Research objectives and general considerations for pragmatic clinical trials of pain treatments: IMMPACT statement

David J. Hohenschurz-Schmidt, Pain Research, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.
Dan Cherkin, Department of Family Medicine, University of Washington and Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States.
Andrew S. Rice, Pain Research, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.
Robert H. Dworkin, Department of Anesthesiology and Perioperative Medicine, University of Rochester Medical Center, Rochester, NY, United States.
Dennis C. Turk, Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States.
Michael P. McDermott, Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, United States.
Matthew J. Bair, VA Center for Health Information and Communication, Regenstrief Institute, and Indiana University School of Medicine, Indianapolis, IN, United States.
Lynn L. DeBar, Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States.
Robert R. Edwards, Harvard Medical School, Boston, MA, United States.
John T. Farrar, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, United States.
Robert D. Kerns, Departments of Psychiatry, Neurology and Psychology, Yale University, New Haven, CT, United States.
John D. Markman, Neuromedicine Pain Management and Translational Pain Research, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States.
Michael C. Rowbotham, Department of Anesthesia, University of California San Francisco School of Medicine, San Francisco, CA, United States.
Karen J. Sherman, Kaiser Permanente Washington Health Research Institute and Department of Epidemiology, University of Washington, Seattle WA, United States.
Ajay D. Wasan, Departments of Anesthesiology & Perioperative Medicine, and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Penney Cowan, American Chronic Pain Association, Rocklin, CA, United States.
Paul Desjardins, Department of Diagnostic Sciences, School of Dental Medicine, Rutgers University, Newark, NJ, United States.
McKenzie Ferguson, Department of Pharmacy Practice, Southern Illinois University Edwardsville, Edwardsville, IL, United States.
Roy Freeman, Department of Neurology, Harvard Medical School, Boston, MA, United States.
Jennifer S. Gewandter, Department of Anesthesiology and Perioperative, University of Rochester, Rochester, NY, United States.
Ian Gilron, Departments of Anesthesiology & Perioperative Medicine, Biomedical & Molecular Sciences, Centre for Neuroscience Studies, and School of Policy Studies, Queen's University, Kingston, ON, Canada.
Hanna Grol-Prokopczyk, Department of Sociology, University at Buffalo, State University of New York, Buffalo NY, United States.
Sharon H. Hertz, Hertz and Fields Consulting, Inc, Silver Spring, MD, United States.
Smriti Iyengar, Eli Lilly and Company, Indianapolis, IN, United States.
Cornelia Kamp, Center for Health and Technology (CHeT), Clinical Materials Services Unit (CMSU), University of Rochester Medical Center, Rochester, NY, United States.
Barbara I. Karp, National Institutes of Health, Bethesda, MD, United States.
Bethea A. Kleykamp, Department of Anesthesiology and Perioperative Medicine, University of Rochester Medical Center, Rochester, NY, United States.
John D. Loeser, Departments of Neurological Surgery and Anesthesia and Pain Medicine, University of Washington, Seattle, WA, United States.
Sean Mackey, Department of Anesthesiology, Perioperative, and Pain Medicine, Neurosciences and Neurology, Stanford University School of Medicine, Palo Alto, CA, United States.
Richard Malamut, Collegium Pharmaceuticals, Stoughton, MA, United States.
Ewan McNicol, Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences, Boston, MA, United States.
Kushang V. Patel, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States.

Document Type

Journal Article

Publication Date

3-22-2023

Journal

Pain

DOI

10.1097/j.pain.0000000000002888

Abstract

Many questions regarding the clinical management of people experiencing pain and related health policy decision-making may best be answered by pragmatic controlled trials. To generate clinically relevant and widely applicable findings, such trials aim to reproduce elements of routine clinical care or are embedded within clinical workflows. In contrast with traditional efficacy trials, pragmatic trials are intended to address a broader set of external validity questions critical for stakeholders (clinicians, healthcare leaders, policymakers, insurers, and patients) in considering the adoption and use of evidence-based treatments in daily clinical care. This article summarizes methodological considerations for pragmatic trials, mainly concerning methods of fundamental importance to the internal validity of trials. The relationship between these methods and common pragmatic trials methods and goals is considered, recognizing that the resulting trial designs are highly dependent on the specific research question under investigation. The basis of this statement was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) systematic review of methods and a consensus meeting. The meeting was organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership. The consensus process was informed by expert presentations, panel and consensus discussions, and a preparatory systematic review. In the context of pragmatic trials of pain treatments, we present fundamental considerations for the planning phase of pragmatic trials, including the specification of trial objectives, the selection of adequate designs, and methods to enhance internal validity while maintaining the ability to answer pragmatic research questions.

Department

Neurology

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