Scientific Publications by FDA Staff

Pain 2013 Nov;154(11):2324-34

Abuse liability measures for use in analgesic clinical trials in patients with pain: IMMPACT recommendations.

O'Connor AB, Turk DC, Dworkin RH, Katz NP, Colucci R, Haythornthwaite JA, Klein M, O'Brien C, Posner K, Rappaport BA, Reisfield G, Adams EH, Balster RL, Bigelow GE, Burke LB, Comer SD, Cone E, Cowan P, Denisco RA, Farrar JT, Foltin RW, Haddox JD, Hertz S, Jay GW, Junor R, Kopecky EA, Leiderman DB, McDermott MP, Palmer PP, Raja SN, Rauschkolb C, Rowbotham MC, Sampaio C, Setnik B, Smith SM, Sokolowska M, Stauffer JW, Walsh SL, Zacny JP

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.