An empirical and normative critique of "off-label" prescribing as a category of medicines use.

Background and Aim: Off-label prescribing involves the use of medicines in a manner that has not been endorsed by regulatory authorities. The ethical, epistemic and clinical implications of off-label prescribing have been brought into sharp focus due to its ubiquity, and a series of high profile legal settlements between the US Department of Justice and pharmaceutical companies for purposefully marketing medicines off-label. The objective of this research was to contribute to the debate about off-label drug prescribing by exploring it as a practical quandary that physicians and decision makers regularly face. Methods: This empirical bioethics study was conducted in two phases: an in-depth investigation of three case studies of off-label prescribing and semi-structured interviews with physicians about their prescribing practices. Main Findings: The concept of a medicine being off-label is almost never invoked as a reason for prescribing or not prescribing a medicine. This is not surprising given that medical practice is not purely technical but rather political and deliberative and shaped by numerous intersecting ethical and epistemic concerns. Science as a problem solving strategy will therefore likely fail to resolve disputes about off-label prescribing. As long as regulation is primarily construed as a method for evaluating science, it will fail to address the challenge of off-label prescribing. Eight alternative warrants are identified as justifications for off-label prescribing. Conclusion: The phrase off-label confuses rather than illuminates the issues related to medicines regulation and governance as it conflates practices that are qualitatively different. It also conflates issues of evidence and justification with issues of process. In order to move debates and research about off-label prescribing forward, researchers, policy makers, and other stakeholders need to develop a more nuanced understanding of the different rationales that drive off-label prescribing. Whether or not a medicine is being used off-label is far less important than what might be suggested by the dominant discourse on the topic