Pragmatism in Clinical Trials Calls for Departures from Traditional Research Ethics: An Analysis of the Arguments

Abstract

Pragmatic clinical trials (PCTs) are considered a valuable means to directly improve day-to-day patient care through the comparison of health interventions in real world conditions. Increasing pragmatism in clinical research, however, calls for departures from the well-controlled conditions that are typically required for randomized trials by ethical and regulatory bodies. Such requirements are believed to impact scientific validity, generalizability and operational feasibility. Advocates of more lenient ethical and regulatory requirements for PCTs reject the moral distinction between clinical research and care, and propose a transition to a learning health care system that continuously generates knowledge through routine practice. Such claims have led to the following question: what are the arguments supporting departures from current trial ethics regulations and how well do they hold once applied to different varieties of PCTs? In the literature, three arguments are commonly offered as necessary, justificatory conditions: (1) the PCT poses minimal risks, (2) the PCT does not violate patient expectations, and (3) the PCT is socially valuable and impracticable otherwise. Interpretation of these conditions is ambiguous and contested, though there seems to be some common ground for less stringent oversight practices for specific, selected examples of standard of care PCTs. Application of the conditions to other varieties of PCTs, however, demonstrates that making broad ethical assertions about PCTs in general is flawed due to the variability in morally salient features. Transparency to the public and stakeholder engagement are crucial for enabling those PCTs that hold promise to change real world health care the most.