How to do it. Organise a multicentre trial.

Abstract

Multicentre and single centre clinical trials share methodological problems which are well known (box). Multicentre trials do, however, have several distinct advantages. They provide: (a) larger sample size so that the result is more precise, appropriate subgroup analysis is more feasible, and there is a lower risk of an apparently "negative" result when the treatment is, in truth, effective; (b) quicker results before people lose scientific and commercial interest in the treatment and before it is modified or the theoretical indications for it are changed; (c) wider dissemination of the results and, possibly, more widespread belief in their validity; (d) standardised definitions of disease and measurements of outcome among centres and among countries in international trials; (e) a wider range of clinical and methodological skills to solve protocol problems; (f) usually a wider range of patients, facilitating the generalisation of results, which can be broadly applied to future patients in other centres and other countries; (g) large negative trials which are more likely to be published than small negative trials. This is important otherwise small positive trials, which are more likely to be submitted for publication and probably more likely to be accepted rather than small negative trials, will tend to dominate the scientific literature; (h) less suspicion and rivalry among centres and countries without necessarily suppressing healthy competition; (i) less scientific isolation; (I) better national and international collaboration; (k) facilitation of further multicentre trials of potentially important treatments, provided that the initial trial is not too demanding. The difficulties of multicentre trials compared with single centre trials mainly concern the coordination of many people in several centres and even countries (see box on next page). There are usually several possible solutions, the best depending on circumstances , geography, number of centres, budget, and so on. What follows is not meant to be an ossified blueprint but some suggestions. Suggestions, moreover, which have not been tested in randomised trials but which, at least, are based on some experience.