The conduct of clinical trials for medicinal products in europe in the light of the European clinical trials directive. Review of regulatory and practical aspects in the different countries.

The purpose of the clinical trial guidelines is to harmonise legislation in order to ensure consistency within Europe and thereby promote Europe's attractiveness for clinical research while maintaining or improving the protection of subjects who agree to participate. The French administrative system has hitherto been relatively favourable (with simple notification to a single Ethics Committee per study); it is thus important to maintain competitiveness in these respects, given that, in other areas (the time it takes to establish agreements, recruitment, etc.), other countries have the advantage. At the moment, this Directive has not been entirely transposed into French law. The pilot period established by the Afssaps (French drug agency) has made it possible to determine very quickly how to set things up. For Ethics Committees, the situation is more critical in that many points remain that need to be finalised (selection of members, internal rules, Competent Authority/Ethics Committee relationship, etc.). The Giens workshop issued a number of proposals and it hopes, through the Afssaps)/DGS (French agency of health in government)/LEEM Steering Group (French pharmaceutical companies association), to be able to help establish an efficient system which also correctly protect the patient.

Quantification methods were developed for selection bias by predictability of allocations with unequal block randomization.

BACKGROUND AND OBJECTIVE: A selection of patients for a controlled clinical trial may be biased because of prior knowledge of the treatment. With randomized blocks of known or guessed lengths, some allocations can be predicted with certainty. Previously described methods determine the proportion of predictable cases for blocks of equal lengths. It may be useful to make a calculation for unequal blocks as well to find a method that reduces this predictability. STUDY DESIGN AND SETTING: Quantification methods are developed for series of two and three unequal blocks, using the probability of identifying a long block when it comes before a short one if it starts with a sequence incompatible with the content of a short block. Results are compared with the recently described maximal allocation procedure. RESULTS: Predictability is not always reduced by unequal blocks and is even worse in some cases, compared to equal blocks. Predictability is not necessarily decreased with the maximal allocation procedure. CONCLUSIONS: Before choosing an allocation method, it is important to quantify the predictability of possible options to reduce selection bias. Several practical recommendations are formulated for choosing methods, taking this risk of bias into account.