Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®)

Abstract

Currently, there are no validated tools to assess drug abuse potential during clinical trials. Because of its ease of implementation, its systematic approach, and its preliminary validation results, MADDERS could provide such a tool for clinical trials. (Am J Addict 2016;25:641-651).

Measures That Identify Prescription Medication Misuse, Abuse, and Related Events in Clinical Trials: ACTTION Critique and Recommended Considerations

“…Other measures of inappropriate medication use that were briefly considered during the meeting, but that were not well-suited to evaluating and classifying inappropriate medication use events, have been reviewed previously ([28]; see also Table 2 for a summary). Only 2 recently developed approaches (i.e., Self-Reported Misuse, Abuse, and Diversion [SR-MAD] instrument for prescription opioids [25]; Misuse, Abuse, and Diversion Drug Event Reporting System [MADDERS [29]]) that were created specifically to address the gaps in procedures for identifying and adjudicating inappropriate use events occurring in clinical trials were examined in depth. The ALERTT group focused on details presented during the meeting and in articles that have been published since the meeting [25, 29] regarding each tool’s ease of implementation, ability to retrospectively and prospectively identify behaviors suggestive of MAREs, standardization of event adjudication, and ability to gather comprehensive and exhaustive information when behaviors suggestive of inappropriate use events arise in prospective trials.…”

“…Only 2 recently developed approaches (i.e., Self-Reported Misuse, Abuse, and Diversion [SR-MAD] instrument for prescription opioids [25]; Misuse, Abuse, and Diversion Drug Event Reporting System [MADDERS [29]]) that were created specifically to address the gaps in procedures for identifying and adjudicating inappropriate use events occurring in clinical trials were examined in depth. The ALERTT group focused on details presented during the meeting and in articles that have been published since the meeting [25, 29] regarding each tool’s ease of implementation, ability to retrospectively and prospectively identify behaviors suggestive of MAREs, standardization of event adjudication, and ability to gather comprehensive and exhaustive information when behaviors suggestive of inappropriate use events arise in prospective trials. Subsequent to the meeting, a Web of Science search (http://webofknowledge.com; February 20, 2017) for articles citing the standardized MAREs classification and definition system [27] was conducted and did not identify any additional assessment methods.…”

“…Subsequent to the meeting, a Web of Science search (http://webofknowledge.com; February 20, 2017) for articles citing the standardized MAREs classification and definition system [27] was conducted and did not identify any additional assessment methods. In addition, Web of Science searches (February 20, 2017) did not identify any publications citing SR-MAD [25] or MADDERS [29] that provided additional information regarding the use of these tools to capture inappropriate medication use events in a clinical trial. In this article, we briefly describe each tool, followed by examples of how each might be applied, as well as an evaluation of the strengths, limitations, and available data regarding each tool’s measurement properties.…”

“…This assessment system can be used retrospectively and prospectively to evaluate triggering adverse events (AEs; e.g., overdose, convulsion, agitation) and drug accountability discrepancies (e.g., missing doses, evidence of tampering) occurring in clinical trials that potentially reflect MAREs [29]. Using MADDERS to identify MAREs and the putative intent involves: (1) trained adjudicators evaluating triggering AEs and drug accountability discrepancies that occurred during a completed clinical trial (i.e., retrospective assessment), or (2) trained study staff implementing standardized forms to probe triggering AEs and drug accountability discrepancies that are then classified by trained site investigators into the MARE categories during an ongoing clinical trial (i.e., prospective assessment).…”

“…MADDERS also seeks out additional information regarding triggering AEs and drug accountability discrepancies [29]. For example, if retrospective assessment of a clinical trial identified a participant who had a triggering AE of “feeling drunk”, then the entire AE narrative including any available trial data relevant to the event, information about the occurrence of any drug accountability discrepancies, and any additional information requested by adjudicators would be extracted from the patient-level data and provided to adjudicators who would classify the event into the MARE categories.…”