0A4F4F9BD490A749D5437F821CF06DF1
Guideline for Good Clinical Practice (GCP) E6 (R1)
https://www.sfda.gov.sa/en/drug/Clinical_Trials/Regulations%20Guidelines%20and%20Guidance/Guide_GCP_E6_R1.pdf
http://leaux.net/URLS/ConvertAPI Text Files/B0C2A7CFAF5FC061689B30C225C523EE.en.txt
Examining the file media/Synopses/B0C2A7CFAF5FC061689B30C225C523EE.html:
This file was generated: 2020-07-14 10:43:07
| 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 / nomad
Searching for indicator nomads:
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p.000010: Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics
p.000010: for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for
p.000010: Expedited Reporting).
p.000010:
p.000010: 1.61 Vulnerable Subjects
p.000010:
p.000010: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether
p.000010: justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a
p.000010: hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure,
p.000010: such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory
p.000010: personnel, employees of the
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects
p.000011: include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons,
p.000011: patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those
p.000011: incapable of giving consent.
p.000011: 1.62 Well-being (of the trial subjects)
p.000011:
p.000011: The physical and mental integrity of the subjects participating in a clinical trial.
p.000011:
p.000011:
p.000011:
p.000011:
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p.000012: 12
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2. THE PRINCIPLES OF ICH GCP
p.000012:
p.000012: 2.1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the
p.000012: Declaration of Helsinki, and that are consistent with GCP and the with SFDA requirement(s).
p.000012: 2.2 Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated
p.000012: benefit for the individual trial subject and society. A trial should be initiated and continued only if the
p.000012: anticipated benefits justify the risks.
p.000012: 2.3 The rights, safety, and well-being of the trial subjects are the most important
p.000012: considerations and should prevail over interests of science and society.
p.000012: 2.4 The available nonclinical and clinical information on an investigational product should be adequate to support
p.000012: the proposed clinical trial.
...
Political / political affiliation
Searching for indicator party:
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p.000003: An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial.
p.000003: 1.15 Compliance (in relation to trials)
p.000003: Adherence to all the trial-related requirements, Good Clinical Practice (GCP) requirements, and the SFDA requirements.
p.000003: 1.16 Confidentiality
p.000003:
p.000003: Prevention of disclosure, to other than authorized individuals, of a sponsor's proprietary information or of
p.000003: a subject's identity.
p.000003: 1.17 Contract
p.000003:
p.000003: A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on
p.000003: delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve
p.000003: as the basis of a contract.
p.000003: 1.18 Coordinating Committee
p.000003:
p.000003: A committee that a sponsor may organize to coordinate the conduct of a multicentre trial.
p.000003:
p.000003: 1.19 Coordinating Investigator
p.000003:
p.000003: An investigator assigned the responsibility for the coordination of investigators at different centres
p.000003: participating in a multicentre trial.
p.000003:
p.000004: 4
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004: 1.20 Contract Research Organization (CRO)
p.000004:
p.000004: A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or
p.000004: more of a sponsor's trial-related duties and functions.
p.000004: 1.21 Direct Access
p.000004: Permission to examine, analyze, verify, and reproduce any records and reports that are important to
p.000004: evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatory authorities, sponsor's
p.000004: monitors and auditors) with direct access should take all reasonable precautions within the constraints of the
p.000004: applicable regulatory requirement(s) to maintain the confidentiality of subjects' identities and sponsor’s proprietary
p.000004: information.
p.000004: 1.22 Documentation
p.000004:
p.000004: All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records, and
p.000004: scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a
p.000004: trial, the factors affecting a trial, and the actions taken.
p.000004: 1.23 Essential Documents
p.000004: Documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data
p.000004: produced (see 8. Essential Documents for the Conduct of a Clinical Trial).
p.000004: 1.24 Good Clinical Practice (GCP)
p.000004:
p.000004: A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical
p.000004: trials that provides assurance that the data and reported results are credible and accurate, and that the rights,
p.000004: integrity, and confidentiality of trial subjects are protected.
p.000004: 1.25 Independent Data-Monitoring Committee (IDMC) (Data and Safety Monitoring Board, Monitoring Committee, Data
p.000004: Monitoring Committee)
p.000004: An independent data-monitoring committee that may be established by the sponsor to assess at intervals the progress of
p.000004: a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to
p.000004: continue, modify, or stop a trial.
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000005: 5
p.000005:
p.000005:
...
p.000061: protocol or
p.000061: Investigator’s Brochure)
p.000061: To document instructions needed to ensure X X proper storage, packaging,
p.000061: dispensing and
p.000061: disposition of investigational products and trial-related materials
p.000061:
p.000061:
p.000061: 8.2.15 SHIPPING RECORDS FOR INVESTIGATIONAL PRODUCT(S) AND TRIAL-RELATED MATERIALS
p.000061: To document shipment dates, batch numbers X X and method of shipment of
p.000061: investigational
p.000061: product(s) and trial-related materials. Allows tracking of product batch, review of shipping conditions, and
p.000061: accountability
p.000061:
p.000061:
p.000061:
p.000061: 8.2.16 CERTIFICATE(S) OF ANALYSIS OF INVESTIGATIONAL PRODUCT(S) SHIPPED
p.000061: To document identity, purity, and strength of X investigational
p.000061: product(s) to be used in the
p.000061: trial
p.000061:
p.000061:
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p.000061:
p.000062: 62
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062: Title of Document Purpose
p.000062: Located in Files of
p.000062:
p.000062:
p.000062:
p.000062: Investigator/
p.000062: Institution
p.000062: Sponsor
p.000062:
p.000062:
p.000062: 8.2.17 DECODING PROCEDURES FOR BLINDED TRIALS
p.000062: To document how, in case of an emergency, identity of blinded investigational product can be revealed without breaking
p.000062: the blind for the remaining subjects' treatment
p.000062: X X
p.000062: (third party if applicable)
p.000062:
p.000062:
p.000062:
p.000062: 8.2.18 MASTER RANDOMISATION LIST
p.000062: To document method for randomisation of trial population
p.000062: X
p.000062: (third party if applicable)
p.000062:
p.000062:
p.000062: 8.2.19 PRE-TRIAL MONITORING REPORT
p.000062: To document that the site is suitable for the X trial (may
p.000062: be combined with 8.2.20)
p.000062:
p.000062:
p.000062:
p.000062: 8.2.20 TRIAL INITIATION
p.000062: MONITORING REPORT
p.000062: To document that trial procedures were X X reviewed
p.000062: with the investigator and the
p.000062: investigator’s trial staff ( may be combined with 8.2.19)
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000063: 63
p.000063:
p.000063:
p.000063:
p.000063:
p.000063:
p.000063: 8.3 During the Clinical Conduct of the Trial
p.000063: In addition to having on file the above documents, the following should be added to the files during the trial as
p.000063: evidence that all new relevant information is documented as it becomes available
p.000063:
p.000063: Title of Document Purpose
p.000063: Located in Files of
p.000063:
p.000063:
p.000063:
p.000063: Investigator/
p.000063: Institution
p.000063: Sponsor
p.000063:
p.000063: 8.3.1 INVESTIGATOR’S BROCHURE UPDATES To document that investigator is
p.000063: X X
p.000063: informed in a timely manner of relevant information as it becomes available
p.000063:
p.000063:
p.000063:
p.000063: 8.3.2 ANY REVISION TO:
p.000063: - protocol/amendment(s) and CRF
p.000063: - informed consent form
p.000063: - any other written information provided to subjects
p.000063: - advertisement for subject recruitment (if used)
...
Political / vulnerable
Searching for indicator vulnerable:
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p.000009:
p.000009:
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000010:
p.000010:
p.000010:
p.000010:
p.000010: 1.55 Standard Operating Procedures (SOPs)
p.000010:
p.000010: Detailed, written instructions to achieve uniformity of the performance of a specific function.
p.000010:
p.000010: 1.56 Subinvestigator
p.000010:
p.000010: Any individual member of the clinical trial team designated and supervised by the investigator at a trial site to
p.000010: perform critical trial-related procedures and/or to make important trial-related decisions (e.g., associates,
p.000010: residents, research fellows). See also Investigator.
p.000010: 1.57 Subject/Trial Subject
p.000010: An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or
p.000010: as a control.
p.000010: 1.58 Subject Identification Code
p.000010: A unique identifier assigned by the investigator to each trial subject to protect the subject's identity and used in
p.000010: lieu of the subject's name when the investigator reports adverse events and/or other trial related data.
p.000010: 1.59 Trial Site
p.000010:
p.000010: The location(s) where trial-related activities are actually conducted.
p.000010:
p.000010: 1.60 Unexpected Adverse Drug Reaction
p.000010:
p.000010: An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g.,
p.000010: Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics
p.000010: for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for
p.000010: Expedited Reporting).
p.000010:
p.000010: 1.61 Vulnerable Subjects
p.000010:
p.000010: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether
p.000010: justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a
p.000010: hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure,
p.000010: such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory
p.000010: personnel, employees of the
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects
p.000011: include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons,
p.000011: patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those
p.000011: incapable of giving consent.
p.000011: 1.62 Well-being (of the trial subjects)
p.000011:
p.000011: The physical and mental integrity of the subjects participating in a clinical trial.
p.000011:
p.000011:
p.000011:
p.000011:
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p.000012: 12
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2. THE PRINCIPLES OF ICH GCP
p.000012:
p.000012: 2.1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the
p.000012: Declaration of Helsinki, and that are consistent with GCP and the with SFDA requirement(s).
p.000012: 2.2 Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated
...
p.000012: 2.7 The medical care given to, and medical decisions made on behalf of, subjects should always be the
p.000012: responsibility of a qualified physician or, when appropriate, of a qualified dentist.
p.000012: 2.8 Each individual involved in conducting a trial should be qualified by education, training, and experience to
p.000012: perform his or her respective task(s).
p.000012: 2.9 Freely given informed consent should be obtained from every subject prior to clinical trial participation.
p.000012: 2.10 All clinical trial information should be recorded, handled, and stored in a way that allows its accurate
p.000012: reporting, interpretation and verification.
p.000012: 2.11 The confidentiality of records that could identify subjects should be protected.
p.000012: 2.12 Investigational products should be manufactured, handled, and stored in accordance with applicable good
p.000012: manufacturing practice (GMP). They should be used in accordance with the approved protocol.
p.000012: 2.13 Systems with procedures that assure the quality of every aspect of the trial should be implemented.
p.000012:
p.000013: 13
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013: 3. INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC)
p.000013: 3.1 Responsibilities
p.000013: 3.1.1 An IRB/IEC should safeguard the rights, safety, and well-being of all trial subjects. Special
p.000013: attention should be paid to trials that may include vulnerable subjects.
p.000013: 3.1.2 The IRB/IEC should obtain the following documents:
p.000013:
p.000013: trial protocol(s)/amendment(s), written informed consent form(s) and consent form updates that the investigator
p.000013: proposes for use in the trial, subject recruitment procedures (e.g. advertisements), written information to be
p.000013: provided to subjects, Investigator's Brochure (IB), available safety information, information about
p.000013: payments and compensation available to subjects, the investigator’s current curriculum vitae and/or other
p.000013: documentation evidencing qualifications, and any other documents that the IRB/IEC may need to fulfil its
p.000013: responsibilities.
p.000013: The IRB/IEC should review a proposed clinical trial within a reasonable time and document its views in
p.000013: writing, clearly identifying the trial, the documents reviewed and the dates for the following:
p.000013: - approval/favourable opinion;
p.000013:
p.000013: - modifications required prior to its approval/favourable opinion;
p.000013:
p.000013: - disapproval / negative opinion; and
p.000013:
p.000013: - termination/suspension of any prior approval/favourable opinion.
p.000013:
p.000013: 3.1.3 The IRB/IEC should consider the qualifications of the investigator for the proposed trial, as documented
p.000013: by a current curriculum vitae and/or by any other relevant documentation the IRB/IEC requests.
...
Health / Cognitive Impairment
Searching for indicator impaired:
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p.000049: described under the following headings where appropriate:
p.000049: − Single dose
p.000049:
p.000049: − Repeated dose
p.000049:
p.000049: − Carcinogenicity
p.000049:
p.000049: − Special studies (e.g. irritancy and sensitisation)
p.000049:
p.000049: − Reproductive toxicity
p.000049:
p.000049: − Genotoxicity (mutagenicity)
p.000049:
p.000049: 7.3.6 Effects in Humans Introduction:
p.000049: A thorough discussion of the known effects of the investigational product(s) in humans should be provided,
p.000049: including information on pharmacokinetics, metabolism, pharmacodynamics, dose response, safety,
p.000049: efficacy, and other pharmacological activities. Where possible, a summary of each completed clinical
p.000049: trial should be provided. Information should also be provided regarding results of any use of the
p.000049: investigational product(s) other than from in clinical trials, such as from experience during marketing.
p.000049: (a) Pharmacokinetics and Product Metabolism in Humans
p.000050: 50
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050: − A summary of information on the pharmacokinetics of the investigational product(s) should be presented, including the
p.000050: following, if available:
p.000050: − Pharmacokinetics (including metabolism, as appropriate, and absorption, plasma protein binding, distribution,
p.000050: and elimination).
p.000050: − Bioavailability of the investigational product (absolute, where possible, and/or relative) using a reference
p.000050: dosage form.
p.000050: − Population subgroups (e.g., gender, age, and impaired organ function).
p.000050:
p.000050: − Interactions (e.g., product-product interactions and effects of food).
p.000050:
p.000050: − Other pharmacokinetic data (e.g., results of population studies performed within clinical trial(s).
p.000050: (b) Safety and Efficacy
p.000050:
p.000050: A summary of information should be provided about the investigational product's/products'
p.000050: (including metabolites, where appropriate) safety, pharmacodynamics, efficacy, and dose
p.000050: response that were obtained from preceding trials in humans (healthy volunteers and/or patients).
p.000050: The implications of this information should be discussed. In cases where a number of clinical trials have been
p.000050: completed, the use of summaries of safety and efficacy across multiple trials by indications in subgroups
p.000050: may provide a clear presentation of the data. Tabular summaries of adverse drug reactions for all the clinical
p.000050: trials (including those for all the studied indications) would be useful. Important differences in adverse
p.000050: drug reaction patterns/incidences across indications or subgroups should be discussed.
p.000050: The IB should provide a description of the possible risks and adverse drug reactions to be anticipated on the basis of
p.000050: prior experiences with the product under investigation and with related products. A description should also be provided
p.000050: of the precautions or special monitoring to be done as part of the investigational use of the product(s).
p.000050: (c) Marketing Experience
p.000050:
...
Health / Drug Usage
Searching for indicator drug:
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p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Guideline for Good Clinical Practice (GCP) E6(R1)
p.000001:
p.000001: Adopted from International Council For Harmonisation of Technical Requirements for Registration of Pharmaceuticals for
p.000001: Human Use (ICH)
p.000001:
p.000001:
p.000001:
p.000001: Version 2.0
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Date of adoption 20/01/2013
p.000001:
p.000001: Date of implementation 20/04/2013
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: GUIDELINE FOR GOOD CLINICAL PRACTICE (GCP) E6(R1)
p.000001: Version 2.0
p.000001:
p.000001: Drug Sector
p.000001: Saudi Food & Drug Authority
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Please visit SFDA’s website at http://www.sfda.gov.sa/En/Drug for the latest update
p.000001:
p.000001:
p.000001:
p.000001: For Inquiries Inspection.Drug@sfda.gov.sa For Comments or Suggestions Drug.Comments@sfda.gov.sa
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: i
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Drug Sector Vision and Mission
p.000001:
p.000001: Vision
p.000001:
p.000001: To be the leading regional Drug Regulatory Authority for pharmaceuticals and cosmetic products, with professional
p.000001: excellence and services that contribute to the protection and advancement of public health in the Kingdom of Saudi
p.000001: Arabia.
p.000001: ةيؤرلا
p.000001:
p.000001: ةيماح في مهست ةيزتمم ةينهبم هتامدخ مدقيو ،ليمجتلا تاضرحت سمو ةيودلا لىع ةباقرلا في اً ييملقا اً دئار ءاولدا عاطق نوكي
p.000001: نأ
p.000001: .ةيدوعسلا ةيبرعلا ةكلملما في ةحصلا زيزعتو
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Mission
p.000001:
p.000001: Protecting public health by ensuring safety, quality, efficacy and accessibility of human, veterinary drugs and
p.000001: biological products, and safety of cosmetics, through administration of a national regulatory system which is
p.000001: consistent with international best practice. Through our mission, we also provide accurate and scientific-based
p.000001: information to the public and healthcare professionals.
p.000001: لةاسرلا
p.000001:
p.000001:
p.000001: داوم ةملاسو ةيويلحا تاجتنلماو ةيرطيبلاو ةيشربلا ةيودل
p.000001: ا رفوتو ةيلاعفو ةدوجو نامأ
p.000001: نماض للاخ نم ةماعلا ةحصلا ةيماح
p.000001:
p.000001: ةيملع سسأ
p.000001: لىع ةينبلما ةيئاولدا تامولعلما يمدقتو ةيلولدا تاسرمالما لضفأ
p.000001: عم قفاوتم ةباقرلل نيطو ماظن قيبطت برع ليمجتلا
p.000001: .ينيحصلا ينينهلماو ةماعلل
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: ii
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Document Control
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Version
p.000001:
p.000001:
p.000001: 1.1
p.000001:
p.000001: 1.2
p.000001: 1.2
p.000001: 1.3
p.000001: 1.3
p.000001:
p.000001:
p.000001: 2.0
p.000001: Author
p.000001:
p.000001:
p.000001: Clinical trial committee members
p.000001: Clinical trial dept. team Clinical trial dept. team Clinical trial dept. team Clinical trial dept. team GCP inspection
p.000001: dept. team
p.000001: Implementation Date
p.000001: Sep /2008
p.000001:
p.000001: Oct/2009 Jan/2010 Jan/2013 Apr/2013
p.000001:
p.000001: 5/12/2017
p.000001:
p.000001: Comments
p.000001:
p.000001: Initial draft for internal consultation
p.000001: Published for comments Final
p.000001: Published for comments Final
p.000001: This guideline replaces "Clinical Trials Requirements Guidelines".
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: iii
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: FOREWORD
p.000001:
p.000001: This guidance has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by
p.000001: the regulatory parties, in accordance with the ICH Process.
p.000001:
p.000001: In adopting this ICH guidance, Saudi Food and Drug Authority (SFDA) endorses the principles and practices
p.000001: described therein. This document should be read in conjunction with the accompanying notice and the relevant sections
p.000001: of other applicable guidances.
p.000001:
p.000001: Guidance documents are meant to provide assistance to industry and health care professionals on how to
p.000001: comply with the policies and governing statutes and regulations. They also serve to provide review and compliance
p.000001: guidance to staff, thereby ensuring that mandates are implemented in a fair, consistent and effective manner.
p.000001:
p.000001: Guidance documents are administrative instruments not having force of law and, as such, allow for flexibility in
p.000001: approach. Alternate approaches to the principles and practices described in this document may be acceptable
p.000001: provided they are supported by adequate scientific justification. Alternate approaches should be discussed in
p.000001: advance with the relevant program area to avoid the possible finding that applicable statutory or regulatory
p.000001: requirements have not been met.
p.000001:
p.000001: As a corollary to the above, it is equally important to note that SFDA reserves the right to request information or
p.000001: material, or define conditions not specifically described in this guidance, in order to allow the Department
p.000001: to adequately assess the safety, efficacy or quality of a therapeutic product. Saudi Food and Drug Authority is
p.000001: committed to ensuring that such requests are justifiable and that decisions are clearly documented.
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: iv
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Contents
p.000001: INTRODUCTION
p.000001: 1
p.000001: 1. GLOSSARY
p.000002: 2
p.000002: 2. THE PRINCIPLES OF ICH GCP
p.000013: 13
p.000013: 3. INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC)
p.000014: 14
p.000014: 3.1 Responsibilities
p.000014: 14
p.000014: 3.2 Composition, Functions and Operations
p.000015: 15
p.000015: 3.3 Procedures
p.000016: 16
p.000016: 3.4 Records
p.000017: 17
p.000017: 4. INVESTIGATOR
p.000017: 17
p.000017: 4.1 Investigator's Qualifications and Agreements
p.000017: 17
p.000017: 4.2 Adequate Resources
p.000018: 18
p.000018: 4.3 Medical Care of Trial Subjects
p.000018: 18
p.000018: 4.4 Communication with IRB/IEC
p.000019: 19
p.000019: 4.5 Compliance with Protocol
p.000019: 19
p.000019: 4.6 Investigational Product(s)
p.000020: 20
p.000020: 4.7 Randomization Procedures and Unblinding 21
p.000020: 4.8 Informed Consent of Trial Subjects
p.000021: 21
p.000021: 4.9 Records and Reports
p.000025: 25
p.000025: 4.10 Progress Reports
p.000026: 26
p.000026: 4.11 Safety Reporting
p.000027: 27
p.000027: 4.12 Premature Termination or Suspension of a Trial 27
p.000027: 4.13 Final Report(s) by Investigator
p.000028: 28
p.000028: 5. SPONSOR
p.000028: 28
p.000028: 5.1 Quality Assurance and Quality Control
p.000028: 28
p.000028: 5.2 Contract Research Organization (CRO)
p.000028: 28
p.000028: 5.3 Medical Expertise
p.000029: 29
p.000029: 5.4 Trial Design
p.000029: 29
p.000029: 5.5 Trial Management, Data Handling, and Record Keeping 29
p.000029: 5.6 Investigator Selection
p.000031: 31
p.000031: 5.7 Allocation of Responsibilities
p.000032: 32
p.000032: 5.8 Compensation to Subjects and Investigators
p.000032: 32
p.000032: v
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032: 5.9 Financing
p.000032: 32
p.000032: 5.10 Notification/Submission to Regulatory Authority(ies) 33
p.000032: 5.11 Confirmation of Review by IRB/IEC
p.000033: 33
p.000033: 5.12 Information on Investigational Product(s)
p.000033: 33
p.000033: 5.13 Manufacturing, Packaging, Labelling, and Coding Investigational Product(s) 34
p.000033: 5.14 Supplying and Handling Investigational Product(s) 34
p.000033: 5.15 Record Access
p.000036: 36
p.000036: 5.16 Safety Information
p.000036: 36
p.000036: 5.17 Adverse Drug Reaction Reporting
p.000036: 36
p.000036: 5.18 Monitoring
p.000036: 36
p.000036: 5.18.1 Purpose
p.000036: 36
p.000036: 5.18.2 Selection and Qualifications of Monitors 37
p.000036: 5.18.3 Extent and Nature of Monitoring
p.000037: 37
p.000037: 5.18.4 Monitor's Responsibilities
p.000037: 37
p.000037: 5.18.5 Monitoring Procedures
p.000040: 40
p.000040: 5.18.6 Monitoring Report
p.000040: 40
p.000040: 5.19 Audit
p.000040: 40
p.000040: 5.19.1 Purpose
p.000041: 41
p.000041: 5.19.2 Selection and Qualification of Auditors 41
p.000041: 5.19.3 Auditing Procedures
p.000041: 41
p.000041: 5.20 Noncompliance
p.000041: 41
p.000041: 5.21 Premature Termination or Suspension of a Trial 42
p.000041: 5.22 Clinical Trial/Study Reports
p.000042: 42
p.000042: 5.23 Multicentre Trials
p.000042: 42
p.000042: 6. CLINICAL TRIAL PROTOCOL AND PROTOCOL AMENDMENT(S) 43
p.000042: 6.1 General Information
p.000043: 43
p.000043: 6.2 Background Information
p.000043: 43
p.000043: 6.3 Trial Objectives and Purpose
p.000044: 44
p.000044: 6.4 Trial Design
p.000044: 44
p.000044: 6.5 Selection and Withdrawal of Subjects
p.000044: 44
p.000044: 6.6 Treatment of Subjects
p.000045: 45
p.000045: 6.7 Assessment of Efficacy
p.000045: 45
p.000045: 6.8 Assessment of Safety
p.000045: 45
p.000045: vi
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045: 6.9 Statistics
p.000045: 45
p.000045: 6.10 Direct Access to Source Data/Documents
p.000046: 46
p.000046: 6.11 Quality Control and Quality Assurance
p.000046: 46
...
p.000048: 48
p.000048: 7.3.6 Effects in Humans
p.000050: 50
p.000050: 7.3.7 Summary of Data and Guidance for the Investigator 52
p.000050: 7.4 APPENDIX 1:
p.000053: 53
p.000053: 7.5 APPENDIX 2:
p.000054: 54
p.000054: 8. ESSENTIAL DOCUMENTS FOR THE CONDUCT OF A CLINICAL TRIAL 55
p.000054: 8.1 Introduction
p.000055: 55
p.000055: 8.2 Before the Clinical Phase of the Trial Commences 56
p.000055: 8.3 During the Clinical Conduct of the Trial
p.000064: 64
p.000064: 8.4 After Completion or Termination of the Trial
p.000072: 72
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: vii
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: INTRODUCTION
p.000072:
p.000072:
p.000072: Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing,
p.000072: conducting, recording and reporting trials that involve the participation of human subjects. Compliance with this
p.000072: standard provides public assurance that the rights, safety and well-being of trial subjects are protected, consistent
p.000072: with the principles that have their origin in the Declaration of Helsinki, and that the clinical trial data are
p.000072: credible.
p.000072: The objective of this ICH GCP Guideline is to provide a unified standard for the European Union (EU), Japan and the
p.000072: United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these
p.000072: jurisdictions and in other jurisdictions who are willing to adopt such mutual recognition such as Saudi food and drug
p.000072: authority (SFDA) in Saudi Arabia.
p.000072: The guideline was developed with consideration of the current good clinical practices of the European Union, Japan, and
p.000072: the United States, as well as those of Australia, Canada, the Nordic countries and the World Health Organization (WHO).
p.000072: This guideline should be followed when generating clinical trial data that are intended to be submitted to the SFDA.
p.000072: The principles established in this guideline may also be applied to other clinical investigations that may have an
p.000072: impact on the safety and well-being of human subjects.
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000001: 1
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: 1. GLOSSARY
p.000001:
p.000001:
p.000001: 1.1 Adverse Drug Reaction (ADR)
p.000001: In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as
p.000001: the therapeutic dose(s) may not be established: all noxious and unintended responses to a medicinal
p.000001: product related to any dose should be considered adverse drug reactions. The phrase responses to a medicinal
p.000001: product means that a causal relationship between a medicinal product and an adverse event is at least a reasonable
p.000001: possibility, i.e. the relationship cannot be ruled out.
p.000001: Regarding marketed medicinal products: a response to a drug which is noxious and unintended and which occurs at
p.000001: doses normally used in man for prophylaxis, diagnosis, or therapy of diseases or for modification of
p.000001: physiological function (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for
p.000001: Expedited Reporting).
p.000001:
p.000001: 1.2 Adverse Event (AE)
p.000001:
p.000001: Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product
p.000001: and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can
p.000001: therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease
p.000001: temporally associated with the use of a medicinal (investigational) product, whether or not related to
p.000001: the medicinal (investigational) product. (see the ICH Guideline for Clinical Safety Data Management:
p.000001: Definitions and Standards for Expedited Reporting).
p.000001:
p.000001: 1.3 Amendment (to the protocol)
p.000001:
p.000001: See Protocol Amendment.
p.000001:
p.000001: 1.4 Applicable Regulatory Requirement(s)
p.000001: Any law(s) and regulation(s) addressing the conduct of clinical trials of investigational products.
p.000001:
p.000001:
p.000001:
p.000001:
p.000002: 2
p.000002:
p.000002:
p.000002:
p.000002:
p.000002:
p.000002: 1.5 Approval (in relation to Institutional Review Boards)
p.000002:
p.000002: The affirmative decision of the IRB that the clinical trial has been reviewed and may be conducted at
p.000002: the institution site within the constraints set forth by the IRB, the institution, Good Clinical Practice (GCP), and
p.000002: with the SFDA requirements.
p.000002: 1.6 Audit
p.000002:
...
p.000005: protocol, the suitability of the investigator(s), facilities, and the methods and material to be used in
p.000005: obtaining and documenting informed consent of the trial subjects.
p.000005: The legal status, composition, function, operations and regulatory requirements pertaining to Independent Ethics
p.000005: Committees may differ among countries, but should allow the Independent Ethics Committee to act in agreement with GCP
p.000005: as described in this guideline. The legal status, composition, function, operations and regulatory requirements
p.000005: pertaining to IEC in Saudi Arabia are governed by Law of Ethics of Research on Living Creatures.
p.000005:
p.000005: 1.28 Informed Consent
p.000005: A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after
p.000005: having been informed of all aspects of the trial that are relevant to the subject's decision to participate. Informed
p.000005: consent is documented by means of a written, signed and dated informed consent form.
p.000005: 1.29 Inspection
p.000005: The act by SFDA of conducting an official review of documents, facilities, records, and any other resources that are
p.000005: deemed by the Saudi Food and Drug Authority to be related to the clinical trial and that may be located at the site
p.000005: of the trial, at the sponsor's and/or contract
p.000005:
p.000005:
p.000005:
p.000006: 6
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006: research organization’s (CRO’s) facilities, or at other establishments deemed appropriate by the SFDA.
p.000006: 1.30 Institution (medical)
p.000006:
p.000006: Any public or private entity or agency or medical or dental facility where clinical trials are conducted.
p.000006: 1.31 Institutional Review Board (IRB)
p.000006: An independent body constituted of medical, scientific, and non-scientific members, whose responsibility is to
p.000006: ensure the protection of the rights, safety and well-being of human subjects involved in a trial by, among other
p.000006: things, reviewing, approving, and providing continuing review of trial protocol and amendments and of the methods
p.000006: and material to be used in obtaining and documenting informed consent of the trial subjects.
p.000006: 1.32 Interim Clinical Trial/Study Report
p.000006:
p.000006: A report of intermediate results and their evaluation based on analyses performed during the course of a trial.
p.000006: 1.33 Investigational Product
p.000006: A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial,
p.000006: including a product with a marketing authorization when used or assembled (formulated or packaged) in a way
p.000006: different from the approved form, or when used for an unapproved indication, or when used to gain further
p.000006: information about an approved use.
...
p.000008: 8
p.000008:
p.000008:
p.000008:
p.000008:
p.000008:
p.000008: 1.44 Protocol
p.000008:
p.000008: A document that describes the objective(s), design, methodology, statistical considerations, and organization of a
p.000008: trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other
p.000008: protocol referenced documents. Throughout the ICH GCP Guideline the term protocol refers to protocol and protocol
p.000008: amendments.
p.000008: 1.45 Protocol Amendment
p.000008:
p.000008: A written description of a change(s) to or formal clarification of a protocol.
p.000008:
p.000008: 1.46 Quality Assurance (QA)
p.000008:
p.000008: All those planned and systematic actions that are established to ensure that the trial is performed and the data are
p.000008: generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and SFDA
p.000008: requirement(s).
p.000008: 1.47 Quality Control (QC)
p.000008:
p.000008: The operational techniques and activities undertaken within the quality assurance system to verify that the
p.000008: requirements for quality of the trial-related activities have been fulfilled.
p.000008: 1.48 Randomization
p.000008:
p.000008: The process of assigning trial subjects to treatment or control groups using an element of chance to determine the
p.000008: assignments in order to reduce bias.
p.000008: 1.49 Regulatory Authorities
p.000008:
p.000008: Bodies having the power to regulate. In the ICH GCP guideline the expression Regulatory Authorities
p.000008: includes the authorities that review submitted clinical data and those that conduct inspections (see 1.29). These
p.000008: bodies are sometimes referred to as competent authorities.
p.000008: 1.50 Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (Serious ADR)
p.000008:
p.000008: Any untoward medical occurrence that at any dose:
p.000008:
p.000008: - results in death,
p.000008:
p.000008: - is life-threatening,
p.000008:
p.000008: - requires inpatient hospitalization or prolongation of existing hospitalization,
p.000008:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: - results in persistent or significant disability/incapacity, or
p.000009: - is a congenital anomaly/birth defect
p.000009:
p.000009: (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting).
p.000009:
p.000009: 1.51 Source Data
p.000009: All information in original records and certified copies of original records of clinical findings, observations, or
p.000009: other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are
p.000009: contained in source documents (original records or certified copies).
p.000009: 1.52 Source Documents
p.000009:
p.000009: Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes,
p.000009: memoranda, subjects' diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated
p.000009: instruments, copies or transcriptions certified after verification as being accurate copies, microfiches,
p.000009: photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the
p.000009: laboratories and at medico-technical departments involved in the clinical trial).
p.000009: 1.53 Sponsor
p.000009:
p.000009: An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or
p.000009: financing of a clinical trial.
p.000009: 1.54 Sponsor-Investigator
p.000009: An individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate
p.000009: direction the investigational product is administered to, dispensed to, or used by a subject. The term does not include
p.000009: any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of
p.000009: a sponsor-investigator include both those of a sponsor and those of an investigator.
p.000009:
p.000009:
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000010:
p.000010:
p.000010:
p.000010:
p.000010: 1.55 Standard Operating Procedures (SOPs)
p.000010:
p.000010: Detailed, written instructions to achieve uniformity of the performance of a specific function.
p.000010:
p.000010: 1.56 Subinvestigator
p.000010:
p.000010: Any individual member of the clinical trial team designated and supervised by the investigator at a trial site to
p.000010: perform critical trial-related procedures and/or to make important trial-related decisions (e.g., associates,
p.000010: residents, research fellows). See also Investigator.
p.000010: 1.57 Subject/Trial Subject
p.000010: An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or
p.000010: as a control.
p.000010: 1.58 Subject Identification Code
p.000010: A unique identifier assigned by the investigator to each trial subject to protect the subject's identity and used in
p.000010: lieu of the subject's name when the investigator reports adverse events and/or other trial related data.
p.000010: 1.59 Trial Site
p.000010:
p.000010: The location(s) where trial-related activities are actually conducted.
p.000010:
p.000010: 1.60 Unexpected Adverse Drug Reaction
p.000010:
p.000010: An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g.,
p.000010: Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics
p.000010: for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for
p.000010: Expedited Reporting).
p.000010:
p.000010: 1.61 Vulnerable Subjects
p.000010:
p.000010: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether
p.000010: justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a
p.000010: hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure,
p.000010: such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory
p.000010: personnel, employees of the
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects
p.000011: include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons,
...
p.000015: established.
p.000015: 3.3.2 Scheduling, notifying its members of, and conducting its meetings.
p.000015: 3.3.3 Conducting initial and continuing review of trials.
p.000015: 3.3.4 Determining the frequency of continuing review, as appropriate.
p.000015: 3.3.5 Providing expedited review and approval/favourable opinion of minor change(s) in ongoing trials that
p.000015: have the approval/favourable opinion of the IRB/IEC.
p.000015: 3.3.6 Specifying that no subject should be admitted to a trial before the IRB/IEC issues its written
p.000015: approval/favourable opinion of the trial.
p.000015: 3.3.7 Specifying that no deviations from, or changes of, the protocol should be initiated without prior written
p.000015: IRB/IEC approval/favourable opinion of an appropriate amendment, except when necessary to eliminate immediate
p.000015: hazards to the subjects or when the change(s) involves only logistical administrative aspects of the
p.000015: trial (e.g., change of monitor(s), telephone number(s)) (see 4.5.2).
p.000015: 3.3.8 Specifying that the investigator should promptly report to the IRB/IEC:
p.000015:
p.000015: (a) Deviations from, or changes of, the protocol to eliminate immediate hazards to the trial subjects (see 3.3.7,
p.000015: 4.5.2, 4.5.4).
p.000016: 16
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: (b) Changes increasing the risk to subjects and/or affecting significantly the conduct of the trial (see 4.10.2).
p.000016: (c) All adverse drug reactions (ADRs) that are both serious and unexpected.
p.000016:
p.000016: (d) New information that may affect adversely the safety of the subjects or the conduct of the trial.
p.000016: 3.3.9 Ensuring that the IRB/IEC promptly notify in writing the investigator/institution
p.000016: concerning:
p.000016: (a) Its trial-related decisions/opinions.
p.000016:
p.000016: (b) The reasons for its decisions/opinions.
p.000016:
p.000016: (c) Procedures for appeal of its decisions/opinions.
p.000016:
p.000016: 3.4 Records
p.000016: The IRB/IEC should retain all relevant records (e.g., written procedures, membership lists, lists of
p.000016: occupations/affiliations of members, submitted documents, minutes of meetings, and correspondence) for a period of at
p.000016: least 3 years after completion of the trial and make them available upon request from the SFDA or any relevant
p.000016: regulatory authority(ies).
p.000016: The IRB/IEC may be asked by investigators, sponsors or regulatory authorities to provide its written procedures and
p.000016: membership lists.
p.000016:
p.000016: 4. INVESTIGATOR
p.000016: 4.1 Investigator's Qualifications and Agreement
p.000016: 4.1.1 The investigator(s) should be qualified by education, training, and experience to assume
p.000016: responsibility for the proper conduct of the trial, should meet all the qualifications specified by the SFDA
p.000016: requirement(s), and should provide evidence of such qualifications through up- to-date curriculum vitae and/or other
p.000016: relevant documentation requested by the sponsor, the IRB/IEC, and/or the SFDA.
p.000016:
p.000016:
p.000016:
p.000017: 17
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
...
p.000025:
p.000025: 4.9.6 The financial aspects of the trial should be documented in an agreement between the sponsor and the
p.000025: investigator/institution.
p.000025: 4.9.7 Upon request of the monitor, auditor, IRB/IEC, or SFDA, the investigator/institution should make available for
p.000025: direct access all requested trial-related records.
p.000025: 4.10 Progress Reports
p.000025: 4.10.1 The investigator should submit written summaries of the trial status to the IRB/IEC annually, or
p.000025: more frequently, if requested by the IRB/IEC.
p.000025: 4.10.2 The investigator should promptly provide written reports to the sponsor, the IRB/IEC (see 3.3.8) and, where
p.000025: applicable, the institution on any changes significantly affecting the conduct of the trial, and/or increasing the risk
p.000025: to subjects.
p.000025:
p.000025:
p.000025:
p.000026: 26
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026: 4.11 Safety Reporting
p.000026: 4.11.1 All serious adverse events (SAEs) should be reported immediately to the sponsor except for those SAEs that
p.000026: the protocol or other document (e.g., Investigator's Brochure) identifies as not needing immediate
p.000026: reporting. The immediate reports should be followed promptly by detailed, written reports. The immediate and
p.000026: follow-up reports should identify subjects by unique code numbers assigned to the trial subjects rather than by the
p.000026: subjects' names, personal identification numbers, and/or addresses. The investigator should also comply with the
p.000026: SFDA requirement(s) related to the reporting of unexpected serious adverse drug reactions to the SFDA and the IRB/IEC.
p.000026: 4.11.2 Adverse events and/or laboratory abnormalities identified in the protocol as critical to safety evaluations
p.000026: should be reported to the sponsor according to the reporting requirements and within the time periods
p.000026: specified by the sponsor in the protocol.
p.000026: 4.11.3 For reported deaths, the investigator should supply the sponsor and the IRB/IEC with any additional requested
p.000026: information (e.g., autopsy reports and terminal medical reports).
p.000026: 4.12 Premature Termination or Suspension of a Trial
p.000026: If the trial is prematurely terminated or suspended for any reason, the investigator/institution should promptly inform
p.000026: the trial subjects, should assure appropriate therapy and follow-up for the subjects, and, where required by the
p.000026: applicable regulatory requirement(s), should inform the SFDA. In addition:
p.000026: 4.12.1 If the investigator terminates or suspends a trial without prior agreement of the sponsor, the investigator
p.000026: should inform the institution where applicable, and the investigator/institution should
p.000026: promptly inform the sponsor and the IRB/IEC, and should provide the sponsor and the IRB/IEC a detailed
p.000026: written explanation of the termination or suspension.
p.000026: 4.12.2 If the sponsor terminates or suspends a trial (see 5.21), the investigator should promptly inform the
p.000026: institution where applicable and the investigator/institution should promptly inform the IRB/IEC and provide the
p.000026: IRB/IEC a detailed written explanation of the termination or suspension.
p.000026:
p.000026:
p.000026:
p.000027: 27
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
...
p.000031: (b) to comply with procedures for data recording/reporting;
p.000031:
p.000031: (c) to permit monitoring, auditing and inspection (see 4.1.4) and
p.000031:
p.000031: (d) to retain the trial related essential documents until the sponsor informs the
p.000031: investigator/institution these documents are no longer needed (see 4.9.4 and 5.5.12).
p.000031: The sponsor and the investigator/institution should sign the protocol, or an alternative document, to
p.000031: confirm this agreement.
p.000031: 5.7 Allocation of Responsibilities
p.000031: Prior to initiating a trial, the sponsor should define, establish, and allocate all trial-related duties and functions.
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 5.8 Compensation to Subjects and Investigators
p.000031: 5.8.1 The sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator/the
p.000031: institution against claims arising from the trial, except for claims that arise from malpractice and/or negligence.
p.000031: 5.8.2 The sponsor's policies and procedures should address the costs of treatment of trial subjects in the event of
p.000031: trial-related injuries in accordance with the SFDA requirement(s).
p.000031: 5.8.3 When trial subjects receive compensation, the method and manner of compensation should comply with SFDA
p.000031: requirement(s).
p.000031: 5.9 Financing
p.000031: The financial aspects of the trial should be documented in an agreement between the sponsor and the
p.000031: investigator/institution.
p.000031:
p.000031:
p.000031:
p.000032: 32
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032: 5.10 Notification/Submission to Saudi food and drug authority
p.000032: Before initiating the clinical trial(s), the sponsor should submit any required application(s) to the SFDA for review,
p.000032: acceptance, and/or permission (as required by the SFDA Guidelines - Guidance and requirements for conducting
p.000032: clinical trials on drugs) to begin the trial(s). Any notification/submission should be dated and
p.000032: contain sufficient information to identify the protocol.
p.000032: 5.11 Confirmation of Review by IRB/IEC
p.000032: 5.11.1 The sponsor should obtain from the investigator/institution:
p.000032:
p.000032: (a) The name and address of the investigator's/institution’s IRB/IEC.
p.000032:
p.000032: (b) A statement obtained from the IRB/IEC that it is organized and operates according to GCP and the applicable laws
p.000032: and regulations.
p.000032: (c) Documented IRB/IEC approval/favourable opinion and, if requested by the sponsor, a current copy of protocol,
p.000032: written informed consent form(s) and any other written information to be provided to subjects, subject
p.000032: recruiting procedures, and documents related to payments and compensation available to the subjects, and any other
p.000032: documents that the IRB/IEC may have requested.
p.000032: 5.11.2 If the IRB/IEC conditions its approval/favourable opinion upon change(s) in any aspect of the trial, such as
p.000032: modification(s) of the protocol, written informed consent form and any other written information to be provided to
p.000032: subjects, and/or other procedures, the sponsor should obtain from the investigator/institution a copy of the
...
p.000034: (b) Maintain sufficient quantities of the investigational product(s) used in the trials to reconfirm
p.000034: specifications, should this become necessary, and maintain records of batch sample analyses and characteristics. To the
p.000034: extent stability permits, samples should be retained either until the analyses of the trial data are complete or as
p.000034: required by the SFDA requirement(s), whichever represents the longer retention period.
p.000034:
p.000034:
p.000034:
p.000034:
p.000035: 35
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: 5.15 Record Access
p.000035: 5.15.1 The sponsor should ensure that it is specified in the protocol or other written agreement that the
p.000035: investigator(s)/institution(s) provide direct access to source data/documents for trial-related monitoring, audits,
p.000035: IRB/IEC review, and regulatory inspection.
p.000035: 5.15.2 The sponsor should verify that each subject has consented, in writing, to direct access to his/her original
p.000035: medical records for trial-related monitoring, audit, IRB/IEC review, and regulatory inspection.
p.000035: 5.16 Safety Information
p.000035: 5.16.1 The sponsor is responsible for the ongoing safety evaluation of the investigational product(s).
p.000035: 5.16.2 The sponsor should promptly notify all concerned investigator(s)/institution(s) and the SFDA of findings that
p.000035: could affect adversely the safety of subjects, impact the conduct of the trial, or alter the IRB/IEC's
p.000035: approval/favourable opinion to continue the trial.
p.000035: 5.17 Adverse Drug Reaction Reporting
p.000035: 5.17.1 The sponsor should expedite the reporting to all concerned
p.000035: investigator(s)/institutions(s), to the IRB(s)/IEC(s), where required, and to the SFDA of all adverse drug reactions
p.000035: (ADRs) that are both serious and unexpected.
p.000035: 5.17.2 Such expedited reports should comply with the SFDA requirement(s) and with the ICH Guideline for Clinical
p.000035: Safety Data Management: Definitions and Standards for Expedited Reporting.
p.000035: 5.17.3 The sponsor should submit to the SFDA all safety updates and periodic reports, as required by SFDA
p.000035: requirement(s).
p.000035: 5.18 Monitoring
p.000035: 5.18.1 Purpose
p.000035: The purposes of trial monitoring are to verify that:
p.000035:
p.000035: (a) The rights and well-being of human subjects are protected.
p.000035:
p.000035: (b) The reported trial data are accurate, complete, and verifiable from source documents.
p.000035:
p.000035:
p.000035:
p.000036: 36
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036: (c) The conduct of the trial is in compliance with the currently approved
p.000036: protocol/amendment(s), with GCP, and with the SFDA requirement(s).
p.000036: 5.18.2 Selection and Qualifications of Monitors
p.000036: (a) Monitors should be appointed by the sponsor.
p.000036:
p.000036: (b) Monitors should be appropriately trained, and should have the scientific and/or clinical knowledge
p.000036: needed to monitor the trial adequately. A monitor’s qualifications should be documented.
p.000036: (c) Monitors should be thoroughly familiar with the investigational product(s), the protocol, written
p.000036: informed consent form and any other written information to be provided to subjects, the sponsor’s SOPs, GCP,
p.000036: and the SFDA requirement(s).
p.000036: 5.18.3 Extent and Nature of Monitoring
p.000036: The sponsor should ensure that the trials are adequately monitored. The sponsor should determine the appropriate extent
...
p.000050: 50
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050: − A summary of information on the pharmacokinetics of the investigational product(s) should be presented, including the
p.000050: following, if available:
p.000050: − Pharmacokinetics (including metabolism, as appropriate, and absorption, plasma protein binding, distribution,
p.000050: and elimination).
p.000050: − Bioavailability of the investigational product (absolute, where possible, and/or relative) using a reference
p.000050: dosage form.
p.000050: − Population subgroups (e.g., gender, age, and impaired organ function).
p.000050:
p.000050: − Interactions (e.g., product-product interactions and effects of food).
p.000050:
p.000050: − Other pharmacokinetic data (e.g., results of population studies performed within clinical trial(s).
p.000050: (b) Safety and Efficacy
p.000050:
p.000050: A summary of information should be provided about the investigational product's/products'
p.000050: (including metabolites, where appropriate) safety, pharmacodynamics, efficacy, and dose
p.000050: response that were obtained from preceding trials in humans (healthy volunteers and/or patients).
p.000050: The implications of this information should be discussed. In cases where a number of clinical trials have been
p.000050: completed, the use of summaries of safety and efficacy across multiple trials by indications in subgroups
p.000050: may provide a clear presentation of the data. Tabular summaries of adverse drug reactions for all the clinical
p.000050: trials (including those for all the studied indications) would be useful. Important differences in adverse
p.000050: drug reaction patterns/incidences across indications or subgroups should be discussed.
p.000050: The IB should provide a description of the possible risks and adverse drug reactions to be anticipated on the basis of
p.000050: prior experiences with the product under investigation and with related products. A description should also be provided
p.000050: of the precautions or special monitoring to be done as part of the investigational use of the product(s).
p.000050: (c) Marketing Experience
p.000050:
p.000050: The IB should identify countries where the investigational product has been marketed or approved. Any significant
p.000050: information arising from the marketed use should be summarised (e.g., formulations, dosages, routes of
p.000050: administration, and adverse product reactions). The IB should also identify all the countries where the
p.000050: investigational product did not receive approval/registration for marketing or was withdrawn from
p.000050: marketing/registration.
p.000050:
p.000050:
p.000050:
p.000050:
p.000051: 51
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051: 7.3.7 Summary of Data and Guidance for the Investigator
p.000051: This section should provide an overall discussion of the nonclinical and clinical data, and should summarise the
p.000051: information from various sources on different aspects of the investigational product(s), wherever possible. In
p.000051: this way, the investigator can be provided with the most informative interpretation of the available data and
p.000051: with an assessment of the implications of the information for future clinical trials.
p.000051: Where appropriate, the published reports on related products should be discussed. This could help the investigator to
p.000051: anticipate adverse drug reactions or other problems in clinical trials.
p.000051: The overall aim of this section is to provide the investigator with a clear understanding of the possible risks and
p.000051: adverse reactions, and of the specific tests, observations, and precautions that may be needed for a clinical trial.
p.000051: This understanding should be based on the available physical, chemical, pharmaceutical, pharmacological, toxicological,
p.000051: and clinical information on the investigational product(s). Guidance should also be provided to the clinical
p.000051: investigator on the recognition and treatment of possible overdose and adverse drug reactions that is based on
p.000051: previous human experience and on the pharmacology of the investigational product.
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: 7.4 APPENDIX 1:
p.000052:
p.000052:
p.000052: TITLE PAGE (Example) SPONSOR'S NAME
p.000052:
p.000052: Product:
p.000052:
p.000052: Research Number:
p.000052:
p.000052: Name(s): Chemical, Generic (if approved)
p.000052:
p.000052: Trade Name(s) (if legally permissible and desired by the sponsor)
p.000052:
p.000052: INVESTIGATOR'S BROCHURE
p.000052:
p.000052: Edition Number:
p.000052:
p.000052: Release Date:
p.000052:
p.000052:
p.000052: Replaces Previous Edition Number: Date:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000053: 53
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053: 7.5 APPENDIX 2:
p.000053:
p.000053:
p.000053: TABLE OF CONTENTS OF INVESTIGATOR'S BROCHURE (Example)
p.000053:
p.000053: - Confidentiality Statement
p.000053: (optional)...............................................................................
p.000053:
p.000053: - Signature Page
p.000053: (optional)................................................................................................
p.000053:
p.000053: 1 Table of
...
p.000068:
p.000068:
p.000068:
p.000068: Title of Document Purpose
p.000068: Located in Files of
p.000068:
p.000068:
p.000068:
p.000068: Investigator/
p.000068: Institution
p.000068: Sponsor
p.000068:
p.000068:
p.000068: 8.3.14 SIGNED, DATED AND
p.000068: COMPLETED
p.000068: CASE REPORT FORMS (CRF)
p.000068: To document that the investigator or authorised member of the investigator’s staff confirms the
p.000068: observations recorded
p.000068: X
p.000068: (copy)
p.000068: X
p.000068: (original)
p.000068:
p.000068:
p.000068: 8.3.15 DOCUMENTATION OF CRF CORRECTIONS
p.000068: To document all changes/additions or corrections made to CRF after initial data were recorded
p.000068: X
p.000068: (copy)
p.000068: X
p.000068: (original)
p.000068:
p.000068:
p.000068:
p.000068: 8.3.16 NOTIFICATION BY
p.000068: ORIGINATING INVESTIGATOR TO SPONSOR OF SERIOUS ADVERSE EVENTS AND RELATED REPORTS
p.000068: Notification by originating investigator to X X sponsor of
p.000068: serious adverse events and related
p.000068: reports in accordance with 4.11
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000069: 69
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: Title of Document Purpose
p.000069: Located in Files of
p.000069:
p.000069:
p.000069:
p.000069: Investigator/
p.000069: Institution
p.000069: Sponsor
p.000069:
p.000069:
p.000069: 8.3.17 NOTIFICATION BY SPONSOR AND/OR INVESTIGATOR, WHERE APPLICABLE, TO SFDA AND IRB(S)/IEC(S) OF UNEXPECTED
p.000069: SERIOUS ADVERSE DRUG REACTIONS AND OF OTHER SAFETY INFORMATION
p.000069: Notification by sponsor and/or investigator, where applicable, to regulatory authorities and IRB(s)/IEC(s) of
p.000069: unexpected serious adverse drug reactions in accordance with 5.17 and
p.000069: 4.11.1 and of other safety information in accordance with 5.16.2 and 4.11.2
p.000069: X X
p.000069: (where required)
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: 8.3.18 NOTIFICATION BY SPONSOR TO INVESTIGATORS OF SAFETY INFORMATION
p.000069: Notification by sponsor to investigators of X X safety information
p.000069: in accordance with 5.16.2
p.000069:
p.000069:
p.000069:
p.000069: 8.3.19 INTERIM OR ANNUAL
p.000069: REPORTS TO IRB/IEC AND
p.000069: SFDA
p.000069: Interim or annual reports provided to IRB/IEC in accordance with 4.10 and to authority(ies) in accordance with 5.17.3
p.000069: X X
p.000069: (where required)
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: Title of Document Purpose
p.000069: Located in Files of
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000070: 70
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070: Investigator/
p.000070: Institution
p.000070: Sponsor
p.000070:
p.000070:
p.000070: 8.3.20 SUBJECT SCREENING LOG To document identification of subjects who
p.000070: entered pre-trial screening
p.000070: X X
p.000070: (where required)
p.000070:
p.000070:
p.000070:
p.000070: 8.3.21 SUBJECT IDENTIFICATION CODE LIST
p.000070: To document that investigator/institution X keeps a confidential list of names of
p.000070: all
p.000070: subjects allocated to trial numbers on enrolling in the trial. Allows
...
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p.000013: by a current curriculum vitae and/or by any other relevant documentation the IRB/IEC requests.
p.000013: 3.1.4 The IRB/IEC should conduct continuing review of each ongoing trial at intervals appropriate to
p.000013: the degree of risk to human subjects, but at least once per year.
p.000013: 3.1.5 The IRB/IEC may request more information than is outlined in paragraph 4.8.10 be given to subjects when, in
p.000013: the judgement of the IRB/IEC, the additional information would add meaningfully to the protection of the rights, safety
p.000013: and/or well-being of the subjects.
p.000013:
p.000013:
p.000014: 14
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014: 3.1.6 When a non-therapeutic trial is to be carried out with the consent of the subject’s legally acceptable
p.000014: representative (see 4.8.12, 4.8.14), the IRB/IEC should determine that the proposed protocol and/or other
p.000014: document(s) adequately addresses relevant ethical concerns and meets applicable regulatory requirements for such
p.000014: trials.
p.000014: 3.1.7 Where the protocol indicates that prior consent of the trial subject or the subject’s legally acceptable
p.000014: representative is not possible (see 4.8.15), the IRB/IEC should determine that the proposed protocol and/or other
p.000014: document(s) adequately addresses relevant ethical concerns.
p.000014: 3.1.8 The IRB/IEC should review both the amount and method of payment to subjects to assure that neither
p.000014: presents problems of coercion or undue influence on the trial subjects. Payments to a subject should be
p.000014: prorated and not wholly contingent on completion of the trial by the subject.
p.000014: 3.1.9 The IRB/IEC should ensure that information regarding payment to subjects, including the methods, amounts,
p.000014: and schedule of payment to trial subjects, is set forth in the written informed consent form and any other written
p.000014: information to be provided to subjects. The way payment will be prorated should be specified.
p.000014: 3.2 Composition, Functions and Operations
p.000014: 3.2.1 The IRB/IEC should consist of a reasonable number of members, who collectively have the qualifications and
p.000014: experience to review and evaluate the science, medical aspects, and ethics of the proposed trial. It is recommended
p.000014: that the IRB/IEC should include:
p.000014: (a) At least five members.
p.000014:
p.000014: (b) At least one member whose primary area of interest is in a nonscientific area.
p.000014:
p.000014: (c) At least one member who is independent of the institution/trial site.
p.000014:
p.000014: Only those IRB/IEC members who are independent of the investigator and the sponsor of the trial should vote/provide
p.000014: opinion on a trial-related matter.
p.000014: A list of IRB/IEC members and their qualifications should be maintained.
p.000014:
p.000014: The legal status, composition, function, operations and regulatory requirements pertaining to IEC in Saudi Arabia are
p.000014: governed by Law of Ethics of Research on Living Creatures.
p.000015: 15
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
...
p.000020: 4.8 Informed Consent of Trial Subjects
p.000020: 4.8.1 In obtaining and documenting informed consent, the investigator should comply with SFDA
p.000020: requirement(s), and should adhere to GCP and to the ethical principles that have their origin in the Declaration
p.000020: of Helsinki. Prior to the beginning of the trial, the investigator should have the IRB/IEC's written
p.000020: approval/favourable opinion of the written informed consent form and any other written information to be provided to
p.000020: subjects.
p.000020: 4.8.2 The written informed consent form and any other written information to be provided to subjects should be
p.000020: revised whenever important new information becomes available that may be relevant to the subject’s consent. Any revised
p.000020: written informed consent form, and written information should receive the IRB/IEC's approval/favourable opinion in
p.000020: advance of use. The subject or the subject’s legally acceptable representative should be informed in a timely manner if
p.000020: new information becomes available that may be relevant to the subject’s willingness to continue participation in the
p.000020: trial. The communication of this information should be documented.
p.000020: 4.8.3 Neither the investigator, nor the trial staff, should coerce or unduly influence a subject to participate or
p.000020: to continue to participate in a trial.
p.000020: 4.8.4 None of the oral and written information concerning the trial, including the written informed
p.000020: consent form, should contain any language that causes the subject or the subject's legally acceptable representative to
p.000020: waive or to appear to waive any legal rights, or that releases or appears to release the investigator, the institution,
p.000020: the sponsor, or their agents from liability for negligence.
p.000020:
p.000020:
p.000021: 21
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 4.8.5 The investigator, or a person designated by the investigator, should fully inform the subject or, if the
p.000021: subject is unable to provide informed consent, the subject's legally acceptable representative, of all pertinent
p.000021: aspects of the trial including the written information and the approval/ favourable opinion by the IRB/IEC.
p.000021: 4.8.6 The language used in the oral and written information about the trial, including the written informed
p.000021: consent form, should be as non-technical as practical and should be understandable to the
p.000021: subject or the subject's legally acceptable representative and the impartial witness, where applicable.
p.000021: 4.8.7 Before informed consent may be obtained, the investigator, or a person designated by the investigator,
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p.000047: 47
p.000047:
p.000047:
p.000047:
p.000047:
p.000047:
p.000047: 7.2.2 Confidentiality Statement
p.000047: The sponsor may wish to include a statement instructing the investigator/recipients to treat the IB as a
p.000047: confidential document for the sole information and use of the investigator's team and the IRB/IEC.
p.000047: 7.3 Contents of the Investigator’s Brochure
p.000047: The IB should contain the following sections, each with literature references where appropriate:
p.000047:
p.000047: 7.3.1 Table of Contents
p.000047: An example of the Table of Contents is given in Appendix 2
p.000047:
p.000047: 7.3.2 Summary
p.000047: A brief summary (preferably not exceeding two pages) should be given, highlighting the significant physical,
p.000047: chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic, and clinical information
p.000047: available that is relevant to the stage of clinical development of the investigational product.
p.000047: 7.3.3 Introduction
p.000047: A brief introductory statement should be provided that contains the chemical name (and generic and trade name(s) when
p.000047: approved) of the investigational product(s), all active ingredients, the investigational product (s )
p.000047: pharmacological class and its expected position within this class (e.g. advantages), the rationale for performing
p.000047: research with the investigational product(s), and the anticipated prophylactic, therapeutic, or
p.000047: diagnostic indication(s). Finally, the introductory statement should provide the general approach to be followed in
p.000047: evaluating the investigational product.
p.000047: 7.3.4 Physical, Chemical, and Pharmaceutical Properties and Formulation
p.000047: A description should be provided of the investigational product substance(s) (including the chemical and/or structural
p.000047: formula(e)), and a brief summary should be given of the relevant physical, chemical, and pharmaceutical properties.
p.000047: To permit appropriate safety measures to be taken in the course of the trial, a description of the formulation(s) to be
p.000047: used, including excipients, should be provided and justified if clinically relevant. Instructions for the storage and
p.000047: handling of the dosage form(s) should also be given.
p.000047: Any structural similarities to other known compounds should be mentioned.
p.000047:
p.000047: 7.3.5 Nonclinical Studies Introduction:
p.000047: The results of all relevant nonclinical pharmacology, toxicology, pharmacokinetic, and investigational product
p.000047: metabolism studies should be provided in summary form. This summary should address the methodology used, the
p.000047: results, and a discussion of the
p.000048: 48
p.000048:
p.000048:
p.000048:
p.000048:
p.000048:
p.000048: relevance of the findings to the investigated therapeutic and the possible unfavourable and unintended effects in
p.000048: humans.
p.000048: The information provided may include the following, as appropriate, if known/available:
p.000048: • Species tested
p.000048:
p.000048: • Number and sex of animals in each group
p.000048:
p.000048: • Unit dose (e.g., milligram/kilogram (mg/kg))
p.000048:
p.000048: • Dose interval
p.000048:
p.000048: • Route of administration
p.000048:
p.000048: • Duration of dosing
p.000048:
p.000048: • Information on systemic distribution
p.000048:
p.000048: • Duration of post-exposure follow-up
p.000048:
p.000048: • Results, including the following aspects:
p.000048:
p.000048: − Nature and frequency of pharmacological or toxic effects
p.000048:
p.000048: − Severity or intensity of pharmacological or toxic effects
p.000048:
p.000048: − Time to onset of effects
...
Health / Healthy People
Searching for indicator volunteers:
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p.000049: efficacy, and other pharmacological activities. Where possible, a summary of each completed clinical
p.000049: trial should be provided. Information should also be provided regarding results of any use of the
p.000049: investigational product(s) other than from in clinical trials, such as from experience during marketing.
p.000049: (a) Pharmacokinetics and Product Metabolism in Humans
p.000050: 50
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050: − A summary of information on the pharmacokinetics of the investigational product(s) should be presented, including the
p.000050: following, if available:
p.000050: − Pharmacokinetics (including metabolism, as appropriate, and absorption, plasma protein binding, distribution,
p.000050: and elimination).
p.000050: − Bioavailability of the investigational product (absolute, where possible, and/or relative) using a reference
p.000050: dosage form.
p.000050: − Population subgroups (e.g., gender, age, and impaired organ function).
p.000050:
p.000050: − Interactions (e.g., product-product interactions and effects of food).
p.000050:
p.000050: − Other pharmacokinetic data (e.g., results of population studies performed within clinical trial(s).
p.000050: (b) Safety and Efficacy
p.000050:
p.000050: A summary of information should be provided about the investigational product's/products'
p.000050: (including metabolites, where appropriate) safety, pharmacodynamics, efficacy, and dose
p.000050: response that were obtained from preceding trials in humans (healthy volunteers and/or patients).
p.000050: The implications of this information should be discussed. In cases where a number of clinical trials have been
p.000050: completed, the use of summaries of safety and efficacy across multiple trials by indications in subgroups
p.000050: may provide a clear presentation of the data. Tabular summaries of adverse drug reactions for all the clinical
p.000050: trials (including those for all the studied indications) would be useful. Important differences in adverse
p.000050: drug reaction patterns/incidences across indications or subgroups should be discussed.
p.000050: The IB should provide a description of the possible risks and adverse drug reactions to be anticipated on the basis of
p.000050: prior experiences with the product under investigation and with related products. A description should also be provided
p.000050: of the precautions or special monitoring to be done as part of the investigational use of the product(s).
p.000050: (c) Marketing Experience
p.000050:
p.000050: The IB should identify countries where the investigational product has been marketed or approved. Any significant
p.000050: information arising from the marketed use should be summarised (e.g., formulations, dosages, routes of
p.000050: administration, and adverse product reactions). The IB should also identify all the countries where the
p.000050: investigational product did not receive approval/registration for marketing or was withdrawn from
p.000050: marketing/registration.
p.000050:
p.000050:
p.000050:
p.000050:
p.000051: 51
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051: 7.3.7 Summary of Data and Guidance for the Investigator
...
Health / Mentally Disabled
Searching for indicator disability:
(return to top)
p.000008: amendments.
p.000008: 1.45 Protocol Amendment
p.000008:
p.000008: A written description of a change(s) to or formal clarification of a protocol.
p.000008:
p.000008: 1.46 Quality Assurance (QA)
p.000008:
p.000008: All those planned and systematic actions that are established to ensure that the trial is performed and the data are
p.000008: generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and SFDA
p.000008: requirement(s).
p.000008: 1.47 Quality Control (QC)
p.000008:
p.000008: The operational techniques and activities undertaken within the quality assurance system to verify that the
p.000008: requirements for quality of the trial-related activities have been fulfilled.
p.000008: 1.48 Randomization
p.000008:
p.000008: The process of assigning trial subjects to treatment or control groups using an element of chance to determine the
p.000008: assignments in order to reduce bias.
p.000008: 1.49 Regulatory Authorities
p.000008:
p.000008: Bodies having the power to regulate. In the ICH GCP guideline the expression Regulatory Authorities
p.000008: includes the authorities that review submitted clinical data and those that conduct inspections (see 1.29). These
p.000008: bodies are sometimes referred to as competent authorities.
p.000008: 1.50 Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (Serious ADR)
p.000008:
p.000008: Any untoward medical occurrence that at any dose:
p.000008:
p.000008: - results in death,
p.000008:
p.000008: - is life-threatening,
p.000008:
p.000008: - requires inpatient hospitalization or prolongation of existing hospitalization,
p.000008:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: - results in persistent or significant disability/incapacity, or
p.000009: - is a congenital anomaly/birth defect
p.000009:
p.000009: (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting).
p.000009:
p.000009: 1.51 Source Data
p.000009: All information in original records and certified copies of original records of clinical findings, observations, or
p.000009: other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are
p.000009: contained in source documents (original records or certified copies).
p.000009: 1.52 Source Documents
p.000009:
p.000009: Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes,
p.000009: memoranda, subjects' diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated
p.000009: instruments, copies or transcriptions certified after verification as being accurate copies, microfiches,
p.000009: photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the
p.000009: laboratories and at medico-technical departments involved in the clinical trial).
p.000009: 1.53 Sponsor
p.000009:
p.000009: An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or
p.000009: financing of a clinical trial.
p.000009: 1.54 Sponsor-Investigator
p.000009: An individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate
p.000009: direction the investigational product is administered to, dispensed to, or used by a subject. The term does not include
p.000009: any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of
...
Health / Mentally Incapacitated
Searching for indicator incapable:
(return to top)
p.000010: for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for
p.000010: Expedited Reporting).
p.000010:
p.000010: 1.61 Vulnerable Subjects
p.000010:
p.000010: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether
p.000010: justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a
p.000010: hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure,
p.000010: such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory
p.000010: personnel, employees of the
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects
p.000011: include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons,
p.000011: patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those
p.000011: incapable of giving consent.
p.000011: 1.62 Well-being (of the trial subjects)
p.000011:
p.000011: The physical and mental integrity of the subjects participating in a clinical trial.
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2. THE PRINCIPLES OF ICH GCP
p.000012:
p.000012: 2.1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the
p.000012: Declaration of Helsinki, and that are consistent with GCP and the with SFDA requirement(s).
p.000012: 2.2 Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated
p.000012: benefit for the individual trial subject and society. A trial should be initiated and continued only if the
p.000012: anticipated benefits justify the risks.
p.000012: 2.3 The rights, safety, and well-being of the trial subjects are the most important
p.000012: considerations and should prevail over interests of science and society.
p.000012: 2.4 The available nonclinical and clinical information on an investigational product should be adequate to support
p.000012: the proposed clinical trial.
p.000012: 2.5 Clinical trials should be scientifically sound, and described in a clear, detailed protocol.
...
Health / Physically Disabled
Searching for indicator illness:
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p.000017: the SFDA.
p.000017: 4.1.5 The investigator should maintain a list of appropriately qualified persons to whom the investigator
p.000017: has delegated significant trial-related duties.
p.000017: 4.2 Adequate Resources
p.000017: 4.2.1 The investigator should be able to demonstrate (e.g., based on retrospective data) a potential for recruiting the
p.000017: required number of suitable subjects within the agreed recruitment period.
p.000017: 4.2.2 The investigator should have sufficient time to properly conduct and complete the trial within the agreed trial
p.000017: period.
p.000017: 4.2.3 The investigator should have available an adequate number of qualified staff and adequate facilities for the
p.000017: foreseen duration of the trial to conduct the trial properly and safely.
p.000017: 4.2.4 The investigator should ensure that all persons assisting with the trial are adequately informed about the
p.000017: protocol, the investigational product(s), and their trial-related duties and functions.
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017: 4.3 Medical Care of Trial Subjects
p.000017: 4.3.1 A qualified physician (or dentist, when appropriate), who is an investigator or a sub- investigator
p.000017: for the trial, should be responsible for all trial-related medical (or dental) decisions.
p.000017: 4.3.2 During and following a subject's participation in a trial, the investigator/institution should ensure that
p.000017: adequate medical care is provided to a subject for any adverse events, including clinically significant laboratory
p.000017: values, related to the trial. The investigator/institution should inform a subject when medical care is needed
p.000017: for intercurrent illness(es) of which the investigator becomes aware.
p.000018: 18
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018: 4.3.3 It is recommended that the investigator inform the subject's primary physician about the subject's
p.000018: participation in the trial if the subject has a primary physician and if the subject agrees to the primary physician
p.000018: being informed.
p.000018: 4.3.4 Although a subject is not obliged to give his/her reason(s) for withdrawing prematurely from a trial, the
p.000018: investigator should make a reasonable effort to ascertain the reason(s), while fully respecting the subject's rights.
p.000018: 4.4 Communication with IRB/IEC
p.000018: 4.4.1 Before initiating a trial, the investigator/institution should have written and dated
p.000018: approval/favourable opinion from the IRB/IEC for the trial protocol, written informed consent form, consent
p.000018: form updates, subject recruitment procedures (e.g., advertisements), and any other written information to be provided
p.000018: to subjects.
p.000018: 4.4.2 As part of the investigator's/institution’s written application to the IRB/IEC, the
p.000018: investigator/institution should provide the IRB/IEC with a current copy of the Investigator's
p.000018: Brochure. If the Investigator's Brochure is updated during the trial, the investigator/institution should
p.000018: supply a copy of the updated Investigator’s Brochure to the IRB/IEC.
p.000018: 4.4.3 During the trial the investigator/institution should provide to the IRB/IEC all documents subject to review.
p.000018:
p.000018:
p.000018: 4.5 Compliance with Protocol
...
Health / Terminally Ill
Searching for indicator terminal:
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p.000025: more frequently, if requested by the IRB/IEC.
p.000025: 4.10.2 The investigator should promptly provide written reports to the sponsor, the IRB/IEC (see 3.3.8) and, where
p.000025: applicable, the institution on any changes significantly affecting the conduct of the trial, and/or increasing the risk
p.000025: to subjects.
p.000025:
p.000025:
p.000025:
p.000026: 26
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026: 4.11 Safety Reporting
p.000026: 4.11.1 All serious adverse events (SAEs) should be reported immediately to the sponsor except for those SAEs that
p.000026: the protocol or other document (e.g., Investigator's Brochure) identifies as not needing immediate
p.000026: reporting. The immediate reports should be followed promptly by detailed, written reports. The immediate and
p.000026: follow-up reports should identify subjects by unique code numbers assigned to the trial subjects rather than by the
p.000026: subjects' names, personal identification numbers, and/or addresses. The investigator should also comply with the
p.000026: SFDA requirement(s) related to the reporting of unexpected serious adverse drug reactions to the SFDA and the IRB/IEC.
p.000026: 4.11.2 Adverse events and/or laboratory abnormalities identified in the protocol as critical to safety evaluations
p.000026: should be reported to the sponsor according to the reporting requirements and within the time periods
p.000026: specified by the sponsor in the protocol.
p.000026: 4.11.3 For reported deaths, the investigator should supply the sponsor and the IRB/IEC with any additional requested
p.000026: information (e.g., autopsy reports and terminal medical reports).
p.000026: 4.12 Premature Termination or Suspension of a Trial
p.000026: If the trial is prematurely terminated or suspended for any reason, the investigator/institution should promptly inform
p.000026: the trial subjects, should assure appropriate therapy and follow-up for the subjects, and, where required by the
p.000026: applicable regulatory requirement(s), should inform the SFDA. In addition:
p.000026: 4.12.1 If the investigator terminates or suspends a trial without prior agreement of the sponsor, the investigator
p.000026: should inform the institution where applicable, and the investigator/institution should
p.000026: promptly inform the sponsor and the IRB/IEC, and should provide the sponsor and the IRB/IEC a detailed
p.000026: written explanation of the termination or suspension.
p.000026: 4.12.2 If the sponsor terminates or suspends a trial (see 5.21), the investigator should promptly inform the
p.000026: institution where applicable and the investigator/institution should promptly inform the IRB/IEC and provide the
p.000026: IRB/IEC a detailed written explanation of the termination or suspension.
p.000026:
p.000026:
p.000026:
p.000027: 27
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027: 4.12.3 If the IRB/IEC terminates or suspends its approval/favourable opinion of a trial (see
p.000027: 3.1.2 and 3.3.9), the investigator should inform the institution where applicable and the investigator/institution
p.000027: should promptly notify the sponsor and provide the sponsor with a detailed written explanation of the termination or
p.000027: suspension.
p.000027: 4.13 Final Report(s) by Investigator
p.000027: Upon completion of the trial, the investigator, where applicable, should inform the institution; the
...
Social / Access to Social Goods
Searching for indicator access:
(return to top)
p.000020: 4.8 Informed Consent of Trial Subjects
p.000021: 21
p.000021: 4.9 Records and Reports
p.000025: 25
p.000025: 4.10 Progress Reports
p.000026: 26
p.000026: 4.11 Safety Reporting
p.000027: 27
p.000027: 4.12 Premature Termination or Suspension of a Trial 27
p.000027: 4.13 Final Report(s) by Investigator
p.000028: 28
p.000028: 5. SPONSOR
p.000028: 28
p.000028: 5.1 Quality Assurance and Quality Control
p.000028: 28
p.000028: 5.2 Contract Research Organization (CRO)
p.000028: 28
p.000028: 5.3 Medical Expertise
p.000029: 29
p.000029: 5.4 Trial Design
p.000029: 29
p.000029: 5.5 Trial Management, Data Handling, and Record Keeping 29
p.000029: 5.6 Investigator Selection
p.000031: 31
p.000031: 5.7 Allocation of Responsibilities
p.000032: 32
p.000032: 5.8 Compensation to Subjects and Investigators
p.000032: 32
p.000032: v
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032: 5.9 Financing
p.000032: 32
p.000032: 5.10 Notification/Submission to Regulatory Authority(ies) 33
p.000032: 5.11 Confirmation of Review by IRB/IEC
p.000033: 33
p.000033: 5.12 Information on Investigational Product(s)
p.000033: 33
p.000033: 5.13 Manufacturing, Packaging, Labelling, and Coding Investigational Product(s) 34
p.000033: 5.14 Supplying and Handling Investigational Product(s) 34
p.000033: 5.15 Record Access
p.000036: 36
p.000036: 5.16 Safety Information
p.000036: 36
p.000036: 5.17 Adverse Drug Reaction Reporting
p.000036: 36
p.000036: 5.18 Monitoring
p.000036: 36
p.000036: 5.18.1 Purpose
p.000036: 36
p.000036: 5.18.2 Selection and Qualifications of Monitors 37
p.000036: 5.18.3 Extent and Nature of Monitoring
p.000037: 37
p.000037: 5.18.4 Monitor's Responsibilities
p.000037: 37
p.000037: 5.18.5 Monitoring Procedures
p.000040: 40
p.000040: 5.18.6 Monitoring Report
p.000040: 40
p.000040: 5.19 Audit
p.000040: 40
p.000040: 5.19.1 Purpose
p.000041: 41
p.000041: 5.19.2 Selection and Qualification of Auditors 41
p.000041: 5.19.3 Auditing Procedures
p.000041: 41
p.000041: 5.20 Noncompliance
p.000041: 41
p.000041: 5.21 Premature Termination or Suspension of a Trial 42
p.000041: 5.22 Clinical Trial/Study Reports
p.000042: 42
p.000042: 5.23 Multicentre Trials
p.000042: 42
p.000042: 6. CLINICAL TRIAL PROTOCOL AND PROTOCOL AMENDMENT(S) 43
p.000042: 6.1 General Information
p.000043: 43
p.000043: 6.2 Background Information
p.000043: 43
p.000043: 6.3 Trial Objectives and Purpose
p.000044: 44
p.000044: 6.4 Trial Design
p.000044: 44
p.000044: 6.5 Selection and Withdrawal of Subjects
p.000044: 44
p.000044: 6.6 Treatment of Subjects
p.000045: 45
p.000045: 6.7 Assessment of Efficacy
p.000045: 45
p.000045: 6.8 Assessment of Safety
p.000045: 45
p.000045: vi
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045: 6.9 Statistics
p.000045: 45
p.000045: 6.10 Direct Access to Source Data/Documents
p.000046: 46
p.000046: 6.11 Quality Control and Quality Assurance
p.000046: 46
p.000046: 6.12 Ethics
p.000046: 46
p.000046: 6.13 Data Handling and Record Keeping
p.000046: 46
p.000046: 6.14 Financing and Insurance
p.000046: 46
p.000046: 6.15 Publication Policy
p.000046: 46
p.000046: 6.16 Supplements
p.000046: 46
p.000046: 7. INVESTIGATOR’S BROCHURE
p.000046: 46
p.000046: 7.1 Introduction
p.000046: 46
p.000046: 7.2 General Considerations
p.000047: 47
p.000047: 7.2.1 Title Page
p.000047: 47
p.000047: 7.2.2 Confidentiality Statement
p.000048: 48
p.000048: 7.3 Contents of the Investigator’s Brochure
p.000048: 48
p.000048: 7.3.1 Table of Contents
p.000048: 48
p.000048: 7.3.2 Summary
p.000048: 48
p.000048: 7.3.3 Introduction
p.000048: 48
p.000048: 7.3.4 Physical, Chemical, and Pharmaceutical Properties and Formulation 48
p.000048: 7.3.5 Nonclinical Studies
p.000048: 48
p.000048: 7.3.6 Effects in Humans
p.000050: 50
p.000050: 7.3.7 Summary of Data and Guidance for the Investigator 52
p.000050: 7.4 APPENDIX 1:
p.000053: 53
p.000053: 7.5 APPENDIX 2:
p.000054: 54
p.000054: 8. ESSENTIAL DOCUMENTS FOR THE CONDUCT OF A CLINICAL TRIAL 55
p.000054: 8.1 Introduction
p.000055: 55
p.000055: 8.2 Before the Clinical Phase of the Trial Commences 56
p.000055: 8.3 During the Clinical Conduct of the Trial
p.000064: 64
p.000064: 8.4 After Completion or Termination of the Trial
p.000072: 72
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: vii
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
...
p.000003: into a single report.(see the ICH for Structure and content for Clinical Study Reports)
p.000003:
p.000003: 1.14 Comparator (Product)
p.000003: An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial.
p.000003: 1.15 Compliance (in relation to trials)
p.000003: Adherence to all the trial-related requirements, Good Clinical Practice (GCP) requirements, and the SFDA requirements.
p.000003: 1.16 Confidentiality
p.000003:
p.000003: Prevention of disclosure, to other than authorized individuals, of a sponsor's proprietary information or of
p.000003: a subject's identity.
p.000003: 1.17 Contract
p.000003:
p.000003: A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on
p.000003: delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve
p.000003: as the basis of a contract.
p.000003: 1.18 Coordinating Committee
p.000003:
p.000003: A committee that a sponsor may organize to coordinate the conduct of a multicentre trial.
p.000003:
p.000003: 1.19 Coordinating Investigator
p.000003:
p.000003: An investigator assigned the responsibility for the coordination of investigators at different centres
p.000003: participating in a multicentre trial.
p.000003:
p.000004: 4
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004: 1.20 Contract Research Organization (CRO)
p.000004:
p.000004: A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or
p.000004: more of a sponsor's trial-related duties and functions.
p.000004: 1.21 Direct Access
p.000004: Permission to examine, analyze, verify, and reproduce any records and reports that are important to
p.000004: evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatory authorities, sponsor's
p.000004: monitors and auditors) with direct access should take all reasonable precautions within the constraints of the
p.000004: applicable regulatory requirement(s) to maintain the confidentiality of subjects' identities and sponsor’s proprietary
p.000004: information.
p.000004: 1.22 Documentation
p.000004:
p.000004: All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records, and
p.000004: scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a
p.000004: trial, the factors affecting a trial, and the actions taken.
p.000004: 1.23 Essential Documents
p.000004: Documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data
p.000004: produced (see 8. Essential Documents for the Conduct of a Clinical Trial).
p.000004: 1.24 Good Clinical Practice (GCP)
p.000004:
p.000004: A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical
p.000004: trials that provides assurance that the data and reported results are credible and accurate, and that the rights,
p.000004: integrity, and confidentiality of trial subjects are protected.
p.000004: 1.25 Independent Data-Monitoring Committee (IDMC) (Data and Safety Monitoring Board, Monitoring Committee, Data
p.000004: Monitoring Committee)
p.000004: An independent data-monitoring committee that may be established by the sponsor to assess at intervals the progress of
p.000004: a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to
p.000004: continue, modify, or stop a trial.
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000005: 5
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005: 1.26 Impartial Witness
p.000005:
...
p.000021:
p.000021: (a) That the trial involves research.
p.000022: 22
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022: (b) The purpose of the trial.
p.000022:
p.000022: (c) The trial treatment(s) and the probability for random assignment to each treatment.
p.000022:
p.000022: (d) The trial procedures to be followed, including all invasive procedures.
p.000022:
p.000022: (e) The subject's responsibilities.
p.000022:
p.000022: (f) Those aspects of the trial that are experimental.
p.000022:
p.000022: (g) The reasonably foreseeable risks or inconveniences to the subject and, when applicable, to an embryo, fetus, or
p.000022: nursing infant.
p.000022: (h) The reasonably expected benefits. When there is no intended clinical benefit to the subject, the subject should be
p.000022: made aware of this.
p.000022: (i) The alternative procedure(s) or course(s) of treatment that may be available to the subject, and their
p.000022: important potential benefits and risks.
p.000022: (j) The compensation and/or treatment available to the subject in the event of trial-related injury.
p.000022: (k) The anticipated prorated payment, if any, to the subject for participating in the trial.
p.000022:
p.000022: (l) The anticipated expenses, if any, to the subject for participating in the trial.
p.000022:
p.000022: (m) That the subject's participation in the trial is voluntary and that the subject may refuse to participate or
p.000022: withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is otherwise entitled.
p.000022: (n) That the monitor(s), the auditor(s), the IRB/IEC, and the SFDA will be granted direct access to the subject's
p.000022: original medical records for verification of clinical trial procedures and/or data, without violating the
p.000022: confidentiality of the subject, to the extent permitted by the applicable laws and regulations and that, by signing a
p.000022: written informed consent form, the subject or the subject's legally acceptable representative is authorizing such
p.000022: access.
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023: (o) That records identifying the subject will be kept confidential and, to the extent permitted by the applicable laws
p.000023: and/or regulations, will not be made publicly available. If the results of the trial are published, the subject’s
p.000023: identity will remain confidential.
p.000023: (p) That the subject or the subject's legally acceptable representative will be informed in a timely manner if
p.000023: information becomes available that may be relevant to the subject's willingness to continue participation in
p.000023: the trial.
p.000023: (q) The person(s) to contact for further information regarding the trial and the rights of trial subjects, and whom to
p.000023: contact in the event of trial-related injury.
p.000023: (r) The foreseeable circumstances and/or reasons under which the subject's participation in the trial may be
p.000023: terminated.
p.000023: (s) The expected duration of the subject's participation in the trial.
p.000023:
p.000023: (t) The approximate number of subjects involved in the trial.
p.000023:
p.000023: 4.8.11 Prior to participation in the trial, the subject or the subject's legally acceptable representative
p.000023: should receive a copy of the signed and dated written informed consent form and any other written information
p.000023: provided to the subjects. During a subject’s participation in the trial, the subject or the subject’s legally
p.000023: acceptable representative should receive a copy of the signed and dated consent form updates and a copy of any
p.000023: amendments to the written information provided to subjects.
...
p.000025: 5.18.4 (n)). Sponsors should provide guidance to investigators and/or the investigators' designated representatives on
p.000025: making such corrections. Sponsors should have written procedures to assure that changes or corrections in CRFs made by
p.000025: sponsor's designated representatives are documented, are necessary, and are endorsed by the investigator. The
p.000025: investigator should retain records of the changes and corrections.
p.000025: 4.9.4 The investigator/institution should maintain the trial documents as specified in Essential Documents for the
p.000025: Conduct of a Clinical Trial (see 8.) and as required by the applicable regulatory requirement(s). The
p.000025: investigator/institution should take measures to prevent accidental or premature destruction of these documents.
p.000025: 4.9.5 Essential documents should be retained until at least 2 years after the last approval of a marketing
p.000025: application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or
p.000025: at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product.
p.000025: These documents should be retained for a longer period however if required by the applicable regulatory requirements or
p.000025: by an agreement with the sponsor. It is the responsibility of the sponsor to inform the investigator/institution as to
p.000025: when these documents no longer need to be retained (see 5.5.12).
p.000025:
p.000025: 4.9.6 The financial aspects of the trial should be documented in an agreement between the sponsor and the
p.000025: investigator/institution.
p.000025: 4.9.7 Upon request of the monitor, auditor, IRB/IEC, or SFDA, the investigator/institution should make available for
p.000025: direct access all requested trial-related records.
p.000025: 4.10 Progress Reports
p.000025: 4.10.1 The investigator should submit written summaries of the trial status to the IRB/IEC annually, or
p.000025: more frequently, if requested by the IRB/IEC.
p.000025: 4.10.2 The investigator should promptly provide written reports to the sponsor, the IRB/IEC (see 3.3.8) and, where
p.000025: applicable, the institution on any changes significantly affecting the conduct of the trial, and/or increasing the risk
p.000025: to subjects.
p.000025:
p.000025:
p.000025:
p.000026: 26
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026: 4.11 Safety Reporting
p.000026: 4.11.1 All serious adverse events (SAEs) should be reported immediately to the sponsor except for those SAEs that
p.000026: the protocol or other document (e.g., Investigator's Brochure) identifies as not needing immediate
p.000026: reporting. The immediate reports should be followed promptly by detailed, written reports. The immediate and
p.000026: follow-up reports should identify subjects by unique code numbers assigned to the trial subjects rather than by the
p.000026: subjects' names, personal identification numbers, and/or addresses. The investigator should also comply with the
p.000026: SFDA requirement(s) related to the reporting of unexpected serious adverse drug reactions to the SFDA and the IRB/IEC.
p.000026: 4.11.2 Adverse events and/or laboratory abnormalities identified in the protocol as critical to safety evaluations
p.000026: should be reported to the sponsor according to the reporting requirements and within the time periods
p.000026: specified by the sponsor in the protocol.
...
p.000026: written explanation of the termination or suspension.
p.000026: 4.12.2 If the sponsor terminates or suspends a trial (see 5.21), the investigator should promptly inform the
p.000026: institution where applicable and the investigator/institution should promptly inform the IRB/IEC and provide the
p.000026: IRB/IEC a detailed written explanation of the termination or suspension.
p.000026:
p.000026:
p.000026:
p.000027: 27
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027: 4.12.3 If the IRB/IEC terminates or suspends its approval/favourable opinion of a trial (see
p.000027: 3.1.2 and 3.3.9), the investigator should inform the institution where applicable and the investigator/institution
p.000027: should promptly notify the sponsor and provide the sponsor with a detailed written explanation of the termination or
p.000027: suspension.
p.000027: 4.13 Final Report(s) by Investigator
p.000027: Upon completion of the trial, the investigator, where applicable, should inform the institution; the
p.000027: investigator/institution should provide the IRB/IEC with a summary of the trial’s outcome, and the SFDA with any
p.000027: reports required.
p.000027:
p.000027: 5. SPONSOR
p.000027: 5.1 Quality Assurance and Quality Control
p.000027: 5.1.1 The sponsor is responsible for implementing and maintaining quality assurance and quality control systems
p.000027: with written SOPs to ensure that trials are conducted and data are generated, documented (recorded), and
p.000027: reported in compliance with the protocol, GCP, and the SFDA requirement(s).
p.000027: 5.1.2 The sponsor is responsible for securing agreement from all involved parties to ensure direct access (see 1.21)
p.000027: to all trial related sites, source data/documents, and reports for the purpose of monitoring and auditing by the
p.000027: sponsor, and inspection by domestic and foreign regulatory authorities.
p.000027: 5.1.3 Quality control should be applied to each stage of data handling to ensure that all data are reliable and have
p.000027: been processed correctly.
p.000027: 5.1.4 Agreements, made by the sponsor with the investigator/institution and any other parties involved with the
p.000027: clinical trial, should be in writing, as part of the protocol or in a separate agreement.
p.000027: 5.2 Contract Research Organization (CRO)
p.000027: 5.2.1 A sponsor may transfer any or all of the sponsor's trial-related duties and functions to a CRO, but the
p.000027: ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor. The CRO should
p.000027: implement quality assurance and quality control.
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028: 5.2.2 Any trial-related duty and function that is transferred to and assumed by a CRO should be specified in
p.000028: writing.
p.000028: 5.2.3 Any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by
p.000028: the sponsor.
p.000028: 5.2.4 All references to a sponsor in this guideline also apply to a CRO to the extent that a CRO has assumed the
p.000028: trial related duties and functions of a sponsor.
p.000028: 5.3 Medical Expertise
p.000028: The sponsor should designate appropriately qualified medical personnel who will be readily available to
p.000028: advise on trial related medical questions or problems. If necessary, outside consultant(s) may be appointed
p.000028: for this purpose.
p.000028: 5.4 Trial Design
...
p.000028: Structure and Content of Clinical Study Reports, and other appropriate ICH guidance on trial design, protocol and
p.000028: conduct.
p.000028: 5.5 Trial Management, Data Handling, and Record Keeping
p.000028: 5.5.1 The sponsor should utilize appropriately qualified individuals to supervise the overall conduct of
p.000028: the trial, to handle the data, to verify the data, to conduct the statistical analyses, and to prepare the trial
p.000028: reports.
p.000028: 5.5.2 The sponsor may consider establishing an independent data-monitoring committee (IDMC) to assess the
p.000028: progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to
p.000028: recommend to the sponsor whether to continue, modify, or stop a trial. The IDMC should have written operating
p.000028: procedures and maintain written records of all its meetings.
p.000028:
p.000028:
p.000028:
p.000029: 29
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: 5.5.3 When using electronic trial data handling and/or remote electronic trial data systems, the sponsor should:
p.000029: (a) Ensure and document that the electronic data processing system(s) conforms to the sponsor’s established
p.000029: requirements for completeness, accuracy, reliability, and consistent intended performance (i.e. validation).
p.000029: (b) Maintains SOPs for using these systems.
p.000029:
p.000029: (c) Ensure that the systems are designed to permit data changes in such a way that the data changes are documented and
p.000029: that there is no deletion of entered data (i.e. maintain an audit trail, data trail, edit trail).
p.000029: (d) Maintain a security system that prevents unauthorized access to the data.
p.000029:
p.000029: (e) Maintain a list of the individuals who are authorized to make data changes (see 4.1.5 and 4.9.3).
p.000029: (f) Maintain adequate backup of the data.
p.000029:
p.000029: (g) Safeguard the blinding, if any (e.g. maintain the blinding during data entry and processing).
p.000029: 5.5.4 If data are transformed during processing, it should always be possible to compare the original data and
p.000029: observations with the processed data.
p.000029: 5.5.5 The sponsor should use an unambiguous subject identification code (see 1.58) that allows identification of all
p.000029: the data reported for each subject.
p.000029: 5.5.6 The sponsor, or other owners of the data, should retain all of the sponsor-specific essential documents
p.000029: pertaining to the trial (see 8. Essential Documents for the Conduct of a Clinical Trial).
p.000029: 5.5.7 The sponsor should retain all sponsor-specific essential documents in conformance with the SFDA requirement(s)
p.000029: where the product is approved, and/or where the sponsor intends to apply for approval(s).
p.000029: 5.5.8 If the sponsor discontinues the clinical development of an investigational product (i.e. for any or all
p.000029: indications, routes of administration, or dosage forms), the sponsor should
p.000029:
p.000030: 30
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030: maintain all sponsor-specific essential documents for at least 2 years after formal discontinuation or in
p.000030: conformance with the SFDA requirement(s).
p.000030: 5.5.9 If the sponsor discontinues the clinical development of an investigational product, the sponsor
p.000030: should notify all the trial investigators/institutions and all the regulatory authorities.
p.000030: 5.5.10 Any transfer of ownership of the data should be reported to the SFDA.
...
p.000034: trial and documentation thereof. The procedures should address adequate and safe receipt, handling, storage,
p.000034: dispensing, retrieval of unused product from subjects, and return of unused investigational product(s) to the sponsor
p.000034: (or alternative disposition if authorized by the sponsor and in compliance with the SFDA requirement(s)).
p.000034: 5.14.4 The sponsor should:
p.000034:
p.000034: (a) Ensure timely delivery of investigational product(s) to the investigator(s).
p.000034:
p.000034: (b) Maintain records that document shipment, receipt, disposition, return, and destruction of the investigational
p.000034: product(s) (see 8. Essential Documents for the Conduct of a Clinical Trial).
p.000034: (c) Maintain a system for retrieving investigational products and documenting this retrieval (e.g. for deficient
p.000034: product recall, reclaim after trial completion, expired product reclaim).
p.000034: (d) Maintain a system for the disposition of unused investigational product(s) and for the documentation of this
p.000034: disposition.
p.000034: 5.14.5 The sponsor should:
p.000034:
p.000034: (a) Take steps to ensure that the investigational product(s) are stable over the period of use.
p.000034: (b) Maintain sufficient quantities of the investigational product(s) used in the trials to reconfirm
p.000034: specifications, should this become necessary, and maintain records of batch sample analyses and characteristics. To the
p.000034: extent stability permits, samples should be retained either until the analyses of the trial data are complete or as
p.000034: required by the SFDA requirement(s), whichever represents the longer retention period.
p.000034:
p.000034:
p.000034:
p.000034:
p.000035: 35
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: 5.15 Record Access
p.000035: 5.15.1 The sponsor should ensure that it is specified in the protocol or other written agreement that the
p.000035: investigator(s)/institution(s) provide direct access to source data/documents for trial-related monitoring, audits,
p.000035: IRB/IEC review, and regulatory inspection.
p.000035: 5.15.2 The sponsor should verify that each subject has consented, in writing, to direct access to his/her original
p.000035: medical records for trial-related monitoring, audit, IRB/IEC review, and regulatory inspection.
p.000035: 5.16 Safety Information
p.000035: 5.16.1 The sponsor is responsible for the ongoing safety evaluation of the investigational product(s).
p.000035: 5.16.2 The sponsor should promptly notify all concerned investigator(s)/institution(s) and the SFDA of findings that
p.000035: could affect adversely the safety of subjects, impact the conduct of the trial, or alter the IRB/IEC's
p.000035: approval/favourable opinion to continue the trial.
p.000035: 5.17 Adverse Drug Reaction Reporting
p.000035: 5.17.1 The sponsor should expedite the reporting to all concerned
p.000035: investigator(s)/institutions(s), to the IRB(s)/IEC(s), where required, and to the SFDA of all adverse drug reactions
p.000035: (ADRs) that are both serious and unexpected.
p.000035: 5.17.2 Such expedited reports should comply with the SFDA requirement(s) and with the ICH Guideline for Clinical
p.000035: Safety Data Management: Definitions and Standards for Expedited Reporting.
p.000035: 5.17.3 The sponsor should submit to the SFDA all safety updates and periodic reports, as required by SFDA
p.000035: requirement(s).
p.000035: 5.18 Monitoring
p.000035: 5.18.1 Purpose
p.000035: The purposes of trial monitoring are to verify that:
p.000035:
p.000035: (a) The rights and well-being of human subjects are protected.
p.000035:
p.000035: (b) The reported trial data are accurate, complete, and verifiable from source documents.
p.000035:
p.000035:
p.000035:
p.000036: 36
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
...
p.000039: sponsor’s designated representative.
p.000039: 5.19 Audit
p.000039: If or when sponsors perform audits, as part of implementing quality assurance, they should consider:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000040: 40
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040: 5.19.1 Purpose
p.000040: The purpose of a sponsor's audit, which is independent of and separate from routine monitoring or quality control
p.000040: functions, should be to evaluate trial conduct and compliance with the protocol, SOPs, GCP, and the SFDA
p.000040: requirements.
p.000040: 5.19.2 Selection and Qualification of Auditors
p.000040: (a) The sponsor should appoint individuals, who are independent of the clinical trials/systems, to conduct
p.000040: audits.
p.000040: (b) The sponsor should ensure that the auditors are qualified by training and experience to conduct audits properly. An
p.000040: auditor’s qualifications should be documented.
p.000040: 5.19.3 Auditing Procedures
p.000040: (a) The sponsor should ensure that the auditing of clinical trials/systems is conducted in accordance with the
p.000040: sponsor's written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit
p.000040: reports.
p.000040: (b) The sponsor's audit plan and procedures for a trial audit should be guided by the importance of the trial to
p.000040: submissions to SFDA , the number of subjects in the trial, the type and complexity of the trial, the level of risks to
p.000040: the trial subjects, and any identified problem(s).
p.000040: (c) The observations and findings of the auditor(s) should be documented.
p.000040:
p.000040: (d) To preserve the independence and value of the audit function, the SFDA will not routinely request the audit
p.000040: reports. SFDA may seek access to an audit report on a case by case basis when evidence of serious GCP non-compliance
p.000040: exists, or in the course of legal proceedings.
p.000040: (e) When required by applicable law or regulation, the sponsor should provide an audit certificate.
p.000040: 5.20 Noncompliance
p.000040: 5.20.1 Noncompliance with the protocol, SOPs, GCP, and/or SFDA requirement(s) by an
p.000040: investigator/institution, or by member(s) of the sponsor's staff should lead to prompt action by the sponsor to secure
p.000040: compliance.
p.000041: 41
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: 5.20.2 If the monitoring and/or auditing identifies serious and/or persistent noncompliance on the part of an
p.000041: investigator/institution, the sponsor should terminate the investigator's/institution’s participation
p.000041: in the trial. When an investigator's/institution’s participation is terminated because of noncompliance, the
p.000041: sponsor should notify promptly the SFDA.
p.000041: 5.21 Premature Termination or Suspension of a Trial
p.000041: If a trial is prematurely terminated or suspended, the sponsor should promptly inform the
p.000041: investigators/institutions, and the SFDA of the termination or suspension and the reason(s) for the termination or
p.000041: suspension. The IRB/IEC should also be informed promptly and provided the reason(s) for the termination or suspension
p.000041: by the sponsor or by the investigator/institution, as specified by the SFDA requirement(s).
p.000041: 5.22 Clinical Trial/Study Reports
p.000041: Whether the trial is completed or prematurely terminated, the sponsor should ensure that the clinical trial reports are
p.000041: prepared and provided to the regulatory agency(ies). The sponsor should also ensure that the clinical trial reports in
...
p.000044: 6.7.2 Methods and timing for assessing, recording, and analysing of efficacy parameters.
p.000044:
p.000044: 6.8 Assessment of Safety
p.000044: 6.8.1 Specification of safety parameters.
p.000044: 6.8.2 The methods and timing for assessing, recording, and analysing safety parameters.
p.000044: 6.8.3 Procedures for eliciting reports of and for recording and reporting adverse event and intercurrent illnesses.
p.000044: 6.8.4 The type and duration of the follow-up of subjects after adverse events.
p.000044:
p.000044: 6.9 Statistics
p.000044: 6.9.1 A description of the statistical methods to be employed, including timing of any planned interim
p.000044: analysis(ses).
p.000044: 6.9.2 The number of subjects planned to be enrolled. In multicentre trials, the numbers of enrolled subjects
p.000044: projected for each trial site should be specified. Reason for choice of sample size, including reflections on (or
p.000044: calculations of) the power of the trial and clinical justification.
p.000044: 6.9.3 The level of significance to be used.
p.000044: 6.9.4 Criteria for the termination of the trial.
p.000044: 6.9.5 Procedure for accounting for missing, unused, and spurious data.
p.000044: 6.9.6 Procedures for reporting any deviation(s) from the original statistical plan (any deviation(s) from
p.000044: the original statistical plan should be described and justified in protocol and/or in the final report, as
p.000044: appropriate).
p.000044: 6.9.7 The selection of subjects to be included in the analyses (e.g. all randomized subjects, all dosed subjects,
p.000044: all eligible subjects, evaluable subjects).
p.000044:
p.000044:
p.000044:
p.000045: 45
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045: 6.10 Direct Access to Source Data/Documents
p.000045: The sponsor should ensure that it is specified in the protocol or other written agreement that the
p.000045: investigator(s)/institution(s) will permit trial-related monitoring, audits, IRB/IEC review, and SFDA inspection(s),
p.000045: providing direct access to source data/documents.
p.000045: 6.11 Quality Control and Quality Assurance
p.000045:
p.000045:
p.000045: 6.12 Ethics
p.000045: Description of ethical considerations relating to the trial.
p.000045:
p.000045:
p.000045: 6.13 Data Handling and Record Keeping
p.000045:
p.000045:
p.000045: 6.14 Financing and Insurance
p.000045: Financing and insurance if not addressed in a separate agreement.
p.000045:
p.000045:
p.000045: 6.15 Publication Policy
p.000045: Publication policy, if not addressed in a separate agreement.
p.000045:
p.000045:
p.000045: 6.16 Supplements
p.000045: (NOTE: Since the protocol and the clinical trial/study report are closely related, further relevant information can be
p.000045: found in the ICH Guideline for Structure and Content of Clinical Study Reports.)
p.000045:
p.000045: 7. INVESTIGATOR’S BROCHURE
p.000045:
p.000045:
p.000045: 7.1 Introduction
p.000045: The Investigator's Brochure (IB) is a compilation of the clinical and nonclinical data on the investigational
p.000045: product(s) that are relevant to the study of the product(s) in human subjects. Its purpose is to provide the
p.000045: investigators and others involved in the trial with the information to facilitate their understanding of the rationale
p.000045: for, and their compliance with, many key features of the protocol, such as the dose, dose frequency/interval, methods
p.000045: of administration: and safety monitoring procedures. The IB also provides insight to support the clinical management of
p.000045: the study subjects during the course of the clinical trial. The information should be presented in a
p.000045:
p.000046: 46
p.000046:
p.000046:
p.000046:
p.000046:
p.000046:
p.000046: concise, simple, objective, balanced, and non-promotional form that enables a clinician, or potential
...
p.000066: (see 8.2.15.) X X
p.000066:
p.000066:
p.000066:
p.000066: 8.3.9 CERTIFICATE(S) OF ANALYSIS FOR NEW BATCHES OF INVESTIGATIONAL PRODUCTS
p.000066: (see 8.2.16) X
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000067: 67
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: Title of Document Purpose
p.000067: Located in Files of
p.000067:
p.000067:
p.000067:
p.000067: Investigator/
p.000067: Institution
p.000067: Sponsor
p.000067:
p.000067:
p.000067: 8.3.10 MONITORING VISIT REPORTS
p.000067: To document site visits by, and findings of, X the monitor
p.000067:
p.000067:
p.000067:
p.000067: 8.3.11 RELEVANT COMMUNICATIONS OTHER
p.000067: THAN SITE VISITS
p.000067: - letters
p.000067: - meeting notes
p.000067: - notes of telephone calls
p.000067: To document any agreements or significant X X discussions
p.000067: regarding trial administration,
p.000067: protocol violations, trial conduct, adverse event (AE) reporting
p.000067:
p.000067:
p.000067: 8.3.12 SIGNED INFORMED
p.000067: CONSENT FORMS
p.000067: To document that consent is obtained in X accordance with GCP and protocol and dated
p.000067: prior to participation of each subject in trial. Also to document direct access permission (see 8.2.3)
p.000067:
p.000067: 8.3.13 SOURCE DOCUMENTS To document the existence of the subject and X
p.000067: substantiate integrity of trial data collected. To include original documents related to the trial, to medical
p.000067: treatment, and history of subject
p.000067:
p.000067:
p.000067:
p.000067:
p.000068: 68
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068: Title of Document Purpose
p.000068: Located in Files of
p.000068:
p.000068:
p.000068:
p.000068: Investigator/
p.000068: Institution
p.000068: Sponsor
p.000068:
p.000068:
p.000068: 8.3.14 SIGNED, DATED AND
p.000068: COMPLETED
p.000068: CASE REPORT FORMS (CRF)
p.000068: To document that the investigator or authorised member of the investigator’s staff confirms the
p.000068: observations recorded
p.000068: X
p.000068: (copy)
p.000068: X
p.000068: (original)
p.000068:
p.000068:
p.000068: 8.3.15 DOCUMENTATION OF CRF CORRECTIONS
p.000068: To document all changes/additions or corrections made to CRF after initial data were recorded
p.000068: X
p.000068: (copy)
p.000068: X
p.000068: (original)
p.000068:
p.000068:
p.000068:
p.000068: 8.3.16 NOTIFICATION BY
p.000068: ORIGINATING INVESTIGATOR TO SPONSOR OF SERIOUS ADVERSE EVENTS AND RELATED REPORTS
p.000068: Notification by originating investigator to X X sponsor of
p.000068: serious adverse events and related
p.000068: reports in accordance with 4.11
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000069: 69
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
...
Social / Age
Searching for indicator age:
(return to top)
p.000049: described under the following headings where appropriate:
p.000049: − Single dose
p.000049:
p.000049: − Repeated dose
p.000049:
p.000049: − Carcinogenicity
p.000049:
p.000049: − Special studies (e.g. irritancy and sensitisation)
p.000049:
p.000049: − Reproductive toxicity
p.000049:
p.000049: − Genotoxicity (mutagenicity)
p.000049:
p.000049: 7.3.6 Effects in Humans Introduction:
p.000049: A thorough discussion of the known effects of the investigational product(s) in humans should be provided,
p.000049: including information on pharmacokinetics, metabolism, pharmacodynamics, dose response, safety,
p.000049: efficacy, and other pharmacological activities. Where possible, a summary of each completed clinical
p.000049: trial should be provided. Information should also be provided regarding results of any use of the
p.000049: investigational product(s) other than from in clinical trials, such as from experience during marketing.
p.000049: (a) Pharmacokinetics and Product Metabolism in Humans
p.000050: 50
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050: − A summary of information on the pharmacokinetics of the investigational product(s) should be presented, including the
p.000050: following, if available:
p.000050: − Pharmacokinetics (including metabolism, as appropriate, and absorption, plasma protein binding, distribution,
p.000050: and elimination).
p.000050: − Bioavailability of the investigational product (absolute, where possible, and/or relative) using a reference
p.000050: dosage form.
p.000050: − Population subgroups (e.g., gender, age, and impaired organ function).
p.000050:
p.000050: − Interactions (e.g., product-product interactions and effects of food).
p.000050:
p.000050: − Other pharmacokinetic data (e.g., results of population studies performed within clinical trial(s).
p.000050: (b) Safety and Efficacy
p.000050:
p.000050: A summary of information should be provided about the investigational product's/products'
p.000050: (including metabolites, where appropriate) safety, pharmacodynamics, efficacy, and dose
p.000050: response that were obtained from preceding trials in humans (healthy volunteers and/or patients).
p.000050: The implications of this information should be discussed. In cases where a number of clinical trials have been
p.000050: completed, the use of summaries of safety and efficacy across multiple trials by indications in subgroups
p.000050: may provide a clear presentation of the data. Tabular summaries of adverse drug reactions for all the clinical
p.000050: trials (including those for all the studied indications) would be useful. Important differences in adverse
p.000050: drug reaction patterns/incidences across indications or subgroups should be discussed.
p.000050: The IB should provide a description of the possible risks and adverse drug reactions to be anticipated on the basis of
p.000050: prior experiences with the product under investigation and with related products. A description should also be provided
p.000050: of the precautions or special monitoring to be done as part of the investigational use of the product(s).
...
Social / Ethnicity
Searching for indicator ethnic:
(return to top)
p.000010:
p.000010: An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g.,
p.000010: Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics
p.000010: for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for
p.000010: Expedited Reporting).
p.000010:
p.000010: 1.61 Vulnerable Subjects
p.000010:
p.000010: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether
p.000010: justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a
p.000010: hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure,
p.000010: such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory
p.000010: personnel, employees of the
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects
p.000011: include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons,
p.000011: patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those
p.000011: incapable of giving consent.
p.000011: 1.62 Well-being (of the trial subjects)
p.000011:
p.000011: The physical and mental integrity of the subjects participating in a clinical trial.
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2. THE PRINCIPLES OF ICH GCP
p.000012:
p.000012: 2.1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the
p.000012: Declaration of Helsinki, and that are consistent with GCP and the with SFDA requirement(s).
p.000012: 2.2 Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated
p.000012: benefit for the individual trial subject and society. A trial should be initiated and continued only if the
p.000012: anticipated benefits justify the risks.
p.000012: 2.3 The rights, safety, and well-being of the trial subjects are the most important
p.000012: considerations and should prevail over interests of science and society.
...
Social / Fetus/Neonate
Searching for indicator fetus:
(return to top)
p.000021: personally dated the informed consent form, the witness should sign and personally date the consent form. By
p.000021: signing the consent form, the witness attests that the information in the consent form and any other written
p.000021: information was accurately explained to, and apparently understood by, the subject or the subject's legally
p.000021: acceptable representative, and that informed consent was freely given by the subject or the subject’s legally
p.000021: acceptable representative.
p.000021: 4.8.10 Both the informed consent discussion and the written informed consent form and any other written information
p.000021: to be provided to subjects should include explanations of the following:
p.000021:
p.000021: (a) That the trial involves research.
p.000022: 22
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022: (b) The purpose of the trial.
p.000022:
p.000022: (c) The trial treatment(s) and the probability for random assignment to each treatment.
p.000022:
p.000022: (d) The trial procedures to be followed, including all invasive procedures.
p.000022:
p.000022: (e) The subject's responsibilities.
p.000022:
p.000022: (f) Those aspects of the trial that are experimental.
p.000022:
p.000022: (g) The reasonably foreseeable risks or inconveniences to the subject and, when applicable, to an embryo, fetus, or
p.000022: nursing infant.
p.000022: (h) The reasonably expected benefits. When there is no intended clinical benefit to the subject, the subject should be
p.000022: made aware of this.
p.000022: (i) The alternative procedure(s) or course(s) of treatment that may be available to the subject, and their
p.000022: important potential benefits and risks.
p.000022: (j) The compensation and/or treatment available to the subject in the event of trial-related injury.
p.000022: (k) The anticipated prorated payment, if any, to the subject for participating in the trial.
p.000022:
p.000022: (l) The anticipated expenses, if any, to the subject for participating in the trial.
p.000022:
p.000022: (m) That the subject's participation in the trial is voluntary and that the subject may refuse to participate or
p.000022: withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is otherwise entitled.
p.000022: (n) That the monitor(s), the auditor(s), the IRB/IEC, and the SFDA will be granted direct access to the subject's
p.000022: original medical records for verification of clinical trial procedures and/or data, without violating the
p.000022: confidentiality of the subject, to the extent permitted by the applicable laws and regulations and that, by signing a
p.000022: written informed consent form, the subject or the subject's legally acceptable representative is authorizing such
p.000022: access.
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
...
Social / Homeless Persons
Searching for indicator homeless:
(return to top)
p.000010: Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics
p.000010: for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for
p.000010: Expedited Reporting).
p.000010:
p.000010: 1.61 Vulnerable Subjects
p.000010:
p.000010: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether
p.000010: justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a
p.000010: hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure,
p.000010: such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory
p.000010: personnel, employees of the
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects
p.000011: include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons,
p.000011: patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those
p.000011: incapable of giving consent.
p.000011: 1.62 Well-being (of the trial subjects)
p.000011:
p.000011: The physical and mental integrity of the subjects participating in a clinical trial.
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2. THE PRINCIPLES OF ICH GCP
p.000012:
p.000012: 2.1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the
p.000012: Declaration of Helsinki, and that are consistent with GCP and the with SFDA requirement(s).
p.000012: 2.2 Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated
p.000012: benefit for the individual trial subject and society. A trial should be initiated and continued only if the
p.000012: anticipated benefits justify the risks.
p.000012: 2.3 The rights, safety, and well-being of the trial subjects are the most important
p.000012: considerations and should prevail over interests of science and society.
p.000012: 2.4 The available nonclinical and clinical information on an investigational product should be adequate to support
...
Social / Infant
Searching for indicator infant:
(return to top)
p.000021: signing the consent form, the witness attests that the information in the consent form and any other written
p.000021: information was accurately explained to, and apparently understood by, the subject or the subject's legally
p.000021: acceptable representative, and that informed consent was freely given by the subject or the subject’s legally
p.000021: acceptable representative.
p.000021: 4.8.10 Both the informed consent discussion and the written informed consent form and any other written information
p.000021: to be provided to subjects should include explanations of the following:
p.000021:
p.000021: (a) That the trial involves research.
p.000022: 22
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022: (b) The purpose of the trial.
p.000022:
p.000022: (c) The trial treatment(s) and the probability for random assignment to each treatment.
p.000022:
p.000022: (d) The trial procedures to be followed, including all invasive procedures.
p.000022:
p.000022: (e) The subject's responsibilities.
p.000022:
p.000022: (f) Those aspects of the trial that are experimental.
p.000022:
p.000022: (g) The reasonably foreseeable risks or inconveniences to the subject and, when applicable, to an embryo, fetus, or
p.000022: nursing infant.
p.000022: (h) The reasonably expected benefits. When there is no intended clinical benefit to the subject, the subject should be
p.000022: made aware of this.
p.000022: (i) The alternative procedure(s) or course(s) of treatment that may be available to the subject, and their
p.000022: important potential benefits and risks.
p.000022: (j) The compensation and/or treatment available to the subject in the event of trial-related injury.
p.000022: (k) The anticipated prorated payment, if any, to the subject for participating in the trial.
p.000022:
p.000022: (l) The anticipated expenses, if any, to the subject for participating in the trial.
p.000022:
p.000022: (m) That the subject's participation in the trial is voluntary and that the subject may refuse to participate or
p.000022: withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is otherwise entitled.
p.000022: (n) That the monitor(s), the auditor(s), the IRB/IEC, and the SFDA will be granted direct access to the subject's
p.000022: original medical records for verification of clinical trial procedures and/or data, without violating the
p.000022: confidentiality of the subject, to the extent permitted by the applicable laws and regulations and that, by signing a
p.000022: written informed consent form, the subject or the subject's legally acceptable representative is authorizing such
p.000022: access.
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023: (o) That records identifying the subject will be kept confidential and, to the extent permitted by the applicable laws
...
Social / Linguistic Proficiency
Searching for indicator language:
(return to top)
p.000020: of Helsinki. Prior to the beginning of the trial, the investigator should have the IRB/IEC's written
p.000020: approval/favourable opinion of the written informed consent form and any other written information to be provided to
p.000020: subjects.
p.000020: 4.8.2 The written informed consent form and any other written information to be provided to subjects should be
p.000020: revised whenever important new information becomes available that may be relevant to the subject’s consent. Any revised
p.000020: written informed consent form, and written information should receive the IRB/IEC's approval/favourable opinion in
p.000020: advance of use. The subject or the subject’s legally acceptable representative should be informed in a timely manner if
p.000020: new information becomes available that may be relevant to the subject’s willingness to continue participation in the
p.000020: trial. The communication of this information should be documented.
p.000020: 4.8.3 Neither the investigator, nor the trial staff, should coerce or unduly influence a subject to participate or
p.000020: to continue to participate in a trial.
p.000020: 4.8.4 None of the oral and written information concerning the trial, including the written informed
p.000020: consent form, should contain any language that causes the subject or the subject's legally acceptable representative to
p.000020: waive or to appear to waive any legal rights, or that releases or appears to release the investigator, the institution,
p.000020: the sponsor, or their agents from liability for negligence.
p.000020:
p.000020:
p.000021: 21
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 4.8.5 The investigator, or a person designated by the investigator, should fully inform the subject or, if the
p.000021: subject is unable to provide informed consent, the subject's legally acceptable representative, of all pertinent
p.000021: aspects of the trial including the written information and the approval/ favourable opinion by the IRB/IEC.
p.000021: 4.8.6 The language used in the oral and written information about the trial, including the written informed
p.000021: consent form, should be as non-technical as practical and should be understandable to the
p.000021: subject or the subject's legally acceptable representative and the impartial witness, where applicable.
p.000021: 4.8.7 Before informed consent may be obtained, the investigator, or a person designated by the investigator,
p.000021: should provide the subject or the subject's legally acceptable representative ample time and opportunity to inquire
p.000021: about details of the trial and to decide whether or not to participate in the trial. All questions about the
p.000021: trial should be answered to the satisfaction of the subject or the subject's legally acceptable representative.
p.000021: 4.8.8 Prior to a subject’s participation in the trial, the written informed consent form should be signed and
p.000021: personally dated by the subject or by the subject's legally acceptable representative, and by the person who
p.000021: conducted the informed consent discussion.
p.000021: 4.8.9 If a subject is unable to read or if a legally acceptable representative is unable to read, an impartial
p.000021: witness should be present during the entire informed consent discussion. After the written informed consent form and
p.000021: any other written information to be provided to subjects, is read and explained to the subject or the
...
Social / Marital Status
Searching for indicator single:
(return to top)
p.000001: Definitions and Standards for Expedited Reporting).
p.000001:
p.000001: 1.3 Amendment (to the protocol)
p.000001:
p.000001: See Protocol Amendment.
p.000001:
p.000001: 1.4 Applicable Regulatory Requirement(s)
p.000001: Any law(s) and regulation(s) addressing the conduct of clinical trials of investigational products.
p.000001:
p.000001:
p.000001:
p.000001:
p.000002: 2
p.000002:
p.000002:
p.000002:
p.000002:
p.000002:
p.000002: 1.5 Approval (in relation to Institutional Review Boards)
p.000002:
p.000002: The affirmative decision of the IRB that the clinical trial has been reviewed and may be conducted at
p.000002: the institution site within the constraints set forth by the IRB, the institution, Good Clinical Practice (GCP), and
p.000002: with the SFDA requirements.
p.000002: 1.6 Audit
p.000002:
p.000002: A systematic and independent examination of trial related activities and documents to determine whether the evaluated
p.000002: trial related activities were conducted, and the data were recorded, analyzed and accurately reported
p.000002: according to the protocol, sponsor's standard operating procedures (SOPs), Good Clinical Practice (GCP), and the
p.000002: SFDA requirement(s).
p.000002: 1.7 Audit Certificate
p.000002:
p.000002: A declaration of confirmation by the auditor that an audit has taken place.
p.000002:
p.000002: 1.8 Audit Report
p.000002:
p.000002: A written evaluation by the sponsor's auditor of the results of the audit.
p.000002:
p.000002: 1.9 Audit Trail
p.000002:
p.000002: Documentation that allows reconstruction of the course of events.
p.000002:
p.000002: 1.10 Blinding/Masking
p.000002: A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s).
p.000002: Single-blinding usually refers to the subject(s) being unaware, and double- blinding usually refers to the
p.000002: subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment
p.000002: assignment(s).
p.000002: 1.11 Case Report Form (CRF)
p.000002:
p.000002: A printed, optical, or electronic document designed to record all of the protocol required information to
p.000002: be reported to the sponsor on each trial subject.
p.000002: 1.12 Clinical Trial/Study
p.000002:
p.000002: Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other
p.000002: pharmacodynamic effects of an investigational product(s), and/or to identify any
p.000002:
p.000003: 3
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003: adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and
p.000003: excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. The terms
p.000003: clinical trial and clinical study are synonymous.
p.000003: 1.13 Clinical Trial/Study Report
p.000003: A written description of a trial/study of any therapeutic, prophylactic, or diagnostic agent conducted in
p.000003: human subjects, in which the clinical and statistical description, presentations, and analyses are fully integrated
p.000003: into a single report.(see the ICH for Structure and content for Clinical Study Reports)
p.000003:
p.000003: 1.14 Comparator (Product)
p.000003: An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial.
p.000003: 1.15 Compliance (in relation to trials)
p.000003: Adherence to all the trial-related requirements, Good Clinical Practice (GCP) requirements, and the SFDA requirements.
p.000003: 1.16 Confidentiality
p.000003:
p.000003: Prevention of disclosure, to other than authorized individuals, of a sponsor's proprietary information or of
p.000003: a subject's identity.
p.000003: 1.17 Contract
p.000003:
p.000003: A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on
p.000003: delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve
p.000003: as the basis of a contract.
p.000003: 1.18 Coordinating Committee
p.000003:
p.000003: A committee that a sponsor may organize to coordinate the conduct of a multicentre trial.
p.000003:
p.000003: 1.19 Coordinating Investigator
p.000003:
p.000003: An investigator assigned the responsibility for the coordination of investigators at different centres
p.000003: participating in a multicentre trial.
p.000003:
p.000004: 4
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004: 1.20 Contract Research Organization (CRO)
p.000004:
p.000004: A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or
p.000004: more of a sponsor's trial-related duties and functions.
p.000004: 1.21 Direct Access
...
p.000006: information about an approved use.
p.000006: 1.34 Investigator
p.000006: A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of
p.000006: individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal
p.000006: investigator. See also Subinvestigator.
p.000006: 1.35 Investigator / Institution
p.000006:
p.000006: An expression meaning "the investigator and/or institution.
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000007: 7
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: 1.36 Investigator's Brochure
p.000007:
p.000007: A compilation of the clinical and nonclinical data on the investigational product(s) which is relevant to the study of
p.000007: the investigational product(s) in human subjects (see 7. Investigator’s Brochure).
p.000007: 1.37 Legally Acceptable Representative
p.000007:
p.000007: An individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective
p.000007: subject, to the subject's participation in the clinical trial.
p.000007: 1.38 Monitoring
p.000007:
p.000007: The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded,
p.000007: and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and
p.000007: the applicable with SFDArequirement(s).
p.000007: 1.39 Monitoring Report
p.000007: A written report from the monitor to the sponsor after each site visit and/or other trial-related communication
p.000007: according to the sponsor’s SOPs.
p.000007: 1.40 Multicentre Trial
p.000007:
p.000007: A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more
p.000007: than one investigator.
p.000007: 1.41 Nonclinical Study
p.000007:
p.000007: Biomedical studies not performed on human subjects.
p.000007:
p.000007: 1.42 Opinion (in relation to Independent Ethics Committee)
p.000007:
p.000007: The judgement and/or the advice provided by an Independent Ethics Committee (IEC).
p.000007:
p.000007: 1.43 Original Medical Record
p.000007:
p.000007: See Source Documents.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000008: 8
p.000008:
p.000008:
p.000008:
p.000008:
p.000008:
p.000008: 1.44 Protocol
p.000008:
p.000008: A document that describes the objective(s), design, methodology, statistical considerations, and organization of a
p.000008: trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other
p.000008: protocol referenced documents. Throughout the ICH GCP Guideline the term protocol refers to protocol and protocol
p.000008: amendments.
p.000008: 1.45 Protocol Amendment
p.000008:
p.000008: A written description of a change(s) to or formal clarification of a protocol.
p.000008:
p.000008: 1.46 Quality Assurance (QA)
p.000008:
p.000008: All those planned and systematic actions that are established to ensure that the trial is performed and the data are
p.000008: generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and SFDA
p.000008: requirement(s).
p.000008: 1.47 Quality Control (QC)
p.000008:
p.000008: The operational techniques and activities undertaken within the quality assurance system to verify that the
...
p.000048: and nontoxic dose findings in the same animal species should be compared (i.e., the therapeutic index should be
p.000048: discussed). The relevance of this information to the proposed human dosing should be addressed. Whenever possible,
p.000048: comparisons should be made in terms of blood/tissue levels rather than on a mg/kg basis.
p.000048:
p.000048:
p.000049: 49
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049: (a) Nonclinical Pharmacology
p.000049:
p.000049: A summary of the pharmacological aspects of the investigational product and, where appropriate, its significant
p.000049: metabolites studied in animals, should be included. Such a summary should incorporate studies that assess
p.000049: potential therapeutic activity (e.g. efficacy models, receptor binding, and specificity) as well as those that
p.000049: assess safety (e.g., special studies to assess pharmacological actions other than the intended therapeutic
p.000049: effect(s)).
p.000049: (b) Pharmacokinetics and Product Metabolism in Animals
p.000049:
p.000049: A summary of the pharmacokinetics and biological transformation and disposition of the investigational product in all
p.000049: species studied should be given. The discussion of the findings should address the absorption and the local and
p.000049: systemic bioavailability of the investigational product and its metabolites, and their
p.000049: relationship to the pharmacological and toxicological findings in animal species.
p.000049: (c) Toxicology
p.000049:
p.000049: A summary of the toxicological effects found in relevant studies conducted in different animal species should be
p.000049: described under the following headings where appropriate:
p.000049: − Single dose
p.000049:
p.000049: − Repeated dose
p.000049:
p.000049: − Carcinogenicity
p.000049:
p.000049: − Special studies (e.g. irritancy and sensitisation)
p.000049:
p.000049: − Reproductive toxicity
p.000049:
p.000049: − Genotoxicity (mutagenicity)
p.000049:
p.000049: 7.3.6 Effects in Humans Introduction:
p.000049: A thorough discussion of the known effects of the investigational product(s) in humans should be provided,
p.000049: including information on pharmacokinetics, metabolism, pharmacodynamics, dose response, safety,
p.000049: efficacy, and other pharmacological activities. Where possible, a summary of each completed clinical
p.000049: trial should be provided. Information should also be provided regarding results of any use of the
p.000049: investigational product(s) other than from in clinical trials, such as from experience during marketing.
p.000049: (a) Pharmacokinetics and Product Metabolism in Humans
p.000050: 50
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050: − A summary of information on the pharmacokinetics of the investigational product(s) should be presented, including the
p.000050: following, if available:
p.000050: − Pharmacokinetics (including metabolism, as appropriate, and absorption, plasma protein binding, distribution,
p.000050: and elimination).
p.000050: − Bioavailability of the investigational product (absolute, where possible, and/or relative) using a reference
p.000050: dosage form.
p.000050: − Population subgroups (e.g., gender, age, and impaired organ function).
p.000050:
p.000050: − Interactions (e.g., product-product interactions and effects of food).
p.000050:
...
Social / Presence of Coercion
Searching for indicator coerce:
(return to top)
p.000020: investigational product(s).
p.000020: 4.8 Informed Consent of Trial Subjects
p.000020: 4.8.1 In obtaining and documenting informed consent, the investigator should comply with SFDA
p.000020: requirement(s), and should adhere to GCP and to the ethical principles that have their origin in the Declaration
p.000020: of Helsinki. Prior to the beginning of the trial, the investigator should have the IRB/IEC's written
p.000020: approval/favourable opinion of the written informed consent form and any other written information to be provided to
p.000020: subjects.
p.000020: 4.8.2 The written informed consent form and any other written information to be provided to subjects should be
p.000020: revised whenever important new information becomes available that may be relevant to the subject’s consent. Any revised
p.000020: written informed consent form, and written information should receive the IRB/IEC's approval/favourable opinion in
p.000020: advance of use. The subject or the subject’s legally acceptable representative should be informed in a timely manner if
p.000020: new information becomes available that may be relevant to the subject’s willingness to continue participation in the
p.000020: trial. The communication of this information should be documented.
p.000020: 4.8.3 Neither the investigator, nor the trial staff, should coerce or unduly influence a subject to participate or
p.000020: to continue to participate in a trial.
p.000020: 4.8.4 None of the oral and written information concerning the trial, including the written informed
p.000020: consent form, should contain any language that causes the subject or the subject's legally acceptable representative to
p.000020: waive or to appear to waive any legal rights, or that releases or appears to release the investigator, the institution,
p.000020: the sponsor, or their agents from liability for negligence.
p.000020:
p.000020:
p.000021: 21
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 4.8.5 The investigator, or a person designated by the investigator, should fully inform the subject or, if the
p.000021: subject is unable to provide informed consent, the subject's legally acceptable representative, of all pertinent
p.000021: aspects of the trial including the written information and the approval/ favourable opinion by the IRB/IEC.
p.000021: 4.8.6 The language used in the oral and written information about the trial, including the written informed
p.000021: consent form, should be as non-technical as practical and should be understandable to the
p.000021: subject or the subject's legally acceptable representative and the impartial witness, where applicable.
...
Social / Racial Minority
Searching for indicator minority:
(return to top)
p.000010:
p.000010: An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g.,
p.000010: Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics
p.000010: for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for
p.000010: Expedited Reporting).
p.000010:
p.000010: 1.61 Vulnerable Subjects
p.000010:
p.000010: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether
p.000010: justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a
p.000010: hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure,
p.000010: such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory
p.000010: personnel, employees of the
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects
p.000011: include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons,
p.000011: patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those
p.000011: incapable of giving consent.
p.000011: 1.62 Well-being (of the trial subjects)
p.000011:
p.000011: The physical and mental integrity of the subjects participating in a clinical trial.
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2. THE PRINCIPLES OF ICH GCP
p.000012:
p.000012: 2.1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the
p.000012: Declaration of Helsinki, and that are consistent with GCP and the with SFDA requirement(s).
p.000012: 2.2 Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated
p.000012: benefit for the individual trial subject and society. A trial should be initiated and continued only if the
p.000012: anticipated benefits justify the risks.
p.000012: 2.3 The rights, safety, and well-being of the trial subjects are the most important
p.000012: considerations and should prevail over interests of science and society.
...
Social / Soldier
Searching for indicator armed forces:
(return to top)
p.000010: A unique identifier assigned by the investigator to each trial subject to protect the subject's identity and used in
p.000010: lieu of the subject's name when the investigator reports adverse events and/or other trial related data.
p.000010: 1.59 Trial Site
p.000010:
p.000010: The location(s) where trial-related activities are actually conducted.
p.000010:
p.000010: 1.60 Unexpected Adverse Drug Reaction
p.000010:
p.000010: An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g.,
p.000010: Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics
p.000010: for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for
p.000010: Expedited Reporting).
p.000010:
p.000010: 1.61 Vulnerable Subjects
p.000010:
p.000010: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether
p.000010: justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a
p.000010: hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure,
p.000010: such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory
p.000010: personnel, employees of the
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects
p.000011: include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons,
p.000011: patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those
p.000011: incapable of giving consent.
p.000011: 1.62 Well-being (of the trial subjects)
p.000011:
p.000011: The physical and mental integrity of the subjects participating in a clinical trial.
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2. THE PRINCIPLES OF ICH GCP
p.000012:
p.000012: 2.1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the
p.000012: Declaration of Helsinki, and that are consistent with GCP and the with SFDA requirement(s).
...
Social / Trade Union Membership
Searching for indicator union:
(return to top)
p.000048: 48
p.000048: 7.3.1 Table of Contents
p.000048: 48
p.000048: 7.3.2 Summary
p.000048: 48
p.000048: 7.3.3 Introduction
p.000048: 48
p.000048: 7.3.4 Physical, Chemical, and Pharmaceutical Properties and Formulation 48
p.000048: 7.3.5 Nonclinical Studies
p.000048: 48
p.000048: 7.3.6 Effects in Humans
p.000050: 50
p.000050: 7.3.7 Summary of Data and Guidance for the Investigator 52
p.000050: 7.4 APPENDIX 1:
p.000053: 53
p.000053: 7.5 APPENDIX 2:
p.000054: 54
p.000054: 8. ESSENTIAL DOCUMENTS FOR THE CONDUCT OF A CLINICAL TRIAL 55
p.000054: 8.1 Introduction
p.000055: 55
p.000055: 8.2 Before the Clinical Phase of the Trial Commences 56
p.000055: 8.3 During the Clinical Conduct of the Trial
p.000064: 64
p.000064: 8.4 After Completion or Termination of the Trial
p.000072: 72
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: vii
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: INTRODUCTION
p.000072:
p.000072:
p.000072: Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing,
p.000072: conducting, recording and reporting trials that involve the participation of human subjects. Compliance with this
p.000072: standard provides public assurance that the rights, safety and well-being of trial subjects are protected, consistent
p.000072: with the principles that have their origin in the Declaration of Helsinki, and that the clinical trial data are
p.000072: credible.
p.000072: The objective of this ICH GCP Guideline is to provide a unified standard for the European Union (EU), Japan and the
p.000072: United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these
p.000072: jurisdictions and in other jurisdictions who are willing to adopt such mutual recognition such as Saudi food and drug
p.000072: authority (SFDA) in Saudi Arabia.
p.000072: The guideline was developed with consideration of the current good clinical practices of the European Union, Japan, and
p.000072: the United States, as well as those of Australia, Canada, the Nordic countries and the World Health Organization (WHO).
p.000072: This guideline should be followed when generating clinical trial data that are intended to be submitted to the SFDA.
p.000072: The principles established in this guideline may also be applied to other clinical investigations that may have an
p.000072: impact on the safety and well-being of human subjects.
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000001: 1
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: 1. GLOSSARY
p.000001:
p.000001:
p.000001: 1.1 Adverse Drug Reaction (ADR)
p.000001: In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as
p.000001: the therapeutic dose(s) may not be established: all noxious and unintended responses to a medicinal
p.000001: product related to any dose should be considered adverse drug reactions. The phrase responses to a medicinal
p.000001: product means that a causal relationship between a medicinal product and an adverse event is at least a reasonable
p.000001: possibility, i.e. the relationship cannot be ruled out.
p.000001: Regarding marketed medicinal products: a response to a drug which is noxious and unintended and which occurs at
p.000001: doses normally used in man for prophylaxis, diagnosis, or therapy of diseases or for modification of
...
Social / Unemployment
Searching for indicator unemployed:
(return to top)
p.000010: 1.59 Trial Site
p.000010:
p.000010: The location(s) where trial-related activities are actually conducted.
p.000010:
p.000010: 1.60 Unexpected Adverse Drug Reaction
p.000010:
p.000010: An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g.,
p.000010: Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics
p.000010: for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for
p.000010: Expedited Reporting).
p.000010:
p.000010: 1.61 Vulnerable Subjects
p.000010:
p.000010: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether
p.000010: justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a
p.000010: hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure,
p.000010: such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory
p.000010: personnel, employees of the
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects
p.000011: include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons,
p.000011: patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those
p.000011: incapable of giving consent.
p.000011: 1.62 Well-being (of the trial subjects)
p.000011:
p.000011: The physical and mental integrity of the subjects participating in a clinical trial.
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2. THE PRINCIPLES OF ICH GCP
p.000012:
p.000012: 2.1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the
p.000012: Declaration of Helsinki, and that are consistent with GCP and the with SFDA requirement(s).
p.000012: 2.2 Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated
p.000012: benefit for the individual trial subject and society. A trial should be initiated and continued only if the
p.000012: anticipated benefits justify the risks.
...
Social / Youth/Minors
Searching for indicator minor:
(return to top)
p.000015: 15
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015: 3.2.2 The IRB/IEC should perform its functions according to written operating procedures, should maintain
p.000015: written records of its activities and minutes of its meetings, and should comply with GCP and with the SFDA
p.000015: requirement(s).
p.000015: 3.2.3 An IRB/IEC should make its decisions at announced meetings at which at least a quorum, as stipulated in its
p.000015: written operating procedures, is present.
p.000015: 3.2.4 Only members who participate in the IRB/IEC review and discussion should vote/provide their opinion and/or
p.000015: advise.
p.000015: 3.2.5 The investigator may provide information on any aspect of the trial, but should not participate
p.000015: in the deliberations of the IRB/IEC or in the vote/opinion of the IRB/IEC.
p.000015: 3.2.6 An IRB/IEC may invite nonmembers with expertise in special areas for assistance.
p.000015:
p.000015: 3.3 Procedures
p.000015: The IRB/IEC should establish, document in writing, and follow its procedures, which should include:
p.000015: 3.3.1 Determining its composition (names and qualifications of the members) and the authority under which it is
p.000015: established.
p.000015: 3.3.2 Scheduling, notifying its members of, and conducting its meetings.
p.000015: 3.3.3 Conducting initial and continuing review of trials.
p.000015: 3.3.4 Determining the frequency of continuing review, as appropriate.
p.000015: 3.3.5 Providing expedited review and approval/favourable opinion of minor change(s) in ongoing trials that
p.000015: have the approval/favourable opinion of the IRB/IEC.
p.000015: 3.3.6 Specifying that no subject should be admitted to a trial before the IRB/IEC issues its written
p.000015: approval/favourable opinion of the trial.
p.000015: 3.3.7 Specifying that no deviations from, or changes of, the protocol should be initiated without prior written
p.000015: IRB/IEC approval/favourable opinion of an appropriate amendment, except when necessary to eliminate immediate
p.000015: hazards to the subjects or when the change(s) involves only logistical administrative aspects of the
p.000015: trial (e.g., change of monitor(s), telephone number(s)) (see 4.5.2).
p.000015: 3.3.8 Specifying that the investigator should promptly report to the IRB/IEC:
p.000015:
p.000015: (a) Deviations from, or changes of, the protocol to eliminate immediate hazards to the trial subjects (see 3.3.7,
p.000015: 4.5.2, 4.5.4).
p.000016: 16
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: (b) Changes increasing the risk to subjects and/or affecting significantly the conduct of the trial (see 4.10.2).
p.000016: (c) All adverse drug reactions (ADRs) that are both serious and unexpected.
p.000016:
p.000016: (d) New information that may affect adversely the safety of the subjects or the conduct of the trial.
p.000016: 3.3.9 Ensuring that the IRB/IEC promptly notify in writing the investigator/institution
p.000016: concerning:
p.000016: (a) Its trial-related decisions/opinions.
p.000016:
p.000016: (b) The reasons for its decisions/opinions.
p.000016:
...
Social / education
Searching for indicator education:
(return to top)
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2. THE PRINCIPLES OF ICH GCP
p.000012:
p.000012: 2.1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the
p.000012: Declaration of Helsinki, and that are consistent with GCP and the with SFDA requirement(s).
p.000012: 2.2 Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated
p.000012: benefit for the individual trial subject and society. A trial should be initiated and continued only if the
p.000012: anticipated benefits justify the risks.
p.000012: 2.3 The rights, safety, and well-being of the trial subjects are the most important
p.000012: considerations and should prevail over interests of science and society.
p.000012: 2.4 The available nonclinical and clinical information on an investigational product should be adequate to support
p.000012: the proposed clinical trial.
p.000012: 2.5 Clinical trials should be scientifically sound, and described in a clear, detailed protocol.
p.000012: 2.6 A trial should be conducted in compliance with the protocol that has received prior institutional
p.000012: review board (IRB)/independent ethics committee (IEC) approval/favourable opinion.
p.000012: 2.7 The medical care given to, and medical decisions made on behalf of, subjects should always be the
p.000012: responsibility of a qualified physician or, when appropriate, of a qualified dentist.
p.000012: 2.8 Each individual involved in conducting a trial should be qualified by education, training, and experience to
p.000012: perform his or her respective task(s).
p.000012: 2.9 Freely given informed consent should be obtained from every subject prior to clinical trial participation.
p.000012: 2.10 All clinical trial information should be recorded, handled, and stored in a way that allows its accurate
p.000012: reporting, interpretation and verification.
p.000012: 2.11 The confidentiality of records that could identify subjects should be protected.
p.000012: 2.12 Investigational products should be manufactured, handled, and stored in accordance with applicable good
p.000012: manufacturing practice (GMP). They should be used in accordance with the approved protocol.
p.000012: 2.13 Systems with procedures that assure the quality of every aspect of the trial should be implemented.
p.000012:
p.000013: 13
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013: 3. INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC)
p.000013: 3.1 Responsibilities
p.000013: 3.1.1 An IRB/IEC should safeguard the rights, safety, and well-being of all trial subjects. Special
p.000013: attention should be paid to trials that may include vulnerable subjects.
p.000013: 3.1.2 The IRB/IEC should obtain the following documents:
p.000013:
p.000013: trial protocol(s)/amendment(s), written informed consent form(s) and consent form updates that the investigator
p.000013: proposes for use in the trial, subject recruitment procedures (e.g. advertisements), written information to be
...
p.000015:
p.000015: (a) Deviations from, or changes of, the protocol to eliminate immediate hazards to the trial subjects (see 3.3.7,
p.000015: 4.5.2, 4.5.4).
p.000016: 16
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: (b) Changes increasing the risk to subjects and/or affecting significantly the conduct of the trial (see 4.10.2).
p.000016: (c) All adverse drug reactions (ADRs) that are both serious and unexpected.
p.000016:
p.000016: (d) New information that may affect adversely the safety of the subjects or the conduct of the trial.
p.000016: 3.3.9 Ensuring that the IRB/IEC promptly notify in writing the investigator/institution
p.000016: concerning:
p.000016: (a) Its trial-related decisions/opinions.
p.000016:
p.000016: (b) The reasons for its decisions/opinions.
p.000016:
p.000016: (c) Procedures for appeal of its decisions/opinions.
p.000016:
p.000016: 3.4 Records
p.000016: The IRB/IEC should retain all relevant records (e.g., written procedures, membership lists, lists of
p.000016: occupations/affiliations of members, submitted documents, minutes of meetings, and correspondence) for a period of at
p.000016: least 3 years after completion of the trial and make them available upon request from the SFDA or any relevant
p.000016: regulatory authority(ies).
p.000016: The IRB/IEC may be asked by investigators, sponsors or regulatory authorities to provide its written procedures and
p.000016: membership lists.
p.000016:
p.000016: 4. INVESTIGATOR
p.000016: 4.1 Investigator's Qualifications and Agreement
p.000016: 4.1.1 The investigator(s) should be qualified by education, training, and experience to assume
p.000016: responsibility for the proper conduct of the trial, should meet all the qualifications specified by the SFDA
p.000016: requirement(s), and should provide evidence of such qualifications through up- to-date curriculum vitae and/or other
p.000016: relevant documentation requested by the sponsor, the IRB/IEC, and/or the SFDA.
p.000016:
p.000016:
p.000016:
p.000017: 17
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017: 4.1.2 The investigator should be thoroughly familiar with the appropriate use of the investigational product(s), as
p.000017: described in the protocol, in the current Investigator's Brochure, in the product information and in other information
p.000017: sources provided by the sponsor.
p.000017: 4.1.3 The investigator should be aware of, and should comply with, GCP and the SFDA requirements.
p.000017: 4.1.4 The investigator/institution should permit monitoring and auditing by the sponsor, and inspection by
p.000017: the SFDA.
p.000017: 4.1.5 The investigator should maintain a list of appropriately qualified persons to whom the investigator
p.000017: has delegated significant trial-related duties.
p.000017: 4.2 Adequate Resources
p.000017: 4.2.1 The investigator should be able to demonstrate (e.g., based on retrospective data) a potential for recruiting the
p.000017: required number of suitable subjects within the agreed recruitment period.
p.000017: 4.2.2 The investigator should have sufficient time to properly conduct and complete the trial within the agreed trial
p.000017: period.
p.000017: 4.2.3 The investigator should have available an adequate number of qualified staff and adequate facilities for the
p.000017: foreseen duration of the trial to conduct the trial properly and safely.
...
Social / embryo
Searching for indicator embryo:
(return to top)
p.000021: has orally consented to the subject’s participation in the trial and, if capable of doing so, has signed and
p.000021: personally dated the informed consent form, the witness should sign and personally date the consent form. By
p.000021: signing the consent form, the witness attests that the information in the consent form and any other written
p.000021: information was accurately explained to, and apparently understood by, the subject or the subject's legally
p.000021: acceptable representative, and that informed consent was freely given by the subject or the subject’s legally
p.000021: acceptable representative.
p.000021: 4.8.10 Both the informed consent discussion and the written informed consent form and any other written information
p.000021: to be provided to subjects should include explanations of the following:
p.000021:
p.000021: (a) That the trial involves research.
p.000022: 22
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022: (b) The purpose of the trial.
p.000022:
p.000022: (c) The trial treatment(s) and the probability for random assignment to each treatment.
p.000022:
p.000022: (d) The trial procedures to be followed, including all invasive procedures.
p.000022:
p.000022: (e) The subject's responsibilities.
p.000022:
p.000022: (f) Those aspects of the trial that are experimental.
p.000022:
p.000022: (g) The reasonably foreseeable risks or inconveniences to the subject and, when applicable, to an embryo, fetus, or
p.000022: nursing infant.
p.000022: (h) The reasonably expected benefits. When there is no intended clinical benefit to the subject, the subject should be
p.000022: made aware of this.
p.000022: (i) The alternative procedure(s) or course(s) of treatment that may be available to the subject, and their
p.000022: important potential benefits and risks.
p.000022: (j) The compensation and/or treatment available to the subject in the event of trial-related injury.
p.000022: (k) The anticipated prorated payment, if any, to the subject for participating in the trial.
p.000022:
p.000022: (l) The anticipated expenses, if any, to the subject for participating in the trial.
p.000022:
p.000022: (m) That the subject's participation in the trial is voluntary and that the subject may refuse to participate or
p.000022: withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is otherwise entitled.
p.000022: (n) That the monitor(s), the auditor(s), the IRB/IEC, and the SFDA will be granted direct access to the subject's
p.000022: original medical records for verification of clinical trial procedures and/or data, without violating the
p.000022: confidentiality of the subject, to the extent permitted by the applicable laws and regulations and that, by signing a
p.000022: written informed consent form, the subject or the subject's legally acceptable representative is authorizing such
p.000022: access.
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
...
Social / employees
Searching for indicator employees:
(return to top)
p.000010: 1.57 Subject/Trial Subject
p.000010: An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or
p.000010: as a control.
p.000010: 1.58 Subject Identification Code
p.000010: A unique identifier assigned by the investigator to each trial subject to protect the subject's identity and used in
p.000010: lieu of the subject's name when the investigator reports adverse events and/or other trial related data.
p.000010: 1.59 Trial Site
p.000010:
p.000010: The location(s) where trial-related activities are actually conducted.
p.000010:
p.000010: 1.60 Unexpected Adverse Drug Reaction
p.000010:
p.000010: An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g.,
p.000010: Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics
p.000010: for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for
p.000010: Expedited Reporting).
p.000010:
p.000010: 1.61 Vulnerable Subjects
p.000010:
p.000010: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether
p.000010: justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a
p.000010: hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure,
p.000010: such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory
p.000010: personnel, employees of the
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects
p.000011: include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons,
p.000011: patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those
p.000011: incapable of giving consent.
p.000011: 1.62 Well-being (of the trial subjects)
p.000011:
p.000011: The physical and mental integrity of the subjects participating in a clinical trial.
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2. THE PRINCIPLES OF ICH GCP
p.000012:
...
Social / gender
Searching for indicator gender:
(return to top)
p.000049: (c) Toxicology
p.000049:
p.000049: A summary of the toxicological effects found in relevant studies conducted in different animal species should be
p.000049: described under the following headings where appropriate:
p.000049: − Single dose
p.000049:
p.000049: − Repeated dose
p.000049:
p.000049: − Carcinogenicity
p.000049:
p.000049: − Special studies (e.g. irritancy and sensitisation)
p.000049:
p.000049: − Reproductive toxicity
p.000049:
p.000049: − Genotoxicity (mutagenicity)
p.000049:
p.000049: 7.3.6 Effects in Humans Introduction:
p.000049: A thorough discussion of the known effects of the investigational product(s) in humans should be provided,
p.000049: including information on pharmacokinetics, metabolism, pharmacodynamics, dose response, safety,
p.000049: efficacy, and other pharmacological activities. Where possible, a summary of each completed clinical
p.000049: trial should be provided. Information should also be provided regarding results of any use of the
p.000049: investigational product(s) other than from in clinical trials, such as from experience during marketing.
p.000049: (a) Pharmacokinetics and Product Metabolism in Humans
p.000050: 50
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050: − A summary of information on the pharmacokinetics of the investigational product(s) should be presented, including the
p.000050: following, if available:
p.000050: − Pharmacokinetics (including metabolism, as appropriate, and absorption, plasma protein binding, distribution,
p.000050: and elimination).
p.000050: − Bioavailability of the investigational product (absolute, where possible, and/or relative) using a reference
p.000050: dosage form.
p.000050: − Population subgroups (e.g., gender, age, and impaired organ function).
p.000050:
p.000050: − Interactions (e.g., product-product interactions and effects of food).
p.000050:
p.000050: − Other pharmacokinetic data (e.g., results of population studies performed within clinical trial(s).
p.000050: (b) Safety and Efficacy
p.000050:
p.000050: A summary of information should be provided about the investigational product's/products'
p.000050: (including metabolites, where appropriate) safety, pharmacodynamics, efficacy, and dose
p.000050: response that were obtained from preceding trials in humans (healthy volunteers and/or patients).
p.000050: The implications of this information should be discussed. In cases where a number of clinical trials have been
p.000050: completed, the use of summaries of safety and efficacy across multiple trials by indications in subgroups
p.000050: may provide a clear presentation of the data. Tabular summaries of adverse drug reactions for all the clinical
p.000050: trials (including those for all the studied indications) would be useful. Important differences in adverse
p.000050: drug reaction patterns/incidences across indications or subgroups should be discussed.
p.000050: The IB should provide a description of the possible risks and adverse drug reactions to be anticipated on the basis of
p.000050: prior experiences with the product under investigation and with related products. A description should also be provided
...
Social / philosophical differences/differences of opinion
Searching for indicator opinion:
(return to top)
p.000004: integrity, and confidentiality of trial subjects are protected.
p.000004: 1.25 Independent Data-Monitoring Committee (IDMC) (Data and Safety Monitoring Board, Monitoring Committee, Data
p.000004: Monitoring Committee)
p.000004: An independent data-monitoring committee that may be established by the sponsor to assess at intervals the progress of
p.000004: a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to
p.000004: continue, modify, or stop a trial.
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000005: 5
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005: 1.26 Impartial Witness
p.000005:
p.000005: A person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who
p.000005: attends the informed consent process if the subject or the subject’s legally acceptable representative cannot read, and
p.000005: who reads the informed consent form and any other written information supplied to the subject.
p.000005: 1.27 Independent Ethics Committee (IEC)
p.000005: An independent body (a review board or a committee, institutional, regional, national, or supranational),
p.000005: constituted of medical professionals and non-medical members, whose responsibility it is to ensure the
p.000005: protection of the rights, safety and well-being of human subjects involved in a trial and to provide public assurance
p.000005: of that protection, by, among other things, reviewing and approving / providing favourable opinion on, the trial
p.000005: protocol, the suitability of the investigator(s), facilities, and the methods and material to be used in
p.000005: obtaining and documenting informed consent of the trial subjects.
p.000005: The legal status, composition, function, operations and regulatory requirements pertaining to Independent Ethics
p.000005: Committees may differ among countries, but should allow the Independent Ethics Committee to act in agreement with GCP
p.000005: as described in this guideline. The legal status, composition, function, operations and regulatory requirements
p.000005: pertaining to IEC in Saudi Arabia are governed by Law of Ethics of Research on Living Creatures.
p.000005:
p.000005: 1.28 Informed Consent
p.000005: A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after
p.000005: having been informed of all aspects of the trial that are relevant to the subject's decision to participate. Informed
p.000005: consent is documented by means of a written, signed and dated informed consent form.
p.000005: 1.29 Inspection
p.000005: The act by SFDA of conducting an official review of documents, facilities, records, and any other resources that are
p.000005: deemed by the Saudi Food and Drug Authority to be related to the clinical trial and that may be located at the site
p.000005: of the trial, at the sponsor's and/or contract
...
p.000006: investigator. See also Subinvestigator.
p.000006: 1.35 Investigator / Institution
p.000006:
p.000006: An expression meaning "the investigator and/or institution.
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000007: 7
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: 1.36 Investigator's Brochure
p.000007:
p.000007: A compilation of the clinical and nonclinical data on the investigational product(s) which is relevant to the study of
p.000007: the investigational product(s) in human subjects (see 7. Investigator’s Brochure).
p.000007: 1.37 Legally Acceptable Representative
p.000007:
p.000007: An individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective
p.000007: subject, to the subject's participation in the clinical trial.
p.000007: 1.38 Monitoring
p.000007:
p.000007: The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded,
p.000007: and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and
p.000007: the applicable with SFDArequirement(s).
p.000007: 1.39 Monitoring Report
p.000007: A written report from the monitor to the sponsor after each site visit and/or other trial-related communication
p.000007: according to the sponsor’s SOPs.
p.000007: 1.40 Multicentre Trial
p.000007:
p.000007: A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more
p.000007: than one investigator.
p.000007: 1.41 Nonclinical Study
p.000007:
p.000007: Biomedical studies not performed on human subjects.
p.000007:
p.000007: 1.42 Opinion (in relation to Independent Ethics Committee)
p.000007:
p.000007: The judgement and/or the advice provided by an Independent Ethics Committee (IEC).
p.000007:
p.000007: 1.43 Original Medical Record
p.000007:
p.000007: See Source Documents.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000008: 8
p.000008:
p.000008:
p.000008:
p.000008:
p.000008:
p.000008: 1.44 Protocol
p.000008:
p.000008: A document that describes the objective(s), design, methodology, statistical considerations, and organization of a
p.000008: trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other
p.000008: protocol referenced documents. Throughout the ICH GCP Guideline the term protocol refers to protocol and protocol
p.000008: amendments.
p.000008: 1.45 Protocol Amendment
p.000008:
p.000008: A written description of a change(s) to or formal clarification of a protocol.
p.000008:
p.000008: 1.46 Quality Assurance (QA)
p.000008:
p.000008: All those planned and systematic actions that are established to ensure that the trial is performed and the data are
p.000008: generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and SFDA
p.000008: requirement(s).
p.000008: 1.47 Quality Control (QC)
p.000008:
p.000008: The operational techniques and activities undertaken within the quality assurance system to verify that the
p.000008: requirements for quality of the trial-related activities have been fulfilled.
p.000008: 1.48 Randomization
p.000008:
p.000008: The process of assigning trial subjects to treatment or control groups using an element of chance to determine the
p.000008: assignments in order to reduce bias.
p.000008: 1.49 Regulatory Authorities
p.000008:
...
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2. THE PRINCIPLES OF ICH GCP
p.000012:
p.000012: 2.1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the
p.000012: Declaration of Helsinki, and that are consistent with GCP and the with SFDA requirement(s).
p.000012: 2.2 Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated
p.000012: benefit for the individual trial subject and society. A trial should be initiated and continued only if the
p.000012: anticipated benefits justify the risks.
p.000012: 2.3 The rights, safety, and well-being of the trial subjects are the most important
p.000012: considerations and should prevail over interests of science and society.
p.000012: 2.4 The available nonclinical and clinical information on an investigational product should be adequate to support
p.000012: the proposed clinical trial.
p.000012: 2.5 Clinical trials should be scientifically sound, and described in a clear, detailed protocol.
p.000012: 2.6 A trial should be conducted in compliance with the protocol that has received prior institutional
p.000012: review board (IRB)/independent ethics committee (IEC) approval/favourable opinion.
p.000012: 2.7 The medical care given to, and medical decisions made on behalf of, subjects should always be the
p.000012: responsibility of a qualified physician or, when appropriate, of a qualified dentist.
p.000012: 2.8 Each individual involved in conducting a trial should be qualified by education, training, and experience to
p.000012: perform his or her respective task(s).
p.000012: 2.9 Freely given informed consent should be obtained from every subject prior to clinical trial participation.
p.000012: 2.10 All clinical trial information should be recorded, handled, and stored in a way that allows its accurate
p.000012: reporting, interpretation and verification.
p.000012: 2.11 The confidentiality of records that could identify subjects should be protected.
p.000012: 2.12 Investigational products should be manufactured, handled, and stored in accordance with applicable good
p.000012: manufacturing practice (GMP). They should be used in accordance with the approved protocol.
p.000012: 2.13 Systems with procedures that assure the quality of every aspect of the trial should be implemented.
p.000012:
p.000013: 13
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013: 3. INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC)
p.000013: 3.1 Responsibilities
p.000013: 3.1.1 An IRB/IEC should safeguard the rights, safety, and well-being of all trial subjects. Special
p.000013: attention should be paid to trials that may include vulnerable subjects.
p.000013: 3.1.2 The IRB/IEC should obtain the following documents:
p.000013:
p.000013: trial protocol(s)/amendment(s), written informed consent form(s) and consent form updates that the investigator
p.000013: proposes for use in the trial, subject recruitment procedures (e.g. advertisements), written information to be
p.000013: provided to subjects, Investigator's Brochure (IB), available safety information, information about
p.000013: payments and compensation available to subjects, the investigator’s current curriculum vitae and/or other
p.000013: documentation evidencing qualifications, and any other documents that the IRB/IEC may need to fulfil its
p.000013: responsibilities.
p.000013: The IRB/IEC should review a proposed clinical trial within a reasonable time and document its views in
p.000013: writing, clearly identifying the trial, the documents reviewed and the dates for the following:
p.000013: - approval/favourable opinion;
p.000013:
p.000013: - modifications required prior to its approval/favourable opinion;
p.000013:
p.000013: - disapproval / negative opinion; and
p.000013:
p.000013: - termination/suspension of any prior approval/favourable opinion.
p.000013:
p.000013: 3.1.3 The IRB/IEC should consider the qualifications of the investigator for the proposed trial, as documented
p.000013: by a current curriculum vitae and/or by any other relevant documentation the IRB/IEC requests.
p.000013: 3.1.4 The IRB/IEC should conduct continuing review of each ongoing trial at intervals appropriate to
p.000013: the degree of risk to human subjects, but at least once per year.
p.000013: 3.1.5 The IRB/IEC may request more information than is outlined in paragraph 4.8.10 be given to subjects when, in
p.000013: the judgement of the IRB/IEC, the additional information would add meaningfully to the protection of the rights, safety
p.000013: and/or well-being of the subjects.
p.000013:
p.000013:
p.000014: 14
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014: 3.1.6 When a non-therapeutic trial is to be carried out with the consent of the subject’s legally acceptable
p.000014: representative (see 4.8.12, 4.8.14), the IRB/IEC should determine that the proposed protocol and/or other
p.000014: document(s) adequately addresses relevant ethical concerns and meets applicable regulatory requirements for such
p.000014: trials.
p.000014: 3.1.7 Where the protocol indicates that prior consent of the trial subject or the subject’s legally acceptable
p.000014: representative is not possible (see 4.8.15), the IRB/IEC should determine that the proposed protocol and/or other
p.000014: document(s) adequately addresses relevant ethical concerns.
p.000014: 3.1.8 The IRB/IEC should review both the amount and method of payment to subjects to assure that neither
p.000014: presents problems of coercion or undue influence on the trial subjects. Payments to a subject should be
p.000014: prorated and not wholly contingent on completion of the trial by the subject.
p.000014: 3.1.9 The IRB/IEC should ensure that information regarding payment to subjects, including the methods, amounts,
p.000014: and schedule of payment to trial subjects, is set forth in the written informed consent form and any other written
p.000014: information to be provided to subjects. The way payment will be prorated should be specified.
p.000014: 3.2 Composition, Functions and Operations
p.000014: 3.2.1 The IRB/IEC should consist of a reasonable number of members, who collectively have the qualifications and
p.000014: experience to review and evaluate the science, medical aspects, and ethics of the proposed trial. It is recommended
p.000014: that the IRB/IEC should include:
p.000014: (a) At least five members.
p.000014:
p.000014: (b) At least one member whose primary area of interest is in a nonscientific area.
p.000014:
p.000014: (c) At least one member who is independent of the institution/trial site.
p.000014:
p.000014: Only those IRB/IEC members who are independent of the investigator and the sponsor of the trial should vote/provide
p.000014: opinion on a trial-related matter.
p.000014: A list of IRB/IEC members and their qualifications should be maintained.
p.000014:
p.000014: The legal status, composition, function, operations and regulatory requirements pertaining to IEC in Saudi Arabia are
p.000014: governed by Law of Ethics of Research on Living Creatures.
p.000015: 15
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015: 3.2.2 The IRB/IEC should perform its functions according to written operating procedures, should maintain
p.000015: written records of its activities and minutes of its meetings, and should comply with GCP and with the SFDA
p.000015: requirement(s).
p.000015: 3.2.3 An IRB/IEC should make its decisions at announced meetings at which at least a quorum, as stipulated in its
p.000015: written operating procedures, is present.
p.000015: 3.2.4 Only members who participate in the IRB/IEC review and discussion should vote/provide their opinion and/or
p.000015: advise.
p.000015: 3.2.5 The investigator may provide information on any aspect of the trial, but should not participate
p.000015: in the deliberations of the IRB/IEC or in the vote/opinion of the IRB/IEC.
p.000015: 3.2.6 An IRB/IEC may invite nonmembers with expertise in special areas for assistance.
p.000015:
p.000015: 3.3 Procedures
p.000015: The IRB/IEC should establish, document in writing, and follow its procedures, which should include:
p.000015: 3.3.1 Determining its composition (names and qualifications of the members) and the authority under which it is
p.000015: established.
p.000015: 3.3.2 Scheduling, notifying its members of, and conducting its meetings.
p.000015: 3.3.3 Conducting initial and continuing review of trials.
p.000015: 3.3.4 Determining the frequency of continuing review, as appropriate.
p.000015: 3.3.5 Providing expedited review and approval/favourable opinion of minor change(s) in ongoing trials that
p.000015: have the approval/favourable opinion of the IRB/IEC.
p.000015: 3.3.6 Specifying that no subject should be admitted to a trial before the IRB/IEC issues its written
p.000015: approval/favourable opinion of the trial.
p.000015: 3.3.7 Specifying that no deviations from, or changes of, the protocol should be initiated without prior written
p.000015: IRB/IEC approval/favourable opinion of an appropriate amendment, except when necessary to eliminate immediate
p.000015: hazards to the subjects or when the change(s) involves only logistical administrative aspects of the
p.000015: trial (e.g., change of monitor(s), telephone number(s)) (see 4.5.2).
p.000015: 3.3.8 Specifying that the investigator should promptly report to the IRB/IEC:
p.000015:
p.000015: (a) Deviations from, or changes of, the protocol to eliminate immediate hazards to the trial subjects (see 3.3.7,
p.000015: 4.5.2, 4.5.4).
p.000016: 16
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: (b) Changes increasing the risk to subjects and/or affecting significantly the conduct of the trial (see 4.10.2).
p.000016: (c) All adverse drug reactions (ADRs) that are both serious and unexpected.
p.000016:
p.000016: (d) New information that may affect adversely the safety of the subjects or the conduct of the trial.
p.000016: 3.3.9 Ensuring that the IRB/IEC promptly notify in writing the investigator/institution
p.000016: concerning:
p.000016: (a) Its trial-related decisions/opinions.
p.000016:
p.000016: (b) The reasons for its decisions/opinions.
p.000016:
p.000016: (c) Procedures for appeal of its decisions/opinions.
p.000016:
p.000016: 3.4 Records
p.000016: The IRB/IEC should retain all relevant records (e.g., written procedures, membership lists, lists of
p.000016: occupations/affiliations of members, submitted documents, minutes of meetings, and correspondence) for a period of at
p.000016: least 3 years after completion of the trial and make them available upon request from the SFDA or any relevant
p.000016: regulatory authority(ies).
...
p.000017: 4.2.4 The investigator should ensure that all persons assisting with the trial are adequately informed about the
p.000017: protocol, the investigational product(s), and their trial-related duties and functions.
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017: 4.3 Medical Care of Trial Subjects
p.000017: 4.3.1 A qualified physician (or dentist, when appropriate), who is an investigator or a sub- investigator
p.000017: for the trial, should be responsible for all trial-related medical (or dental) decisions.
p.000017: 4.3.2 During and following a subject's participation in a trial, the investigator/institution should ensure that
p.000017: adequate medical care is provided to a subject for any adverse events, including clinically significant laboratory
p.000017: values, related to the trial. The investigator/institution should inform a subject when medical care is needed
p.000017: for intercurrent illness(es) of which the investigator becomes aware.
p.000018: 18
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018: 4.3.3 It is recommended that the investigator inform the subject's primary physician about the subject's
p.000018: participation in the trial if the subject has a primary physician and if the subject agrees to the primary physician
p.000018: being informed.
p.000018: 4.3.4 Although a subject is not obliged to give his/her reason(s) for withdrawing prematurely from a trial, the
p.000018: investigator should make a reasonable effort to ascertain the reason(s), while fully respecting the subject's rights.
p.000018: 4.4 Communication with IRB/IEC
p.000018: 4.4.1 Before initiating a trial, the investigator/institution should have written and dated
p.000018: approval/favourable opinion from the IRB/IEC for the trial protocol, written informed consent form, consent
p.000018: form updates, subject recruitment procedures (e.g., advertisements), and any other written information to be provided
p.000018: to subjects.
p.000018: 4.4.2 As part of the investigator's/institution’s written application to the IRB/IEC, the
p.000018: investigator/institution should provide the IRB/IEC with a current copy of the Investigator's
p.000018: Brochure. If the Investigator's Brochure is updated during the trial, the investigator/institution should
p.000018: supply a copy of the updated Investigator’s Brochure to the IRB/IEC.
p.000018: 4.4.3 During the trial the investigator/institution should provide to the IRB/IEC all documents subject to review.
p.000018:
p.000018:
p.000018: 4.5 Compliance with Protocol
p.000018: 4.5.1 The investigator/institution should conduct the trial in compliance with the protocol agreed to by the sponsor
p.000018: and by the SFDA and which was given approval/favourable opinion by the IRB/IEC. The investigator/institution and the
p.000018: sponsor should sign the protocol, or an alternative contract, to confirm agreement.
p.000018: 4.5.2 The investigator should not implement any deviation from, or changes of the protocol without
p.000018: agreement by the sponsor and prior review and documented approval/favourable opinion from the IRB/IEC of an
p.000018: amendment, except where necessary to eliminate an immediate hazard(s) to trial subjects, or when the change(s)
p.000018: involves only logistical or administrative aspects of the trial (e.g., change in monitor(s), change of
p.000018: telephone number(s)).
p.000019: 19
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019: 4.5.3 The investigator, or person designated by the investigator, should document and explain any deviation from the
p.000019: approved protocol.
p.000019: 4.5.4 The investigator may implement a deviation from, or a change of, the protocol to eliminate an immediate
p.000019: hazard(s) to trial subjects without prior IRB/IEC approval/favourable opinion. As soon as possible, the
p.000019: implemented deviation or change, the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be
p.000019: submitted:
p.000019: (a) to the IRB/IEC for review and approval/favourable opinion,
p.000019:
p.000019: (b) to the sponsor for agreement and, if required,
p.000019:
p.000019: (c) to the SFDA .
p.000019:
p.000019: 4.6 Investigational Product(s)
p.000019: 4.6.1 Responsibility for investigational product(s) accountability at the trial site(s) rests with the
p.000019: investigator/institution.
p.000019: 4.6.2 Where allowed/required, the investigator/institution may/should assign some or all of the
p.000019: investigator's/institution’s duties for investigational product(s) accountability at the trial site(s) to an
p.000019: appropriate pharmacist or another appropriate individual who is under the supervision of the
p.000019: investigator/institution..
p.000019: 4.6.3 The investigator/institution and/or a pharmacist or other appropriate individual, who is designated
p.000019: by the investigator/institution, should maintain records of the product's delivery to the trial site, the inventory at
p.000019: the site, the use by each subject, and the return to the sponsor or alternative disposition of unused product(s). These
p.000019: records should include dates, quantities, batch/serial numbers, expiration dates (if applicable), and the
p.000019: unique code numbers assigned to the investigational product(s) and trial subjects. Investigators should maintain
p.000019: records that document adequately that the subjects were provided the doses specified by the protocol and
p.000019: reconcile all investigational product(s) received from the sponsor.
p.000019: 4.6.4 The investigational product(s) should be stored as specified by the sponsor (see 5.13.2 and 5.14.3) and in
p.000019: accordance with applicable SFDA requirement(s).
p.000019: 4.6.5 The investigator should ensure that the investigational product(s) are used only in accordance with
p.000019: the approved protocol.
p.000019:
p.000020: 20
p.000020:
p.000020:
p.000020:
p.000020:
p.000020:
p.000020: 4.6.6 The investigator, or a person designated by the investigator/institution, should explain the correct use of
p.000020: the investigational product(s) to each subject and should check, at intervals appropriate for the trial, that each
p.000020: subject is following the instructions properly.
p.000020: 4.7 Randomization Procedures and Unblinding
p.000020: The investigator should follow the trial's randomization procedures, if any, and should ensure that the code is broken
p.000020: only in accordance with the protocol. If the trial is blinded, the investigator should promptly document and explain to
p.000020: the sponsor any premature unblinding (e.g., accidental unblinding, unblinding due to a serious adverse event) of the
p.000020: investigational product(s).
p.000020: 4.8 Informed Consent of Trial Subjects
p.000020: 4.8.1 In obtaining and documenting informed consent, the investigator should comply with SFDA
p.000020: requirement(s), and should adhere to GCP and to the ethical principles that have their origin in the Declaration
p.000020: of Helsinki. Prior to the beginning of the trial, the investigator should have the IRB/IEC's written
p.000020: approval/favourable opinion of the written informed consent form and any other written information to be provided to
p.000020: subjects.
p.000020: 4.8.2 The written informed consent form and any other written information to be provided to subjects should be
p.000020: revised whenever important new information becomes available that may be relevant to the subject’s consent. Any revised
p.000020: written informed consent form, and written information should receive the IRB/IEC's approval/favourable opinion in
p.000020: advance of use. The subject or the subject’s legally acceptable representative should be informed in a timely manner if
p.000020: new information becomes available that may be relevant to the subject’s willingness to continue participation in the
p.000020: trial. The communication of this information should be documented.
p.000020: 4.8.3 Neither the investigator, nor the trial staff, should coerce or unduly influence a subject to participate or
p.000020: to continue to participate in a trial.
p.000020: 4.8.4 None of the oral and written information concerning the trial, including the written informed
p.000020: consent form, should contain any language that causes the subject or the subject's legally acceptable representative to
p.000020: waive or to appear to waive any legal rights, or that releases or appears to release the investigator, the institution,
p.000020: the sponsor, or their agents from liability for negligence.
p.000020:
p.000020:
p.000021: 21
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 4.8.5 The investigator, or a person designated by the investigator, should fully inform the subject or, if the
p.000021: subject is unable to provide informed consent, the subject's legally acceptable representative, of all pertinent
p.000021: aspects of the trial including the written information and the approval/ favourable opinion by the IRB/IEC.
p.000021: 4.8.6 The language used in the oral and written information about the trial, including the written informed
p.000021: consent form, should be as non-technical as practical and should be understandable to the
p.000021: subject or the subject's legally acceptable representative and the impartial witness, where applicable.
p.000021: 4.8.7 Before informed consent may be obtained, the investigator, or a person designated by the investigator,
p.000021: should provide the subject or the subject's legally acceptable representative ample time and opportunity to inquire
p.000021: about details of the trial and to decide whether or not to participate in the trial. All questions about the
p.000021: trial should be answered to the satisfaction of the subject or the subject's legally acceptable representative.
p.000021: 4.8.8 Prior to a subject’s participation in the trial, the written informed consent form should be signed and
p.000021: personally dated by the subject or by the subject's legally acceptable representative, and by the person who
p.000021: conducted the informed consent discussion.
p.000021: 4.8.9 If a subject is unable to read or if a legally acceptable representative is unable to read, an impartial
p.000021: witness should be present during the entire informed consent discussion. After the written informed consent form and
...
p.000023: amendments to the written information provided to subjects.
p.000023: 4.8.12 When a clinical trial (therapeutic or non-therapeutic) includes subjects who can only be enrolled in the trial
p.000023: with the consent of the subject’s legally acceptable representative (e.g., minors, or patients with severe dementia),
p.000023: the subject should be informed about the trial to the extent compatible with the subject’s understanding and, if
p.000023: capable, the subject should sign and personally date the written informed consent.
p.000023: 4.8.13 Except as described in 4.8.14, a non-therapeutic trial (i.e. a trial in which there is no anticipated direct
p.000023: clinical benefit to the subject), should be conducted in subjects who personally give consent and who sign and date the
p.000023: written informed consent form.
p.000023: 4.8.14 Non-therapeutic trials may be conducted in subjects with consent of a legally acceptable representative
p.000023: provided the following conditions are fulfilled:
p.000023:
p.000024: 24
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024: (a) The objectives of the trial can not be met by means of a trial in subjects who can give informed consent
p.000024: personally.
p.000024: (b) The foreseeable risks to the subjects are low.
p.000024:
p.000024: (c) The negative impact on the subject’s well-being is minimized and low.
p.000024:
p.000024: (d) The trial is not prohibited by law.
p.000024:
p.000024: (e) The approval/favourable opinion of the IRB/IEC is expressly sought on the inclusion of such subjects, and the
p.000024: written approval/ favourable opinion covers this aspect.
p.000024: Such trials, unless an exception is justified, should be conducted in patients having a disease or condition for which
p.000024: the investigational product is intended. Subjects in these trials should be particularly closely monitored and should
p.000024: be withdrawn if they appear to be unduly distressed.
p.000024: 4.8.15 In emergency situations, when prior consent of the subject is not possible, the consent of the subject's
p.000024: legally acceptable representative, if present, should be requested. When prior consent of the subject is not
p.000024: possible, and the subject’s legally acceptable representative is not available, enrolment of the subject
p.000024: should require measures described in the protocol and/or elsewhere, with documented approval/favourable
p.000024: opinion by the IRB/IEC, to protect the rights, safety and well-being of the subject and to ensure compliance with
p.000024: applicable regulatory requirements. The subject or the subject's legally acceptable representative should be
p.000024: informed about the trial as soon as possible and consent to continue and other consent as appropriate (see 4.8.10)
p.000024: should be requested.
p.000024: 4.9 Records and Reports
p.000024: 4.9.1 The investigator should ensure the accuracy, completeness, legibility, and timeliness of the data reported to
p.000024: the sponsor in the CRFs and in all required reports.
p.000024: 4.9.2 Data reported on the CRF, that are derived from source documents, should be consistent with the source
p.000024: documents or the discrepancies should be explained.
p.000024: 4.9.3 Any change or correction to a CRF should be dated, initialed, and explained (if necessary) and
p.000024: should not obscure the original entry (i.e. an audit trail should be
p.000025: 25
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025: maintained); this applies to both written and electronic changes or corrections (see
p.000025: 5.18.4 (n)). Sponsors should provide guidance to investigators and/or the investigators' designated representatives on
p.000025: making such corrections. Sponsors should have written procedures to assure that changes or corrections in CRFs made by
p.000025: sponsor's designated representatives are documented, are necessary, and are endorsed by the investigator. The
p.000025: investigator should retain records of the changes and corrections.
...
p.000026: should be reported to the sponsor according to the reporting requirements and within the time periods
p.000026: specified by the sponsor in the protocol.
p.000026: 4.11.3 For reported deaths, the investigator should supply the sponsor and the IRB/IEC with any additional requested
p.000026: information (e.g., autopsy reports and terminal medical reports).
p.000026: 4.12 Premature Termination or Suspension of a Trial
p.000026: If the trial is prematurely terminated or suspended for any reason, the investigator/institution should promptly inform
p.000026: the trial subjects, should assure appropriate therapy and follow-up for the subjects, and, where required by the
p.000026: applicable regulatory requirement(s), should inform the SFDA. In addition:
p.000026: 4.12.1 If the investigator terminates or suspends a trial without prior agreement of the sponsor, the investigator
p.000026: should inform the institution where applicable, and the investigator/institution should
p.000026: promptly inform the sponsor and the IRB/IEC, and should provide the sponsor and the IRB/IEC a detailed
p.000026: written explanation of the termination or suspension.
p.000026: 4.12.2 If the sponsor terminates or suspends a trial (see 5.21), the investigator should promptly inform the
p.000026: institution where applicable and the investigator/institution should promptly inform the IRB/IEC and provide the
p.000026: IRB/IEC a detailed written explanation of the termination or suspension.
p.000026:
p.000026:
p.000026:
p.000027: 27
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027: 4.12.3 If the IRB/IEC terminates or suspends its approval/favourable opinion of a trial (see
p.000027: 3.1.2 and 3.3.9), the investigator should inform the institution where applicable and the investigator/institution
p.000027: should promptly notify the sponsor and provide the sponsor with a detailed written explanation of the termination or
p.000027: suspension.
p.000027: 4.13 Final Report(s) by Investigator
p.000027: Upon completion of the trial, the investigator, where applicable, should inform the institution; the
p.000027: investigator/institution should provide the IRB/IEC with a summary of the trial’s outcome, and the SFDA with any
p.000027: reports required.
p.000027:
p.000027: 5. SPONSOR
p.000027: 5.1 Quality Assurance and Quality Control
p.000027: 5.1.1 The sponsor is responsible for implementing and maintaining quality assurance and quality control systems
p.000027: with written SOPs to ensure that trials are conducted and data are generated, documented (recorded), and
p.000027: reported in compliance with the protocol, GCP, and the SFDA requirement(s).
p.000027: 5.1.2 The sponsor is responsible for securing agreement from all involved parties to ensure direct access (see 1.21)
p.000027: to all trial related sites, source data/documents, and reports for the purpose of monitoring and auditing by the
p.000027: sponsor, and inspection by domestic and foreign regulatory authorities.
p.000027: 5.1.3 Quality control should be applied to each stage of data handling to ensure that all data are reliable and have
p.000027: been processed correctly.
p.000027: 5.1.4 Agreements, made by the sponsor with the investigator/institution and any other parties involved with the
p.000027: clinical trial, should be in writing, as part of the protocol or in a separate agreement.
p.000027: 5.2 Contract Research Organization (CRO)
...
p.000030: regulatory requirement(s) or if needed by the sponsor.
p.000030: 5.5.12 The sponsor should inform the investigator(s)/institution(s) in writing of the need for record
p.000030: retention and should notify the investigator(s)/institution(s) in writing when the trial related records are no longer
p.000030: needed.
p.000030:
p.000030:
p.000030:
p.000030: 5.6 Investigator Selection
p.000030: 5.6.1 The sponsor is responsible for selecting the investigator(s)/institution(s). Each investigator
p.000030: should be qualified by training and experience and should have adequate resources (see 4.1, 4.2) to properly
p.000030: conduct the trial for which the investigator is selected. If organization of a coordinating committee
p.000030: and/or selection of coordinating investigator(s) are to be utilized in multicentre trials, their organization
p.000030: and/or selection are the sponsor's responsibility.
p.000030: 5.6.2 Before entering an agreement with an investigator/institution to conduct a trial, the sponsor
p.000030: should provide the investigator(s)/institution(s) with the protocol and an up-to- date Investigator's Brochure,
p.000030: and should provide sufficient time for the investigator/institution to review the protocol and the
p.000030: information provided.
p.000030: 5.6.3 The sponsor should obtain the investigator's/institution's agreement:
p.000030:
p.000030:
p.000030:
p.000030:
p.000031: 31
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: (a) to conduct the trial in compliance with GCP, with the SFDA requirement(s) (see 4.1.3), and with the protocol agreed
p.000031: to by the sponsor and given approval/favourable opinion by the IRB/IEC (see 4.5.1);
p.000031: (b) to comply with procedures for data recording/reporting;
p.000031:
p.000031: (c) to permit monitoring, auditing and inspection (see 4.1.4) and
p.000031:
p.000031: (d) to retain the trial related essential documents until the sponsor informs the
p.000031: investigator/institution these documents are no longer needed (see 4.9.4 and 5.5.12).
p.000031: The sponsor and the investigator/institution should sign the protocol, or an alternative document, to
p.000031: confirm this agreement.
p.000031: 5.7 Allocation of Responsibilities
p.000031: Prior to initiating a trial, the sponsor should define, establish, and allocate all trial-related duties and functions.
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 5.8 Compensation to Subjects and Investigators
p.000031: 5.8.1 The sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator/the
p.000031: institution against claims arising from the trial, except for claims that arise from malpractice and/or negligence.
p.000031: 5.8.2 The sponsor's policies and procedures should address the costs of treatment of trial subjects in the event of
p.000031: trial-related injuries in accordance with the SFDA requirement(s).
p.000031: 5.8.3 When trial subjects receive compensation, the method and manner of compensation should comply with SFDA
p.000031: requirement(s).
p.000031: 5.9 Financing
p.000031: The financial aspects of the trial should be documented in an agreement between the sponsor and the
p.000031: investigator/institution.
p.000031:
p.000031:
p.000031:
p.000032: 32
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032: 5.10 Notification/Submission to Saudi food and drug authority
p.000032: Before initiating the clinical trial(s), the sponsor should submit any required application(s) to the SFDA for review,
p.000032: acceptance, and/or permission (as required by the SFDA Guidelines - Guidance and requirements for conducting
p.000032: clinical trials on drugs) to begin the trial(s). Any notification/submission should be dated and
p.000032: contain sufficient information to identify the protocol.
p.000032: 5.11 Confirmation of Review by IRB/IEC
p.000032: 5.11.1 The sponsor should obtain from the investigator/institution:
p.000032:
p.000032: (a) The name and address of the investigator's/institution’s IRB/IEC.
p.000032:
p.000032: (b) A statement obtained from the IRB/IEC that it is organized and operates according to GCP and the applicable laws
p.000032: and regulations.
p.000032: (c) Documented IRB/IEC approval/favourable opinion and, if requested by the sponsor, a current copy of protocol,
p.000032: written informed consent form(s) and any other written information to be provided to subjects, subject
p.000032: recruiting procedures, and documents related to payments and compensation available to the subjects, and any other
p.000032: documents that the IRB/IEC may have requested.
p.000032: 5.11.2 If the IRB/IEC conditions its approval/favourable opinion upon change(s) in any aspect of the trial, such as
p.000032: modification(s) of the protocol, written informed consent form and any other written information to be provided to
p.000032: subjects, and/or other procedures, the sponsor should obtain from the investigator/institution a copy of the
p.000032: modification(s) made and the date approval/favourable opinion was given by the IRB/IEC.
p.000032: 5.11.3 The sponsor should obtain from the investigator/institution documentation and dates of any IRB/IEC
p.000032: reapprovals/re-evaluations with favourable opinion, and of any withdrawals or suspensions of approval/favourable
p.000032: opinion.
p.000032: 5.12 Information on Investigational Product(s)
p.000032: 5.12.1 When planning trials, the sponsor should ensure that sufficient safety and efficacy data from nonclinical
p.000032: studies and/or clinical trials are available to support human exposure by the route, at the dosages, for the duration,
p.000032: and in the trial population to be studied.
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: 5.12.2 The sponsor should update the Investigator's Brochure as significant new information becomes
p.000033: available (see 7. Investigator's Brochure).
p.000033: 5.13 Manufacturing, Packaging, Labelling, and Coding Investigational Product(s)
p.000033: 5.13.1 The sponsor should ensure that the investigational product(s) (including active comparator(s)
p.000033: and placebo, if applicable) is characterized as appropriate to the stage of development of the product(s), is
p.000033: manufactured in accordance with any applicable GMP, and is coded and labelled in a manner that protects the blinding,
p.000033: if applicable. In addition, the labelling should comply with SFDA as described in the Labelling Memo no. 1811 dated
p.000033: 16/1/1436AH.
p.000033: 5.13.2 The sponsor should determine, for the investigational product(s), acceptable storage temperatures,
p.000033: storage conditions (e.g. protection from light), storage times, reconstitution fluids and procedures, and devices for
p.000033: product infusion, if any. The sponsor should inform all involved parties (e.g. monitors, investigators, pharmacists,
p.000033: storage managers) of these determinations.
p.000033: 5.13.3 The investigational product(s) should be packaged to prevent contamination and unacceptable
p.000033: deterioration during transport and storage.
p.000033: 5.13.4 In blinded trials, the coding system for the investigational product(s) should include a mechanism
p.000033: that permits rapid identification of the product(s) in case of a medical emergency, but does not permit
p.000033: undetectable breaks of the blinding.
p.000033: 5.13.5 If significant formulation changes are made in the investigational or comparator product(s) during the course
p.000033: of clinical development, the results of any additional studies of the formulated product(s) (e.g.
p.000033: stability, dissolution rate, bioavailability) needed to assess whether these changes would significantly alter
p.000033: the pharmacokinetic profile of the product should be available prior to the use of the new formulation in clinical
p.000033: trials.
p.000033: 5.14 Supplying and Handling Investigational Product(s)
p.000033: 5.14.1 The sponsor is responsible for supplying the investigator(s)/institution(s) with the investigational
p.000033: product(s).
p.000033:
p.000033:
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: 5.14.2 The sponsor should not supply an investigator/institution with the investigational product(s)
p.000034: until the sponsor obtains all required documentation (e.g. approval/favourable opinion from IRB/IEC and SFDA.
p.000034: 5.14.3 The sponsor should ensure that written procedures include instructions that the
p.000034: investigator/institution should follow for the handling and storage of investigational product(s) for the
p.000034: trial and documentation thereof. The procedures should address adequate and safe receipt, handling, storage,
p.000034: dispensing, retrieval of unused product from subjects, and return of unused investigational product(s) to the sponsor
p.000034: (or alternative disposition if authorized by the sponsor and in compliance with the SFDA requirement(s)).
p.000034: 5.14.4 The sponsor should:
p.000034:
p.000034: (a) Ensure timely delivery of investigational product(s) to the investigator(s).
p.000034:
p.000034: (b) Maintain records that document shipment, receipt, disposition, return, and destruction of the investigational
p.000034: product(s) (see 8. Essential Documents for the Conduct of a Clinical Trial).
p.000034: (c) Maintain a system for retrieving investigational products and documenting this retrieval (e.g. for deficient
p.000034: product recall, reclaim after trial completion, expired product reclaim).
p.000034: (d) Maintain a system for the disposition of unused investigational product(s) and for the documentation of this
p.000034: disposition.
p.000034: 5.14.5 The sponsor should:
p.000034:
p.000034: (a) Take steps to ensure that the investigational product(s) are stable over the period of use.
p.000034: (b) Maintain sufficient quantities of the investigational product(s) used in the trials to reconfirm
p.000034: specifications, should this become necessary, and maintain records of batch sample analyses and characteristics. To the
p.000034: extent stability permits, samples should be retained either until the analyses of the trial data are complete or as
p.000034: required by the SFDA requirement(s), whichever represents the longer retention period.
p.000034:
p.000034:
p.000034:
p.000034:
p.000035: 35
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: 5.15 Record Access
p.000035: 5.15.1 The sponsor should ensure that it is specified in the protocol or other written agreement that the
p.000035: investigator(s)/institution(s) provide direct access to source data/documents for trial-related monitoring, audits,
p.000035: IRB/IEC review, and regulatory inspection.
p.000035: 5.15.2 The sponsor should verify that each subject has consented, in writing, to direct access to his/her original
p.000035: medical records for trial-related monitoring, audit, IRB/IEC review, and regulatory inspection.
p.000035: 5.16 Safety Information
p.000035: 5.16.1 The sponsor is responsible for the ongoing safety evaluation of the investigational product(s).
p.000035: 5.16.2 The sponsor should promptly notify all concerned investigator(s)/institution(s) and the SFDA of findings that
p.000035: could affect adversely the safety of subjects, impact the conduct of the trial, or alter the IRB/IEC's
p.000035: approval/favourable opinion to continue the trial.
p.000035: 5.17 Adverse Drug Reaction Reporting
p.000035: 5.17.1 The sponsor should expedite the reporting to all concerned
p.000035: investigator(s)/institutions(s), to the IRB(s)/IEC(s), where required, and to the SFDA of all adverse drug reactions
p.000035: (ADRs) that are both serious and unexpected.
p.000035: 5.17.2 Such expedited reports should comply with the SFDA requirement(s) and with the ICH Guideline for Clinical
p.000035: Safety Data Management: Definitions and Standards for Expedited Reporting.
p.000035: 5.17.3 The sponsor should submit to the SFDA all safety updates and periodic reports, as required by SFDA
p.000035: requirement(s).
p.000035: 5.18 Monitoring
p.000035: 5.18.1 Purpose
p.000035: The purposes of trial monitoring are to verify that:
p.000035:
p.000035: (a) The rights and well-being of human subjects are protected.
p.000035:
p.000035: (b) The reported trial data are accurate, complete, and verifiable from source documents.
p.000035:
p.000035:
p.000035:
p.000036: 36
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036: (c) The conduct of the trial is in compliance with the currently approved
p.000036: protocol/amendment(s), with GCP, and with the SFDA requirement(s).
p.000036: 5.18.2 Selection and Qualifications of Monitors
p.000036: (a) Monitors should be appointed by the sponsor.
p.000036:
p.000036: (b) Monitors should be appropriately trained, and should have the scientific and/or clinical knowledge
p.000036: needed to monitor the trial adequately. A monitor’s qualifications should be documented.
...
p.000041:
p.000041: 5.20.2 If the monitoring and/or auditing identifies serious and/or persistent noncompliance on the part of an
p.000041: investigator/institution, the sponsor should terminate the investigator's/institution’s participation
p.000041: in the trial. When an investigator's/institution’s participation is terminated because of noncompliance, the
p.000041: sponsor should notify promptly the SFDA.
p.000041: 5.21 Premature Termination or Suspension of a Trial
p.000041: If a trial is prematurely terminated or suspended, the sponsor should promptly inform the
p.000041: investigators/institutions, and the SFDA of the termination or suspension and the reason(s) for the termination or
p.000041: suspension. The IRB/IEC should also be informed promptly and provided the reason(s) for the termination or suspension
p.000041: by the sponsor or by the investigator/institution, as specified by the SFDA requirement(s).
p.000041: 5.22 Clinical Trial/Study Reports
p.000041: Whether the trial is completed or prematurely terminated, the sponsor should ensure that the clinical trial reports are
p.000041: prepared and provided to the regulatory agency(ies). The sponsor should also ensure that the clinical trial reports in
p.000041: marketing applications meet the standards of the ICH Guideline for Structure and Content of Clinical Study Reports.
p.000041: (NOTE: The ICH Guideline for Structure and Content of Clinical Study Reports specifies that abbreviated study reports
p.000041: may be acceptable in certain cases.)
p.000041: 5.23 Multicentre Trials
p.000041: For multicentre trials, the sponsor should ensure that:
p.000041:
p.000041: 5.23.1 All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor and, if
p.000041: required, by the SFDA, and given approval/favourable opinion by the IRB/IEC.
p.000041: 5.23.2 The CRFs are designed to capture the required data at all multicentre trial sites. For those investigators who
p.000041: are collecting additional data, supplemental CRFs should also be provided that are designed to capture the additional
p.000041: data.
p.000041: 5.23.3 The responsibilities of coordinating investigator(s) and the other participating investigators
p.000041: are documented prior to the start of the trial.
p.000041:
p.000041:
p.000042: 42
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042: 5.23.4 All investigators are given instructions on following the protocol, on complying with a uniform set of
p.000042: standards for the assessment of clinical and laboratory findings, and on completing the CRFs.
p.000042: 5.23.5 Communication between investigators is facilitated.
p.000042:
p.000042:
p.000042: 6. CLINICAL TRIAL PROTOCOL AND PROTOCOL AMENDMENT(S)
p.000042: The contents of a trial protocol should generally include the following topics. However, site specific information may
p.000042: be provided on separate protocol page(s), or addressed in a separate agreement, and some of the information
p.000042: listed below may be contained in other protocol referenced documents, such as an Investigator’s Brochure.
p.000042: 6.1 General Information
p.000042: 6.1.1 Protocol title, protocol identifying number, and date. Any amendment(s) should also bear the amendment
p.000042: number(s) and date(s).
p.000042: 6.1.2 Name and address of the sponsor and monitor (if other than the sponsor).
p.000042: 6.1.3 Name and title of the person(s) authorized to sign the protocol and the protocol amendment(s) for
p.000042: the sponsor.
p.000042: 6.1.4 Name, title, address, and telephone number(s) of the sponsor's medical expert (or dentist when appropriate)
...
p.000056: (where required)
p.000056: To document that compensation to X X subject(s) for trial-related
p.000056: injury will be
p.000056: available
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000057: 57
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: Title of Document Purpose
p.000057: Located in Files of
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: 8.2.6 SIGNED AGREEMENT BETWEEN INVOLVED PARTIES, e.g.:
p.000057:
p.000057:
p.000057:
p.000057: To document agreements
p.000057: Investigator/
p.000057: Institution
p.000057: Sponsor
p.000057:
p.000057: - investigator/institution and
p.000057: X X
p.000057: sponsor
p.000057:
p.000057: - investigator/institution and CRO
p.000057: X X
p.000057: (where required)
p.000057:
p.000057:
p.000057:
p.000057: - sponsor and CRO
p.000057: X
p.000057:
p.000057:
p.000057: - investigator/institution and
p.000057: X X
p.000057: authority(ies)
p.000057:
p.000057: (where required)
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000058: 58
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: Title of Document Purpose
p.000058: Located in Files of
p.000058:
p.000058:
p.000058:
p.000058: Investigator/
p.000058: Institution
p.000058: Sponsor
p.000058:
p.000058:
p.000058: 8.2.7 DATED, DOCUMENTED APPROVAL/FAVOURABLE OPINION OF INSTITUTIONAL REVIEW BOARD (IRB)
p.000058: /INDEPENDENT ETHICS COMMITTEE (IEC) OF THE FOLLOWING:
p.000058: - protocol and any amendments
p.000058:
p.000058: - CRF (if applicable)
p.000058: - informed consent form(s)
p.000058: - any other written information to be provided to the subject(s)
p.000058: -advertisement for subject recruitment (if used)
p.000058: - subject compensation (if any)
p.000058: - any other documents given approval/ favourable opinion
p.000058: To document that the trial has been X X subject to IRB/IEC
p.000058: review and
p.000058: given approval/favourable opinion. To identify the version number and date of the document(s) .
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000059: 59
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059: Title of Document Purpose
p.000059: Located in Files of
p.000059:
p.000059:
p.000059:
p.000059: Investigator/
p.000059: Institution
p.000059: Sponsor
p.000059:
p.000059:
p.000059: 8.2.8 INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE COMPOSITION
p.000059: To document that the IRB/IEC is constituted in agreement with GCP
p.000059: X X
p.000059: (where required)
p.000059:
p.000059:
p.000059:
p.000059:
p.000059: 8.2.9 REGULATORY AUTHORITY(IES) AUTHORISATION/APPROVAL/ NOTIFICATION OF PROTOCOL
p.000059: (where required)
p.000059: To document appropriate authorisation/approval/notification by
p.000059: the regulatory authority(ies) has been obtained prior to initiation of the trial in compliance with the
p.000059: applicable regulatory requirement(s)
p.000059: X
p.000059: (where required)
p.000059: X
p.000059: (where required)
p.000059:
p.000059:
p.000059: 8.2.10 CURRICULUM VITAE AND/OR OTHER RELEVANT DOCUMENTS EVIDENCING QUALIFICATIONS OF
p.000059: INVESTIGATOR(S) AND SUB- INVESTIGATOR(S)
p.000059: To document qualifications and eligibility to X X conduct trial
p.000059: and/or provide medical
p.000059: supervision of subjects
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
...
p.000063:
p.000063:
p.000063:
p.000063:
p.000063:
p.000063: 8.3 During the Clinical Conduct of the Trial
p.000063: In addition to having on file the above documents, the following should be added to the files during the trial as
p.000063: evidence that all new relevant information is documented as it becomes available
p.000063:
p.000063: Title of Document Purpose
p.000063: Located in Files of
p.000063:
p.000063:
p.000063:
p.000063: Investigator/
p.000063: Institution
p.000063: Sponsor
p.000063:
p.000063: 8.3.1 INVESTIGATOR’S BROCHURE UPDATES To document that investigator is
p.000063: X X
p.000063: informed in a timely manner of relevant information as it becomes available
p.000063:
p.000063:
p.000063:
p.000063: 8.3.2 ANY REVISION TO:
p.000063: - protocol/amendment(s) and CRF
p.000063: - informed consent form
p.000063: - any other written information provided to subjects
p.000063: - advertisement for subject recruitment (if used)
p.000063: To document revisions of these trial X X related documents that take
p.000063: effect
p.000063: during trial
p.000063:
p.000063:
p.000063:
p.000063:
p.000063:
p.000063:
p.000063:
p.000063:
p.000063:
p.000063:
p.000064: 64
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064: Title of Document Purpose
p.000064: Located in Files of
p.000064:
p.000064:
p.000064:
p.000064: Investigator/
p.000064: Institution
p.000064: Sponsor
p.000064:
p.000064:
p.000064: 8.3.3 DATED, DOCUMENTED APPROVAL/FAVOURABLE OPINION OF
p.000064: INSTITUTIONAL REVIEW BOARD (IRB)
p.000064: /INDEPENDENT ETHICS COMMITTEE (IEC) OF THE FOLLOWING:
p.000064: - protocol amendment(s)
p.000064: - revision(s) of:
p.000064: - informed consent form
p.000064: - any other written information to be provided to the subject
p.000064: - advertisement for subject recruitment (if used)
p.000064: - any other documents given approval/favourable opinion
p.000064: - continuing review of trial (where required)
p.000064: To document that the amendment(s) X X and/or revision(s) have been subject
p.000064: to IRB/IEC review and were given approval/favourable opinion. To identify the version number and date of the
p.000064: document(s).
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000065: 65
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065: Title of Document Purpose
p.000065: Located in Files of
p.000065:
p.000065:
p.000065:
p.000065: Investigator/
p.000065: Institution
p.000065: Sponsor
p.000065:
p.000065:
p.000065: 8.3.4 REGULATORY AUTHORITY(IES) AUTHORISATIONS/APPROVALS/NOTIFICATIONS WHERE REQUIRED FOR:
p.000065: - protocol amendment(s) and other documents
p.000065: To document compliance with applicable regulatory requirements
p.000065: X X
p.000065: (where required)
p.000065:
p.000065:
p.000065:
p.000065: 8.3.5 CURRICULUM VITAE FOR NEW INVESTIGATOR(S) AND/OR SUB- INVESTIGATOR(S)
p.000065: (see 8.2.10) X X
p.000065:
p.000065:
p.000065:
p.000065: 8.3.6 UPDATES TO NORMAL VALUE(S)/RANGE(S) FOR MEDICAL/ LABORATORY/ TECHNICAL PROCEDURE(S)/TEST(S)
p.000065: INCLUDED IN THE PROTOCOL
p.000065: To document normal values and X X ranges that are revised during
p.000065: the
p.000065: trial (see 8.2.11)
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000066: 66
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066: Title of Document Purpose
p.000066: Located in Files of
p.000066:
p.000066:
p.000066:
...
General/Other / Incapacitated
Searching for indicator incapacity:
(return to top)
p.000008:
p.000008: A written description of a change(s) to or formal clarification of a protocol.
p.000008:
p.000008: 1.46 Quality Assurance (QA)
p.000008:
p.000008: All those planned and systematic actions that are established to ensure that the trial is performed and the data are
p.000008: generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and SFDA
p.000008: requirement(s).
p.000008: 1.47 Quality Control (QC)
p.000008:
p.000008: The operational techniques and activities undertaken within the quality assurance system to verify that the
p.000008: requirements for quality of the trial-related activities have been fulfilled.
p.000008: 1.48 Randomization
p.000008:
p.000008: The process of assigning trial subjects to treatment or control groups using an element of chance to determine the
p.000008: assignments in order to reduce bias.
p.000008: 1.49 Regulatory Authorities
p.000008:
p.000008: Bodies having the power to regulate. In the ICH GCP guideline the expression Regulatory Authorities
p.000008: includes the authorities that review submitted clinical data and those that conduct inspections (see 1.29). These
p.000008: bodies are sometimes referred to as competent authorities.
p.000008: 1.50 Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (Serious ADR)
p.000008:
p.000008: Any untoward medical occurrence that at any dose:
p.000008:
p.000008: - results in death,
p.000008:
p.000008: - is life-threatening,
p.000008:
p.000008: - requires inpatient hospitalization or prolongation of existing hospitalization,
p.000008:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: - results in persistent or significant disability/incapacity, or
p.000009: - is a congenital anomaly/birth defect
p.000009:
p.000009: (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting).
p.000009:
p.000009: 1.51 Source Data
p.000009: All information in original records and certified copies of original records of clinical findings, observations, or
p.000009: other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are
p.000009: contained in source documents (original records or certified copies).
p.000009: 1.52 Source Documents
p.000009:
p.000009: Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes,
p.000009: memoranda, subjects' diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated
p.000009: instruments, copies or transcriptions certified after verification as being accurate copies, microfiches,
p.000009: photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the
p.000009: laboratories and at medico-technical departments involved in the clinical trial).
p.000009: 1.53 Sponsor
p.000009:
p.000009: An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or
p.000009: financing of a clinical trial.
p.000009: 1.54 Sponsor-Investigator
p.000009: An individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate
p.000009: direction the investigational product is administered to, dispensed to, or used by a subject. The term does not include
p.000009: any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of
p.000009: a sponsor-investigator include both those of a sponsor and those of an investigator.
p.000009:
...
General/Other / Natural Hazards
Searching for indicator hazard:
(return to top)
p.000018: approval/favourable opinion from the IRB/IEC for the trial protocol, written informed consent form, consent
p.000018: form updates, subject recruitment procedures (e.g., advertisements), and any other written information to be provided
p.000018: to subjects.
p.000018: 4.4.2 As part of the investigator's/institution’s written application to the IRB/IEC, the
p.000018: investigator/institution should provide the IRB/IEC with a current copy of the Investigator's
p.000018: Brochure. If the Investigator's Brochure is updated during the trial, the investigator/institution should
p.000018: supply a copy of the updated Investigator’s Brochure to the IRB/IEC.
p.000018: 4.4.3 During the trial the investigator/institution should provide to the IRB/IEC all documents subject to review.
p.000018:
p.000018:
p.000018: 4.5 Compliance with Protocol
p.000018: 4.5.1 The investigator/institution should conduct the trial in compliance with the protocol agreed to by the sponsor
p.000018: and by the SFDA and which was given approval/favourable opinion by the IRB/IEC. The investigator/institution and the
p.000018: sponsor should sign the protocol, or an alternative contract, to confirm agreement.
p.000018: 4.5.2 The investigator should not implement any deviation from, or changes of the protocol without
p.000018: agreement by the sponsor and prior review and documented approval/favourable opinion from the IRB/IEC of an
p.000018: amendment, except where necessary to eliminate an immediate hazard(s) to trial subjects, or when the change(s)
p.000018: involves only logistical or administrative aspects of the trial (e.g., change in monitor(s), change of
p.000018: telephone number(s)).
p.000019: 19
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019: 4.5.3 The investigator, or person designated by the investigator, should document and explain any deviation from the
p.000019: approved protocol.
p.000019: 4.5.4 The investigator may implement a deviation from, or a change of, the protocol to eliminate an immediate
p.000019: hazard(s) to trial subjects without prior IRB/IEC approval/favourable opinion. As soon as possible, the
p.000019: implemented deviation or change, the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be
p.000019: submitted:
p.000019: (a) to the IRB/IEC for review and approval/favourable opinion,
p.000019:
p.000019: (b) to the sponsor for agreement and, if required,
p.000019:
p.000019: (c) to the SFDA .
p.000019:
p.000019: 4.6 Investigational Product(s)
p.000019: 4.6.1 Responsibility for investigational product(s) accountability at the trial site(s) rests with the
p.000019: investigator/institution.
p.000019: 4.6.2 Where allowed/required, the investigator/institution may/should assign some or all of the
p.000019: investigator's/institution’s duties for investigational product(s) accountability at the trial site(s) to an
p.000019: appropriate pharmacist or another appropriate individual who is under the supervision of the
p.000019: investigator/institution..
p.000019: 4.6.3 The investigator/institution and/or a pharmacist or other appropriate individual, who is designated
p.000019: by the investigator/institution, should maintain records of the product's delivery to the trial site, the inventory at
p.000019: the site, the use by each subject, and the return to the sponsor or alternative disposition of unused product(s). These
p.000019: records should include dates, quantities, batch/serial numbers, expiration dates (if applicable), and the
p.000019: unique code numbers assigned to the investigational product(s) and trial subjects. Investigators should maintain
p.000019: records that document adequately that the subjects were provided the doses specified by the protocol and
...
General/Other / Public Emergency
Searching for indicator emergency:
(return to top)
p.000010:
p.000010: 1.60 Unexpected Adverse Drug Reaction
p.000010:
p.000010: An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g.,
p.000010: Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics
p.000010: for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for
p.000010: Expedited Reporting).
p.000010:
p.000010: 1.61 Vulnerable Subjects
p.000010:
p.000010: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether
p.000010: justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a
p.000010: hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure,
p.000010: such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory
p.000010: personnel, employees of the
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects
p.000011: include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons,
p.000011: patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those
p.000011: incapable of giving consent.
p.000011: 1.62 Well-being (of the trial subjects)
p.000011:
p.000011: The physical and mental integrity of the subjects participating in a clinical trial.
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
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p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2. THE PRINCIPLES OF ICH GCP
p.000012:
p.000012: 2.1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the
p.000012: Declaration of Helsinki, and that are consistent with GCP and the with SFDA requirement(s).
p.000012: 2.2 Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated
p.000012: benefit for the individual trial subject and society. A trial should be initiated and continued only if the
p.000012: anticipated benefits justify the risks.
p.000012: 2.3 The rights, safety, and well-being of the trial subjects are the most important
...
p.000023: 4.8.13 Except as described in 4.8.14, a non-therapeutic trial (i.e. a trial in which there is no anticipated direct
p.000023: clinical benefit to the subject), should be conducted in subjects who personally give consent and who sign and date the
p.000023: written informed consent form.
p.000023: 4.8.14 Non-therapeutic trials may be conducted in subjects with consent of a legally acceptable representative
p.000023: provided the following conditions are fulfilled:
p.000023:
p.000024: 24
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024: (a) The objectives of the trial can not be met by means of a trial in subjects who can give informed consent
p.000024: personally.
p.000024: (b) The foreseeable risks to the subjects are low.
p.000024:
p.000024: (c) The negative impact on the subject’s well-being is minimized and low.
p.000024:
p.000024: (d) The trial is not prohibited by law.
p.000024:
p.000024: (e) The approval/favourable opinion of the IRB/IEC is expressly sought on the inclusion of such subjects, and the
p.000024: written approval/ favourable opinion covers this aspect.
p.000024: Such trials, unless an exception is justified, should be conducted in patients having a disease or condition for which
p.000024: the investigational product is intended. Subjects in these trials should be particularly closely monitored and should
p.000024: be withdrawn if they appear to be unduly distressed.
p.000024: 4.8.15 In emergency situations, when prior consent of the subject is not possible, the consent of the subject's
p.000024: legally acceptable representative, if present, should be requested. When prior consent of the subject is not
p.000024: possible, and the subject’s legally acceptable representative is not available, enrolment of the subject
p.000024: should require measures described in the protocol and/or elsewhere, with documented approval/favourable
p.000024: opinion by the IRB/IEC, to protect the rights, safety and well-being of the subject and to ensure compliance with
p.000024: applicable regulatory requirements. The subject or the subject's legally acceptable representative should be
p.000024: informed about the trial as soon as possible and consent to continue and other consent as appropriate (see 4.8.10)
p.000024: should be requested.
p.000024: 4.9 Records and Reports
p.000024: 4.9.1 The investigator should ensure the accuracy, completeness, legibility, and timeliness of the data reported to
p.000024: the sponsor in the CRFs and in all required reports.
p.000024: 4.9.2 Data reported on the CRF, that are derived from source documents, should be consistent with the source
p.000024: documents or the discrepancies should be explained.
p.000024: 4.9.3 Any change or correction to a CRF should be dated, initialed, and explained (if necessary) and
p.000024: should not obscure the original entry (i.e. an audit trail should be
p.000025: 25
p.000025:
p.000025:
p.000025:
...
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: 5.12.2 The sponsor should update the Investigator's Brochure as significant new information becomes
p.000033: available (see 7. Investigator's Brochure).
p.000033: 5.13 Manufacturing, Packaging, Labelling, and Coding Investigational Product(s)
p.000033: 5.13.1 The sponsor should ensure that the investigational product(s) (including active comparator(s)
p.000033: and placebo, if applicable) is characterized as appropriate to the stage of development of the product(s), is
p.000033: manufactured in accordance with any applicable GMP, and is coded and labelled in a manner that protects the blinding,
p.000033: if applicable. In addition, the labelling should comply with SFDA as described in the Labelling Memo no. 1811 dated
p.000033: 16/1/1436AH.
p.000033: 5.13.2 The sponsor should determine, for the investigational product(s), acceptable storage temperatures,
p.000033: storage conditions (e.g. protection from light), storage times, reconstitution fluids and procedures, and devices for
p.000033: product infusion, if any. The sponsor should inform all involved parties (e.g. monitors, investigators, pharmacists,
p.000033: storage managers) of these determinations.
p.000033: 5.13.3 The investigational product(s) should be packaged to prevent contamination and unacceptable
p.000033: deterioration during transport and storage.
p.000033: 5.13.4 In blinded trials, the coding system for the investigational product(s) should include a mechanism
p.000033: that permits rapid identification of the product(s) in case of a medical emergency, but does not permit
p.000033: undetectable breaks of the blinding.
p.000033: 5.13.5 If significant formulation changes are made in the investigational or comparator product(s) during the course
p.000033: of clinical development, the results of any additional studies of the formulated product(s) (e.g.
p.000033: stability, dissolution rate, bioavailability) needed to assess whether these changes would significantly alter
p.000033: the pharmacokinetic profile of the product should be available prior to the use of the new formulation in clinical
p.000033: trials.
p.000033: 5.14 Supplying and Handling Investigational Product(s)
p.000033: 5.14.1 The sponsor is responsible for supplying the investigator(s)/institution(s) with the investigational
p.000033: product(s).
p.000033:
p.000033:
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: 5.14.2 The sponsor should not supply an investigator/institution with the investigational product(s)
p.000034: until the sponsor obtains all required documentation (e.g. approval/favourable opinion from IRB/IEC and SFDA.
p.000034: 5.14.3 The sponsor should ensure that written procedures include instructions that the
p.000034: investigator/institution should follow for the handling and storage of investigational product(s) for the
p.000034: trial and documentation thereof. The procedures should address adequate and safe receipt, handling, storage,
p.000034: dispensing, retrieval of unused product from subjects, and return of unused investigational product(s) to the sponsor
p.000034: (or alternative disposition if authorized by the sponsor and in compliance with the SFDA requirement(s)).
p.000034: 5.14.4 The sponsor should:
p.000034:
...
p.000061: Located in Files of
p.000061:
p.000061:
p.000061:
p.000061: Investigator/
p.000061: Institution
p.000061: Sponsor
p.000061:
p.000061:
p.000061: 8.2.14 INSTRUCTIONS FOR HANDLING OF INVESTIGATIONAL PRODUCT(S) AND TRIAL-RELATED MATERIALS (if not included in
p.000061: protocol or
p.000061: Investigator’s Brochure)
p.000061: To document instructions needed to ensure X X proper storage, packaging,
p.000061: dispensing and
p.000061: disposition of investigational products and trial-related materials
p.000061:
p.000061:
p.000061: 8.2.15 SHIPPING RECORDS FOR INVESTIGATIONAL PRODUCT(S) AND TRIAL-RELATED MATERIALS
p.000061: To document shipment dates, batch numbers X X and method of shipment of
p.000061: investigational
p.000061: product(s) and trial-related materials. Allows tracking of product batch, review of shipping conditions, and
p.000061: accountability
p.000061:
p.000061:
p.000061:
p.000061: 8.2.16 CERTIFICATE(S) OF ANALYSIS OF INVESTIGATIONAL PRODUCT(S) SHIPPED
p.000061: To document identity, purity, and strength of X investigational
p.000061: product(s) to be used in the
p.000061: trial
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000062: 62
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062: Title of Document Purpose
p.000062: Located in Files of
p.000062:
p.000062:
p.000062:
p.000062: Investigator/
p.000062: Institution
p.000062: Sponsor
p.000062:
p.000062:
p.000062: 8.2.17 DECODING PROCEDURES FOR BLINDED TRIALS
p.000062: To document how, in case of an emergency, identity of blinded investigational product can be revealed without breaking
p.000062: the blind for the remaining subjects' treatment
p.000062: X X
p.000062: (third party if applicable)
p.000062:
p.000062:
p.000062:
p.000062: 8.2.18 MASTER RANDOMISATION LIST
p.000062: To document method for randomisation of trial population
p.000062: X
p.000062: (third party if applicable)
p.000062:
p.000062:
p.000062: 8.2.19 PRE-TRIAL MONITORING REPORT
p.000062: To document that the site is suitable for the X trial (may
p.000062: be combined with 8.2.20)
p.000062:
p.000062:
p.000062:
p.000062: 8.2.20 TRIAL INITIATION
p.000062: MONITORING REPORT
p.000062: To document that trial procedures were X X reviewed
p.000062: with the investigator and the
p.000062: investigator’s trial staff ( may be combined with 8.2.19)
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000063: 63
p.000063:
p.000063:
p.000063:
p.000063:
p.000063:
p.000063: 8.3 During the Clinical Conduct of the Trial
p.000063: In addition to having on file the above documents, the following should be added to the files during the trial as
p.000063: evidence that all new relevant information is documented as it becomes available
p.000063:
p.000063: Title of Document Purpose
p.000063: Located in Files of
p.000063:
p.000063:
p.000063:
p.000063: Investigator/
p.000063: Institution
p.000063: Sponsor
p.000063:
...
General/Other / Relationship to Authority
Searching for indicator authority:
(return to top)
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Guideline for Good Clinical Practice (GCP) E6(R1)
p.000001:
p.000001: Adopted from International Council For Harmonisation of Technical Requirements for Registration of Pharmaceuticals for
p.000001: Human Use (ICH)
p.000001:
p.000001:
p.000001:
p.000001: Version 2.0
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Date of adoption 20/01/2013
p.000001:
p.000001: Date of implementation 20/04/2013
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: GUIDELINE FOR GOOD CLINICAL PRACTICE (GCP) E6(R1)
p.000001: Version 2.0
p.000001:
p.000001: Drug Sector
p.000001: Saudi Food & Drug Authority
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Please visit SFDA’s website at http://www.sfda.gov.sa/En/Drug for the latest update
p.000001:
p.000001:
p.000001:
p.000001: For Inquiries Inspection.Drug@sfda.gov.sa For Comments or Suggestions Drug.Comments@sfda.gov.sa
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: i
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Drug Sector Vision and Mission
p.000001:
p.000001: Vision
p.000001:
p.000001: To be the leading regional Drug Regulatory Authority for pharmaceuticals and cosmetic products, with professional
p.000001: excellence and services that contribute to the protection and advancement of public health in the Kingdom of Saudi
p.000001: Arabia.
p.000001: ةيؤرلا
p.000001:
p.000001: ةيماح في مهست ةيزتمم ةينهبم هتامدخ مدقيو ،ليمجتلا تاضرحت سمو ةيودلا لىع ةباقرلا في اً ييملقا اً دئار ءاولدا عاطق نوكي
p.000001: نأ
p.000001: .ةيدوعسلا ةيبرعلا ةكلملما في ةحصلا زيزعتو
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Mission
p.000001:
p.000001: Protecting public health by ensuring safety, quality, efficacy and accessibility of human, veterinary drugs and
p.000001: biological products, and safety of cosmetics, through administration of a national regulatory system which is
p.000001: consistent with international best practice. Through our mission, we also provide accurate and scientific-based
p.000001: information to the public and healthcare professionals.
p.000001: لةاسرلا
p.000001:
p.000001:
p.000001: داوم ةملاسو ةيويلحا تاجتنلماو ةيرطيبلاو ةيشربلا ةيودل
p.000001: ا رفوتو ةيلاعفو ةدوجو نامأ
p.000001: نماض للاخ نم ةماعلا ةحصلا ةيماح
p.000001:
p.000001: ةيملع سسأ
p.000001: لىع ةينبلما ةيئاولدا تامولعلما يمدقتو ةيلولدا تاسرمالما لضفأ
p.000001: عم قفاوتم ةباقرلل نيطو ماظن قيبطت برع ليمجتلا
p.000001: .ينيحصلا ينينهلماو ةماعلل
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: ii
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Document Control
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Version
p.000001:
p.000001:
p.000001: 1.1
p.000001:
p.000001: 1.2
p.000001: 1.2
p.000001: 1.3
p.000001: 1.3
p.000001:
p.000001:
p.000001: 2.0
p.000001: Author
p.000001:
p.000001:
p.000001: Clinical trial committee members
p.000001: Clinical trial dept. team Clinical trial dept. team Clinical trial dept. team Clinical trial dept. team GCP inspection
p.000001: dept. team
p.000001: Implementation Date
p.000001: Sep /2008
p.000001:
p.000001: Oct/2009 Jan/2010 Jan/2013 Apr/2013
p.000001:
p.000001: 5/12/2017
p.000001:
p.000001: Comments
p.000001:
p.000001: Initial draft for internal consultation
p.000001: Published for comments Final
p.000001: Published for comments Final
p.000001: This guideline replaces "Clinical Trials Requirements Guidelines".
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: iii
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: FOREWORD
p.000001:
p.000001: This guidance has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by
p.000001: the regulatory parties, in accordance with the ICH Process.
p.000001:
p.000001: In adopting this ICH guidance, Saudi Food and Drug Authority (SFDA) endorses the principles and practices
p.000001: described therein. This document should be read in conjunction with the accompanying notice and the relevant sections
p.000001: of other applicable guidances.
p.000001:
p.000001: Guidance documents are meant to provide assistance to industry and health care professionals on how to
p.000001: comply with the policies and governing statutes and regulations. They also serve to provide review and compliance
p.000001: guidance to staff, thereby ensuring that mandates are implemented in a fair, consistent and effective manner.
p.000001:
p.000001: Guidance documents are administrative instruments not having force of law and, as such, allow for flexibility in
p.000001: approach. Alternate approaches to the principles and practices described in this document may be acceptable
p.000001: provided they are supported by adequate scientific justification. Alternate approaches should be discussed in
p.000001: advance with the relevant program area to avoid the possible finding that applicable statutory or regulatory
p.000001: requirements have not been met.
p.000001:
p.000001: As a corollary to the above, it is equally important to note that SFDA reserves the right to request information or
p.000001: material, or define conditions not specifically described in this guidance, in order to allow the Department
p.000001: to adequately assess the safety, efficacy or quality of a therapeutic product. Saudi Food and Drug Authority is
p.000001: committed to ensuring that such requests are justifiable and that decisions are clearly documented.
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: iv
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Contents
p.000001: INTRODUCTION
p.000001: 1
p.000001: 1. GLOSSARY
p.000002: 2
p.000002: 2. THE PRINCIPLES OF ICH GCP
p.000013: 13
p.000013: 3. INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC)
p.000014: 14
p.000014: 3.1 Responsibilities
p.000014: 14
p.000014: 3.2 Composition, Functions and Operations
p.000015: 15
p.000015: 3.3 Procedures
p.000016: 16
p.000016: 3.4 Records
p.000017: 17
p.000017: 4. INVESTIGATOR
p.000017: 17
p.000017: 4.1 Investigator's Qualifications and Agreements
p.000017: 17
p.000017: 4.2 Adequate Resources
p.000018: 18
p.000018: 4.3 Medical Care of Trial Subjects
p.000018: 18
p.000018: 4.4 Communication with IRB/IEC
p.000019: 19
p.000019: 4.5 Compliance with Protocol
p.000019: 19
p.000019: 4.6 Investigational Product(s)
p.000020: 20
p.000020: 4.7 Randomization Procedures and Unblinding 21
p.000020: 4.8 Informed Consent of Trial Subjects
p.000021: 21
p.000021: 4.9 Records and Reports
p.000025: 25
p.000025: 4.10 Progress Reports
p.000026: 26
p.000026: 4.11 Safety Reporting
p.000027: 27
p.000027: 4.12 Premature Termination or Suspension of a Trial 27
p.000027: 4.13 Final Report(s) by Investigator
p.000028: 28
p.000028: 5. SPONSOR
p.000028: 28
p.000028: 5.1 Quality Assurance and Quality Control
p.000028: 28
p.000028: 5.2 Contract Research Organization (CRO)
p.000028: 28
p.000028: 5.3 Medical Expertise
p.000029: 29
p.000029: 5.4 Trial Design
p.000029: 29
p.000029: 5.5 Trial Management, Data Handling, and Record Keeping 29
p.000029: 5.6 Investigator Selection
p.000031: 31
p.000031: 5.7 Allocation of Responsibilities
p.000032: 32
p.000032: 5.8 Compensation to Subjects and Investigators
p.000032: 32
p.000032: v
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032: 5.9 Financing
p.000032: 32
p.000032: 5.10 Notification/Submission to Regulatory Authority(ies) 33
p.000032: 5.11 Confirmation of Review by IRB/IEC
p.000033: 33
p.000033: 5.12 Information on Investigational Product(s)
p.000033: 33
p.000033: 5.13 Manufacturing, Packaging, Labelling, and Coding Investigational Product(s) 34
p.000033: 5.14 Supplying and Handling Investigational Product(s) 34
p.000033: 5.15 Record Access
p.000036: 36
p.000036: 5.16 Safety Information
p.000036: 36
p.000036: 5.17 Adverse Drug Reaction Reporting
p.000036: 36
p.000036: 5.18 Monitoring
p.000036: 36
p.000036: 5.18.1 Purpose
p.000036: 36
p.000036: 5.18.2 Selection and Qualifications of Monitors 37
p.000036: 5.18.3 Extent and Nature of Monitoring
p.000037: 37
p.000037: 5.18.4 Monitor's Responsibilities
p.000037: 37
p.000037: 5.18.5 Monitoring Procedures
p.000040: 40
p.000040: 5.18.6 Monitoring Report
p.000040: 40
p.000040: 5.19 Audit
p.000040: 40
p.000040: 5.19.1 Purpose
p.000041: 41
p.000041: 5.19.2 Selection and Qualification of Auditors 41
p.000041: 5.19.3 Auditing Procedures
p.000041: 41
p.000041: 5.20 Noncompliance
p.000041: 41
p.000041: 5.21 Premature Termination or Suspension of a Trial 42
p.000041: 5.22 Clinical Trial/Study Reports
p.000042: 42
p.000042: 5.23 Multicentre Trials
p.000042: 42
p.000042: 6. CLINICAL TRIAL PROTOCOL AND PROTOCOL AMENDMENT(S) 43
p.000042: 6.1 General Information
p.000043: 43
p.000043: 6.2 Background Information
p.000043: 43
...
p.000050: 50
p.000050: 7.3.7 Summary of Data and Guidance for the Investigator 52
p.000050: 7.4 APPENDIX 1:
p.000053: 53
p.000053: 7.5 APPENDIX 2:
p.000054: 54
p.000054: 8. ESSENTIAL DOCUMENTS FOR THE CONDUCT OF A CLINICAL TRIAL 55
p.000054: 8.1 Introduction
p.000055: 55
p.000055: 8.2 Before the Clinical Phase of the Trial Commences 56
p.000055: 8.3 During the Clinical Conduct of the Trial
p.000064: 64
p.000064: 8.4 After Completion or Termination of the Trial
p.000072: 72
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: vii
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: INTRODUCTION
p.000072:
p.000072:
p.000072: Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing,
p.000072: conducting, recording and reporting trials that involve the participation of human subjects. Compliance with this
p.000072: standard provides public assurance that the rights, safety and well-being of trial subjects are protected, consistent
p.000072: with the principles that have their origin in the Declaration of Helsinki, and that the clinical trial data are
p.000072: credible.
p.000072: The objective of this ICH GCP Guideline is to provide a unified standard for the European Union (EU), Japan and the
p.000072: United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these
p.000072: jurisdictions and in other jurisdictions who are willing to adopt such mutual recognition such as Saudi food and drug
p.000072: authority (SFDA) in Saudi Arabia.
p.000072: The guideline was developed with consideration of the current good clinical practices of the European Union, Japan, and
p.000072: the United States, as well as those of Australia, Canada, the Nordic countries and the World Health Organization (WHO).
p.000072: This guideline should be followed when generating clinical trial data that are intended to be submitted to the SFDA.
p.000072: The principles established in this guideline may also be applied to other clinical investigations that may have an
p.000072: impact on the safety and well-being of human subjects.
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000001: 1
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: 1. GLOSSARY
p.000001:
p.000001:
p.000001: 1.1 Adverse Drug Reaction (ADR)
p.000001: In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as
p.000001: the therapeutic dose(s) may not be established: all noxious and unintended responses to a medicinal
p.000001: product related to any dose should be considered adverse drug reactions. The phrase responses to a medicinal
p.000001: product means that a causal relationship between a medicinal product and an adverse event is at least a reasonable
p.000001: possibility, i.e. the relationship cannot be ruled out.
p.000001: Regarding marketed medicinal products: a response to a drug which is noxious and unintended and which occurs at
...
p.000005: protocol, the suitability of the investigator(s), facilities, and the methods and material to be used in
p.000005: obtaining and documenting informed consent of the trial subjects.
p.000005: The legal status, composition, function, operations and regulatory requirements pertaining to Independent Ethics
p.000005: Committees may differ among countries, but should allow the Independent Ethics Committee to act in agreement with GCP
p.000005: as described in this guideline. The legal status, composition, function, operations and regulatory requirements
p.000005: pertaining to IEC in Saudi Arabia are governed by Law of Ethics of Research on Living Creatures.
p.000005:
p.000005: 1.28 Informed Consent
p.000005: A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after
p.000005: having been informed of all aspects of the trial that are relevant to the subject's decision to participate. Informed
p.000005: consent is documented by means of a written, signed and dated informed consent form.
p.000005: 1.29 Inspection
p.000005: The act by SFDA of conducting an official review of documents, facilities, records, and any other resources that are
p.000005: deemed by the Saudi Food and Drug Authority to be related to the clinical trial and that may be located at the site
p.000005: of the trial, at the sponsor's and/or contract
p.000005:
p.000005:
p.000005:
p.000006: 6
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006: research organization’s (CRO’s) facilities, or at other establishments deemed appropriate by the SFDA.
p.000006: 1.30 Institution (medical)
p.000006:
p.000006: Any public or private entity or agency or medical or dental facility where clinical trials are conducted.
p.000006: 1.31 Institutional Review Board (IRB)
p.000006: An independent body constituted of medical, scientific, and non-scientific members, whose responsibility is to
p.000006: ensure the protection of the rights, safety and well-being of human subjects involved in a trial by, among other
p.000006: things, reviewing, approving, and providing continuing review of trial protocol and amendments and of the methods
p.000006: and material to be used in obtaining and documenting informed consent of the trial subjects.
p.000006: 1.32 Interim Clinical Trial/Study Report
p.000006:
p.000006: A report of intermediate results and their evaluation based on analyses performed during the course of a trial.
p.000006: 1.33 Investigational Product
p.000006: A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial,
p.000006: including a product with a marketing authorization when used or assembled (formulated or packaged) in a way
p.000006: different from the approved form, or when used for an unapproved indication, or when used to gain further
p.000006: information about an approved use.
p.000006: 1.34 Investigator
...
p.000014: opinion on a trial-related matter.
p.000014: A list of IRB/IEC members and their qualifications should be maintained.
p.000014:
p.000014: The legal status, composition, function, operations and regulatory requirements pertaining to IEC in Saudi Arabia are
p.000014: governed by Law of Ethics of Research on Living Creatures.
p.000015: 15
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015: 3.2.2 The IRB/IEC should perform its functions according to written operating procedures, should maintain
p.000015: written records of its activities and minutes of its meetings, and should comply with GCP and with the SFDA
p.000015: requirement(s).
p.000015: 3.2.3 An IRB/IEC should make its decisions at announced meetings at which at least a quorum, as stipulated in its
p.000015: written operating procedures, is present.
p.000015: 3.2.4 Only members who participate in the IRB/IEC review and discussion should vote/provide their opinion and/or
p.000015: advise.
p.000015: 3.2.5 The investigator may provide information on any aspect of the trial, but should not participate
p.000015: in the deliberations of the IRB/IEC or in the vote/opinion of the IRB/IEC.
p.000015: 3.2.6 An IRB/IEC may invite nonmembers with expertise in special areas for assistance.
p.000015:
p.000015: 3.3 Procedures
p.000015: The IRB/IEC should establish, document in writing, and follow its procedures, which should include:
p.000015: 3.3.1 Determining its composition (names and qualifications of the members) and the authority under which it is
p.000015: established.
p.000015: 3.3.2 Scheduling, notifying its members of, and conducting its meetings.
p.000015: 3.3.3 Conducting initial and continuing review of trials.
p.000015: 3.3.4 Determining the frequency of continuing review, as appropriate.
p.000015: 3.3.5 Providing expedited review and approval/favourable opinion of minor change(s) in ongoing trials that
p.000015: have the approval/favourable opinion of the IRB/IEC.
p.000015: 3.3.6 Specifying that no subject should be admitted to a trial before the IRB/IEC issues its written
p.000015: approval/favourable opinion of the trial.
p.000015: 3.3.7 Specifying that no deviations from, or changes of, the protocol should be initiated without prior written
p.000015: IRB/IEC approval/favourable opinion of an appropriate amendment, except when necessary to eliminate immediate
p.000015: hazards to the subjects or when the change(s) involves only logistical administrative aspects of the
p.000015: trial (e.g., change of monitor(s), telephone number(s)) (see 4.5.2).
p.000015: 3.3.8 Specifying that the investigator should promptly report to the IRB/IEC:
p.000015:
p.000015: (a) Deviations from, or changes of, the protocol to eliminate immediate hazards to the trial subjects (see 3.3.7,
p.000015: 4.5.2, 4.5.4).
p.000016: 16
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: (b) Changes increasing the risk to subjects and/or affecting significantly the conduct of the trial (see 4.10.2).
p.000016: (c) All adverse drug reactions (ADRs) that are both serious and unexpected.
p.000016:
p.000016: (d) New information that may affect adversely the safety of the subjects or the conduct of the trial.
p.000016: 3.3.9 Ensuring that the IRB/IEC promptly notify in writing the investigator/institution
p.000016: concerning:
p.000016: (a) Its trial-related decisions/opinions.
p.000016:
p.000016: (b) The reasons for its decisions/opinions.
p.000016:
p.000016: (c) Procedures for appeal of its decisions/opinions.
p.000016:
p.000016: 3.4 Records
p.000016: The IRB/IEC should retain all relevant records (e.g., written procedures, membership lists, lists of
p.000016: occupations/affiliations of members, submitted documents, minutes of meetings, and correspondence) for a period of at
p.000016: least 3 years after completion of the trial and make them available upon request from the SFDA or any relevant
p.000016: regulatory authority(ies).
p.000016: The IRB/IEC may be asked by investigators, sponsors or regulatory authorities to provide its written procedures and
p.000016: membership lists.
p.000016:
p.000016: 4. INVESTIGATOR
p.000016: 4.1 Investigator's Qualifications and Agreement
p.000016: 4.1.1 The investigator(s) should be qualified by education, training, and experience to assume
p.000016: responsibility for the proper conduct of the trial, should meet all the qualifications specified by the SFDA
p.000016: requirement(s), and should provide evidence of such qualifications through up- to-date curriculum vitae and/or other
p.000016: relevant documentation requested by the sponsor, the IRB/IEC, and/or the SFDA.
p.000016:
p.000016:
p.000016:
p.000017: 17
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017: 4.1.2 The investigator should be thoroughly familiar with the appropriate use of the investigational product(s), as
p.000017: described in the protocol, in the current Investigator's Brochure, in the product information and in other information
p.000017: sources provided by the sponsor.
p.000017: 4.1.3 The investigator should be aware of, and should comply with, GCP and the SFDA requirements.
p.000017: 4.1.4 The investigator/institution should permit monitoring and auditing by the sponsor, and inspection by
p.000017: the SFDA.
p.000017: 4.1.5 The investigator should maintain a list of appropriately qualified persons to whom the investigator
p.000017: has delegated significant trial-related duties.
p.000017: 4.2 Adequate Resources
p.000017: 4.2.1 The investigator should be able to demonstrate (e.g., based on retrospective data) a potential for recruiting the
p.000017: required number of suitable subjects within the agreed recruitment period.
...
p.000031: (b) to comply with procedures for data recording/reporting;
p.000031:
p.000031: (c) to permit monitoring, auditing and inspection (see 4.1.4) and
p.000031:
p.000031: (d) to retain the trial related essential documents until the sponsor informs the
p.000031: investigator/institution these documents are no longer needed (see 4.9.4 and 5.5.12).
p.000031: The sponsor and the investigator/institution should sign the protocol, or an alternative document, to
p.000031: confirm this agreement.
p.000031: 5.7 Allocation of Responsibilities
p.000031: Prior to initiating a trial, the sponsor should define, establish, and allocate all trial-related duties and functions.
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 5.8 Compensation to Subjects and Investigators
p.000031: 5.8.1 The sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator/the
p.000031: institution against claims arising from the trial, except for claims that arise from malpractice and/or negligence.
p.000031: 5.8.2 The sponsor's policies and procedures should address the costs of treatment of trial subjects in the event of
p.000031: trial-related injuries in accordance with the SFDA requirement(s).
p.000031: 5.8.3 When trial subjects receive compensation, the method and manner of compensation should comply with SFDA
p.000031: requirement(s).
p.000031: 5.9 Financing
p.000031: The financial aspects of the trial should be documented in an agreement between the sponsor and the
p.000031: investigator/institution.
p.000031:
p.000031:
p.000031:
p.000032: 32
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032: 5.10 Notification/Submission to Saudi food and drug authority
p.000032: Before initiating the clinical trial(s), the sponsor should submit any required application(s) to the SFDA for review,
p.000032: acceptance, and/or permission (as required by the SFDA Guidelines - Guidance and requirements for conducting
p.000032: clinical trials on drugs) to begin the trial(s). Any notification/submission should be dated and
p.000032: contain sufficient information to identify the protocol.
p.000032: 5.11 Confirmation of Review by IRB/IEC
p.000032: 5.11.1 The sponsor should obtain from the investigator/institution:
p.000032:
p.000032: (a) The name and address of the investigator's/institution’s IRB/IEC.
p.000032:
p.000032: (b) A statement obtained from the IRB/IEC that it is organized and operates according to GCP and the applicable laws
p.000032: and regulations.
p.000032: (c) Documented IRB/IEC approval/favourable opinion and, if requested by the sponsor, a current copy of protocol,
p.000032: written informed consent form(s) and any other written information to be provided to subjects, subject
p.000032: recruiting procedures, and documents related to payments and compensation available to the subjects, and any other
p.000032: documents that the IRB/IEC may have requested.
p.000032: 5.11.2 If the IRB/IEC conditions its approval/favourable opinion upon change(s) in any aspect of the trial, such as
p.000032: modification(s) of the protocol, written informed consent form and any other written information to be provided to
p.000032: subjects, and/or other procedures, the sponsor should obtain from the investigator/institution a copy of the
...
p.000056:
p.000056:
p.000056:
p.000056: - ADVERTISEMENT FOR SUBJECT
p.000056: RECRUITMENT (if used)
p.000056: To document that recruitment measures X are appropriate and not coercive
p.000056:
p.000056:
p.000056:
p.000056: 8.2.4 FINANCIAL ASPECTS OF THE TRIAL To document the financial agreement X
p.000056: X
p.000056: between the investigator/institution and the sponsor for the trial
p.000056:
p.000056:
p.000056:
p.000056: 8.2.5 INSURANCE STATEMENT
p.000056: (where required)
p.000056: To document that compensation to X X subject(s) for trial-related
p.000056: injury will be
p.000056: available
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000057: 57
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: Title of Document Purpose
p.000057: Located in Files of
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: 8.2.6 SIGNED AGREEMENT BETWEEN INVOLVED PARTIES, e.g.:
p.000057:
p.000057:
p.000057:
p.000057: To document agreements
p.000057: Investigator/
p.000057: Institution
p.000057: Sponsor
p.000057:
p.000057: - investigator/institution and
p.000057: X X
p.000057: sponsor
p.000057:
p.000057: - investigator/institution and CRO
p.000057: X X
p.000057: (where required)
p.000057:
p.000057:
p.000057:
p.000057: - sponsor and CRO
p.000057: X
p.000057:
p.000057:
p.000057: - investigator/institution and
p.000057: X X
p.000057: authority(ies)
p.000057:
p.000057: (where required)
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
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p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: Title of Document Purpose
p.000058: Located in Files of
p.000058:
p.000058:
p.000058:
p.000058: Investigator/
p.000058: Institution
p.000058: Sponsor
p.000058:
p.000058:
p.000058: 8.2.7 DATED, DOCUMENTED APPROVAL/FAVOURABLE OPINION OF INSTITUTIONAL REVIEW BOARD (IRB)
p.000058: /INDEPENDENT ETHICS COMMITTEE (IEC) OF THE FOLLOWING:
p.000058: - protocol and any amendments
p.000058:
p.000058: - CRF (if applicable)
p.000058: - informed consent form(s)
p.000058: - any other written information to be provided to the subject(s)
p.000058: -advertisement for subject recruitment (if used)
p.000058: - subject compensation (if any)
p.000058: - any other documents given approval/ favourable opinion
p.000058: To document that the trial has been X X subject to IRB/IEC
p.000058: review and
p.000058: given approval/favourable opinion. To identify the version number and date of the document(s) .
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000059: 59
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059: Title of Document Purpose
p.000059: Located in Files of
p.000059:
p.000059:
p.000059:
p.000059: Investigator/
p.000059: Institution
p.000059: Sponsor
p.000059:
p.000059:
p.000059: 8.2.8 INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE COMPOSITION
p.000059: To document that the IRB/IEC is constituted in agreement with GCP
p.000059: X X
p.000059: (where required)
p.000059:
p.000059:
p.000059:
p.000059:
p.000059: 8.2.9 REGULATORY AUTHORITY(IES) AUTHORISATION/APPROVAL/ NOTIFICATION OF PROTOCOL
p.000059: (where required)
p.000059: To document appropriate authorisation/approval/notification by
p.000059: the regulatory authority(ies) has been obtained prior to initiation of the trial in compliance with the
p.000059: applicable regulatory requirement(s)
p.000059: X
p.000059: (where required)
p.000059: X
p.000059: (where required)
p.000059:
p.000059:
p.000059: 8.2.10 CURRICULUM VITAE AND/OR OTHER RELEVANT DOCUMENTS EVIDENCING QUALIFICATIONS OF
p.000059: INVESTIGATOR(S) AND SUB- INVESTIGATOR(S)
p.000059: To document qualifications and eligibility to X X conduct trial
p.000059: and/or provide medical
p.000059: supervision of subjects
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000060: 60
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060: Title of Document Purpose
p.000060: Located in Files of
p.000060:
p.000060:
p.000060:
p.000060: Investigator/
p.000060: Institution
p.000060: Sponsor
p.000060:
p.000060:
p.000060: 8.2.11 NORMAL VALUE(S)/RANGE(S) FOR MEDICAL/ LABORATORY/TECHNICAL PROCEDURE(S) AND/OR TEST(S) INCLUDED IN THE
p.000060: PROTOCOL
p.000060: To document normal values and/or X X ranges of the tests
p.000060:
p.000060:
p.000060:
p.000060: 8.2.12 MEDICAL/LABORATORY/TECHNICAL PROCEDURES /TESTS
p.000060: - certification or
p.000060: - accreditation or
p.000060: - established quality control and/or external quality assessment or
p.000060: - other validation (where required)
p.000060: To document competence of facility to perform required test(s) , and support reliability of results
p.000060: X X
p.000060: (where required)
p.000060:
p.000060:
...
p.000064:
p.000064: Title of Document Purpose
p.000064: Located in Files of
p.000064:
p.000064:
p.000064:
p.000064: Investigator/
p.000064: Institution
p.000064: Sponsor
p.000064:
p.000064:
p.000064: 8.3.3 DATED, DOCUMENTED APPROVAL/FAVOURABLE OPINION OF
p.000064: INSTITUTIONAL REVIEW BOARD (IRB)
p.000064: /INDEPENDENT ETHICS COMMITTEE (IEC) OF THE FOLLOWING:
p.000064: - protocol amendment(s)
p.000064: - revision(s) of:
p.000064: - informed consent form
p.000064: - any other written information to be provided to the subject
p.000064: - advertisement for subject recruitment (if used)
p.000064: - any other documents given approval/favourable opinion
p.000064: - continuing review of trial (where required)
p.000064: To document that the amendment(s) X X and/or revision(s) have been subject
p.000064: to IRB/IEC review and were given approval/favourable opinion. To identify the version number and date of the
p.000064: document(s).
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000065: 65
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065: Title of Document Purpose
p.000065: Located in Files of
p.000065:
p.000065:
p.000065:
p.000065: Investigator/
p.000065: Institution
p.000065: Sponsor
p.000065:
p.000065:
p.000065: 8.3.4 REGULATORY AUTHORITY(IES) AUTHORISATIONS/APPROVALS/NOTIFICATIONS WHERE REQUIRED FOR:
p.000065: - protocol amendment(s) and other documents
p.000065: To document compliance with applicable regulatory requirements
p.000065: X X
p.000065: (where required)
p.000065:
p.000065:
p.000065:
p.000065: 8.3.5 CURRICULUM VITAE FOR NEW INVESTIGATOR(S) AND/OR SUB- INVESTIGATOR(S)
p.000065: (see 8.2.10) X X
p.000065:
p.000065:
p.000065:
p.000065: 8.3.6 UPDATES TO NORMAL VALUE(S)/RANGE(S) FOR MEDICAL/ LABORATORY/ TECHNICAL PROCEDURE(S)/TEST(S)
p.000065: INCLUDED IN THE PROTOCOL
p.000065: To document normal values and X X ranges that are revised during
p.000065: the
p.000065: trial (see 8.2.11)
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000066: 66
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066: Title of Document Purpose
p.000066: Located in Files of
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066: 8.3.7 UPDATES OF MEDICAL/LABORATORY/ TECHNICAL PROCEDURES/TESTS
p.000066:
p.000066: - certification or
p.000066:
p.000066: - accreditation or
p.000066:
p.000066: - established quality control and/or external quality assessment or
p.000066: - other validation (where required)
p.000066:
p.000066:
p.000066:
p.000066: To document that tests remain adequate throughout the trial period (see 8.2.12)
p.000066: Investigator/
p.000066: Institution
p.000066:
p.000066: X
p.000066: (where required)
p.000066: Sponsor
p.000066:
p.000066:
p.000066: X
p.000066:
p.000066:
...
p.000068: serious adverse events and related
p.000068: reports in accordance with 4.11
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000069: 69
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: Title of Document Purpose
p.000069: Located in Files of
p.000069:
p.000069:
p.000069:
p.000069: Investigator/
p.000069: Institution
p.000069: Sponsor
p.000069:
p.000069:
p.000069: 8.3.17 NOTIFICATION BY SPONSOR AND/OR INVESTIGATOR, WHERE APPLICABLE, TO SFDA AND IRB(S)/IEC(S) OF UNEXPECTED
p.000069: SERIOUS ADVERSE DRUG REACTIONS AND OF OTHER SAFETY INFORMATION
p.000069: Notification by sponsor and/or investigator, where applicable, to regulatory authorities and IRB(s)/IEC(s) of
p.000069: unexpected serious adverse drug reactions in accordance with 5.17 and
p.000069: 4.11.1 and of other safety information in accordance with 5.16.2 and 4.11.2
p.000069: X X
p.000069: (where required)
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: 8.3.18 NOTIFICATION BY SPONSOR TO INVESTIGATORS OF SAFETY INFORMATION
p.000069: Notification by sponsor to investigators of X X safety information
p.000069: in accordance with 5.16.2
p.000069:
p.000069:
p.000069:
p.000069: 8.3.19 INTERIM OR ANNUAL
p.000069: REPORTS TO IRB/IEC AND
p.000069: SFDA
p.000069: Interim or annual reports provided to IRB/IEC in accordance with 4.10 and to authority(ies) in accordance with 5.17.3
p.000069: X X
p.000069: (where required)
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: Title of Document Purpose
p.000069: Located in Files of
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000070: 70
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070: Investigator/
p.000070: Institution
p.000070: Sponsor
p.000070:
p.000070:
p.000070: 8.3.20 SUBJECT SCREENING LOG To document identification of subjects who
p.000070: entered pre-trial screening
p.000070: X X
p.000070: (where required)
p.000070:
p.000070:
p.000070:
p.000070: 8.3.21 SUBJECT IDENTIFICATION CODE LIST
p.000070: To document that investigator/institution X keeps a confidential list of names of
p.000070: all
p.000070: subjects allocated to trial numbers on enrolling in the trial. Allows
p.000070: investigator/institution to reveal identity of any subject
p.000070:
p.000070:
p.000070: 8.3.22 SUBJECT ENROLMENT LOG To document chronological enrolment of X
p.000070: subjects by trial number
p.000070:
p.000070:
p.000070: 8.3.23 INVESTIGATIONAL PRODUCTS
p.000070: ACCOUNTABILITY AT THE SITE
p.000070: To document that investigational product(s) X X have been used
p.000070: according to the protocol
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070: Title of Document Purpose
p.000070: Located in Files of
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000071: 71
p.000071:
p.000071:
p.000071:
p.000071:
p.000071:
p.000071:
...
p.000072: X X
p.000072: (if destroyed at site)
p.000072:
p.000072:
p.000072:
p.000072: 8.4.3 COMPLETED SUBJECT IDENTIFICATION CODE LIST
p.000072: To permit identification of all subjects X enrolled in the trial in case follow-up
p.000072: is
p.000072: required. List should be kept in a confidential manner and for agreed upon time
p.000072:
p.000072:
p.000072:
p.000072: Title of Document Purpose
p.000072: Located in Files of
p.000072:
p.000072: Investigator/
p.000072: Institution
p.000072: Sponsor
p.000072:
p.000072:
p.000072: 8.4.4 AUDIT CERTIFICATE (if available)
p.000072: To document that audit was performed X
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: 8.4.5 FINAL TRIAL CLOSE-OUT MONITORING REPORT
p.000072: To document that all activities required for X
p.000072: trial close-out are completed, and copies of essential documents are held in the appropriate files
p.000072:
p.000072:
p.000072:
p.000072:
p.000073: 73
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073: 8.4.6 TREATMENT ALLOCATION AND DECODING DOCUMENTATION
p.000073:
p.000073: Returned to sponsor to document any X
p.000073: decoding that may have occurred
p.000073:
p.000073:
p.000073: 8.4.7 FINAL REPORT BY INVESTIGATOR TO IRB/IEC WHERE REQUIRED, AND WHERE APPLICABLE, TO THE REGULATORY
p.000073: AUTHORITY(IES)
p.000073: To document completion of the trial X
p.000073:
p.000073: 8.4.8 CLINICAL STUDY REPORT To document results and interpretation of
p.000073: trial
p.000073: X X
p.000073: (if applicable)
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
...
General/Other / participants in a control group
Searching for indicator placebo:
(return to top)
p.000002: Single-blinding usually refers to the subject(s) being unaware, and double- blinding usually refers to the
p.000002: subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment
p.000002: assignment(s).
p.000002: 1.11 Case Report Form (CRF)
p.000002:
p.000002: A printed, optical, or electronic document designed to record all of the protocol required information to
p.000002: be reported to the sponsor on each trial subject.
p.000002: 1.12 Clinical Trial/Study
p.000002:
p.000002: Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other
p.000002: pharmacodynamic effects of an investigational product(s), and/or to identify any
p.000002:
p.000003: 3
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003: adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and
p.000003: excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. The terms
p.000003: clinical trial and clinical study are synonymous.
p.000003: 1.13 Clinical Trial/Study Report
p.000003: A written description of a trial/study of any therapeutic, prophylactic, or diagnostic agent conducted in
p.000003: human subjects, in which the clinical and statistical description, presentations, and analyses are fully integrated
p.000003: into a single report.(see the ICH for Structure and content for Clinical Study Reports)
p.000003:
p.000003: 1.14 Comparator (Product)
p.000003: An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial.
p.000003: 1.15 Compliance (in relation to trials)
p.000003: Adherence to all the trial-related requirements, Good Clinical Practice (GCP) requirements, and the SFDA requirements.
p.000003: 1.16 Confidentiality
p.000003:
p.000003: Prevention of disclosure, to other than authorized individuals, of a sponsor's proprietary information or of
p.000003: a subject's identity.
p.000003: 1.17 Contract
p.000003:
p.000003: A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on
p.000003: delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve
p.000003: as the basis of a contract.
p.000003: 1.18 Coordinating Committee
p.000003:
p.000003: A committee that a sponsor may organize to coordinate the conduct of a multicentre trial.
p.000003:
p.000003: 1.19 Coordinating Investigator
p.000003:
p.000003: An investigator assigned the responsibility for the coordination of investigators at different centres
p.000003: participating in a multicentre trial.
p.000003:
p.000004: 4
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004: 1.20 Contract Research Organization (CRO)
p.000004:
p.000004: A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or
p.000004: more of a sponsor's trial-related duties and functions.
p.000004: 1.21 Direct Access
p.000004: Permission to examine, analyze, verify, and reproduce any records and reports that are important to
p.000004: evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatory authorities, sponsor's
...
p.000005: 1.29 Inspection
p.000005: The act by SFDA of conducting an official review of documents, facilities, records, and any other resources that are
p.000005: deemed by the Saudi Food and Drug Authority to be related to the clinical trial and that may be located at the site
p.000005: of the trial, at the sponsor's and/or contract
p.000005:
p.000005:
p.000005:
p.000006: 6
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006: research organization’s (CRO’s) facilities, or at other establishments deemed appropriate by the SFDA.
p.000006: 1.30 Institution (medical)
p.000006:
p.000006: Any public or private entity or agency or medical or dental facility where clinical trials are conducted.
p.000006: 1.31 Institutional Review Board (IRB)
p.000006: An independent body constituted of medical, scientific, and non-scientific members, whose responsibility is to
p.000006: ensure the protection of the rights, safety and well-being of human subjects involved in a trial by, among other
p.000006: things, reviewing, approving, and providing continuing review of trial protocol and amendments and of the methods
p.000006: and material to be used in obtaining and documenting informed consent of the trial subjects.
p.000006: 1.32 Interim Clinical Trial/Study Report
p.000006:
p.000006: A report of intermediate results and their evaluation based on analyses performed during the course of a trial.
p.000006: 1.33 Investigational Product
p.000006: A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial,
p.000006: including a product with a marketing authorization when used or assembled (formulated or packaged) in a way
p.000006: different from the approved form, or when used for an unapproved indication, or when used to gain further
p.000006: information about an approved use.
p.000006: 1.34 Investigator
p.000006: A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of
p.000006: individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal
p.000006: investigator. See also Subinvestigator.
p.000006: 1.35 Investigator / Institution
p.000006:
p.000006: An expression meaning "the investigator and/or institution.
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000007: 7
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: 1.36 Investigator's Brochure
p.000007:
p.000007: A compilation of the clinical and nonclinical data on the investigational product(s) which is relevant to the study of
p.000007: the investigational product(s) in human subjects (see 7. Investigator’s Brochure).
p.000007: 1.37 Legally Acceptable Representative
p.000007:
p.000007: An individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective
p.000007: subject, to the subject's participation in the clinical trial.
p.000007: 1.38 Monitoring
p.000007:
p.000007: The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded,
p.000007: and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and
p.000007: the applicable with SFDArequirement(s).
p.000007: 1.39 Monitoring Report
...
p.000032: 5.11.2 If the IRB/IEC conditions its approval/favourable opinion upon change(s) in any aspect of the trial, such as
p.000032: modification(s) of the protocol, written informed consent form and any other written information to be provided to
p.000032: subjects, and/or other procedures, the sponsor should obtain from the investigator/institution a copy of the
p.000032: modification(s) made and the date approval/favourable opinion was given by the IRB/IEC.
p.000032: 5.11.3 The sponsor should obtain from the investigator/institution documentation and dates of any IRB/IEC
p.000032: reapprovals/re-evaluations with favourable opinion, and of any withdrawals or suspensions of approval/favourable
p.000032: opinion.
p.000032: 5.12 Information on Investigational Product(s)
p.000032: 5.12.1 When planning trials, the sponsor should ensure that sufficient safety and efficacy data from nonclinical
p.000032: studies and/or clinical trials are available to support human exposure by the route, at the dosages, for the duration,
p.000032: and in the trial population to be studied.
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: 5.12.2 The sponsor should update the Investigator's Brochure as significant new information becomes
p.000033: available (see 7. Investigator's Brochure).
p.000033: 5.13 Manufacturing, Packaging, Labelling, and Coding Investigational Product(s)
p.000033: 5.13.1 The sponsor should ensure that the investigational product(s) (including active comparator(s)
p.000033: and placebo, if applicable) is characterized as appropriate to the stage of development of the product(s), is
p.000033: manufactured in accordance with any applicable GMP, and is coded and labelled in a manner that protects the blinding,
p.000033: if applicable. In addition, the labelling should comply with SFDA as described in the Labelling Memo no. 1811 dated
p.000033: 16/1/1436AH.
p.000033: 5.13.2 The sponsor should determine, for the investigational product(s), acceptable storage temperatures,
p.000033: storage conditions (e.g. protection from light), storage times, reconstitution fluids and procedures, and devices for
p.000033: product infusion, if any. The sponsor should inform all involved parties (e.g. monitors, investigators, pharmacists,
p.000033: storage managers) of these determinations.
p.000033: 5.13.3 The investigational product(s) should be packaged to prevent contamination and unacceptable
p.000033: deterioration during transport and storage.
p.000033: 5.13.4 In blinded trials, the coding system for the investigational product(s) should include a mechanism
p.000033: that permits rapid identification of the product(s) in case of a medical emergency, but does not permit
p.000033: undetectable breaks of the blinding.
p.000033: 5.13.5 If significant formulation changes are made in the investigational or comparator product(s) during the course
p.000033: of clinical development, the results of any additional studies of the formulated product(s) (e.g.
p.000033: stability, dissolution rate, bioavailability) needed to assess whether these changes would significantly alter
p.000033: the pharmacokinetic profile of the product should be available prior to the use of the new formulation in clinical
p.000033: trials.
...
p.000042: 6.1.7 Name(s) and address(es) of the clinical laboratory(ies) and other medical and/or technical
p.000042: department(s) and/or institutions involved in the trial.
p.000042: 6.2 Background Information
p.000042: 6.2.1 Name and description of the investigational product(s).
p.000042: 6.2.2 A summary of findings from nonclinical studies that potentially have clinical significance
p.000042: and from clinical trials that are relevant to the trial.
p.000042: 6.2.3 Summary of the known and potential risks and benefits, if any, to human subjects.
p.000042: 6.2.4 Description of and justification for the route of administration, dosage, dosage regimen, and treatment
p.000042: period(s).
p.000042: 6.2.5 A statement that the trial will be conducted in compliance with the protocol, GCP and the SFDA
p.000042: requirement(s).
p.000042: 6.2.6 Description of the population to be studied
p.000042:
p.000042:
p.000043: 43
p.000043:
p.000043:
p.000043:
p.000043:
p.000043:
p.000043: 6.2.7 References to literature and data that are relevant to the trial, and that provide background for
p.000043: the trial.
p.000043: 6.3 Trial Objectives and Purpose
p.000043: A detailed description of the objectives and the purpose of the trial.
p.000043:
p.000043: 6.4 Trial Design
p.000043: The scientific integrity of the trial and the credibility of the data from the trial depend
p.000043: substantially on the trial design. A description of the trial design, should include:
p.000043: 6.4.1 A specific statement of the primary endpoints and the secondary endpoints, if any, to be measured during the
p.000043: trial.
p.000043: 6.4.2 A description of the type/design of trial to be conducted (e.g. double-blind, placebo- controlled, parallel
p.000043: design) and a schematic diagram of trial design, procedures and stages.
p.000043: 6.4.3 A description of the measures taken to minimize/avoid bias, including:
p.000043:
p.000043: (a) Randomization.
p.000043:
p.000043: (b) Blinding.
p.000043:
p.000043: 6.4.4 A description of the trial treatment(s) and the dosage and dosage regimen of the investigational
p.000043: product(s). Also include a description of the dosage form, packaging, and labelling of the investigational product(s).
p.000043: 6.4.5 The expected duration of subject participation, and a description of the sequence and duration of all trial
p.000043: periods, including follow-up, if any.
p.000043: 6.4.6 A description of the "stopping rules" or "discontinuation criteria" for individual subjects, parts of trial
p.000043: and entire trial.
p.000043: 6.4.7 Accountability procedures for the investigational product(s), including the placebo(s) and comparator(s), if
p.000043: any.
p.000043: 6.4.8 Maintenance of trial treatment randomization codes and procedures for breaking codes.
p.000043: 6.4.9 The identification of any data to be recorded directly on the CRFs (i.e. no prior written or electronic record
p.000043: of data), and to be considered to be source data.
p.000043: 6.5 Selection and Withdrawal of Subjects
p.000043: 6.5.1 Subject inclusion criteria.
p.000043: 6.5.2 Subject exclusion criteria.
p.000043: 6.5.3 Subject withdrawal criteria (i.e. terminating investigational product treatment/trial treatment) and
p.000043: procedures specifying:
p.000043: (a) When and how to withdraw subjects from the trial/ investigational product treatment.
p.000043:
p.000043: (b) The type and timing of the data to be collected for withdrawn subjects.
p.000043:
p.000044: 44
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044: (c) Whether and how subjects are to be replaced.
p.000044:
p.000044: (d) The follow-up for subjects withdrawn from investigational product treatment/trial treatment.
p.000044: 6.6 Treatment of Subjects
p.000044: 6.6.1 The treatment(s) to be administered, including the name(s) of all the product(s), the dose(s), the dosing
p.000044: schedule(s), the route/mode(s) of administration, and the treatment period(s), including the follow-up period(s) for
p.000044: subjects for each investigational product treatment/trial treatment group/arm of the trial.
p.000044: 6.6.2 Medication(s)/treatment(s) permitted (including rescue medication) and not permitted before and/or during the
p.000044: trial.
p.000044: 6.6.3 Procedures for monitoring subject compliance.
p.000044:
p.000044: 6.7 Assessment of Efficacy
p.000044: 6.7.1 Specification of the efficacy parameters.
p.000044: 6.7.2 Methods and timing for assessing, recording, and analysing of efficacy parameters.
p.000044:
...
Orphaned Trigger Words
p.000036: 5.18.4 Monitor's Responsibilities
p.000036: The monitor(s) in accordance with the sponsor’s requirements should ensure that the trial is conducted and documented
p.000036: properly by carrying out the following activities when relevant and necessary to the trial and the trial site:
p.000036: (a) Acting as the main line of communication between the sponsor and the investigator.
p.000036:
p.000036: (b) Verifying that the investigator has adequate qualifications and resources (see 4.1, 4.2, 5.6) and remain
p.000036: adequate throughout the trial period, that facilities, including
p.000036:
p.000037: 37
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037: laboratories, equipment, and staff, are adequate to safely and properly conduct the trial and remain adequate
p.000037: throughout the trial period.
p.000037: (c) Verifying, for the investigational product(s):
p.000037:
p.000037: (i) That storage times and conditions are acceptable, and that supplies are sufficient throughout the trial.
p.000037: (ii) That the investigational product(s) are supplied only to subjects who are eligible to receive it and at the
p.000037: protocol specified dose(s).
p.000037: (iii) That subjects are provided with necessary instruction on properly using, handling, storing, and
p.000037: returning the investigational product(s).
p.000037: (iv) That the receipt, use, and return of the investigational product(s) at the trial sites are controlled and
p.000037: documented adequately.
p.000037: (v) That the disposition of unused investigational product(s) at the trial sites complies with SFDA
p.000037: requirement(s) and is in accordance with the sponsor.
p.000037: (d) Verifying that the investigator follows the approved protocol and all approved amendment(s), if any.
p.000037: (e) Verifying that written informed consent was obtained before each subject's participation in the trial.
p.000037: (f) Ensuring that the investigator receives the current Investigator's Brochure, all documents, and all trial
p.000037: supplies needed to conduct the trial properly and to comply with the SFDA requirement(s).
p.000037: (g) Ensuring that the investigator and the investigator's trial staff are adequately informed about the
p.000037: trial.
p.000037: (h) Verifying that the investigator and the investigator's trial staff are performing the specified trial functions,
p.000037: in accordance with the protocol and any other written agreement between the sponsor and the
p.000037: investigator/institution, and have not delegated these functions to unauthorized individuals.
p.000038: 38
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038: (i) Verifying that the investigator is enroling only eligible subjects.
p.000038:
p.000038: (j) Reporting the subject recruitment rate.
p.000038:
p.000038: (k) Verifying that source documents and other trial records are accurate, complete, kept up-to-date and maintained.
p.000038: (l) Verifying that the investigator provides all the required reports, notifications, applications, and
p.000038: submissions, and that these documents are accurate, complete, timely, legible, dated, and identify the trial.
p.000038: (m) Checking the accuracy and completeness of the CRF entries, source documents and other trial-related records against
p.000038: each other. The monitor specifically should verify that:
p.000038: (i) The data required by the protocol are reported accurately on the CRFs and are consistent with the
p.000038: source documents.
p.000038: (ii) Any dose and/or therapy modifications are well documented for each of the trial subjects.
...
p.000045:
p.000045:
p.000045: 6.12 Ethics
p.000045: Description of ethical considerations relating to the trial.
p.000045:
p.000045:
p.000045: 6.13 Data Handling and Record Keeping
p.000045:
p.000045:
p.000045: 6.14 Financing and Insurance
p.000045: Financing and insurance if not addressed in a separate agreement.
p.000045:
p.000045:
p.000045: 6.15 Publication Policy
p.000045: Publication policy, if not addressed in a separate agreement.
p.000045:
p.000045:
p.000045: 6.16 Supplements
p.000045: (NOTE: Since the protocol and the clinical trial/study report are closely related, further relevant information can be
p.000045: found in the ICH Guideline for Structure and Content of Clinical Study Reports.)
p.000045:
p.000045: 7. INVESTIGATOR’S BROCHURE
p.000045:
p.000045:
p.000045: 7.1 Introduction
p.000045: The Investigator's Brochure (IB) is a compilation of the clinical and nonclinical data on the investigational
p.000045: product(s) that are relevant to the study of the product(s) in human subjects. Its purpose is to provide the
p.000045: investigators and others involved in the trial with the information to facilitate their understanding of the rationale
p.000045: for, and their compliance with, many key features of the protocol, such as the dose, dose frequency/interval, methods
p.000045: of administration: and safety monitoring procedures. The IB also provides insight to support the clinical management of
p.000045: the study subjects during the course of the clinical trial. The information should be presented in a
p.000045:
p.000046: 46
p.000046:
p.000046:
p.000046:
p.000046:
p.000046:
p.000046: concise, simple, objective, balanced, and non-promotional form that enables a clinician, or potential
p.000046: investigator, to understand it and make his/her own unbiased risk-benefit assessment of the appropriateness of the
p.000046: proposed trial. For this reason, a medically qualified person should generally participate in the editing of an IB, but
p.000046: the contents of the IB should be approved by the disciplines that generated the described data.
p.000046: This guideline delineates the minimum information that should be included in an IB and provides
p.000046: suggestions for its layout. It is expected that the type and extent of information available will vary
p.000046: with the stage of development of the investigational product. If the investigational product is marketed
p.000046: and its pharmacology is widely understood by medical practitioners, an extensive IB may not be necessary. Where
p.000046: permitted by SFDA, a basic product information brochure, package leaflet, or labelling may be an appropriate
p.000046: alternative, provided that it includes current, comprehensive, and detailed information on all aspects of
p.000046: the investigational product that might be of importance to the investigator. If a marketed product is being studied for
p.000046: a new use (i.e., a new indication), an IB specific to that new use should be prepared. The IB should be reviewed at
p.000046: least annually and revised as necessary in compliance with a sponsor's written procedures. More frequent revision may
p.000046: be appropriate depending on the stage of development and the generation of relevant new information.
p.000046: However, in accordance with Good Clinical Practice, relevant new information may be so important that it should be
p.000046: communicated to the investigators, and possibly to the Institutional Review Boards (IRBs)/Independent Ethics
p.000046: Committees (IECs) and/or regulatory authorities before it is included in a revised IB.
p.000046: Generally, the sponsor is responsible for ensuring that an up-to-date IB is made available to the investigator(s) and
p.000046: the investigators are responsible for providing the up-to-date IB to the responsible IRBs/IECs. In the case
p.000046: of an investigator sponsored trial, the sponsor-investigator should determine whether a brochure is available from the
p.000046: commercial manufacturer. If the investigational product is provided by the sponsor-investigator, then he or she should
p.000046: provide the necessary information to the trial personnel. In cases where preparation of a formal IB is impractical, the
p.000046: sponsor-investigator should provide, as a substitute, an expanded background information section in the trial
p.000046: protocol that contains the minimum current information described in this guideline.
p.000046: 7.2 General Considerations
p.000046: The IB should include:
p.000046:
p.000046: 7.2.1 Title Page
p.000046: This should provide the sponsor's name, the identity of each investigational product (i.e., research number, chemical
p.000046: or approved generic name, and trade name(s) where legally permissible and desired by the sponsor), and the release
p.000046: date. It is also suggested that an edition number, and a reference to the number and date of the edition it supersedes,
p.000046: be provided. An example is given in Appendix 1.
p.000047: 47
p.000047:
p.000047:
p.000047:
p.000047:
p.000047:
p.000047: 7.2.2 Confidentiality Statement
p.000047: The sponsor may wish to include a statement instructing the investigator/recipients to treat the IB as a
p.000047: confidential document for the sole information and use of the investigator's team and the IRB/IEC.
p.000047: 7.3 Contents of the Investigator’s Brochure
...
p.000054: investigator/institution or sponsor files, or both. It is acceptable to combine some of the documents, provided the
p.000054: individual elements are readily identifiable.
p.000054: Trial master files should be established at the beginning of the trial, both at the investigator/institution’s site and
p.000054: at the sponsor's office. A final close-out of a trial can only be done when the monitor has reviewed both
p.000054: investigator/institution and sponsor files and confirmed that all necessary documents are in the appropriate files.
p.000054: Any or all of the documents addressed in this guideline may be subject to, and should be available for, audit by the
p.000054: sponsor’s auditor and inspection by the SFDA .
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055: 8.2 Before the Clinical Phase of the Trial Commences
p.000055: During this planning stage the following documents should be generated and should be on file before the trial formally
p.000055: starts
p.000055:
p.000055: Title of Document Purpose
p.000055: Located in Files of
p.000055:
p.000055:
p.000055:
p.000055: Investigator/
p.000055: Institution
p.000055: Sponsor
p.000055:
p.000055: 8.2.1 INVESTIGATOR’S BROCHURE To document that relevant and current
p.000055: X X
p.000055: scientific information about the investigational product has been provided to the
p.000055: investigator
p.000055:
p.000055:
p.000055:
p.000055: 8.2.2 SIGNED PROTOCOL AND AMENDMENTS, IF ANY, AND SAMPLE CASE REPORT FORM (CRF)
p.000055: 8.2.3 INFORMATION GIVEN TO TRIAL SUBJECT
p.000055: - INFORMED CONSENT FORM
p.000055:
p.000055: (including all applicable translations)
p.000055: To document investigator and X X
p.000055: sponsor agreement to the
p.000055: protocol/amendment(s) and CRF
p.000055:
p.000055: X X
p.000055:
p.000055:
p.000055: To document the informed consent
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000056: 56
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Title of Document Purpose
p.000056: Located in Files of
p.000056:
p.000056:
p.000056:
p.000056: Investigator/
p.000056: Institution
p.000056: Sponsor
p.000056:
p.000056: - ANY OTHER WRITTEN INFORMATION To document that subjects will be given X
p.000056: X
p.000056: appropriate written information (content and wording) to support their ability to give fully informed consent
p.000056:
p.000056:
p.000056:
p.000056: - ADVERTISEMENT FOR SUBJECT
p.000056: RECRUITMENT (if used)
p.000056: To document that recruitment measures X are appropriate and not coercive
p.000056:
p.000056:
p.000056:
p.000056: 8.2.4 FINANCIAL ASPECTS OF THE TRIAL To document the financial agreement X
p.000056: X
p.000056: between the investigator/institution and the sponsor for the trial
p.000056:
p.000056:
p.000056:
p.000056: 8.2.5 INSURANCE STATEMENT
p.000056: (where required)
p.000056: To document that compensation to X X subject(s) for trial-related
p.000056: injury will be
p.000056: available
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000057: 57
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: Title of Document Purpose
p.000057: Located in Files of
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: 8.2.6 SIGNED AGREEMENT BETWEEN INVOLVED PARTIES, e.g.:
p.000057:
p.000057:
p.000057:
...
Appendix
Indicator List
| Indicator | Vulnerability |
|---|
| access | Access to Social Goods |
| age | Age |
| armed forces | Soldier |
| authority | Relationship to Authority |
| coerce | Presence of Coercion |
| disability | Mentally Disabled |
| drug | Drug Usage |
| education | education |
| embryo | embryo |
| emergency | Public Emergency |
| employees | employees |
| ethnic | Ethnicity |
| fetus | Fetus/Neonate |
| gender | gender |
| hazard | Natural Hazards |
| homeless | Homeless Persons |
| illness | Physically Disabled |
| impaired | Cognitive Impairment |
| incapable | Mentally Incapacitated |
| incapacity | Incapacitated |
| infant | Infant |
| influence | Drug Usage |
| language | Linguistic Proficiency |
| minor | Youth/Minors |
| minority | Racial Minority |
| nomads | nomad |
| opinion | philosophical differences/differences of opinion |
| party | political affiliation |
| placebo | participants in a control group |
| single | Marital Status |
| substance | Drug Usage |
| terminal | Terminally Ill |
| unemployed | Unemployment |
| union | Trade Union Membership |
| volunteers | Healthy People |
| vulnerable | vulnerable |
Indicator Peers (Indicators in Same Vulnerability)
| Indicator | Peers |
|---|
| drug | ['influence', 'substance'] |
| influence | ['drug', 'substance'] |
| substance | ['drug', 'influence'] |
Trigger Words
coercion
consent
ethics
protect
protection
risk
volunteer
Applicable Type / Vulnerability / Indicator Overlay for this Input