The objective of a clinical trial on a health product (medicinal product, device, or cell and gene therapy) is to evaluate the safety and efficacy of the latter in healthy volunteers or patient volunteers. The medicinal product will be able to obtain marketing authorization (MA) issued by the French National Agency for Medicines and Health Products Safety (ANSM) if it is proven to be effective, and if it does not present any hazards to patients and may be used in complete safety.
The clinical evaluation of the safety and efficacy of a new medicinal product takes place in four different, successive phases: each gives rise to a different trial.
Phase I is conducted on a small group of healthy volunteers or patient volunteers, depending on the agent evaluated. This involves testing it in humans for the first time, so as to study its fate in the body over time (kinetics) and to evaluate its toxicity. The volunteers are generally provided with accommodation at a specialist center for a few days. A panel of tests is performed, to verify a vast range of parameters (cardiac, respiratory, blood parameters, etc.).
Phase II is conducted in patient volunteers. The objective is to determine the safety and efficacy of the agent. An initial step serves to determine the minimum effective dose, for which minor or no adverse reactions are observed. This dose will subsequently be administered to 100 to 300 patients (insofar as possible, according to the frequency for the target disease) in order to investigate any therapeutic benefit. These trials take place in a hospital setting.
Phase III serves to evaluate the therapeutic benefit of the medicinal product on a much larger number of patients: from a few hundred to several thousand, for very common disorders, such as hypertension. The volunteers are usually split into two groups to compare the efficacy of the candidate medicinal product with a reference treatment (if one exists) or placebo (a neutral substance).
At the end of these trials, and based on their results, the health authorities decide whether or not to grant marketing authorization (MA) for the investigational medicinal product.
This is then followed by phase IV: this serves to monitor the long-term use of the medicinal product, under actual conditions of use, so as to detect any rare adverse reactions, delayed complications or even prescription bias or improper use.
Trials strictly controlled by law
Human research must meet numerous organizational and ethical criteria, controlled by law, to guarantee the safety of participants. This system is based on extensive reflection, aiming to protect persons taking part in research, whoever they may be (minors, protected adults, adults, patients or vulnerable persons, healthy volunteers), together with their data and biological specimens (blood, tissue, organs). The interests of these individuals must always prevail over scientific and social interests.
In order for a clinical trial to start in France, it must have received:
- a favorable opinion from an ethical research committees (CPP)
- authorization from the French National Agency for Medicines and Health Products Safety (ANSM)
The research must be conducted under the supervision of an investigator who may be either a competent physician, registered with the French Medical Association, or by persons qualified in the relevant research field (midwife, dentist, etc.). The investigator must:
- inform the individuals invited to take part in the research on the study objectives, its methodology, the expected benefits, obligations and foreseeable risks, their right to refuse to take part in the study and to withdraw their consent at any time, and, hence, to end their participation in the study without this having any impact on their future care
- obtain written informed consent from persons agreeing to take part in the study, and ensure that they fully understand the information provided
College of Reviewers: the role of associations
Inserm works closely with patient associations to include them in the expert appraisal process for clinical research projects on human subjects. The Institute asks them to review the information leaflets and consent forms intended for volunteers invited to take part in these trials. Since 2007, the Inserm College of Reviewers association, consisting of 70 patient representatives, has primarily aimed to ensure that the information leaflet and consent form are clear, accessible and comprehensive.
All persons taking part in human research are, moreover, required to be registered by the study sponsor in the national file of healthy volunteers or patient volunteers whose disorder is unrelated to the investigational medicinal product.
Lastly, the sponsor takes out mandatory insurance, to offer compensation for any harm sustained by the participants, caused by the implementation of the study.
Knowledge sharing and transparency: Inserm, a signatory of the joint statement on the public disclosure of clinical trial results
As a sponsor, Inserm has recently committed, by signing a policy promoted by the World Health Organization, to disclose the results – whatever their nature – of trials on medicinal products for which it acts as sponsor. The Institute will offer guidance to scientists in this process, so as to promote scientific knowledge sharing to make progress in public health and contribute to greater transparency in medical research.