Scientific Publications by FDA Staff

J Pain 2015 Feb 3 [Epub ahead of print]

Instruments to identify prescription medication misuse, abuse, and related events in clinical trials: an ACTTION systematic review.

Smith SM, Paillard F, McKeown A, Burke LB, Edwards RR, Katz NP, Papadopoulos EJ, Rappaport BA, Slagle A, Strain EC, Wasan AD, Turk DC, Dworkin RH

Measurement of inappropriate medication use events (e.g., abuse, misuse) in clinical trials is important in characterizing a medication's abuse potential. However, no "gold standard" assessment of inappropriate use events in clinical trials has been identified. In this systematic review, we examine the measurement properties (i.e., content validity, cross-sectional reliability and construct validity, longitudinal construct validity, ability to detect change, and responder definitions) of instruments assessing inappropriate use of opioid and non-opioid prescription medications to identify any that meet U.S. and European regulatory agencies' rigorous standards for outcome measures in clinical trials. Sixteen published instruments were identified, most of which were not designed for the selected concept of interest and context of use. For this reason, many instruments were found to lack adequate content validity (or documentation of content validity) to evaluate current inappropriate medication use events; for example, evaluating inappropriate use across the lifespan rather than current use, including items that did not directly assess inappropriate use (e.g., questions about anger), or failing to capture information pertinent to inappropriate use events (e.g., intention, route of administration). In addition, the psychometric data across all instruments were generally limited in scope. A further limitation is the heterogeneous, non-standardized use of inappropriate medication use terminology. These observations suggest that available instruments are not well suited for assessing current inappropriate medication use within the specific context of clinical trials. Further effort is needed to develop reliable and valid instruments to measure current inappropriate medication use events in clinical trials. PERSPECTIVE: This systematic review evaluates the measurement properties of inappropriate medication use (e.g., abuse, misuse) instruments to determine whether any meet regulatory standards for clinical trial outcome measures to assess abuse potential.