Curt D Furberg
When a new intervention (drug, procedure or device) becomes mainstream care, one hopes that all groups of patients for whom this intervention is intended have been properly studied and, thus, are well defined. This ideal situation rarely applies. The clinical trials conducted to determine efficacy and safety of new interventions are typically designed to be feasible and time and cost efficient. As a consequence, trial populations are typically highly selected and may represent only a subset of the patients for whom the intervention is targeted. Thus, the applicability of the trial findings to other subpopulations has to be based on extrapolations. Some of these extrapolations are reasonable, while others are debatable.
Five considerations often influence trial design1: the desire for a study population that (1) is aetiologically homogeneous, (2) is most likely to respond favourably to the intervention, (3) is least likely to suffer adverse events, (4) has no or limited co-morbidity, and (5) most likely will consist of good compliers. The inclusion and exclusion criteria in the trial protocol define those patients with a given condition who are eligible for trial participation or the so-called study population. In addition, all trial participants, by definition, must consent to participate in a research project. Those enrolled constitute the study sample.
This article highlights the conflict between the needs of an optimal research design and a desire from the clinical perspective to determine if all patient groups stand to benefit from a new intervention. The outcome chosen for a clinical trial often influences the interpretation of results. The problem of application of research findings will be illustrated by examples from the literature.
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