The shrinking scope of pragmatic trials: a methodological reflection on their domain of applicability

All the applied sciences face an equivalent challenge of generalizing from restricted settings, prototypes, samples, case studies, simulations, and demonstration projects. [...]the ability to generalize from a trial is not confined to the single dimension (e.g., some patients to all patients). 1.3 Applicability We have followed the significant retreat from the original, rose-tinted expectation that pragmatic trials would enjoy widespread use across real-world practice to the current, hard-headed view that particular pragmatic trials will only find application in corresponding clinical settings. Within that trial population, there will still be residual variation (albeit more limited than at posttrial, postapproval, etc.) in terms of age, sex, disease etiology, patient history, concomitant exposures, competing risks, and genetic background.