The FDA Guidance for Industry: Abuse-Deterrent Opioids-Evaluation and Labeling was published in April 2015. Since then questions have been raised regarding how to determine the relative abuse-deterrent (AD) effect of an AD formulation (a test product) compared to an immidiate release (IR) or NonAD extended release (ER) formulation of the same opioid (a positive control) and how to define a responder for responder analysis in clinical abuse potential studies. These questions are reasonable and important for the assessment of AD effect of an AD formulation. This article discusses the principles of the statistical assessment in this area and gives details on how to calculate sample size for the primary comparison in the study and how to perform the statistical analyses. In addition, the article also discusses the reason why the non-inferiority test is not proper for the comparison between a test product and an approved AD version of the same opioid product. Finally, a gatekeeping testing procedure is proposed for this comparison with an example.
Keywords: abuse-deterrent formulation; clinical abuse potential study; closed testing procedure; gatekeeping testing procedure; opioid product.