Therapeutic inferences for individual patients

Increased awareness of the gap between controlled research and medical practice has raised concerns over whether the special attention of doctors to probability estimates from clinical trials really improves the care of individuals. Evidence-based medicine has acknowledged that research results are not applicable to all kinds of patients, and consequently, has attempted to overcome this limitation by introducing improvements in the design and analysis of clinical trials.

A clinical case is used to highlight the premises required to support reasonable extrapolations from controlled research to individuals. Then, the prospects of two key methodological improvements - pragmatic randomized controlled trials and subgroup analysis - are critically appraised.

A principle to guide therapeutic inferences is suggested. According to this principle, the probabilities of interest for purposes of therapeutic decision making are those of the set defined by everything that is relevant to the patient and the outcome of interest at the time of the decision. It is argued that the conditions necessary to authorize automatic extrapolations of research results to specific patients are highly demanding. Furthermore, these requirements are rarely accomplished in real practice, even in the event that probability estimates come from samples generally taken as representative and are derived from specific subsets of patients.

Clinicians should generally avoid unreflective extrapolations from research and address, as explicitly as possible, the challenge of estimating probabilities for individual patients. A key element of this task is the integration of data from research and non-research sources.