Transcript french regulation of biomedical research involving human beings

FRENCH REGULATION OF
BIOMEDICAL RESEARCH
INVOLVING HUMAN BEINGS
Judge Christian Byk, Secr.Gl
Internat.l Assoc.of Law, Ethics and
Science
The Historical Context


-
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
For the protection of human subjects
For the quality and competivity of the drug
industry
The International Context
Main international sources
-The Nuremberg Code(1947)
-The HelsinkiDeclaration (WMA,1964 modif.)
-The ManillaDeclaration(CIOMS,1982,modif.)
 Main European Sources
-The Oviedo Convention(CofEur,1997) and its
Protocol on Biomedical Research,2005)
-The European Union Directive 2001

The Main Features of the French
Regulation




Definition of Biomedical Research
Prerequisite Conditions that must be
fulfilled in order to conduct a biomedical
research
Conducting a biomedical research
Sanctions
Definition of Biomedical Research

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
Definition of Biomedical Research
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.

Conditions to be fulfilled prior to
any research
Subjective conditions
-conditions related to those who initiate the
research
-conditions related to the research subjects

Objective conditions
-conditions related to the research protocol
-conditions related to the premises where the
research is conducted
-specific conditions for drug research

Subjective Conditions
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

Conditions related to those who
initiate the research

-
-
-
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
The Investigator
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 »
Conditions related to the Research
Subjects
Definition
Only born and living human beings can be subjects
to biomedical research (under the 1988 Act)
 Consequently are excluded:
-Dead persons except if they have consented when
alive
-Fœtus and embryos:they are covered by specific
legislations

Common Rules
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

Common Rules
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.

Specific Rules
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:
-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
Informed Consent-Common Rules
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.

Informed Consent-Common Rules

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.
Informed Consent-Specific Rules
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

Informed Consent-Specific Rules
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

Objective Conditions
The existence of a protocol
 The necessity of a positive decision of an
ethics committee
 The authorisation of the competent
authorithy
 Conditions related to the premises where
research are conducted
 Conditions concerning drug research

The Protocol and other related
information


-
-
The research protocol should fully
described the objective,
conception,methodology and organisation
of the research
The other related information
The brochure for the investigator
The financial information:specific taxes
must have been paid to the Drug Agency
The role of the Ethics Review
Committee



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…
The committee ensures that legal requirements
are respected and controls the scientific
pertinence of the research
The Decison of the Ethics Review
Committee




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
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
The Authorisation of the Competent
Authority




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…
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
The Authorisation of the Competent
Authority




The authority may raise objections
If the protocol is not modified, the
autorisation is refused
The granted autorisation is valid for one
year
The decision may be appealed in an
administrative court
The Premises where the Research
are conducted

-
-
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
The Premises where the Research
are conducted
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 Premises where the Research
are conducted
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

Conditions related to Drugs
Good Production Practices
According to the European directive of 8th
Oct.2003, Good Production Practices of
drugs apply also to experimental drugs
 Labelling
The GPP includes rules on labelling that are
aimed to ensure the safety of the subjects
involved in biomedical research

Conducting a Biomedical Research



Duties towards the hospital where the
research is conducted
Duties towards the public authorities
Duties towars the subjects
Duties towards the Hospital
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

Duties towards the Hospital
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)
 Other products or exams are assumed by
the promotor

Duties towards the Public
Authorities
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

Duties towards the Public
Authorities
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)

Duties towards the Public
Authorities
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

Duties towards the Research
Subjects
Compensation
No payment is accepted but a limited
compensation is allowed except for
minors,inmates and uncapacitated adults
 Damages
-the promotor is presumed responsible f
-in other cases, the State compensation system
(ONIAM) may function
- An insurance is compulsory for the promotor

Duties towards the Research
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

Duties towards the Research
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

Sanctions
Penalties
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
the investigator (as a physician) and the promotor (as a
pharmacist )
 Administrative sanctions by the competent public
authorities
