Author: Mark Heinemann, Princpal Regulatory Consultant, RWE and Insights, inVentiv Health
An important modification of the French research law framework occurred in November 2016 with the coming into force of decree No. 2016-1537. The law describes the modalities for research involving humans and eventually adds ‘non-interventional research’ to the research law framework.
The most recent legislative name, “research involving the human being”, applies to any research designed to increase scientific knowledge, with or without interventional measures.
Three types of research can be distinguished:
- Interventional research with above minimal risk: corresponds to the previous understanding of biomedical research on drugs, medical devices, other health products or research without health products.
- Here, CPP (Ethics Committee) approval, ANSM (Competent Authority) authorization and, in case of Phase I research, the authorization of a research facility remain required.
- Interventional research that involves minimal risks and constraints: includes in relation to the current medical practice one or more additional interventions that are listed exhaustively in an annex 1 to the law.
- The minimal nature of the risks and constraints linked to the implementation of the intervention(s) shall be assessed in the light of the age, physical condition and possible pathology of the person eligible for the research and frequency, duration and possible combinations of these interventions.
- Minimal risk research must be declared to the ANSM but does not require prior authorization. Minimal risk research requires insurance.
- The French Direction Générale de la Santé (DGS) defined the acceptable threshold of risk by establishing a list of minimal risk research
- Any research involving a medicinal product for human use is excluded from the minimal risk research scope!
- Non-interventional research: research without any risk or constraint added by the research, without any modification of the usual medical care. Distinguish between:
- Research with patients: must obtain a favorable opinion of a CPP and requires prior notification to the ANSM. Study-specific insurance is not required.
- Research on retrospective data: shall be sent to the CEREES (Committee for Expertise in Research, Studies and Evaluations in the field of Health) for advice (to the CCTIRS until April 2017). No CPP approval needed.
- The generation of a collection of elements of human origin and the change of purpose of such a collection or of a collection generated earlier must also obtain the favorable opinion of a CPP.
Sponsors may request preliminary CPP advice on the qualification of a research project.
So What is the Impact for Non-Interventional Studies?
Non-interventional research is now subject to notification to ANSM and the approval of a CPP if patients are involved. As a result of the new CPP requirement, submission to the CCTIRS advisory committee is not applicable any longer.
A registration number must be obtained from ANSM prior to submission of the project to a CPP. This number, called ‘ID-RCB’, is a unique identifier for research projects conducted in France (not to confound with the EudraCT number).
In accordance with the new legislation, CPPs are assigned randomly to examine a research project.
The random assignment of a CPP is carried out via a website; essential information to provide at this step is the ANSM registration number. An e-mail validation process follows the submission and confirmations are sent to the applicant and to the applicable CPP.
The content, format and procedures to follow for presenting a non-interventional research submission dossier to a CPP were published in December 2016: documents to include are among others the study protocol, a French synopsis and individual patient informed consent or a description of procedure for obtaining a non-opposition statement.
Once available, the applicant must provide a copy of the approval and the research synopsis to ANSM.
In addition to CCP approval and ANSM declaration, non-interventional research is subject to authorization by the French Data Protection Agency ‘CNIL’.
CNIL takes its decision following a favorable opinion of the applicable CPP for research involving the human person, including non-interventional research.
Simplified declaration procedures are made available by CNIL in the field of health research: sponsors may complete a compliance statement for the declaration of health research projects if the research falls in one of the following categories:
- Declaration MR-001 for research requiring individual patient consent (for interventional or biomedical research, including minimal risk and stress research, clinical trials of drugs, and research that requires an examination of genetic characteristics) – Note: not applicable for non-interventional research
- Declaration MR-003 for research not requiring individual patient consent, such as data collections of health related data for research purposes, research in routine care, non-interventional research and cluster clinical drug trials. – Note: not applicable for non-interventional research if individual patient consent is used
If the above described simplified declaration method MR-003 cannot be applied, the usual CNIL authorization process becomes applicable.
There is a up to 60 days turnaround timeframe for obtaining CPP opinion and CNIL authorization, however, CNIL’s evaluation period may be renewed once and extended for another 30 days. Recent experience also shows that CNIL’s timelines are much longer than they should be and overall study start-up timelines may be longer than expected.
<<Learn more in our NIS Considerations – France Report, published in February 2017>>>