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FDA Releases Updated Guidelines for the Development of Drugs to Treat OUD Disorder

December 3, 2020
With opioid use disorder on the rise due to the COVID pandemic, the agency revisits drug development targets.

COVID-19 has been getting all the attention this year but, unfortunately, that doesn’t mean other health crises have gone away – including in the pain management field. Some are getting worse. Social disruption, increased stress due to the pandemic and resultant economic crisis, and difficulties accessing routine medical care have increased the incidence of opioid use disorder (OUD) in many areas of the United States.1,2

In an editorial titled “An Epidemic in the Midst of a Pandemic: Opioid Use Disorder and COVID-19,” Alexander et al, wrote, “Although the pandemic threatens everyone, it is a particularly grave risk to the millions of Americans with opioid use disorder, who ­– ­already vulnerable and marginalized—are heavily dependent on face-to-face health care delivery.”2 In addition to the need for access to care, the need for better medications for treating OUD is becoming increasingly urgent.

To address the gap, the FDA announced this past fall a final guidance for the development of drugs to treat OUD. “As we combat the COVID-19 crisis, we are also focused on addressing the other health crises facing our country, including the ongoing substance use disorder and overdose crisis that our country is battling. … One way we are doing so is through exploring new ways to measure effectiveness of treatments, as we seek to help individuals with opioid use disorder, FDA Commissioner Stephen M. Hahn, MD, said when announcing the updated guidance.3

The final guidance is only slightly modified from the draft version and builds on a separate but related final guidance for industry outlining trial design related to the study of depot buprenorphine products. The buprenorphine product guidance was issued in February 2019.

Trial Design Recommendations around OUD

The final guidance addresses issues in selecting study populations, particularly advising when patients with current opioid use are and are not appropriate for inclusion, and specifies when different trial designs are best employed. FDA encourages researchers to evaluate outcomes such as overall mortality and overdose mortality, the need for emergency medical intervention, and Hepatitis C infection or reinfection. The document also details how changes in drug use patterns can be evaluated and used as endpoints.

Expanded Endpoints for OUD Outcomes Research

In addition, the guidance encourages developers to go beyond using just a reduction of drug-taking behavior as an endpoint, and to look at outcome measures that are important to clinicians, patients, patients’ families, and communities.

Obtaining reports from patients and family members for determining the most concerning symptoms of OUD are also recommended. Specifically, FDA suggests developing a patient-reported outcome instrument to evaluate such changes as improvement in sleep or mood, and says a similar instrument could also be useful in measuring the intensity of the urge to use drugs. The guidance offers specific suggestions for developing patient-reported outcome instruments, such as determining what magnitude of change in a given patient-reported outcome represents a clinical benefit and how long that change must be maintained to sustain that benefit.

Other outcome measures are discussed as well. These include a reduction in hospitalizations, an increase in the ability to return to work, school, or other activities. FDA acknowledges that evaluation of these outcomes will likely require larger trials than ones typically submitted for market approval. However, the agency does encourage collection of this data, pointing out that “using these outcomes as clinical trial endpoints could provide the basis for inclusion in the FDA-approved labeling.”

The guideline states, however, that “retention in treatment is not recommended as a stand-alone endpoint. Many features of trial design can produce incentives to remain in treatment without accruing clinical benefit.”4 Should novel endpoints be used in drug development trials, the agency strongly encourages developers to discuss these plans early in the process of drug development.

The guidance also advises that when selecting endpoints to support efficacy of a particular therapy, developers give due consideration to the risk-benefit equation. If there is a serious risk of adverse events or potential for abuse, demonstrations of benefit will have to be compelling.

Overall, while the pandemic is creating many challenges to treating patients with opioid addiction, this new guidance for OUD drug development offers hope for better treatments to come.

Last updated on: December 11, 2020
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