December 4, 2023
We appreciate the opportunity to comment on the FDA’s proposed guidance regarding: “Stimulant Use Disorders: Developing Drugs for Treatment; Draft Guidance for Industry.”
The National Center for Health Research (NCHR) is a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. we do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.
Since no medical treatments are currently approved by the FDA for the treatment of stimulant use disorders, it is especially important that the FDA require well designed studies based on best practices for the development of treatments for substance use disorders. Randomized, double-blind controlled trials that evaluate meaningful clinical benefits are the standard that should be applied to ensure internal validity and mitigate any bias. For that reason, we do not support the lower standards typical for accelerated approval or breakthrough pathways.
Lines 152-159 recommends the study population for such trials should include individuals whose primary problem is stimulant use disorder. we agree. Moreover, the research should evaluate subpopulations based on which stimulant is being abused and the route of drug use. NCHR strongly recommends that the populations being studied should be diverse and generalizable to the intended patient population. this should include demographic traits such as age and race as well as diversity of comorbid conditions, especially since stimulants may cause cardiovascular issues and other comorbidities. studies investigate subpopulations based on the stimulants of interest (cocaine, methamphetamines, etc.). If the study participants do not include sufficient numbers of these subgroups, the drugs should only be approved for the specific types of stimulants that the patients in the study misused.
NCHR also recommends that the study endpoints use a validated quality-of-life questionnaire specific to substance-use disorders. This would provide insight into the impact of treatment on cravings, risk of relapse and non-completion of treatment, lifestyle factors, and psychosocial factors. In addition, trial designs should include a 30-day metric of study compliance or retention rate, since challenges often arise in the first few days to weeks of treatment for substance use disorders. Since relapse is a normal part of recovery and substance use treatment, using it as a metric of treatment success may be misleading. therefore, a more nuanced metric is needed that also evaluates other metrics such as length of relapse and length of continuation or discontinuation with treatment after a relapse.
In conclusion, any future trials on the treatment of stimulant use disorder should be made on a diverse patient population that accounts for differences in substance use, route of delivery, age, race, and comorbid conditions. Treatment of any substance use disorder is complex, and for that reason, study endpoints should utilize a holistic measure that considers the multitude of factors that go into rehabilitation from a substance use disorder. Such parameters help to ensure that future treatments for stimulant use disorder are safe and effective for use in its intended target population.