Modern trials are most useful when they are pragmatic and explanatory – there is no continuum

Since the groundbreaking work of Schwartz and Lellouch, new approaches and methods have become available that allow researchers to address pragmatic and explanatory questions in parallel in the same trial. Emerging availability of routinely collected "real-world" data, development of decentralized trial techniques, and creation of digital biomarkers allow to observe health outcomes with minimal or no interference in real-world care. This overcomes previous limitations to studying mechanisms of interventions in routine care and makes the idea of a continuum obsolete. We argue that pragmatism and explanatorism need to be understood as two distinct but compatible conceptual dimensions to open new perspectives for using novel technologies to design the most informative clinical trials and make better clinical and regulatory decisions. We base our argument on an analysis of the concept of a continuum and highlight its limitations. We review key trial design features and introduce a new concept that sees explanatory design features as fundamental, invasive or noninvasive, or sufficient or insufficient. We describe their impact on pragmatism and explanatorism and show how multidimensional pragmatic explanatory trials that are most useful are possible today.