Narrative Review

Interpretation of chronic pain clinical trial outcomes: IMMPACT recommended considerations

Smith, Shannon M.^a,b,c,*; Dworkin, Robert H.^a,c,d,e; Turk, Dennis C.^f; McDermott, Michael P.^d,e,g; Eccleston, Christopher^h; Farrar, John T.^i,j; Rowbotham, Michael C.^k; Bhagwagar, Zubin^l,m; Burke, Laurie B.^n,o; Cowan, Penney^p; Ellenberg, Susan S.^j; Evans, Scott R.^q; Freeman, Roy L.^r; Garrison, Louis P.^s; Iyengar, Smriti^t; Jadad, Alejandro^u; Jensen, Mark P.^v; Junor, Roderick^w; Kamp, Cornelia^e,x; Katz, Nathaniel P.^y,z; Kesslak, James Patrick^aa; Kopecky, Ernest A.^bb; Lissin, Dmitri^cc; Markman, John D.^dd; Mease, Philip J.^ee,ff; O'Connor, Alec B.^gg; Patel, Kushang V.^f; Raja, Srinivasa N.^hh; Sampaio, Cristina^ii,jj; Schoenfeld, David^kk; Singh, Jasvinder^ll; Steigerwald, Ilona^mm; Strand, Vibekeⁿⁿ; Tive, Leslie A.^oo; Tobias, Jeffrey^pp; Wasan, Ajay D.^qq; Wilson, Hilary D.^rr

Author Information

^aDepartment of Anesthesiology and Perioperative Medicine, University of Rochester Medical Center, Rochester, NY, United States

^bDepartment of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY, United States

^cDepartment of Psychiatry, University of Rochester Medical Center, Rochester, NY, United States

^dDepartment of Neurology, University of Rochester Medical Center, Rochester, NY, United States

^eCenter for Health and Technology, University of Rochester Medical Center, Rochester, NY, United States

^fAnesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States

^gDepartment of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, United States

^hCentre for Pain Research, The University of Bath, Bath, United Kingdom

ⁱDepartments of Epidemiology, Neurology, and Anesthesia, University of Pennsylvania, Philadelphia, PA, United States

^jCenter for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, United States

^kCPMC Research Institute, Sutter Health, San Francisco, CA, United States

^lDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, United States

^mRallybio, New Haven, CT, United States

ⁿSchool of Pharmacy, University of Maryland, Baltimore, MD, United States

^oLORA Group, LLC, Royal Oak, MD, United States

^pAmerican Chronic Pain Association, Rocklin, CA, United States

^qDepartment of Epidemiology and Biostatistics, The George Washington University, Washington, DC, United States

^rDepartment of Neurology, Harvard Medical School, Boston, MA, United States

^sDepartment of Pharmacy, University of Washington, Seattle, WA, United States

^tEli Lilly and Company, Indianapolis, IN, United States

^uDepartment of Anesthesia, Faculty of Medicine, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

^vDepartment of Rehabilitation Medicine, University of Washington, Seattle, WA, United States

^wEisai Ltd, Hatfield, United Kingdom

^xClinical Materials Services Unit, University of Rochester Medical Center, Rochester, NY, United States

^yTufts University School of Medicine, Boston, MA, United States

^zAnalgesic Solutions, Natick, MA, United States

^aaRevance Therapeutics, Newark, CA, United States

^bbCollegium Pharmaceutical, Inc, Stoughton, MA, United States

^ccScilex Pharmaceuticals, Palo Alto, CA, United States

^ddNeuromedicine Pain Management and Translational Pain Research, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States

^eeRheumatology Clinical Research, Swedish Medical Center, Seattle, WA, United States

^ffUniversity of Washington School of Medicine, Seattle, WA, United States

^ggDepartment of Medicine, University of Rochester Medical Center, Rochester, NY, United States

^hhDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States

ⁱⁱFaculdade Medicinda de Lisboa, Universidade de Lisboa, Lisboa, Portugal

^jjCHDI Foundation, Princeton, NJ, United States

^kkDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States

^llDepartments of Medicine and Epidemiology, University of Alabama at Birmingham School of Medicine, Birmingham, AB, United States

^mmNeumentum, Inc, Palo Alto, CA, United States

ⁿⁿDivision of Immunology/Rheumatology, Stanford University, Palo Alto, CA, United States

^ooPfizer, Inc, New York, NY, United States

^ppAquila Consulting Group, LLC, Petaluma, CA, United States

^qqDepartments of Anesthesiology and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States

^rrBoehringer Ingelheim, Seattle, WA, United States

^*Corresponding author. Address: Department of Anesthesiology and Perioperative Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 604, Rochester, NY 14642. E-mail address: [email protected] (S.M. Smith).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

PAIN 161(11):p 2446-2461, November 2020. | DOI: 10.1097/j.pain.0000000000001952

Buy

Abstract

Interpreting randomized clinical trials (RCTs) is crucial to making decisions regarding the use of analgesic treatments in clinical practice. In this article, we report on an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus meeting organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, the purpose of which was to recommend approaches that facilitate interpretation of analgesic RCTs. We review issues to consider when drawing conclusions from RCTs, as well as common methods for reporting RCT results and the limitations of each method. These issues include the type of trial, study design, statistical analysis methods, magnitude of the estimated beneficial and harmful effects and associated precision, availability of alternative treatments and their benefit–risk profile, clinical importance of the change from baseline both within and between groups, presentation of the outcome data, and the limitations of the approaches used.