Clinical Trials of Antihypertensive Agents

Abstract

Clinical trials of the efficacy of new antihypertensive agents have two principal aims: to define the effective dose range for each drug and to establish its duration of action. There is no ideal trial design for dose ranging. The conventionally used parallel groups design is probably the most practical and allows estimates of response rates at each dose level. Crossover or ascending dose studies may generate dose-response curves that are more relevant clinically, but they are of far longer duration. Recent studies with automated whole-day blood pressure monitoring have shown that standard assumptions about drug duration of action may be misleading. This paper examines these issues and makes suggestions for refining some of the present approaches. We have also briefly looked at practical questions, including problems associated with the diagnosis of hypertension, patients previously on antihypertensive therapy, entry criteria for protocols, and unexpected placebo effects.