and their families? Is adherence to the research protocol a
p.000017: concern? If so, what are the risks of non-adherence?
p.000017: • Are all the procedures or interventions necessary to answer the research question? Can the investigators
p.000017: collect the required information using procedures that the child participants will undergo as part of their normal
p.000017: therapy or monitoring?
p.000017: • Have previous laboratory studies, animal research, studies with adults, or other data provided a sufficient
p.000017: basis for proceeding with research involving children?
p.000017: • Does the study follow principles of sound research design?
p.000017:
p.000017: • What are the theoretical risks involved with the research as proposed? Are data available to estimate the
p.000017: probability and magnitude of each risk as they relate to the categories of children to be included?
p.000017: • Have the investigators provided data on the frequency of adverse events for the procedures at the site in
p.000017: question? For example, sedation for research procedures.
p.000017: Continued...
p.000017:
p.000017:
p.000017:
p.000018: 18
p.000018:
p.000019: 19
p.000019:
...
p.000033:
p.000033: 5.3 Ethics committee review
p.000033: The Council of Europe Protocol to the Convention on Human Rights and Biomedicine on Biomedical Research provides
p.000033: guidance regarding the role of the ethics committee in research.9 According to this guidance, every research project
p.000033: must be submitted for independent examination of its scientific merit, including assessment of the importance of the
p.000033: aim of research and ethical acceptability to an
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000035: 35
p.000035:
p.000035: MRC Ethics Guide: Medical research involving children
p.000035: MRC Ethics Guide: Medical research involving children
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: ethics committee. An examination of the ethical acceptability is necessary to protect the dignity, rights, safety and
p.000035: wellbeing of the research participant. The assessment should draw on an appropriate range of expertise adequately
p.000035: reflecting professional and lay views, therefore a professional opinion should be sought for any research involving
p.000035: children. The ethics committee must be satisfied that dependent persons and vulnerable groups will not be subjected to
p.000035: undue influence.
p.000035: Whilst the Council of Europe protocol is a legal instrument, it has not so far been transposed into UK law. However,
p.000035: the Medicines for Human Use (Clinical Trials) Regulations 2004, which transpose Directive 2001/20/EC into UK law,
p.000035: require that an ethics committee considering a trial involving minors must receive advice on the relevant field of
p.000035: paediatric care.29, 30 A "minor" is defined as a person under the age of 16.
p.000035:
p.000035: 5.4 Children's safety in relation to researchers
p.000035: Any individual recruited by the MRC to work directly with children will undergo security screening, including criminal
p.000035: records review. This includes nurses, survey interviewers and some individuals involved in a clinically invasive
p.000035: capacity, eg, phlebotomists. The MRC expects its grant-holding institutions to do likewise.
p.000035: Security screening is complementary to other good recruitment practices and not a substitute for them. Staff involved
p.000035: in MRC's recruitment process are responsible for ensuring that standard checks are still made.
p.000035:
p.000035: 5.5 Specific situations
p.000035:
p.000035: 5.5.1 Research involving human material
p.000035: Please refer to the MRC guidance Human tissue and biological samples for use in research.12
...
General/Other / Impaired Autonomy
Searching for indicator autonomy:
(return to top)
p.000007: Current ethical principles for conducting research involving children have evolved from the Nuremberg Code which
p.000007: emerged after the Second World War. The Code set out statements of moral, ethical and legal principles relating to
p.000007: research involving human subjects, and included a bar on research involving children. Research was seen as a potential
p.000007: harm from which vulnerable people should be protected. Later, in 1964, the Declaration of Helsinki, drawn up by the
p.000007: World Medical Association, advised that research involving minors could be carried out where "the research is necessary
p.000007: to promote the health of the population represented and this research cannot instead be performed on legally competent
p.000007: persons" and appropriate consent and assent had been obtained.
p.000007: Today, organisations such as the Council for International Organizations of Medical Sciences play a vital part in
p.000007: considering how these ethical principles can be effectively applied. While research may have associated risks, it can
p.000007: also offer potential benefits to all participants, including children. Changes in the way we regard children include a
p.000007: growing recognition of the importance of listening to children's views and wishes, and of their autonomy. This can be
p.000007: observed in
p.000007:
p.000008: 8
p.000008:
p.000009: 9
p.000009:
p.000009: MRC Ethics Guide: Medical research involving children
p.000009: MRC Ethics Guide: Medical research involving children
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: attitudes towards research involving children. Earlier research tended to be on children, with children regarded as
p.000009: subjects of the research. Increasingly, research is conducted with children, who are involved as active participants.
p.000009:
p.000009: 3.2 Methodological challenges
p.000009: Smyth and Weindling describe how the emergence of evidence-based healthcare has led to a greater awareness of the need
p.000009: to evaluate critically what is already known before making recommendations for clinical practice or embarking on
p.000009: further research.14 Studies have shown that in comparison to research on adults, research questions relevant to the
p.000009: health of children may not have been addressed at all, or only by small, poorly designed studies.15
p.000009: Particular methodological challenges occur in research involving children. Childhood forms of many chronic diseases,
p.000009: eg, juvenile chronic arthritis, are uncommon and this may lead to difficulties in gaining statistical power to detect
p.000009: an effective treatment.
...
p.000013: benefits. To ensure that this vulnerable group are not exploited, the General Medical Council advises that it is
p.000013: important to assess carefully the potential benefits and harm to children at all stages of any research. As the
p.000013: benefits of research are not predictable, the researcher must be satisfied that the research is not contrary to the
p.000013: child participant's interests. The foreseeable risks should be kept as low as possible: the potential benefits from the
p.000013: development of treatments and furthering of knowledge must outweigh any foreseeable risks.22
p.000013:
p.000013: Risk - A potential harm; the characteristics of risk include the probability of its occurrence, as well as its
p.000013: magnitude and duration
p.000013:
p.000013: Risks may be estimated as minimal, low or high: i
p.000013:
p.000013: Minimal (the least possible) risk describes procedures such as questioning, observing, and measuring children, provided
p.000013: that procedures are carried out in a sensitive way, respecting the child's autonomy, and that consent has been given.
p.000013: Procedures with minimal risk include obtaining bodily fluids without invasive intervention, eg, taking saliva or urine
p.000013: samples. It is expected that research of minimal risk would not result in more than a very slight and temporary
p.000013: negative impact on the health of the person concerned.
p.000013: Low risk describes procedures that might cause no more than brief pain or tenderness, small bruises or scars, or very
p.000013: slight, temporary distress; eg, a blood test.
p.000013: High risk procedures such as lung or liver biopsy, arterial or lumbar puncture, and cardiac catheterisation are not
p.000013: justified for research purposes alone with children. They should be carried out only when research is combined with
p.000013: diagnosis or treatment intended to benefit the child concerned.
p.000013:
p.000013:
p.000013: i Adapted from RCPCH guidance and Council of Europe guidance.
p.000013:
p.000014: 14
p.000014:
p.000015: 15
p.000015:
p.000015: MRC Ethics Guide: Medical research involving children
p.000015: MRC Ethics Guide: Medical research involving children
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
...
General/Other / Incapacitated
Searching for indicator incapacitated:
(return to top)
p.000041:
p.000041: Risk
p.000041: A potential harm; the characteristics of risk include the probability of its occurrence, as well as its magnitude and
p.000041: duration. For more on assessment and minimising risk see 4.3.
p.000041:
p.000041: MRC Ethics Guide: Medical research involving children
p.000041: MRC Ethics Guide: Medical research involving children
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: 8. Other MRC ethics guidance
p.000041: The MRC produces a wide range of ethics guidance for researchers, which is available at www.mrc.ac.uk and includes the
p.000041: following:
p.000041: • MRC interim guidance on ethics of research involving human material derived from the nervous system (June 2003).
p.000041: • MRC policy on antiretroviral therapy (ART) for people infected with HIV and involved in AIDS research in
p.000041: developing countries – General guidance notes for consideration (2002).
p.000041: • MRC guidance on reviewing research proposals (2001).
p.000041:
p.000041: • Ethical conduct of research on the mentally incapacitated (1993) – to be revised following the introduction of
p.000041: English legislation. This guidance is no longer applicable in Scotland, following the introduction of the Adults with
p.000041: Incapacity (Scotland) Act 2000.
p.000041: • Good research practice (2000).
p.000041:
p.000041: • Personal information in medical research (2000) – also available as Executive Summary (2000). New guidance on
p.000041: Health and Social Care Act 2001: "Section 60" added – January 2003.
p.000041: • Human tissue and biological samples for use in research: operational and ethical guidelines (2001).
p.000041: • Policy and procedure for inquiring into allegations of scientific misconduct (1997).
p.000041: • Research involving human participants in developing societies: ethical guidelines for MRC-sponsored studies
p.000041: (2004).
p.000041: • Responsibility in the use of animals in medical research (1993).
p.000041:
p.000041: • The MRC's terms and conditions for research grants and training awards involving stem cells (2003).
p.000041: • Cluster randomised trials: Methodological and ethical considerations (2002).
p.000041:
p.000041: • MRC guidelines for good clinical practice in clinical trials (1998).
p.000041:
p.000041: • Health Technology Assessment in surgery (2003).
p.000041:
p.000041:
p.000041: Additional guidance available by post includes:
p.000041:
p.000041: • Principles in the assessment and conduct of medical research and publicising results (1995).
p.000041:
p.000041:
p.000041:
p.000044: 44
p.000044:
p.000045: 45
p.000045:
...
Searching for indicator incapacity:
(return to top)
p.000027: treatment if it is felt to be in the best interests of the child or young person.
p.000027:
p.000027: Scotland
p.000027: The Children (Scotland) Act 1995 37 makes provision for cases where a young person aged under 16 is not competent to
p.000027: give legally valid consent. Parental rights enabling parents to carry out parental responsibilities include
p.000027: "safeguarding and promoting the child's health, welfare and development, providing direction and guidance to the child
p.000027: in a manner appropriate to the stage of the child's development and acting as the child's legal representative." Most
p.000027: of these last until the young person is 16 years old or shows competency to make their own decisions. Interestingly, in
p.000027: this Act it is stated that a child of 12 years or more should be presumed to be of sufficient age and maturity to form
p.000027: a view. The parental responsibility to provide guidance continues until the young person is 18. Case law suggests that
p.000027: a parent cannot overrule the decision of a competent child; however this has not yet been added to statute.
p.000027: The Adults with Incapacity (Scotland) Act 2000 38 covers the treatment and welfare of people over the age of 16 who
p.000027: are unable to give consent.
p.000027: In the absence of case law dealing specifically with research, the principles applying to medical treatment in England,
p.000027: Wales, Scotland and Northern Ireland might reasonably be applied to research.
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000029: 29
p.000029:
p.000029: MRC Ethics Guide: Medical research involving children
p.000029: MRC Ethics Guide: Medical research involving children
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: 5.1.4.b Seeking legal advice
p.000029: Researchers should seek legal advice if in any doubt regarding authority to proceed.
p.000029:
p.000029: 5.1.5 How best to seek consent
p.000029: The RCPCH provides guidance on how best to seek consent: 2
p.000029:
p.000029:
p.000029: For consent to be freely given researchers must:
p.000029:
p.000029: • Offer families no financial inducement although expenses should be paid.
p.000029: • Exert no pressure on families.
p.000029: • Give them as much time as possible (a few days for a major study, if at all possible) to consider whether to take
p.000029: part in the project.
...
p.000041: duration. For more on assessment and minimising risk see 4.3.
p.000041:
p.000041: MRC Ethics Guide: Medical research involving children
p.000041: MRC Ethics Guide: Medical research involving children
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: 8. Other MRC ethics guidance
p.000041: The MRC produces a wide range of ethics guidance for researchers, which is available at www.mrc.ac.uk and includes the
p.000041: following:
p.000041: • MRC interim guidance on ethics of research involving human material derived from the nervous system (June 2003).
p.000041: • MRC policy on antiretroviral therapy (ART) for people infected with HIV and involved in AIDS research in
p.000041: developing countries – General guidance notes for consideration (2002).
p.000041: • MRC guidance on reviewing research proposals (2001).
p.000041:
p.000041: • Ethical conduct of research on the mentally incapacitated (1993) – to be revised following the introduction of
p.000041: English legislation. This guidance is no longer applicable in Scotland, following the introduction of the Adults with
p.000041: Incapacity (Scotland) Act 2000.
p.000041: • Good research practice (2000).
p.000041:
p.000041: • Personal information in medical research (2000) – also available as Executive Summary (2000). New guidance on
p.000041: Health and Social Care Act 2001: "Section 60" added – January 2003.
p.000041: • Human tissue and biological samples for use in research: operational and ethical guidelines (2001).
p.000041: • Policy and procedure for inquiring into allegations of scientific misconduct (1997).
p.000041: • Research involving human participants in developing societies: ethical guidelines for MRC-sponsored studies
p.000041: (2004).
p.000041: • Responsibility in the use of animals in medical research (1993).
p.000041:
p.000041: • The MRC's terms and conditions for research grants and training awards involving stem cells (2003).
p.000041: • Cluster randomised trials: Methodological and ethical considerations (2002).
p.000041:
p.000041: • MRC guidelines for good clinical practice in clinical trials (1998).
p.000041:
p.000041: • Health Technology Assessment in surgery (2003).
p.000041:
p.000041:
p.000041: Additional guidance available by post includes:
p.000041:
p.000041: • Principles in the assessment and conduct of medical research and publicising results (1995).
p.000041:
p.000041:
p.000041:
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p.000045:
p.000045: MRC Ethics Guide: Medical research involving children
p.000045: MRC Ethics Guide: Medical research involving children
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
...
p.000045: the laws, regulations and administrative provisions of the Member States relating to the implementation of good
p.000045: clinical practice in the conduct of clinical trials on medicinal products for human use.
p.000045: http://europa.eu.int/eur-lex/pri/en/oj/dat/2001/l_121/l_12120010501en00340044.pdf
p.000045:
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p.000046: 46
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p.000047: 47
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p.000047:
p.000047: MRC Ethics Guide: Medical research involving children
p.000047:
p.000047:
p.000047:
p.000047:
p.000047:
p.000047: 32. Medicines and Healthcare products Regulatory Agency: Description of the Medicines for Human Use (Clinical
p.000047: Trials) Regulations 2004. http://medicines.mhra.gov.uk/ourwork/licensingmeds/types/ctdregs_shortdesc.pdf
p.000047: 33. Central Office for Research Ethics Committees. www.corec.org.uk
p.000047: 34. Seeking Consent:Working with children. Department of Health, 2001. www.dh.gov.uk/PublicationsAndStatistics/
p.000047: Publications/PublicationsPolicyAndGuidance/PublicationsPolicyAndGuidanceArticle/fs/en?CONTENT_ ID=4007005&chk=xFifXP
p.000047: 35. Children Act 1989 (c. 41). www.hmso.gov.uk
p.000047: 36. Children Act (Northern Ireland) Order 1995. www.northernireland-legislation.hmso.gov.uk
p.000047: 37. Children (Scotland) Act 1995. www.hmso.gov.uk
p.000047: 38. Adults with incapacity (Scotland) Act 2000. www.scotland-legislation.hmso.gov.uk
p.000047: 39. Confidentiality: protecting and providing information. London: General Medical Council, 2004.
p.000047: 40. Guidance safeguarding informed parental involvement in clinical research involving newborn babies and
p.000047: infants. London: Royal College of Paediatrics and Child Health, 1999.
p.000047: 41. Department of Health/MRC: Clinical Trials Toolkit. 2004. www.ct-toolkit.ac.uk
p.000047: 42. The Adoption and Children Act 2002. www.hmso.gov.uk/acts/acts2002/20020038.htm
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p.000047:
p.000047:
p.000047: Medical Research Council
p.000047: 20 Park Crescent London W1B 1AL
p.000047: Tel: 020 7636 5422 Fax: 020 7436 6179
p.000048: 48
p.000048: www.mrc.ac.uk
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General/Other / Public Emergency
Searching for indicator emergency:
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p.000001: 5.1.4 Assessing the competence of a child to consent 27
p.000001: 5.1.4.a Children unable to consent to involvement, and parental consent 28
p.000001: 5.1.4.b Seeking legal advice
p.000030: 30
p.000030: 5.1.5 How best to seek consent 30
p.000030: 5.1.6 Seeking consent – a summary 32
p.000030: 5.2 Confidentiality 34
p.000030: 5.3 Ethics committee review 35
p.000030: 5.4 Children's safety in relation to researchers 36
p.000030: 5.5 Specific situations 36
p.000030: 5.5.1 Research involving human material 36
p.000030: 5.5.2 The use of personal information 37
p.000030: 5.5.3 Research involving very young children 37
p.000030: 5.5.4 Emergency situations 37
p.000030: 5.5.5 Including minority groups – equality in research 38
p.000030: 5.5.6 Research in developing countries 39
p.000030: 6. Summary 40
p.000030: 7. Glossary 41
p.000030: 8. Other MRC ethics guidance 44
p.000030: 9. References 46
p.000002: 2
p.000002:
p.000003: 3
p.000003:
p.000003: MRC Ethics Guide: Medical research involving children
p.000003: MRC Ethics Guide: Medical research involving children
p.000003:
p.000003:
p.000003:
p.000003: 1. Introduction
p.000003: 1.1 Purpose
p.000003: These guidelines are designed to be of use to researchers preparing proposals for MRC support for research involving
p.000003: children, and to those planning, undertaking or collaborating in such research. They will also be helpful to other
p.000003: researchers, and to doctors and other health professionals whose patients may be involved in research, to ethics
...
p.000019: MRC Ethics Guide: Medical research involving children
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019: Minimising risk in research involving children - Continued
p.000019:
p.000019: • Are the investigators and other members of the research team qualified to perform each of the procedures or
p.000019: assessments specified in the protocol and recognise potential risks and adverse outcomes? Does the research team have
p.000019: appropriate skills and expertise in caring for children of the ages included in the study?
p.000019: • Will research be performed in a setting that is 'friendly' to children of the ages included in the study? Is
p.000019: the setting appropriate for the physical, clinical, psychological and emotional needs of those age groups?
p.000019: • For research that involves more than minimal risk, does the research protocol have an adequate plan for
p.000019: monitoring the safety of the child participants? Does the monitoring plan provide for the inclusion of professionals
p.000019: with the appropriate expertise in paediatrics?
p.000019: • If the protocol presents the risk of a physical or psychological emergency, is the research setting equipped
p.000019: to respond? Are plans for responding to an emergency specified in the protocol?
p.000019: • What are the stopping rules or 'endpoints' for early discontinuation of the research on the basis of strong
p.000019: findings about harms or benefits? Are they specific and appropriate?
p.000019: • What happens to the data once they are collected? Where are research records stored, and who has access to
p.000019: them? What are the practices and procedures for maintaining the short-term and long-term confidentiality of the data?
p.000019: 5. Children, ethics and the law
p.000019:
p.000019: 5.1 Consent
p.000019:
p.000019: 5.1.1 What is valid consent?
p.000019:
p.000019: Consent – The voluntary agreement of an adult or competent child, based on adequate knowledge and understanding of
p.000019: relevant information, to participate in research
p.000019:
p.000019: Consent is legally valid and professionally acceptable only where the participants (or their parental guardian) are
p.000019: competent to give consent, have been properly informed, and have agreed without coercion.22
p.000019:
p.000019:
p.000019: In the UK, there are now two legal systems running in parallel.The common law applies to research not involving the
p.000019: Clinical Trials Regulations. As of May 2004, the Medicines for Human Use (Clinical Trials) Regulations apply to
...
p.000021: consent can be as valid as written consent for research, unless the Clinical Trials Regulations apply. It is vital that
p.000021: the person seeking consent records in writing that it has been given verbally. It may nevertheless be useful to obtain
p.000021: a signature from the participant or parent where this seems appropriate. It is important to note that under the
p.000021: Clinical Trials Regulations, verbal consent is not valid. The consent must be in writing unless the person giving
p.000021: consent is unable to write or otherwise mark the consent document.
p.000021: Informed consent is only one possible result of the informed choice process; the other possible result is the informed
p.000021: choice not to participate.
p.000021: Possible exceptions – Some research based on observation, on information collated from notes and tests already
p.000021: performed for therapeutic purposes, and public health research may be permissible without consent.2 Further
p.000021: information on the use of personal information in medical research is available from the MRC guidance Personal
p.000021: information in medical research.11
p.000021: Research linked to medical care in an emergency: the handling of this depends on whether the proposed study falls under
p.000021: the Clinical Trials Regulations. For further information please refer to 5.5.4.
p.000021:
p.000021: 5.1.3 Who can give consent, and who should you seek consent from?
p.000021: The law regarding the child's right to consent has developed differently in Scotland than in England, Wales and
p.000021: Northern Ireland – as outlined in 5.1.3a and 5.1.4a below. Generally, where children have sufficient understanding and
p.000021: intelligence to
p.000021: understand what is proposed, it is their consent and not that of their parent/guardian that is required by law.
p.000021: Ethically it is important to involve children as much as possible in decisions about their own health, wellbeing and
p.000021: healthcare. The United Nations Convention on the Rights of the Child states that the child has a right to be informed,
p.000021: to express a view and to influence a decision.27 Methods used to facilitate the consent process should be appropriate
...
p.000029: • The potential benefits and harms (both immediate and long-term).
p.000029: • The name of a researcher whom they can contact with their enquiries.
p.000029: • The name of the doctor directly responsible for the child's care.
p.000029: • How the child can withdraw from the project.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: Researchers must also:
p.000029:
p.000029: • Willingly explain and answer questions throughout the project.
p.000029: • Ensure that other staff caring for child subjects know about the research, and can also explain it if necessary.
p.000029: • Give clearly written patient information leaflets setting out all relevant information for families to keep
p.000029: (guidance on this can be found on the COREC website 33).
p.000029: • Report the results of research to the families involved wherever possible.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000030: 30
p.000030:
p.000031: 31
p.000031:
p.000031: MRC Ethics Guide: Medical research involving children
p.000031: MRC Ethics Guide: Medical research involving children
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 5.1.6 Seeking consent – a summaryiii
p.000031:
p.000031: If research is linked to medical care, it is justifiable in an emergency to start treatment prior to consent being
p.000031: obtained **
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Do the parents consent to the participation of
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: YES NO
p.000031:
p.000031: Is emergency treatment required where treatment is available only as part of a research programme?
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Research cannot go ahead. Parental consent MUST be obtained
p.000031:
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031: Research can go ahead Research cannot go ahead
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Research can go ahead with parental consent
p.000031:
p.000031:
p.000031: NO
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
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p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: Even if the parents have given their consent, the deliberate objection of the child should be
p.000031: * In England, Wales and Northern Ireland parents may overule the child's decision if it is felt to be in the best
p.000031: interests of the child.
p.000031: ** Where parents refuse to give their consent, the courts can overrule if it is felt to be in the best interests of
p.000031: the child.
...
p.000035: records review. This includes nurses, survey interviewers and some individuals involved in a clinically invasive
p.000035: capacity, eg, phlebotomists. The MRC expects its grant-holding institutions to do likewise.
p.000035: Security screening is complementary to other good recruitment practices and not a substitute for them. Staff involved
p.000035: in MRC's recruitment process are responsible for ensuring that standard checks are still made.
p.000035:
p.000035: 5.5 Specific situations
p.000035:
p.000035: 5.5.1 Research involving human material
p.000035: Please refer to the MRC guidance Human tissue and biological samples for use in research.12
p.000035: Further guidance will be issued when the Human Tissue Bill, and equivalent legislation in Scotland, become law.
p.000035: 5.5.2 The use of personal information
p.000035: Please refer to the MRC guidance Personal information in medical research.11
p.000035:
p.000035: 5.5.3 Research involving very young children
p.000035: A parent/guardian's informed consent is necessary for the involvement of babies in research. When a baby is seriously
p.000035: ill and a decision about treatment is required quickly, the pressure on parents is high and the difficulty of obtaining
p.000035: truly informed consent is recognised. The RCPCH provides detailed guidance relating to research involving babies.40
p.000035:
p.000035: 5.5.4 Emergency situations
p.000035: Under common law, provided that the specific approval of a research ethics committee has been obtained for the project
p.000035: overall, it is ethical to carry out research involving children on occasions of extreme urgency without obtaining prior
p.000035: consent. However, there is a lack of clarity in the law about this if the research does not have the potential to
p.000035: benefit the child in question. If in doubt, it would be advisable to seek legal advice in potentially contentious
p.000035: circumstances.
p.000035: Research involving children in an emergency situation may be needed when treatment is available only as part of a
p.000035: research programme. Ethically, if the research does not have the potential to produce results of direct benefit to the
p.000035: individual participant, the Council of Europe recommends that it should only be carried out if it has the aim of
p.000035: contributing or improving understanding of the individual's condition so that it could ultimately confer benefit upon
p.000035: the patient or others with the same condition, and that it entails only minimal risk.9
p.000035: Research involving children in emergency situations should be carried out only where research of comparable
p.000035: effectiveness cannot be carried out on persons in non- emergency situations. The parents and child must be informed
p.000035: about the research as
p.000035:
p.000036: 36
p.000036:
p.000037: 37
p.000037:
p.000037: MRC Ethics Guide: Medical research involving children
p.000037: MRC Ethics Guide: Medical research involving children
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037: soon as possible afterwards and their consent for future involvement sought. It must be made clear that the child (or
p.000037: parent on behalf of a child not yet competent) can withdraw from the study at any point.
p.000037: The Council of Europe provide further guidance on research in emergency clinical situations.9
p.000037: Under the Clinical Trial Regulations, consent must be given on behalf of a minor prior to participation in a trial of
p.000037: an investigational medicinal product in all circumstances; there is currently no exception for emergency situations.
p.000037: However, it is possible for someone other than a parent to give consent as a “legal representative”, if the parent is
p.000037: unable to do so. This could be the doctor primarily responsible for the person’s treatment (if not involved in the
p.000037: trial) or, if they are not available, a person nominated by the healthcare provider.41
p.000037:
p.000037: 5.5.5 Including minority groups – equality in research
p.000037: As with adults it is important to include minority groups in research involving children to ensure that they as a group
p.000037: receive a share of the potential benefits of research.
p.000037: Researchers should be sensitive to cultural issues and particularly to participants' specific concerns and values. For
p.000037: example, whether acceptance of research is necessary from someone in the extended cultural group as well as the
p.000037: immediate family, or whether participants undertake religious fasts that may affect when they can take medicines.
p.000037: When seeking consent where the child or parent needs an interpreter, an independent interpreter is preferable to a
...
p.000037: 5.5.6 Research in developing countries
p.000037: Please refer to MRC guidance on Research involving human participants in developing societies.
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000039: 39
p.000039:
p.000039: MRC Ethics Guide: Medical research involving children
p.000039: MRC Ethics Guide: Medical research involving children
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: 6. Summary
p.000039: Children should be included in medical research only if:
p.000039:
p.000039: • The relevant knowledge cannot be gained through research with adults.
p.000039:
p.000039: • It is approved by the appropriate Research Ethics Committee/s.
p.000039:
p.000039: • Either the participant has given consent where competent, or consent has been given on his or her behalf by a
p.000039: parent or guardian and the participant does not object or appear to object in either words or actions. iv
p.000039:
p.000039:
p.000039:
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p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: iv See 5.5.4 for guidance on emergency situations, when this might not be possible.
p.000039: 7. Glossary
p.000039: The definitions provided here apply as they are used in the above guidelines.
p.000039:
p.000039: Assent
p.000039: A child's affirmative agreement to participate. Failure to object should not be construed as assent.
p.000039: Burden of disease
p.000039: The impact of disease on the individual and on society due to loss of duration and quality of life. Measures include
p.000039: (i) 'morbidity burden', ie, the prevalence of a condition, the range of its severity and the age distribution of the
p.000039: population suffering from the condition, and (ii) the financial burden to society in meeting the obligation to support
p.000039: the individual; for example, in terms of net public expenditure on health services and on social services.
p.000039: Child
p.000039: In the UK, a person under the age of 18. "Young person" is a term often used to describe older children in this age
p.000039: group. The competence of children to consent is discussed in Section 5.
p.000039: Clinical Trials Regulations
p.000039: The Medicines for Human Use (Clinical Trials) Regulations apply to research involving investigational medicinal
p.000039: products (see below). In such studies, informed consent is strictly defined as follows and only consent meeting this
p.000039: definition will suffice:
...
General/Other / Relationship to Authority
Searching for indicator authority:
(return to top)
p.000027: this Act it is stated that a child of 12 years or more should be presumed to be of sufficient age and maturity to form
p.000027: a view. The parental responsibility to provide guidance continues until the young person is 18. Case law suggests that
p.000027: a parent cannot overrule the decision of a competent child; however this has not yet been added to statute.
p.000027: The Adults with Incapacity (Scotland) Act 2000 38 covers the treatment and welfare of people over the age of 16 who
p.000027: are unable to give consent.
p.000027: In the absence of case law dealing specifically with research, the principles applying to medical treatment in England,
p.000027: Wales, Scotland and Northern Ireland might reasonably be applied to research.
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
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p.000029: 29
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p.000029: MRC Ethics Guide: Medical research involving children
p.000029: MRC Ethics Guide: Medical research involving children
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: 5.1.4.b Seeking legal advice
p.000029: Researchers should seek legal advice if in any doubt regarding authority to proceed.
p.000029:
p.000029: 5.1.5 How best to seek consent
p.000029: The RCPCH provides guidance on how best to seek consent: 2
p.000029:
p.000029:
p.000029: For consent to be freely given researchers must:
p.000029:
p.000029: • Offer families no financial inducement although expenses should be paid.
p.000029: • Exert no pressure on families.
p.000029: • Give them as much time as possible (a few days for a major study, if at all possible) to consider whether to take
p.000029: part in the project.
p.000029: • Encourage families to discuss the project with – for example – their relatives, primary health carers – or an
p.000029: independent counsellor where available.
p.000029: • Tell them that they may refuse to take part, or may withdraw at any time even if they have signed a consent form.
p.000029: • Say that they need not give a reason for withdrawing (although their reason may help the researchers and other
p.000029: children in the study).
p.000029: • Assure them that the child patient's treatment will not be prejudiced by withdrawal from research.
p.000029: • Encourage parents/guardians to stay with the child during procedures.
p.000029: • Respond to families' questions, anxiety or distress throughout the study.
p.000029:
p.000029: For consent to be informed researchers must discuss with families:
p.000029:
p.000029: • The purpose of the research.
...
General/Other / Undue Influence
Searching for indicator undue influence:
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p.000033: guidance regarding the role of the ethics committee in research.9 According to this guidance, every research project
p.000033: must be submitted for independent examination of its scientific merit, including assessment of the importance of the
p.000033: aim of research and ethical acceptability to an
p.000033:
p.000033:
p.000034: 34
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p.000035: MRC Ethics Guide: Medical research involving children
p.000035: MRC Ethics Guide: Medical research involving children
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: ethics committee. An examination of the ethical acceptability is necessary to protect the dignity, rights, safety and
p.000035: wellbeing of the research participant. The assessment should draw on an appropriate range of expertise adequately
p.000035: reflecting professional and lay views, therefore a professional opinion should be sought for any research involving
p.000035: children. The ethics committee must be satisfied that dependent persons and vulnerable groups will not be subjected to
p.000035: undue influence.
p.000035: Whilst the Council of Europe protocol is a legal instrument, it has not so far been transposed into UK law. However,
p.000035: the Medicines for Human Use (Clinical Trials) Regulations 2004, which transpose Directive 2001/20/EC into UK law,
p.000035: require that an ethics committee considering a trial involving minors must receive advice on the relevant field of
p.000035: paediatric care.29, 30 A "minor" is defined as a person under the age of 16.
p.000035:
p.000035: 5.4 Children's safety in relation to researchers
p.000035: Any individual recruited by the MRC to work directly with children will undergo security screening, including criminal
p.000035: records review. This includes nurses, survey interviewers and some individuals involved in a clinically invasive
p.000035: capacity, eg, phlebotomists. The MRC expects its grant-holding institutions to do likewise.
p.000035: Security screening is complementary to other good recruitment practices and not a substitute for them. Staff involved
p.000035: in MRC's recruitment process are responsible for ensuring that standard checks are still made.
p.000035:
p.000035: 5.5 Specific situations
p.000035:
p.000035: 5.5.1 Research involving human material
p.000035: Please refer to the MRC guidance Human tissue and biological samples for use in research.12
p.000035: Further guidance will be issued when the Human Tissue Bill, and equivalent legislation in Scotland, become law.
p.000035: 5.5.2 The use of personal information
...
General/Other / declaration of helsinki
Searching for indicator helsinki:
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p.000007: understanding adult diseases thought to have their origins in early life will be hampered, limiting the possibilities
p.000007: of preventive intervention.
p.000007: 3. What has limited research so far, and what are the challenges?
p.000007: Progress in research involving children has been limited primarily by:
p.000007:
p.000007: • Difficulty in reaching consensus about including children in research.
p.000007:
p.000007: • Methodological challenges.
p.000007:
p.000007: • Expense of developing new treatments.
p.000007:
p.000007: • Lack of legal enforcement for paediatric versions of drugs.
p.000007:
p.000007: 3.1 Difficulty in reaching consensus about including children in research
p.000007: Current ethical principles for conducting research involving children have evolved from the Nuremberg Code which
p.000007: emerged after the Second World War. The Code set out statements of moral, ethical and legal principles relating to
p.000007: research involving human subjects, and included a bar on research involving children. Research was seen as a potential
p.000007: harm from which vulnerable people should be protected. Later, in 1964, the Declaration of Helsinki, drawn up by the
p.000007: World Medical Association, advised that research involving minors could be carried out where "the research is necessary
p.000007: to promote the health of the population represented and this research cannot instead be performed on legally competent
p.000007: persons" and appropriate consent and assent had been obtained.
p.000007: Today, organisations such as the Council for International Organizations of Medical Sciences play a vital part in
p.000007: considering how these ethical principles can be effectively applied. While research may have associated risks, it can
p.000007: also offer potential benefits to all participants, including children. Changes in the way we regard children include a
p.000007: growing recognition of the importance of listening to children's views and wishes, and of their autonomy. This can be
p.000007: observed in
p.000007:
p.000008: 8
p.000008:
p.000009: 9
p.000009:
p.000009: MRC Ethics Guide: Medical research involving children
p.000009: MRC Ethics Guide: Medical research involving children
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: attitudes towards research involving children. Earlier research tended to be on children, with children regarded as
...
p.000011: If the answer to any of these questions is yes, children may ethically be involved in this research, and may benefit
p.000011: from it.
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000013: 13
p.000013:
p.000013: MRC Ethics Guide: Medical research involving children
p.000013: MRC Ethics Guide: Medical research involving children
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013: When a choice of age groups is possible, older children should be involved in preference to younger ones, although some
p.000013: research questions are specific to younger children and babies.2
p.000013:
p.000013: 4.2 Use of terms 'therapeutic' and 'non-therapeutic' research
p.000013: The distinction drawn previously between therapeutic and non-therapeutic research is now regarded by many as unhelpful
p.000013: and potentially misleading. For example, clinical trials that involve medicines include both therapeutic elements – the
p.000013: medicine being given – and non-therapeutic ones – the taking of a blood sample.
p.000013: Moreover, the term therapeutic can cause confusion if it raises hopes of success whereas the outcome of the research
p.000013: may not provide a treatment that benefits the individual participant. Indeed, some 'therapeutic' research has been
p.000013: considered to be more hazardous than 'non-therapeutic' research. Consequently, the Declaration of Helsinki (2000) no
p.000013: longer uses these terms, setting out instead basic principles for all medical research and additional ones for research
p.000013: combined with medical care.
p.000013: The guidelines from the RCPCH published in 2000 likewise avoid drawing this distinction, highlighting instead the
p.000013: principles that research involving children is important for the benefit of all children, and that a research procedure
p.000013: which cannot directly benefit the child is not necessarily unethical if the findings might benefit future generations
p.000013: of children. Research where there is no benefit to the individual child participant would have to be of minimal risk.
p.000013: This is a major step forward in thinking. The expectation is that children can now begin to reap the benefits of
p.000013: research designed with children in mind.
p.000013: 4.3 Benefit, harm and risk
p.000013: In the past, the concern to protect children from the potential harms of research may have denied them potential
p.000013: benefits. To ensure that this vulnerable group are not exploited, the General Medical Council advises that it is
...
p.000041:
p.000041:
p.000044: 44
p.000044:
p.000045: 45
p.000045:
p.000045: MRC Ethics Guide: Medical research involving children
p.000045: MRC Ethics Guide: Medical research involving children
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045: 9. References
p.000045: 1. The ethical conduct of research on children. London: Medical Research Council (MRC), 1991.
p.000045: 2. Royal College of Paediatrics and Child Health: Ethics Advisory Committee. 2002. "Guidelines for the ethical
p.000045: conduct of medical research involving children". Reprinted from Archives of Disease in Childhood 82 (2): 177-182.
p.000045: 3. Department of Health: Consent guidance webpages. www.dh.gov.uk/PolicyAndGuidance/
p.000045: HealthAndSocialCareTopics/Consent/ConsentGeneralInformation/fs/en
p.000045: 4. Consent, rights and choices in healthcare for children and young people. London: British Medical
p.000045: Association, 2001.
p.000045: 5. International ethical guidelines for biomedical research involving human subjects. Geneva: Council for
p.000045: International Organizations of Medical Sciences, 2002.
p.000045: 6. Declaration of Helsinki: ethical principles for medical research involving human subjects. Amended by the
p.000045: 52nd World Medical Association (WMA) General Assembly. Ferney-Voltaire:WMA, 2000.
p.000045: 7. International Guidelines for ethical review of epidemiological studies. Geneva: Council for International
p.000045: Organizations of Medical Sciences, 1991.
p.000045: 8. MRC guidelines for good clinical practice in clinical trials. London: MRC, 1998.
p.000045: 9. Additional protocol to the Convention on Human Rights and Biomedicine on Biomedical Research. Strasbourg:
p.000045: Council of Europe, 2004.
p.000045: 10. Declaration of professional ethics.Voorburg: International Statistical Institute, 1985.
p.000045: www.cbs.nl/isi/ethics.htm
p.000045: 11. Personal information in medical research. London: MRC, 2000.
p.000045: 12. Human tissue and biological samples for use in research: operational and ethical guidelines. London: MRC,
p.000045: 2001.
p.000045: 13. Stiller C., Quinn M., Rowan S. 2004. "Childhood cancer". In: The health of children and young people, chapter
p.000045: 13. Office for National Statistics. www.statistics.gov.uk/children/downloads/child_cancer.pdf
p.000045: 14. Smyth R.L.,Weindling A.M. 1999. "Research in children: ethical and scientific aspects". Lancet 354 (suppl
p.000045: II): 21-24.
p.000045: 15. Campbell H., Surry S.A.M., Royle E.M. 1998. "A review of randomised controlled trials published in Archives
p.000045: of Disease in Childhood from 1982-96." Archives of Disease in Childhood 79: 192-197.
...
General/Other / participants in a control group
Searching for indicator placebo:
(return to top)
p.000029:
p.000029: • Offer families no financial inducement although expenses should be paid.
p.000029: • Exert no pressure on families.
p.000029: • Give them as much time as possible (a few days for a major study, if at all possible) to consider whether to take
p.000029: part in the project.
p.000029: • Encourage families to discuss the project with – for example – their relatives, primary health carers – or an
p.000029: independent counsellor where available.
p.000029: • Tell them that they may refuse to take part, or may withdraw at any time even if they have signed a consent form.
p.000029: • Say that they need not give a reason for withdrawing (although their reason may help the researchers and other
p.000029: children in the study).
p.000029: • Assure them that the child patient's treatment will not be prejudiced by withdrawal from research.
p.000029: • Encourage parents/guardians to stay with the child during procedures.
p.000029: • Respond to families' questions, anxiety or distress throughout the study.
p.000029:
p.000029: For consent to be informed researchers must discuss with families:
p.000029:
p.000029: • The purpose of the research.
p.000029: • Whether the child stands to benefit directly and if so how; the difference between research and treatment.
p.000029: • The meaning of relevant research terms and any implications of consent (eg, placebo, randomised double-blind
p.000029: trial).
p.000029: • The nature of each procedure, how often and for how long each may occur.
p.000029: • The potential benefits and harms (both immediate and long-term).
p.000029: • The name of a researcher whom they can contact with their enquiries.
p.000029: • The name of the doctor directly responsible for the child's care.
p.000029: • How the child can withdraw from the project.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: Researchers must also:
p.000029:
p.000029: • Willingly explain and answer questions throughout the project.
p.000029: • Ensure that other staff caring for child subjects know about the research, and can also explain it if necessary.
p.000029: • Give clearly written patient information leaflets setting out all relevant information for families to keep
p.000029: (guidance on this can be found on the COREC website 33).
p.000029: • Report the results of research to the families involved wherever possible.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000030: 30
p.000030:
p.000031: 31
p.000031:
p.000031: MRC Ethics Guide: Medical research involving children
p.000031: MRC Ethics Guide: Medical research involving children
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 5.1.6 Seeking consent – a summaryiii
p.000031:
...
p.000041:
p.000041: Confidentiality
p.000041: The duty of persons to whom personal information has been given not to share the information with any unauthorised
p.000041: person. For more information about what this involves in practice, see 5.2.
p.000041:
p.000041: Competence
p.000041: The ability of a person, given the necessary information, to understand the nature and the consequences of the proposed
p.000041: procedure or treatment, and to use that information to make a valid choice in accordance with their own fundamental
p.000041: values. Please refer to 5.1.4.
p.000041:
p.000041: Consent
p.000041: The voluntary agreement of an adult or competent child, based on adequate knowledge and understanding of relevant
p.000041: information, to participate in research. For further information please refer to Section 5.
p.000041:
p.000041: Family
p.000041: A group of individuals who together form a social structure; a family may or may not include biological relatives.
p.000041:
p.000041:
p.000041: Harm
p.000041: That which adversely affects the interests or welfare of an individual. This may be physical harm, discomfort, anxiety,
p.000041: pain, and psychological
p.000041:
p.000041: disturbance or social disadvantage (ostracism).
p.000041:
p.000041: Investigational medicinal product
p.000041: A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial,
p.000041: including products already with a marketing authorisation but used or assembled (formulated or packaged) in a way
p.000041: different from the authorised form, or when used for an unauthorised indication, or when used to gain further
p.000041: information about the authorised form.31
p.000041:
p.000041: Off-label
p.000041: Term used to describe a medicine used for an indication, dose, or route of administration outside the terms of the
p.000041: product licence.
p.000041:
p.000041: Parent/guardian
p.000041: The term "parent/guardian" is used in these guidelines to describe those with legal responsibility for the child. The
p.000041: Children Act 1989, the Children (Scotland) Act 1995 and the Children (Northern Ireland) Order 1995 set out who has
p.000041: parental responsibility in their respective jurisdictions. The Adoption and Children Act 2002 s111(2) has recently
p.000041: extended the definition of those with legal responsibility for the child to include unmarried fathers who have entered
p.000041: into a legally binding Parental Responsibility Agreement.42
p.000041: The MRC is aware that some children will not be resident with both or either of their parents.
...
Orphaned Trigger Words
Appendix
Indicator List
| Indicator | Vulnerability |
|---|
| HIV | HIV/AIDS |
| access | Access to Social Goods |
| age | Age |
| authority | Relationship to Authority |
| autonomy | Impaired Autonomy |
| blind | visual impairment |
| child | Child |
| children | Child |
| cognitive | Cognitive Impairment |
| criminal | criminal |
| dependent | Dependent |
| disability | Mentally Disabled |
| drug | Drug Usage |
| emergency | Public Emergency |
| emergency situation | patients in emergency situations |
| family | Motherhood/Family |
| fathers | Fathers |
| healthy volunteers | Healthy People |
| helsinki | declaration of helsinki |
| ill | ill |
| illness | Physically Disabled |
| impaired | Cognitive Impairment |
| incapacitated | Incapacitated |
| incapacity | Incapacitated |
| influence | Drug Usage |
| mentally | Mentally Disabled |
| minor | Youth/Minors |
| minority | Racial Minority |
| opinion | philosophical differences/differences of opinion |
| parent | parents |
| parents | parents |
| party | political affiliation |
| placebo | participants in a control group |
| pregnant | Pregnant |
| religious | Religion |
| single | Marital Status |
| stem cells | stem cells |
| substance | Drug Usage |
| undue influence | Undue Influence |
| union | Trade Union Membership |
| unmarried | Marital Status |
| usage | Drug Usage |
| volunteers | Healthy People |
| vulnerability | vulnerable |
| vulnerable | vulnerable |
Indicator Peers (Indicators in Same Vulnerability)
| Indicator | Peers |
|---|
| child | ['children'] |
| children | ['child'] |
| cognitive | ['impaired'] |
| disability | ['mentally'] |
| drug | ['influence', 'substance', 'usage'] |
| healthy volunteers | ['volunteers'] |
| impaired | ['cognitive'] |
| incapacitated | ['incapacity'] |
| incapacity | ['incapacitated'] |
| influence | ['drug', 'substance', 'usage'] |
| mentally | ['disability'] |
| parent | ['parents'] |
| parents | ['parent'] |
| single | ['unmarried'] |
| substance | ['drug', 'influence', 'usage'] |
| unmarried | ['single'] |
| usage | ['drug', 'influence', 'substance'] |
| volunteers | ['healthyXvolunteers'] |
| vulnerability | ['vulnerable'] |
| vulnerable | ['vulnerability'] |
Trigger Words
capacity
coercion
consent
cultural
developing
ethics
harm
protect
protection
risk
sensitive
volunteer
welfare
Applicable Type / Vulnerability / Indicator Overlay for this Input