Statistical issues in the regulation of medicines.

The recent release within the European Union of a draft Note for Guidance from the Commission for Proprietary Medical Products (CPMP) entitled 'Biostatistical methodology in clinical trials in applications for marketing authorisations for medicinal products' has stimulated widespread discussion of the relevant statistical issues. This discussion contains echoes of an earlier debate concerning a closely related U.S. Guideline. The areas of agreement and disagreement between the two guidelines bear close examination as they provide lessons for all statisticians involved in the design and analysis of clinical trials. Notable areas of debate include crossover designs, multi-centre trials, the intention to treat principle, pre-specification of statistical analysis and the ability to generalize results to the wider population of patients. The consequences for the routine involvement of statisticians in this area of work in general, and in the regulatory process in particular, are especially important. This is an illustration of the extent to which drug regulation has influenced, and is continuing to influence, the development of medical statistics throughout the world.