title: Abuse liability measures for use in analgesic clinical trials in patients with pain: IMMPACT recommendations.
abstract: Assessing and mitigating the abuse liability (AL) of analgesics is an urgent clinical and societal problem. Analgesics have traditionally been assessed in randomized clinical trials (RCTs) designed to demonstrate analgesic efficacy relative to placebo or an active comparator. In these trials, rigorous, prospectively designed assessment for AL is generally not performed. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) convened a consensus meeting to review the available evidence and discuss methods for improving the assessment of the AL of analgesics in clinical trials in patients with pain. Recommendations for improved assessment include: (1) performing trials that include individuals with diverse risks of abuse; (2) improving the assessment of AL in clinical trials (eg, training study personnel in the principles of abuse and addiction behaviors, designing the trial to assess AL outcomes as primary or secondary outcome measures depending on the trial objectives); (3) performing standardized assessment of outcomes, including targeted observations by study personnel and using structured adverse events query forms that ask all subjects specifically for certain symptoms (such as euphoria and craving); and (4) collecting detailed information about events of potential concern (eg, unexpected urine drug testing results, loss of study medication, and dropping out of the trial). The authors also propose a research agenda for improving the assessment of AL in future trials.
authors.affiliation: Department of Medicine, University of Rochester, Rochester, NY, USA Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA Department of Anesthesiology, University of Rochester, Rochester, NY, USA Analgesic Solutions, Natick, MA, USA Department of Anesthesiology, Tufts University School of Medicine, Boston, MA, USA Colucci & Associates LLC, Newtown, CT, USA Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA United States Food and Drug Administration, Silver Spring, MD, USA Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA Center for Suicide Risk Assessment, New York State Psychiatric Institute/College of Physicians and Surgeons, Columbia University, New York, NY, USA Department of Psychiatry, University of Florida College of Medicine, Gainesville, FL, USA Covance, Princeton, NJ, USA Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, VA, USA American Chronic Pain Association, Rocklin, CA, USA National Institute on Drug Abuse, Rockville, MD, USA Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA Purdue Pharma LP, Stamford, CT, USA Department of Public Health & Community Medicine, Tufts University School of Medicine, Boston, MA, USA Pfizer Inc, Ann Arbor, MI, USA Eisai Limited, Woodcliff Lake, NJ, USA Endo Pharmaceuticals Inc, Chadds Ford, PA, USA CNS Drug Consulting LLC, McLean, VA, USA Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA AcelRx Pharmaceuticals Inc, Redwood City, CA, USA Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore School of Medicine, MD, USA Johnson & Johnson Pharmaceutical Research & Development LLC, Raritan, NJ, USA California Pacific Medical Center Research Institute, San Francisco, CA, USA Clinical Pharmacology and Therapeutics Laboratory, Faculdade de Medicina de Lisboa, Lisbon, Portugal King Pharmaceuticals Inc, Cary, NC, USA Grünenthal USA Inc, Bedminster, NJ, USA Durect Corporation, Cupertino, CA, USA Department of Behavioral Science, Center on Drug and Alcohol Research, University of Kentucky, KY, USA Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL, USA.
authors.forename: Alec B
authors.initials: AB
authors.lastname: O'Connor
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Turk
authors.forename: Robert H
authors.initials: RH
authors.lastname: Dworkin
authors.forename: Nathaniel P
authors.initials: NP
authors.lastname: Katz
authors.forename: Robert
authors.initials: R
authors.lastname: Colucci
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Haythornthwaite
authors.forename: Michael
authors.initials: M
authors.lastname: Klein
authors.forename: Charles
authors.initials: C
authors.lastname: O'Brien
authors.forename: Kelly
authors.initials: K
authors.lastname: Posner
authors.forename: Bob A
authors.initials: BA
authors.lastname: Rappaport
authors.forename: Gary
authors.initials: G
authors.lastname: Reisfield
authors.forename: Edgar H
authors.initials: EH
authors.lastname: Adams
authors.forename: Robert L
authors.initials: RL
authors.lastname: Balster
authors.forename: George E
authors.initials: GE
authors.lastname: Bigelow
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Burke
authors.forename: Sandra D
authors.initials: SD
authors.lastname: Comer
authors.forename: Edward
authors.initials: E
authors.lastname: Cone
authors.forename: Penney
authors.initials: P
authors.lastname: Cowan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Denisco
authors.forename: John T
authors.initials: JT
authors.lastname: Farrar
authors.forename: Richard W
authors.initials: RW
authors.lastname: Foltin
authors.forename: David J
authors.initials: DJ
authors.lastname: Haddox
authors.forename: Sharon
authors.initials: S
authors.lastname: Hertz
authors.forename: Gary W
authors.initials: GW
authors.lastname: Jay
authors.forename: Roderick
authors.initials: R
authors.lastname: Junor
authors.forename: Ernest A
authors.initials: EA
authors.lastname: Kopecky
authors.forename: Deborah B
authors.initials: DB
authors.lastname: Leiderman
authors.forename: Michael P
authors.initials: MP
authors.lastname: McDermott
authors.forename: Pamela P
authors.initials: PP
authors.lastname: Palmer
authors.forename: Srinivasa N
authors.initials: SN
authors.lastname: Raja
authors.forename: Christine
authors.initials: C
authors.lastname: Rauschkolb
authors.forename: Michael C
authors.initials: MC
authors.lastname: Rowbotham
authors.forename: Cristina
authors.initials: C
authors.lastname: Sampaio
authors.forename: Beatrice
authors.initials: B
authors.lastname: Setnik
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Smith
authors.forename: Marta
authors.initials: M
authors.lastname: Sokolowska
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Stauffer
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Walsh
authors.forename: James P
authors.initials: JP
authors.lastname: Zacny
mesh_terms: D000700:Analgesics; D017326:Clinical Trials, Phase III as Topic; D023381:Endpoint Determination; D006801:Humans; D010146:Pain / Q000188:drug therapy* / Q000453:epidemiology*; D010147:Pain Measurement; D011153:Population; D063487:Prescription Drug Misuse / Q000523:psychology / Q000706:statistics & numerical data*; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012189:Retrospective Studies; D012306:Risk; D012307:Risk Factors; D012959:Socioeconomic Factors; D015813:Substance Abuse Detection; D009626:Terminology as Topic
chemical_list: D000700:Analgesics
keywords: Abuse; Abuse liability; Clinical trial; Opioids; Prescription drug abuse; Risk of abuse; Study design