Adaptation of the application of good clinical practice depending on the features of specific research projects.

The conduct of clinical trials falls within a strict regulatory framework. The objective of the round table was to develop reasonable recommendations for the implementation of GCP according to the type of research and taking in account the risks and challenges related to this research. Two types of risks have been identified: those related to the characteristics of the research and those related to the impact of the study results. The group designed an evaluation table of these risks. The round table focused its investigations on 3 main themes: monitoring, the investigational medicinal product and undesirable effects. Three methods of monitoring adaptation were analysed in terms of advantages and disadvantages: the gradual approach, the central monitoring, monitoring on the basis of sampling. Examination of the investigational medicinal product focused on the medicinal product circuit. The group recommends using the following 'basic' decision-making tree, which takes three elements into account: 1) is it an investigational medicinal product?, 2) do the trial objectives and design require packaging specific to the research?, 3) is the risk of use higher than that in standard practice? Finally, adaptation of the implementation of GCP in terms of pharmacovigilance appeared very limited and could possibly be considered for the medicinal product, the subject of the research, which already holds a marketing authorisation, and for which the safety profile is well known; in this case, only simplified collection of non-serious adverse events may be envisaged, which may be implemented by designing and using a standard collection listing. The adaptation of the implementation of GCP is possible. This firstly takes into account the characteristics of the research: which objectives/which risks/which challenges. The options in terms of adaptation must be pre-defined, documented and justified; if necessary, they will also be re-assessed in the course of analysis.

[A survey on the position of France in international clinical research as assessed by pharmaceutical laboratories]. / Attractivité de la France pour la recherche clinique internationale: une etude du Leem dresse un constat peu favorable et suggère des voies d'amélioration.

In order to evaluate the attractiveness of France for conducting international clinical trials, a survey was performed among pharmaceutical companies that are based in France or that have affiliates in France. The survey concerned international phase II and III clinical studies carried out in 2002 and 2003. Ten pharmaceutical companies representing 36% of the French market completed the survey. 134 trials were analysed in total. France recruited 8.3% of the overall number of patients recruited, and 15.0% of those recruited within Europe. France was within the overall mean with regard to the percentage of active centres (78.5% versus 79.5%) and the percentage of patients evaluable according to protocol (86.8% versus 87.3%). In contrast, France ranked within the last third of analysed countries with respect to the speed of recruitment (1.5 versus 1.9 patients/centre/month), and the number of queries per observation (16.8 versus 10.9). The analysis of the qualitative indicators of performance showed that, although the perception of pharmaceutical companies towards the quality of French medicine and administrative authorities is positive, France notably needs to improve the productivity of its clinical research in order to enhance its attractiveness for the pharmaceutical sponsors of clinical trials.

Subjective outcome measures of drug efficacy.

The use of subjective outcome measures for assessing drug efficacy varies according to the disease in question. Subjective outcome measures used to complement an objective outcome measure can clearly claim the status of a main outcome measure. The validation of an instrument follows an appropriate methodology that focuses on two points: the methods used for its construction are set out and its performance is evaluated in a study. In drug evaluation, the importance of the subjective outcome measure should be discussed, depending on the aim and the disease. The methodology of the study obeys the same rules as when an objective outcome measure is used. The issue of the clinical significance of the results should be broached and discussed. Subjective outcome measures deserve to be considered in the evaluation of the drug because they provide a different and complementary perspective on the disease and the patient, both at the time of obtaining the marketing authorization or when reassessing a drug.

[The challenges of the implementation of the European Directive 2001/20/CE in the main Member States]. / Les enjeux de la transposition de la Directive européenne 2001/20/CE dans les principaux Etats Membres.

Since the publication of Directive 2001/20/EC in the Official Journal of the European Communities on May 1, 2001, the Member States have been preparing its transposition into national legislation for application no later than May 2004. The discussions have proved to relate essentially to the organisation of the Ethics Committees, which must now give a single opinion per Member State, as well as to the time limits for obtaining this opinion and the authorization for a study from the competent authority. These considerations have led to proposals of shorter time limits for products at an early stage of development or involving certain diseases. Despite harmonization of the legislation, the application of the Directive does not eliminate all national differences.