People's Democratic Republic of Algeria Ministry of Population Health and Hospital Reform
Order n ° 387 of July 31, 2006 relating to clinical trials
The Minister of Health, Population and Hospital Reform;
- Having regard to Law No. 85-05 of February 16, 1985, amended and supplemented, relating to the protection and promotion of
health, in particular Articles 178, 168/2, 168/3 and 168/4;
- Having regard to Ordinance No. 95-07 of 23 Châabane 1415 corresponding to January 25, 1995 relating to insurance;
- Having regard to Executive Decree No. 93-53 of June 28, 1993, creating the official bulletin of the Ministry of
health and population;
- Having regard to Executive Decree No. 96-66 of 7 Ramadhan 1416 corresponding to January 27, 1996, fixing the attributions of the
Minister of Health and Population;
- In view of Executive Decree No. 05-428 of 5 Choual 1426 corresponding to November 7, 2005 on the organization of
the administration of the Ministry of Health, Population and Hospital Reform;
- Given Presidential Decree No. 06-176 of 27 Rabie Ethani 1427 corresponding to May 25, 2006
appointing members of the Government;
- Having regard to Order No. 112 / MSP / MIN of October 22, 1995 establishing good clinical practice;
- Considering the decree n ° 44 of September 21, 1998 bearing form of declaration of intention for
testing a drug or similar product.
- Considering the decree n ° 48 of October 7, 1998 relating to the form for declaration of a serious effect likely to be due to
biomedical research on a drug or pharmaceutical product;
- Considering the decree n ° 67 of December 06, 1998 establishing the clinical trials unit.
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Chapter 1: Purpose - definitions
Article 1: The purpose of this decree is to define the conditions under which the
human clinical trials.
Article 2: Clinical trial means any investigation carried out on human subjects with a view to
discover or verify clinical and pharmacological effects of a pharmaceutical product, identify
any adverse reactions in order to assess their efficacy and safety.
The clinical trial includes:
- therapeutic, diagnostic and preventive trials;
- observational studies;
- bioequivalence studies.
Article 3: A clinical trial is said:
- with direct individual benefit (BID) when the patients included in the trial benefit directly
of a possible therapeutic benefit for the management of their pathology.
- Without direct individual benefit (SBID) when the healthy subjects included in the test derive no benefit
direct therapy.
Article 4: Clinical trials require promoters, and / or research organizations called
contract research organization (CRO) and investigators.
Article 5: By promoter is meant any natural or legal person who takes the initiative in a clinical trial.
“Contract research organization” (CRO) means any service provider in the field
clinical trials. This company is assimilated to a promoter.
By investigator is meant any general practitioner or specialist who directs and monitors the performance of the trial
clinical.
Article 6: The terms and concepts commonly used in the field of clinical trials are defined in the
glossary attached in appendix A to this decree
Chapter 2: general provisions
Article 7: Companies providing services in the field of clinical trials are approved by the Minister of
health, population and hospital reform.
Article 8: Any sponsor of a clinical trial on human beings must declare their intention to carry out the latter, at
Minister of Health, Population and Hospital Reform, who issues an authorization to this effect.
The declaration of intent is made in accordance with the form attached in Annex B to this Order.
The Minister of Health, Population and Hospital Reform may, at any time, ask the promoter for
additional information about the clinical trial. He can also, at any time, suspend or prohibit a trial
clinical.
Article 9: No clinical trial can be carried out on humans:
- if it is not based on the latest state of clinical research, scientific knowledge
and on sufficient pre-clinical experimentation;
- if the foreseeable benefit / risk ratio is not for the benefit of the subject included in the research.
Article 10: Clinical trials can only be carried out:
- under the direction and under the supervision of a doctor who can demonstrate appropriate experience;
- under material and technical conditions adapted to the clinical trial and compatible with
imperatives of scientific rigor and safety of the people who lend themselves to this test;
Article 11: Any serious effect likely to be due to research on a pharmaceutical product must be
declared by the promoter, to the Minister of Health, Population and Hospital Reform,
in accordance with the form attached in Annex D to this Order.
Article 12: Minors and people admitted to a health or social establishment cannot be
asked for a clinical trial only if we can expect a direct benefit for their health.
Exceptionally pregnant and nursing mothers may be admitted to trials
clinics if they do not face any foreseeable serious risk to their health or that of their child
and that this research be useful for understanding the phenomena of pregnancy, childbirth or
breastfeeding and if it cannot be done otherwise.
Article 13: People who cannot take part in clinical trials are:
- persons deprived of their liberty by a judicial or administrative decision;
- patients in emergency situations and people hospitalized without consent.
Article 14: For clinical trials without direct individual benefit, the sponsor assumes, even without
fault, compensation for the harmful consequences of the test for the person who lends himself and that
of his assigns, without being able to oppose the act of a third party or the voluntary withdrawal of the
person who had initially agreed to participate in this test.
For clinical trials with direct individual benefit, the sponsor assumes compensation for the consequences
harmful to the test for the person who lends himself and that of his assigns, unless proven to his
charges that the damage is not attributable to his fault or that of any intervener without that can be opposed
made by a third party or the voluntary withdrawal of the person who originally consented to participate in the clinical trial.
Article 15: The promoter is required to take out insurance guaranteeing his civil liability for the activity
that he undertakes.
Article 16: The clinical trial does not give rise to any direct or indirect financial compensation for
persons who lend themselves to it, except reimbursement of expenses incurred by the person who
ready for clinical trial.
Article 17: The carrying out of any clinical trial is subject to a financial agreement between the promoter
and the investigator.
The promoter enters into a financial agreement with the establishment in the event that the clinical trial generates
additional costs.
Article 18: The financial means made available to the investigator must be invested, between
another, for the acquisition of materials and equipment for the service where the clinical trial takes place.
Article 19: The procedures determining the standards and methods applicable to the testing of products
pharmaceuticals are set by order of the Minister of Health, Population and Hospital Reform.
Article 20: Clinical trials must be carried out in accordance with the rules of good practice
laboratory and rules of good clinical practice.
Chapter 3: Consent of the person
Article 21: Prior to carrying out a clinical trial on a person, free consent,
informed and express of it must be collected after the investigator has made known to him:
- the objective of the test, its methodology and its duration;
- the expected benefits, the constraints and the foreseeable risks including in the event of the trial being stopped
before its term.
Article 22: The investigator must inform the person whose consent is sought of his right to
refuse to participate in research or withdraw consent at any time without incurring any liability.
Article 23: Consent is given in writing or, if this is not possible, it is certified by a third party. This
the latter must be completely independent of the investigator and the promoter.
Chapter 4: Protection of persons participating in clinical trials
Article 24: Any clinical trial project must be submitted by the sponsor with the prior opinion of the ethics committee
for clinical trials created in section 25 below.
The ethics committee for clinical trials has one month from the date of receipt of the project
to give his opinion.
Article 25: The Minister of Health creates, in each health region, one or more committee (s)
of ethics for clinical trials.
The ethics committees for clinical trials have their seat in public health establishments.
The organizational and operating procedures for ethics committees for clinical trials are set by
instruction.
Article 26: The ethics committee for clinical trials is an independent body, consisting of nine
(09) people:
- five (05) doctors including a general practitioner;
-     a pharmacist ;
- a senior health technician;
-     a lawyer ;
- a representative of patient associations.
The ethics committee for clinical trials may call on any person likely to help it in
his works.
Article 27: The committee gives its opinion on the conditions of validity of the research with regard to
the protection of individuals, in particular their information before and during the duration of the research and on the
procedures for obtaining their consent, any compensation due, general relevance
of the project and the adequacy between the objectives pursued and the means implemented as well as the qualification of the or
investigators.
Article 28: The Minister of Health, Population and Hospital Reform may dissolve a
ethics committee for clinical trials if the conditions of independence, composition or
necessary to ensure its mission are no longer met.
Article 29: The activities of the ethics committees for clinical trials are supervised by the control unit
clinical trials attached to the pharmacy directorate of the Ministry of Health, Population and
hospital reform.
Chapter 5: Special provisions for clinical trials without direct individual benefit (SBID)
Article 30: Clinical trials without direct individual benefit must not involve any risk
predictable serious for the health of people who lend themselves to it. They must be preceded by a medical examination
of the people concerned. The results of this examination are communicated to them before
expressing their consent.
Article 31: In the case of a clinical trial without direct individual benefit to the people who go there
lend, the promoter can pay these people compensation in compensation for the constraints suffered.
Article 32: The number of clinical trials without direct individual benefit in which a volunteer can participate cannot
exceed three (03) per year.
Article 33: No one can lend himself to several biomedical researches simultaneously.
Article 34: Clinical trials carried out on minors may in no case give rise to the
payment of the compensation provided for in article 31 above.
Article 35: Clinical trials without direct individual benefit can only be carried out in
structures approved by the Minister of Health, Population and Hospital Reform.
Article 36: Trials without therapeutic purpose are subject to the prior opinion of the National Council of
Health Sciences Ethics.
Chapter 6: Miscellaneous and final provisions
Article 37: The Ministry of Health, Population and Hospital Reform maintains a register
declaration of clinical trials in accordance with the model attached in Annex C to this Order.
Article 38: The provisions of decrees n ° 44 of September 21, 1998 and n ° 48 of October 7, 1998 referred to above, are repealed.
Article 39: This order will be published in the official bulletin of the Ministry of Population Health and
hospital reform.
People's Democratic Republic of Algeria Ministry of Population Health and Hospital Reform
Order No. 388 of July 31, 2006
setting the procedures for carrying out a clinical trial
- Having regard to Executive Decree No. 93-53 of June 28, 1993, creating the official bulletin of the Ministry of
health and population;
- Having regard to Executive Decree No. 96-66 of 7 Ramadhan 1416 corresponding to January 27, 1996, fixing the attributions of the
Minister of Health and Population;
- In view of Executive Decree No. 05-428 of 5 Choual 1426 corresponding to November 7, 2005 on the organization of
the administration of the Ministry of Health, Population and Hospital Reform;
- Given Presidential Decree No. 06-176 of 27 Rabie Ethani 1427 corresponding to May 25, 2006
appointing members of the Government;
- Considering decree n ° 387 of July 31, 2006 relating to clinical trials.
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Article 1: The purpose of this decree is to fix the procedures for carrying out a clinical trial.
Article 2: The request for a clinical trial may come from:
- pharmaceutical laboratories;
- medical practitioners in the context of research;
- administrative authorities in connection with the registration of a pharmaceutical product;
- research institutions within the framework of research projects;
- service companies in the field of clinical trials.
Article 3: The clinical trial applicant files a file at the level of the direction in charge of the pharmacy of the
Ministry of Health, Population and Hospital Reform, comprising the following documents:
- the declaration of intention to carry out a clinical trial in accordance with the form established for this purpose;
- the clinical trial protocol as provided for in article 7 below;
- the observation book;
- the investigator's brochure;
- a copy of the civil liability insurance contract taken out by the promoter;
- a copy of the financial agreement between the promoter and the investigator.
The above documents must be submitted in duplicate.
The dossier must be submitted at least two months before the scheduled start of the test.
Article 4: The directorate in charge of pharmacy of the Ministry of Health, Population and Reform
hospital has a maximum of three months from the filing of the file mentioned in article 3
above, to issue the authorization to carry out the clinical trial, to the applicant.
Article 5: The request to carry out a clinical trial may be rejected in the following cases:
- when the file is incomplete;
- when the ethics committee for clinical trials has issued an unfavorable opinion;
- when the clinical trial protocol does not respect the methodological principles described in the
good clinical practice;
- when the place of performance of the clinical trial does not meet the conditions appropriate to
the clinical trial as defined by instruction from the Minister of Health, Population and
of hospital reform.
Article 6: The sponsor appoints an investigator to direct and monitor the performance of the clinical trial.
In the case of a multicentre clinical trial, the sponsor entrusts the execution of the trial to several
investigators, he appoints a principal investigator called the coordinating investigator.
Article 7: The clinical trial is subject to a protocol which is signed by the investigator after he has
expressed his agreement.
Article 8: The investigator must inform the promoter of any critical event occurring during
the clinical trial.
In the event that this event results in a significant change to the clinical trial protocol, it
must be notified to the ethics committee for clinical trials.
Article 9: The investigator and his team must remain available for the duration of the clinical trial.
The investigator must inform the director of the hospital establishment where the clinical trial is taking place, before
the start of it.
Article 10: When the products subject to the clinical trial do not have a marketing authorization
the market in Algeria, an authorization for their customs clearance is issued by the direction in charge of
the pharmacy of the Ministry of Health, Population and Hospital Reform.
Article 11: When there are products left at the end of the clinical trial, the management of the pharmacy will issue a
authorization for their destruction.
Article 12: At the end of the clinical trial, the sponsor must send to the management responsible for
pharmacy of the Ministry of Health, Population and Hospital Reform a report on the progress of
the test and the results obtained.
Article 13: The carrying out of a bioequivalence or bioavailability study is subject
the same procedure as the clinical trial.
Article 14: For the realization of an observational study, the promoter must only deposit at the level of the
Department of Pharmacy of the Ministry of Health, Population and Reform
hospital, the clinical trial protocol and the declaration of intent form
clinical trial established for this purpose.
Article 15: This decree is published in the official bulletin of the Ministry of Health, Population and
hospital reform.
ANNEX A
Glossary
Amendment
Text amending a provision of a clinical research protocol already approved by an ethics committee.
The principal investigator of the trial sends the amendment to the ethics committee.
Two possibilities :
- the amendment does not significantly change the protocol. In this case, the ethics committee is informed but does not give
no opinion ;
- the amendment profoundly modifies the protocol and the possible risks for patients. In this case, the committee
of ethics deliberates and must give an opinion (favorable or not) on the amendment.
AMM (Marketing Authorization)
Administrative authorization issued by the Director of Pharmacy and Equipment to
the pharmaceutical establishment which wishes to put a drug on the Algerian market. The director
of Pharmacy and Equipment makes its decision following the advice of the committee of experts
clinicians.
archiving
All clinical trial documents must be kept for 15 years after the end of the trial,
both by the investigators and by the sponsor.
Quality assurance
System set up to ensure the quality of a clinical trial, the reliability of its results and compliance with
ethics and law during the essay. It includes :
- the quality controls carried out by the clinical research assistant
- the audit
- the inspection carried out by the competent administrative authorities
Audit
Analysis procedure of a clinical trial, carried out by an independent auditor of the trial and mandated by the
promoter in order to ensure the quality of the test, the reliability of its results and respect
during the test of the ethics, the law and the regulations in force. The audit report is the property of
promoter who carried out the financial burden of the audit.
Direct individual benefit (BID)
Clinical research is said to have direct individual benefit when patients included in the trial
will directly benefit from a possible therapeutic benefit for the management of their pathology.
Conversely, any other clinical research is said to have no direct individual benefit when the subjects
healthy or the patients included in the trial do not shoot
no direct therapeutic benefit from the research in which they agreed to participate.
Good Clinical Practice (GCP)
Set of provisions which guarantee the quality and authenticity of information in clinical research
collected and compliance with the law and regulations guaranteeing the rights of people in research
clinical.
bioavailability
Study of the speed and the rate of release of the active principle of a pharmaceutical preparation, determined by
its concentration curve in general circulation as a function of time or by its excretion
in the urine.
bioequivalence
Two drugs are bioequivalent if they are pharmaceutically equivalent and if their bioavailability
(rate and release rate), after administration of the same molar dose, is close enough that one can
can expect essentially the same effects.
Investigator's brochure:
Refers to the comprehensive set of information collected at a given time on a drug, at the development stage
where it is before the AMM. The investigator's brochure must be given before the start of a trial
clinical to any investigator participating in this trial.
The trial sponsor is responsible for writing and regularly updating the brochure (dated, signed).
Observation book:
Document intended to collect as the test progresses, for each subject, the information defined by the
protocol. Information may be collected by any means ensuring the editing and
conservation, and allowing quality control.
Confidentiality:
The medical professional secrecy rule applies to everyone who participates directly (investigating doctor)
or indirectly (ARC, monitors, quality controllers) to clinical research.
Informed consent:
Free and formally expressed acceptance of a person to participate in research
clinical. Consent is said to be "informed" when the person has received it from the doctor
investigator (or a substitute doctor) all information regarding: the objectives of the trial, the
benefits, risks and constraints.
The person's consent can be withdrawn at any time without prejudice to themselves.
Consent is evidenced by the person signing a "
consent "meaning that she received all the information she wanted regarding the test
clinical.
Financial agreement
Contract governing the rights and financial responsibilities of people involved in clinical research.
Test protocol
Text bringing together all the descriptive elements of clinical research and which specifies the conditions in
which this research must be carried out and managed.
Additional research costs
This term defines the cost of research which, in a patient included in a clinical trial, cannot be charged to the
hospital budget but which must be paid for either by the trial sponsor or by a third party
which funds research. This cost of research will be very clearly differentiated from the cost of care that the
Anyway, the patient would have received if he had not been included in this research.
Standard operating procedures
A standard operating procedure (POS) presents in writing the details of the actions to be performed during a measurement
to be made or a decision to be made in a research protocol.
The advantage of a standard operating procedure is that it encourages all investigators to work from
the same way and that it saves them from unfortunate omissions. All kinds of POS can be written in the
clinical research concerning the responsibilities of the promoter, ARCs, investigators,
auditors and inspectors. SOPs must be regularly updated, dated and signed by the person
responsible for their writing.
APPENDIX B
DECLARATION OF INTENT TO TEST A PHARMACEUTICAL PRODUCT
Date of declaration / / /
1. Promoter (name or Registration by administration
name and address) Number:
Date: / / / Stamp
2. Title of the essay:
3. Objective:
4. Research with direct individual benefit: yes no
5. Clinical experimentation phase (I, IIa, IIb, III, IV):
6. Test:
controlled: multicentric: international:
randomized: single blind: double blind:
crossed: parallel groups: open: other, to be specified:
7. Observational study: / ​​/
Pharmacovigilance / / Prevalence / / Pharmacoepidemiology
/ / Pharmaco economics / / Cohort / /
Case-witnesses / / other, to be specified:
8. Bioequivalence study: / ​​/
9. Scheduled date for the start of the search: / / /
10. Expected duration:
MEDICINE OR STUDY PRODUCT
(If the trial involves several drugs or products, use one page for each of them)
11. Special name:
12. Code name:
13. Scientific name and D.C.I of the active principle (s):
14. Pharmaceutical form (pharmacopoeia):
15. Qualitative and quantitative composition (using international non-proprietary names):
16. New active ingredient: yes no
17. Dosage:
18. Manufacturer (s) [name (s) or name (s) and place (s) of manufacture):
19. D. E or A.M.M:
- Algeria: yes no refusal suspension withdrawal
- Abroad (name the main countries):
REFERENCE MEDICINAL PRODUCT
20. Special name:
21. Scientific name and INN of the active principle (s):
22. Pharmaceutical form (pharmacopoeia):
23. Qualitative and quantitative composition of active ingredients (using common names
international):
24. Dosage:
25. Manufacturer (s) [name (s) or name (s) and place (s) of manufacture):
PLACEBO
26. Pharmaceutical form (pharmacopoeia):
27. Manufacturer (s) [name (s) or name (s) and place (s) of manufacture):
INVESTIGATIVE (S)
28. Last name (s) and First name (s)
31. Quality
32. Place of performance
PEOPLE LOOKING FOR RESEARCH
29. Expected number of people:
30. Therapeutic indication:
31. Main inclusion criteria:
32. Duration of treatment or participation per person:
ETHICS COMMITTEE
33. Committee (name and address:
34. Favorable opinion Unfavorable opinion
35. Date of notice:
INSURANCE
36. Insurance company (name or name):
37. Number of contract signed:
Send 3 copies of this declaration to the DPHM
APPENDIX D
DATASHEET OF A SERIOUS ADVERSE EVENT
STUDY :
PROTOCOL:
1. INFORMATION ABOUT THE PATIENT:
Last name First Name :
Patient number
Gender: F M
Date of Birth :
Weight height :
2. DECLARING
Promoter:
Name: Position:
Telephone: Fax:
Investigator:
Test center:
Name: Position:
Telephone: Fax:
3 ADMISSIBLE DRUGS
Drug (s
) of the study
way
Dose
Dated
From start to stop
Reason for prescription
Drug (s
) associated
way
Dose
Dated
From start to stop
Reason for prescription
4. DESCRIPTION OF THE EVENT
(clinical and paraclinical signs)
Date of occurrence (day, month, year): / / / / / / / / / /
Delay after the last dose (day, hour, minute): / / / / / / / / / /
Evolution: - Spontaneous regression yes no
- Regression under treatment yes no
Corrector: - Persistence: yes no - Worsening: yes no
Accountability: - Excluded: yes no - Possible: yes no
- Likely: yes no - Very likely: yes no
Taken measures :
Any
Corrective treatment
Stopping the suspected drug
Re-administration of the suspected product: YES NO Recurrence of the event:
YES NO
5. COMMENTS
Date Stamp Signature of the declarant:
APPENDIX C
NATIONAL REGISTER OF CLINICAL TRIALS
N ° Date of
deposit
Promoter / Trial Monitor
Principal investigator
Test product
Essay title
Date of authorization
Type of test (phase)
Results reporting
Observation