Understanding why restrictive trial eligibility criteria are inappropriate.

Background: An important difference between explanatory and pragmatic clinical trials concerns eligibility criteria. Eligibility criteria are restrictive in explanatory trials, while pragmatic trials are more inclusive or even all-inclusive.

Methods: To better understand the diverging views regarding eligibility criteria, we examine the contrast between theoretical and clinical medicine, and 3 different research contexts: laboratory research, population studies and clinical trials. In each context we review the purpose for selecting study subjects or research material, as well as the type of inductive inference or generalization that is sought by such selection.

Results: In each context, selection concerns different things and serves different purposes: In the laboratory, selection concerns the homogenous research material that will help isolate a causal signal. In the epidemiological context selection concerns the (random) sampling method, designed to produce a representative sample of the population. In the clinical trial setting, selection concerns patients in need of care. Restrictive eligibility criteria become inappropriate in the care setting because the aim of the trial is not to represent a population nor to isolate a causal signal, but to find out which patients benefit from treatment.

Conclusion: The idea of selecting patients comes from methods that belong to theoretical medicine. In the care setting, most clinical trials should be pragmatic and as inclusive as possible.