Development and Validation of a Stimulant Use Disorder Severity Scale - PROJECT SUMMARY Stimulant use and stimulant use disorder (StUD) are major contributors to morbidity and mortality in the U.S., disproportionately impacting racial and ethnic minoritized populations. As there is no U.S. Food and Drug Administration (FDA)-approved medication for StUD, development of medications is a high priority. However, medication development (and private sector investment) has been hampered by the lack of a practical, psychometrically sound, clinically significant, and broadly accepted indicator of treatment response, other than sustained abstinence. Recent FDA guidance for developing medications for treatment of StUD recommends the development of instruments for endpoints reflecting disease severity. In this project, we propose to advance development of the novel Stimulant Use Disorder Severity Scale (StUDSS) as a clinical outcome assessment (COA) qualified by FDA as a Drug Development Tool (DDT), which involves three sequential stages of submission and review outlined in FDA Center for Drug Evaluation and Research (CDER) guidance. This work will be conducted at geographically distinct sites in Connecticut and California to enhance validity across stimulant types and racial/ethnic diverse groups. Development will follow FDA Guidance for patient- reported outcome (PRO) measures. Preparation and submission of a Letter of Intent (LOI) to the CDER COA Qualification Program will initiate the qualification process (UG3 - AIM 1). The StUDSS will be administered to racially and ethnically diverse individuals with StUD (n=40) through 1:1 cognitive interviews to establish content validity and create a finalized instrument (UG3 - AIM 2). Following completion of milestones during the UG3 phase, and with input and recommendations from CDER, a qualification plan (QP) will be prepared and submitted to CDER COA Qualification Program (UH3 – AIM 1). The proposed observational study will involve repeated administration of the StUDSS over a 3-month period among n=300 individuals with StUD across sites at Yale and UCLA to establish reliability and validity (UH3 – AIM 2). This proposal is informed by rigorous prior research by our group and others demonstrating relationship between stimulant use outcome measures and functional outcomes; psychometric characteristics of StUD criteria in DSM-5; and value in measuring change in characteristics that define StUD. Our team brings together expertise in stimulant use research, scale development, substance use disorder diagnostic tools, outcome measurement, and the FDA qualification program. This project will produce: 1) a PRO measuring StUD symptom severity with accompanying content validity data, 2) a QP accepted in CDER COA Qualification Program, and 3) validity and reliability data from a racial and ethnic diverse sample. Preparation of a full qualification package (third and final submission stage) will be dependent on recommendations from QP determination letter and expected to occur after completion of the project period. A validated PRO measuring StUD symptom severity that becomes accepted by FDA as a DDT would be of high impact for advancing medication development, treatment research, and clinical care.
