title: Exploring the ethical and regulatory issues in pragmatic clinical trials.
abstract: The need for high-quality evidence to support decision making about health and health care by patients, physicians, care providers, and policy-makers is well documented. However, serious shortcomings in evidence persist. Pragmatic clinical trials that use novel techniques including emerging information and communication technologies to explore important research questions rapidly and at a fraction of the cost incurred by more "traditional" research methods promise to help close this gap. Nevertheless, while pragmatic clinical trials can bridge clinical practice and research, they may also raise difficult ethical and regulatory challenges. In this article, the authors briefly survey the current state of evidence that is available to inform clinical care and other health-related decisions and discuss the potential for pragmatic clinical trials to improve this state of affairs. They then propose a new working definition for pragmatic research that centers upon fitness for informing decisions about health and health care. Finally, they introduce a project, jointly undertaken by the National Institutes of Health Health Care Systems Research Collaboratory and the National Patient-Centered Clinical Research Network (PCORnet), which addresses 11 key aspects of current systems for regulatory and ethical oversight of clinical research that pose challenges to conducting pragmatic clinical trials. In the series of articles commissioned on this topic published in this issue of Clinical Trials, each of these aspects is addressed in a dedicated article, with a special focus on the interplay between ethical and regulatory considerations and pragmatic clinical research aimed at informing "real-world" choices about health and health care.
authors.affiliation: Division of Cardiology, Department of Medicine, School of Medicine, Duke University, Durham, NC, USA Duke Translational Medicine Institute, Duke University, Durham, NC, USA Current affiliation: US Food and Drug Administration, Silver Spring, MD, USA. This paper was submitted prior to Dr. Califf's appointment to the US Food and Drug Administration Robert.Califf@fda.hhs.gov.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.affiliation: Berman Institute of Bioethics, Johns Hopkins University, Baltimore, MD, USA Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sugarman
mesh_terms: D035843:Biomedical Research / Q000941:ethics* / Q000331:legislation & jurisprudence* / Q000592:standards; D002986:Clinical Trials as Topic / Q000941:ethics* / Q000331:legislation & jurisprudence* / Q000592:standards; D003657:Decision Making / Q000941:ethics*; D006801:Humans; D009316:National Institutes of Health (U.S.); D012107:Research Design / Q000592:standards*; D011795:Surveys and Questionnaires; D014481:United States
keywords: Clinical trials; cluster-randomized trial; ethics; evidence-based medicine; learning health-care system; patient-centered outcomes research; pragmatic clinical trial