A framework for analysis of research risks and benefits to participants in standard of care pragmatic clinical trials

Abstract

Background/Aims: Standard of care pragmatic clinical trials that compare treatments already in use could improve care and reduce costs, but there is considerable debate about the research risks of standard of care pragmatic clinical trials and how to apply informed consent regulations to such trials. We sought to develop a framework integrating the insights from opposing sides of the debate. Methods: We developed a formal risk–benefit analysis framework for standard of care pragmatic clinical trials and then applied it to key provisions of the US federal regulations. Results: Our formal framework for standard of care pragmatic clinical trial risk–benefit analysis takes into account three key considerations: the ex ante estimates of risks and benefits of the treatments to be compared in a standard of care pragmatic clinical trial, the allocation ratios of treatments inside and outside such a trial, and the significance of some participants receiving a different treatment inside a trial than outside the trial. The framework provides practical guidance on how the research ethics regulations on informed consent should be applied to standard of care pragmatic clinical trials. Conclusion: Our proposed formal model makes explicit the relationship between the concepts used by opposing sides of the debate about the research risks of standard of care pragmatic clinical trials and can be used to clarify the implications for informed consent.