[How to evaluate the contribution of fixed dose combinations: the standpoint of the methodologist]

For the epidemiologist, the development of any new therapy or strategy must respond to the following three questions: does a need exist? Is there a new way of meeting that need? Can a valid assessment be made of the efficacy of the new therapy? New antihypertensive treatments or strategies are needed, even in 1994: in France, as in other high-income countries, many hypertensive patients remain inadequately controlled. In the 1993 report of the American Joint National Committee, only 55% of treated hypertensives had blood pressure (BP) measurements of less than 160/95 mm Hg. Therapeutic failure is partly due to ineffective treatment and partly to nonspecific factors, eg inappropriate drug choice or inadequate compliance. Concerning the drug, an innovation beyond new pharmacological approaches may equally involve combinations between already available drugs. As for any new treatment, the choice of drugs and their respective doses must be based on phase I and II trials with appropriate outcome criteria (to evaluate the effect of the combination on any counter-regulatory mechanisms that may be involved). The combination is then compared to other available combinations in phase III and IV studies. The real question, however, would appear to be: does first-line combination therapy improve BP control in comparison with conventional strategy?(ABSTRACT TRUNCATED AT 250 WORDS)