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In France, the Médiator(®) scandal and the trauma it has created, are the source of Law n° 2011-2012 of 29 December 2011 on strengthening safety of drug and health products, intended by the Ministry of Labour, Employment and Health, adopted by the National Assembly and promulgated in order to restore confidence and enhance safety of drug and health products. This new law affects all stakeholders and health professionals impacts key points in the life cycle of the drug: MA, reimbursement, advertising, promotion, distribution, prescription, dispensing, and pharmacovigilance. It also provides for financial, administrative or criminal penalties, which are intended deterrent. Beyond strengthening constraints on safety of health products, this new law in France foreshadowed a revolution in behaviour, attitudes and overall scenery of the health system and no one today knows exactly the outline., (© 2012 Société Française de Pharmacologie et de Thérapeutique.)

The relative added value of a drug is currently evaluated in France by the Transparency Commission (TC) of the National Health Authority (HAS), by assigning a level of Improvement in Actual Benefit (IAB). IAB is based on two parameters, efficacy and safety of the product, in a defined target population, either as compared to one or more other drugs with similar indications, or within therapeutic strategy. The items used for evaluation, including the level of clinical effect, the relevance of the comparator, the choice of comparison criteria and the methodology used (indirect comparison, non-inferiority studies, etc.), have been reviewed by the working group in Giens with regard to an analysis of the opinion on TC issued between 2004 and 2007 in several therapeutic areas First of all, this attempt at rationalisation based on the criteria used to assess the relative added value demonstrated the rareness of direct comparative data, and was followed by a discussion on the possible broadening of the evaluation criteria. The group discussed taking into account the Public Health Impact (PHI), which has now been incorporated into the assessment of Actual Benefit (AB). The group believes that PHI seems to be more related to the notion of IAB than to that of AB. Indeed, it is frequently the relative added value of a new drug that produces an impact in public health. Conversely, considering the comparative evaluation criteria of PHI, which are not systematically taken into account in IMSR (such as improvement in the health of the population, meeting a public health need or impact on the healthcare system), PHI could legitimately be included in the assessment of the relative added value of a drug. Other parameters such as compliance or impact on professional practice have been considered. Thus, the notion of relative added value, evaluated at initial registration, could be based on an expected improvement in medical service. The notion of expected medical service leads to the requirement of producing additional data in real life (post-registration studies), which would support the definitive notion of improvement in actual benefit at the time of renewed registration, while taking into account the place occupied by the drug in the therapeutic strategy.

The charter of medicines promotion recently adopted by France intends to constrain information given by sales representatives to the field of good prescription practices. Over a 11 year period (1994 to end 2004), 362 interdictions of promotional supports have been decided by the director of the French Medicines Agency. This accounts for 0.5% of the about 80 800 promotional supports controlled during this period. A date base shows the representation of the justifications of these interdictions and the predominance of documentation given or showed to the physicians. A challenge for health authorities would be to assess the actual impact of ethical and non ethical promotion.

This paper provides an overview of French pharmaceutical policy between 1980 and 2003, which was dominated by price control and management of the positive list during the 1980s, with new policy instruments being introduced in the 1990s. The development and diffusion of prescription guidelines has been used to promote more appropriate use of medicines, and some measures aimed at developing the generic market have been implemented. In parallel, attempts have been made to set expenditure caps for physicians' prescriptions and for pharmaceutical companies' turnover. This second option seems to be more durable and effective, although its effectiveness in controlling increases in pharmaceutical expenditure remains limited. Pharmaceutical regulation is now more transparent than it used to be, and the monitoring of prescriptions is steadily improving. However, some areas remain problematic, for example over-prescription of certain classes of medicines such as antibiotics and probably psycholeptics.

The participants attending the 1999 French Clinical Pharmacological meeting in Giens eventually reached a consensus about the necessity to set up a clear policy regarding self-medication products in France. Despite a wish by French people to take more responsibility for their own health care, self-medication products' use and development in France have been held back for many years for the reasons reported below. However, self-medication could be developed while respecting or even improving public health care by applying the following key principles: (1) the acknowledgement of a consensual definition. 'A self-medication drug is a drug (the guarantees for which are provided by marketing authorization approval and dispensation and advice of a pharmacist) specifically suitable for use without any physician's prescription'; (2) the advertising of self-medication products to the general public is authorized; (3) the safe use of self-medication products is linked to the selected indications and the relevance of the information provided to the general public; (4) the self-medication drug approval procedure could be simplified, managed by a specific AFSSAPS unit; (5) the role of the pharmacist involved, as well as suitable pharmacovigilance, is mentioned; (6) more than 1000 previously marketed drugs without any clear status, the so called 'grey zone drugs', should be taken into consideration. According to the participants at the meeting, it is possible to set up a new clear and dynamic policy for self-medication products in France in conformity with EU requirements.

Directive 97/55/EC of October 6, 1997 has just amended Directive 84/450/EEC concerning misleading advertising in order for it to encompass comparative advertising. The purpose is to harmonize regulations regarding comparative advertising. Although the basic terms of this Directive are very similar to those imposed in France by the law of January 18, 1992, its transposition should, however, require changes to be made to French law.

In order to improve safety for healthy volunteers to be included in phase I clinical trials, a national data bank will be set up and controlled by the French Ministry of Health. Each investigator responsible for an agreed phase I center will have a personal access code to the central computer in order to consult the national registry before including any healthy volunteer in a study. If the volunteer has already participated in a recent study, the investigator will find 2 important pieces of information in the data bank: the duration of the safety period following the preceding trial and during which the subject is not allowed to participate in another study; the total amount of money received by the subject during the last 12 months in grants for phase I studies; this amount will be limited by the Ministry of Health. This healthy volunteer data bank will decrease the risk of drug interaction and will improve safety in phase I trials. However, many practical and ethical problems remain to be solved.

In France, official guidelines for good clinical practices in clinical trials were issued in 1987. In December 1988, a law was passed that fixed the requirements for carrying out experiments in healthy subjects. It will be completed by official guidelines for the structures in which experiments on healthy subjects (and patients as well, when the investigation would not benefit the health of the patients) may be conducted. Hence a battery of recent legal instructions precisely state what good clinical practices are in the setting of phase I studies. Of particular importance are: subject recruitment and selection methods and procedures; specific competence of the investigator, in particular to interpret the pre-trial data; necessary and sufficient facilities to guarantee the subjects' safety; careful quality control to check all laboratory procedures; necessity of written standard operating procedures.

During the phase I trials, from the juridical point of view, the responsibilities are shared between the pharmaceutical company and the physician who manages the trial. The pharmaceutical company is responsible for the product, the choice of methodology and respect for the regulations. On the financial side, the company is liable for paying any damages. While the trial is being conducted, the physician is responsible both for the choice of the healthy volunteers and for their care.

Industry chooses phase I partners by evaluating quality versus cost. However, since December 20, 1988, in France only those centers, private or public, authorized by the French authorities can be chosen. However, ability to perform rapidly, reliability and worldwide acceptability of results will be considered in choosing the phase I partner.

Between 1982 and 1983, the Commission on Approval for Marketing Medications of the French government made 76 negative decisions based on problems with clinical trials. In 21 instances, the reasons for a temporary negative decision could be resolved from data already on hand or readily available. More serious problems resulted in requests for new studies having better controls, better management of ancillary therapy, more participants, or lasting longer. Indications that denial of the application is likely or outright refusals to grant approval were based on failure to demonstrate efficacy and concerns about toxicity. Analysis of the reasons for negative decisions can ameliorate the clinical trials submitted in support of an application for marketing approval. Improving the design and conduct of clinical trials based on correcting the defects discussed here would benefit the sciences of drug development, regulation, and patient care.