Dose-ranging in clinical trials: rationale and proposed use with placebo or positive controls

Drugs are currently released for general use without substantial knowledge of their minimum and maximum effective dose and their dose-related side effects. There are several plausible explanations for this situation, but in some cases this has resulted in patients receiving larger than necessary or smaller than effective doses and experiencing adverse reactions. A concurrent problem with drug evaluation is the rising concern with the use of placebo controls and the growing pressure to utilize positive-control studies. Such studies have many problems, however, some of which are subtle but nonetheless counterproductive in terms of proving efficacy through rigorous scientific investigation. The use of dose-ranging in clinical trials provides more information regarding a drug's TI and can circumvent some of the problems of placebo- and positive-controlled studies. Thus, such dose-ranging studies should be a feature of the development of most new drugs.