Developing an FDA-Qualified Clinical Outcomes Assessment for Opioid Withdrawal - This proposal responds to RFA-DA-25-028 to develop and validate a Clinical Outcome Assessment (COA) for opioid withdrawal, in line with FDA guidelines for qualification. Given the profound variability observed in the assessment of opioid withdrawal as well as limited psychometric support of existing scales, there is a critical need to develop a reliable and valid consensus measure upon which medications and other interventions for opioid withdrawal management can be evaluated and approved. Our initial step included submitting a Letter of Intent to the FDA, commencing the COA development process. We will build on an existing scale (Short Opiate Withdrawal Scale, SOWS-Gossop), which has formed the basis for the approval of lofexidine for opioid withdrawal and has moderate psychometric support, but is limited in its breadth of symptoms and lacks patient input regarding ratings scale style and anchors. New data collected from focus groups and cognitive interviews across diverse populations, will help refine the COA to better capture the varied manifestations of opioid withdrawal. We will engage participants with lived OUD experiences at all stages of development to ensure the COA reflects real-world challenges and withdrawal symptoms. The project is structured into four specific aims: 1. Iterative Development of a Candidate COA: We will expand upon withdrawal domains consistently recognized across existing scales by integrating insights from nationwide focus groups (UG3 Study 1) and cognitive interviews following precipitated and spontaneous withdrawal experiences elicited in the laboratory (UG3 Study 2) to reflect the contemporary and representative real-world complexities of opioid withdrawal. 2. Formulation and Submission of a Comprehensive COA Qualification Plan (QP): Compile a detailed qualification plan that meets all FDA criteria, highlighting our rigorous, data-driven validation approach. Submission and acceptance of the QP by the FDA will be the benchmark to proceed from UG3 to UH3. 3. Validation of Candidate COA: The COA’s construct validity will be assessed under precipitated and spontaneous withdrawal conditions (UH3 Study 1), comparing it against established measures like the Clinical Opioid Withdrawal Scale. Additionally, the COA will be implemented in a large-scale study involving over 6,000 patients, capturing weekly assessments during OUD treatment and post-discharge, to validate its longitudinal utility and reliability (UH3 Study 2 in partnership with the commercial outcomes assessment vendor Trac9). 4. Preparation of the Final Qualification Package: Compile a comprehensive report detailing the development process, findings, and the tool’s efficacy, validity, and reliability for FDA review. By leveraging robust methodologies and diverse stakeholder input, this project will develop a COA that not only meets FDA standards but also enhances clinical practices and patient outcomes by standardizing opioid withdrawal evaluation. This comprehensive approach ensures the development of a reliable tool that supports future drug development and discovery efforts targeted at mitigating opioid withdrawal symptoms.
