1. FRENCH REGULATION OF BIOMEDICAL RESEARCH INVOLVING HUMAN BEINGS Judge Christian Byk, Secr.Gl Internat.l Assoc.of Law, Ethics and Science

2. The Historical Context A recent legislation (incorporated in the Publ.Health Code) A recent legislation (incorporated in the Publ.Health Code) - The 20th Dec.1988 Act on Biomedical research - The modification of 9th Aug.2004 A necessary regulation A necessary regulation - For the protection of human subjects - For the quality and competivity of the drug industry

3. The International Context Main international sources Main international sources -The Nuremberg Code(1947) -The HelsinkiDeclaration (WMA,1964 modif.) -The ManillaDeclaration(CIOMS,1982,modif.) Main European Sources Main European Sources -The Oviedo Convention(CofEur,1997) and its Protocol on Biomedical Research,2005) -The European Union Directive 2001

4. The Main Features of the French Regulation Definition of Biomedical Research Definition of Biomedical Research Prerequisite Conditions that must be fulfilled in order to conduct a biomedical research Prerequisite Conditions that must be fulfilled in order to conduct a biomedical research Conducting a biomedical research Conducting a biomedical research Sanctions Sanctions

5. Definition of Biomedical Research A Positive Definition: it includes A Positive Definition: it includes -Research on drugs -Research on medical devices -Other researches are listed and defined by a decision of the health Minister

6. Definition of Biomedical Research A negative definition(lower risks research are excluded) A negative definition(lower risks research are excluded) -Non invasive research:those with products used in current practice in conformity with their therapeutical indications -Research aiming to evaluate current health care (except drugs and research on innovative techniques or comparing the safety of medical strategies). But they can only be conducted after an ethics review committee approved them.

7. Conditions to be fulfilled prior to any research Subjective conditions Subjective conditions -conditions related to those who initiate the research -conditions related to the research subjects Objective conditions Objective conditions -conditions related to the research protocol -conditions related to the premises where the research is conducted -specific conditions for drug research

8. Subjective Conditions Conditions related to those who initiate the research Conditions related to those who initiate the research -the Promotor: An individual or an entity that intitiates the research and assumes its management and financing The promotor (or a representative) should be established in the European Union

9. Conditions related to those who initiate the research The Investigator The Investigator - An individual appointed by the Promotor to conduct the research on specified premises. - A Coordinator must be nominated when several investigators have been appointed - The law does not prohibit an individual to be both a promotor and an investigator

10. The Investigator In general, the investigastor must be a physician but: In general, the investigastor must be a physician but: -in research in the field of psychology,a psychologist can also be designated as investigator -in the field of odontology,both a dental surgeon and a qualified physician must be appointed -in research aimming at evaluating current health care, the investigator can be a « qualified person »

11. Conditions related to the Research Subjects Definition Definition Only born and living human beings can be subjects to biomedical research (under the 1988 Act) Consequently are excluded: Consequently are excluded: -Dead persons except if they have consented when alive -Fœtus and embryos:they are covered by specific legislations

12. Common Rules Prerequisite conditions: Prerequisite conditions: -biomedical research shall be based on strong scientific knowledge and preclinical experimentation -biomedical research shall be aimed at developing scientific knowledge on human being -the expected risk should not be disproportionnate with the interest of the sujects or the research -the trouble that may result from the research must be limited as much as possible

13. Common Rules Other conditions: Other conditions: -All the subjects must be clinically examined The results have several functions: to determine the eligiblity of the person as a subject, to bring him/her appropriate information and to serve as an evidence in case the subject will have to claim for damages -Other preventive measures: a person who has no social security cannot become a subject and the participation of subjects in different biomedical research is limited.

14. Specific Rules Categories of persons concerned: Categories of persons concerned: -pregnant and breast-feeding women,inmates (prisonners, mental patients…),minors,uncapacitated adults and adults not able to expresstheir own consent Conditions required: Conditions required: -the expected benefit for the persons concerned justifies the risk OR -there is an expected benefit for other persons in the same category AND -expected risks should be minimal

15. Informed Consent-Common Rules Consent Consent.No one can be involved in a biomedical research without being asked to give a free informed consent prior to the research.In principle, the consent is written but it can be exceptionnally given orally in the presence of an independant witness.

16. Informed Consent-Common Rules Information: written document (summary) Information: written document (summary).scope:objective, methodology, length,expected benefits and risks,decisions of the ethics committee and competent authority,information on the right to withdraw consent….limits:research in psychology may and exceptionnally information concerning the diagnosis of a person may not be revealed when it is the interest of the person concerned.

17. Informed Consent-Specific Rules Uncapacitated persons Uncapacitated persons -consent is given by the legal representatives (in principle both parents for a minor) or by a member of the family or a proxy (for those who have not declared uncapacitated). In all cases, the refusal of the person should be respected -information They received information appropriate to their capacity of understanding and are consulted as much as possible

18. Informed Consent-Specific Rules Biomedical research in emergency situations Biomedical research in emergency situations The ethics committe may authorize the consent to be collected after the research has started when the person is able to express a consent. But the prior consent of the family or a proxy is required if present Dead persons a biomedical research is possible if the person has consented when alive Dead persons a biomedical research is possible if the person has consented when alive

19. Objective Conditions The existence of a protocol The existence of a protocol The necessity of a positive decision of an ethics committee The necessity of a positive decision of an ethics committee The authorisation of the competent The authorisation of the competentauthorithy Conditions related to the premises where research are conducted Conditions related to the premises where research are conducted Conditions concerning drug research Conditions concerning drug research

20. The Protocol and other related information The research protocol should fully described the objective, conception,methodology and organisation of the research The research protocol should fully described the objective, conception,methodology and organisation of the research The other related information The other related information - The brochure for the investigator - The financial information:specific taxes must have been paid to the Drug Agency

21. The role of the Ethics Review Committee Every research protocol shall be submitted to the review of a Committee for the protection of persons Every research protocol shall be submitted to the review of a Committee for the protection of persons Documents to be submitted: protocol, brochure for the investigator,information summary for the subjects, consent forms,insurance… Documents to be submitted: protocol, brochure for the investigator,information summary for the subjects, consent forms,insurance… The committee ensures that legal requirements are respected and controls the scientific pertinence of the research The committee ensures that legal requirements are respected and controls the scientific pertinence of the research

22. The Decison of the Ethics Review Committee No research can be initiated if the decision is negative No research can be initiated if the decision is negative In case of a negative decision, the promotor can however ask for a second review by another committee In case of a negative decision, the promotor can however ask for a second review by another committee A final decison by a committee can be appealed in an administrative court A final decison by a committee can be appealed in an administrative court If the research has not begun a year after a positive decision, the review process shall be started again If the research has not begun a year after a positive decision, the review process shall be started again

23. The Authorisation of the Competent Authority The competent authority: the Drug Agency (AFSSAPS)or the Health Minister The competent authority: the Drug Agency (AFSSAPS)or the Health Minister Main documents to be submitted:protocol, brochure for the investigator,decision of the ethics committee,insurance,scientific data concerning the products… Main documents to be submitted:protocol, brochure for the investigator,decision of the ethics committee,insurance,scientific data concerning the products… Criteria: protecting the subjects by taking into account the safety and quality of the products, the methodology and organisation of the research Criteria: protecting the subjects by taking into account the safety and quality of the products, the methodology and organisation of the research Instruction: no longer than 60 days Instruction: no longer than 60 days

24. The Authorisation of the Competent Authority The authority may raise objections The authority may raise objections If the protocol is not modified, the autorisation is refused If the protocol is not modified, the autorisation is refused The granted autorisation is valid for one year The granted autorisation is valid for one year The decision may be appealed in an administrative court The decision may be appealed in an administrative court

25. The Premises where the Research are conducted Common rules Common rules - a biomedical research can only be conducted in place benefiting of appropriate staff and technical material - When the subject is a patient who needs hospital services, the research shall be done in the hospital premises

26. The Premises where the Research are conducted Premises submitted to an agreement : Premises submitted to an agreement : -premises which are based outside hospitals -health care premises when they are not currently suited for the research The agreement is delivered by the representative of the State in the region The agreement is delivered by the representative of the State in the region

27. The Premises where the Research are conducted Conditions required: Conditions required: - capacity in an emergency situation to treat the subject immediately -appropriate staff and material as well as a good organisation -quality insurance control -protecting confidentiality

28. Conditions related to Drugs Good Production Practices Good Production Practices According to the European directive of 8th Oct.2003, Good Production Practices of drugs apply also to experimental drugs Labelling Labelling The GPP includes rules on labelling that are aimed to ensure the safety of the subjects involved in biomedical research

29. Conducting a Biomedical Research Duties towards the hospital where the research is conducted Duties towards the hospital where the research is conducted Duties towards the public authorities Duties towards the public authorities Duties towars the subjects Duties towars the subjects

30. Duties towards the Hospital The contract with the investigator organises: The contract with the investigator organises: -the missions and duties of the investigator -the missions and duties of the promotor -the financial arrangement The contract shall be approved by the local colege of physicians The contract shall be approved by the local colege of physicians

31. Duties towards the Hospital Delivering products free of charge Delivering products free of charge in principle, the promotor delivers and assumes the cost of experimented products (the social security pays for drugs when used in conformity with their agreement) in principle, the promotor delivers and assumes the cost of experimented products (the social security pays for drugs when used in conformity with their agreement) Other products or exams are assumed by the promotor Other products or exams are assumed by the promotor

32. Duties towards the Public Authorities During the research During the research -Respecting the Good Clinical Practices issued by the Drug Agency -Requiring a new autorisation in case of substantial modification -Notifying undesirable events to the Ethics Committee and Drug Agency

33. Duties towards the Public Authorities The Drug Agency may decide to: The Drug Agency may decide to: -Interrupt the research when the promotor does not respect the legal conditions or when there is a risk for the public health -Impose specific measures -Prohibit the research (same reasons as for interruption)

34. Duties towards the Public Authorities At the end of the research At the end of the research -the promotor shall inform the Ethics Committe and the Authority that the research has ended (witin 90 days) and, if necessary, about the reasons of an earlier end (15 days) -within a year a final report shall be produced with the results of the research -research data shall be stored by the promtor and the investigator during 15 years

35. Duties towards the Research Subjects Compensation Compensation No payment is accepted but a limited compensation is allowed except for minors,inmates and uncapacitated adults Damages Damages -the promotor is presumed responsible f -in other cases, the State compensation system (ONIAM) may function - An insurance is compulsory for the promotor

36. Duties towards the Research Subjects Information of the subjects Information of the subjects -during the research, all substantial modification implies a new consent -after the research, the subject shall receive global information on the results

37. Duties towards the Research Subjects Information on the subjects Information on the subjects -the national data bank of biomedical research is accessible to patients’ groups -the national register of research subjects is a mean to control that the research subjects are not submitted to undue experimentation

38. Sanctions Penalties Penalties a maximum of 3 years imprisonment for not asking the consent or conducting research on vulnerable persons without respecting the legal conditions a maximum of 3 years imprisonment for not asking the consent or conducting research on vulnerable persons without respecting the legal conditions Entities are also submittes to penal law Disciplinary sanctions are possible against Disciplinary sanctions are possible against the investigator (as a physician) and the promotor (as a pharmacist ) Administrative sanctions by the competent public authorities Administrative sanctions by the competent public authorities