Regulatory versus Public Health Requirements in Clinical Trials

Abstract

Clinical trials that are used for regulatory purposes as part of a new drug application are essentially “explanatory”—they test a precise hypothesis on the mode of action of the drug in a well-defined population of patients. In contrast, clinical trials that are used for public health purposes are essentially “pragmatic”—they aim to confirm the benefit of a new treatment in a population at large, the emphasis being on showing whether the treatment is working in practice rather than how it might be working in precisely controlled conditions. Public health trials are simple, large-scale, randomized studies in which minimal data are collected on a question of substantial clinical interest. In such trials, there is no need for a strict control of eligibility criteria, of treatment compliance, of concurrent treatments, of adherence to follow-up schedules, and of thoroughness of evaluation. Attention should be directed instead to the control of the randomization procedure, of the follow-up of all randomized patients, of the methods used to ascertain the endpoints of interest, and of a strict intention-to-treat approach to data collection and analysis. In public health trials, data quality is ensured by limiting data collection to essential, easily available data on well-known, objectively measurable patient and disease characteristics. Public health trials could often advantageously replace nonrandomized postmarketing trials.