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.

Grant Number: 1UG3DA062907-01
NIH Institute/Center: NIH
Principal Investigator: Laura Brandt