The U.S. Food and Drug Administration issued new scientific recommendations aimed at encouraging more widespread innovation and development of novel medication-assisted treatment (MAT) drugs for the treatment of opioid use disorder (OUD). New draft guidance outlines new ways for drug developers to consider measuring and demonstrating the effectiveness and benefits of new or existing MAT products. This new draft guidance is part of the FDA’s ongoing commitment to promote more widespread development, access to and adoption of MAT.
MAT for opioid dependence relies on prescription drugs, including buprenorphine, methadone and naltrexone, to stabilize brain chemistry; reduce or block the euphoric effects of opioids; relieve physiological cravings; and normalize body functions. Regular adherence to MAT helps patients gain control over their use of opioids, without causing the cycle of highs and lows associated with opioid misuse or abuse. MAT, coupled with relevant social, medical and psychological services, is a highly effective treatment for OUD. Additionally, patients receiving MAT cut their risk of death from all causes in half, according to the Substance Abuse and Mental Health Services Administration.
Clinical trials to evaluate effectiveness of MAT for the purposes of FDA approval have generally used reduction in drug-taking behavior (drug use patterns) as an endpoint.
In the guidance FDA encourages drug sponsors to consider a variety of ways to evaluate the effect and clinical benefit of MAT. These include the impact of a new drug on adverse outcomes like mortality (overall mortality or overdose mortality), emergency medical interventions and Hepatitis C seroconversion (the period during which antibodies develop and become detectable).
Efficacy may also be measured by studying the proportion of patients that transition from meeting criteria for being diagnosed with moderate to severe OUD – based on both drug use and its impact on patient wellbeing – at baseline to being considered in remission at the end of the study. Improvements in the ability to resume work, school, or other productive activity may also demonstrate clinical benefit.
While understanding that many of these outcomes could be highly valuable, the agency recognizes that evaluating them could require larger trials than those usually conducted for marketing approval. To that end, the FDA is encouraging sponsors to discuss their plans with the agency early in the drug development process. The agency is also committed to providing assistance to sponsors interested in developing a validated measurement of patient-reported experiences, such as “craving” or “urge to use” opioids, which make it difficult for patients with OUD to sustain recovery. Patient-reported experiences could be used to complement other endpoints and help determine how a new treatment’s effects on such experiences support the goal of sustained clinical response.
FDA remains committed to addressing the epidemic on all fronts, with a significant focus on decreasing exposure to opioids and preventing new addiction by taking new steps to encourage more appropriate prescribing; supporting the treatment of those with OUD and promoting the development of improved as well as lower cost forms of MAT; fostering the development of novel pain treatment therapies that may not be as addictive as opioids, and opioids more resistant to abuse and misuse; and taking action against those who contribute to the illegal importation and sale of opioid products. The FDA will also continue to evaluate how drugs currently on the market are used, in both medical and illicit settings, and take regulatory action where needed.
