Drug Development Must Meet Complex, Diverse Needs Of The Opioid Use Disorder Community

By Joshua M. Cohen, MD, MPH, FAHS, chief medical officer, Braeburn

With almost 80,000 opioid overdose deaths in 2022, the surge in opioid-related overdoses and deaths in the United States has continued at a relentless pace, further heightened by impacts from the COVID-19 pandemic and the increased presence of fentanyl.^1,2 According to research published this spring, three in 10 people in the U.S. say they personally know someone affected by opioid use disorder and, of that group, more than half know someone who has died as a result.³ The ripple effects of this disease can be seen and felt by people of all ages and backgrounds across the country, yet deep-rooted societal stigma remains the greatest barrier to countering one of the most devastating public health catastrophes of our time.

Despite its prevalence, many people — including some healthcare providers — do not recognize opioid use disorder (OUD) as a chronic and treatable relapsing brain disease.^4,5 OUD involves functional changes to brain circuits that may last even after a person has stopped using opioids.⁶ Like those living with other chronic diseases, such as diabetes or heart disease, many people with OUD benefit from treatment with medication for varying lengths of time, sometimes lifelong.⁷ Currently, there are three types of medication approved by the FDA for the treatment of OUD: buprenorphine, methadone, and naltrexone. When used in combination with counseling and other psychosocial support, all three have been shown to be safe and effective in helping people manage withdrawal symptoms, reduce illicit opioid use, and stay in treatment.⁸ Given that all of these medications work differently and are available in different settings, the right medication will vary for each person. With the availability of more options and flexible approaches to treatment, more patients will be able to begin their journey to recovery.

The Path Forward Requires New Discoveries, More Options

Presently, OUD treatment engagement levels are unacceptably low — less than 15% of those with OUD in the U.S. are receiving treatment.⁹ More OUD research and widespread drug development are required to address this profound public health crisis and help the tens of millions of people in the U.S. who suffer with OUD or who are currently in recovery. In order to do so, scientists and pharmaceutical companies must embrace community collaboration and champion innovation for the patients who need these treatment options the most.

Patient-centric approaches are critical, but not exclusive, to this space. The lessons and considerations below can be applied to other disease areas as well to ultimately improve the way our industry approaches research, development, and commercialization. No matter what disease space we work in, we need to meet patients where they are, hear their perspectives about the impacts of their disease on daily life, understand their experiences using and accessing treatments, and deliver options that will support them on the path to positive treatment outcomes.

Designing Clinical Trials With Participants In Mind From The Start

Given the complexities of the OUD landscape, it’s no surprise that the clinical development process for medications for OUD (MOUD) requires an especially thoughtful approach. Beyond the familiar challenges associated with drug development — including rising costs of clinical trials, a complex regulatory environment, long-term safety, and intellectual property protection — companies seeking to bring MOUDs to market must have a deep understanding of the needs of this diverse patient community. Being purposeful with trial design at the front end and maintaining consistent contact with the patient community and regulatory bodies throughout significantly impacts the ability to reach and support patients.

Generally speaking, the population participating in a clinical study should mirror the population impacted by the disease. When it comes to enrollment for MOUD, ensuring diverse representation is critical. Clinical trial sites must become partners in the community to achieve this, and there are some fairly straightforward steps that can be taken to support them in doing so. For example, having patient consent forms and informational materials in multiple languages and establishing diverse participant criteria, including thresholds of non-white participants, in the protocol are essential. Likewise, early and ongoing communication between clinical trial sites, advocacy organizations, and community groups can build patient trust and provide insights and resources to help reach enrollment goals. The more steps that can be taken up front, the greater the likelihood of achieving diverse clinical trials that are truly representative of the patient population.

Geography is another consideration that can be a barrier to diverse representation in clinical trials.¹⁰ In the OUD space and beyond, many clinical trials are executed at large research centers and academic institutions, which are often in larger urban areas, primarily situated in the Northeastern and Western U.S.¹¹ Clinical research also can be offered by specialists in smaller areas to address issues of access and opportunity and, when possible, home or virtual visits should be considered to replace site appointments. For many people living with OUD, transportation is necessary to access treatment centers conducting studies, so having reliable transportation to a clinical trial site may pose a challenge as well.⁷ Arranging round-trip ride services or offering reimbursement for transportation and parking can alleviate stress and remove logistical challenges, (e.g., finding parking, relying on a care partner, taking time off work, costs) and make trial participation possible for more patients, while increasing the likelihood of  long-term patient engagement and retention. By removing geographical barriers, we can help ensure more people living with OUD will have the opportunity to take part in clinical trials, thereby increasing participant diversity.

Once patients are enrolled, it is important to maintain their participation for the duration of the trial. As with other substance use disorder studies, there is typically a higher dropout rate seen in clinical trials for OUD than with other diseases. This happens for a variety of reasons, including lack of stability in social, employment, or living situations, legal problems, or difficulty pursuing and sustaining recovery in the face of substance dependence. Fear of social stigma and concerns about confidentiality may also serve as barriers.¹² When retention issues occur, additional patients must be recruited in order to reach the thresholds necessary to establish the safety and efficacy profile of the treatment being studied, resulting in financial drain, costly delays, and the loss of valuable data that can significantly impact the discovery of useful treatment options— but, most importantly, it can result in potential risk to the patient who is no longer receiving the care within the clinical trial.^12,13 Motivating patients to continue participation by ensuring proper communication, explaining the importance of their participation, and making sure they know they are heard, safe, appreciated, and taken care of should always be priorities to help improve the experience and retain clinical trial participants.¹³ It’s important to listen and understand the needs of the patient community you are researching in order to establish a participant-friendly environment. This may mean offering flexible appointment times, taking extra steps to ensure confidence in confidentiality, providing more frequent touchpoints, and providing appropriate compensation for visits, such as reimbursing participants for their travel and time, when possible.¹² Strategies should be adapted to address the specific circumstances and experiences of each and every patient population.

Another unique consideration for trials involving people with OUD is the use of placebos in study designs where a standard of care exists. People with OUD are at a higher risk of overdose, which can be life-threatening.⁴ Head-to-head studies can be extremely challenging, but understanding the efficacy of the product being studied, along with its comparative efficacy versus the standard of care is hugely powerful. It is critical to assess the risks to patients and collaborate closely with regulatory bodies to create and execute a clinical trial program that will secure the results needed to establish the efficacy and safety profile of a product, while also making sure that study participants are being protected as much as possible. Careful study design and thoughtful identification of endpoints directly impact the ability to navigate the regulatory review and approval process and, ultimately, bring much-needed treatment options to patients who need them.

Authenticity And Collaboration Are Key

In the fight to end opioid and substance use disorders, a single drug will not have the power to offer the full solution. Pharmaceutical companies must be effective partners with the recovery community. We must be bold and willing to take risks that are rooted in our learnings from patients, healthcare professionals, and others in the industry. I have learned that in the substance use disorder space, and in the pharmaceutical industry more broadly, organizations may all have different strengths. Some excel with early-stage research, with scientists who are doing great research with new and existing molecules, while others have infrastructure that supports late-stage clinical development and commercialization. By working together and capitalizing on each company’s strengths, we can continue the advancement of discoveries, development, and delivery of treatments that ultimately serve patients.

We cannot lose sight of the fact that every participant involved in a clinical trial has their own personal circumstances and complex needs — and these human needs must remain the driving force throughout the drug development process. Beyond medication, effective treatment for OUD often requires a comprehensive approach to address the physical, psychological, and social aspects of addiction.⁸

Patients need faster and more innovative research and, with their participation, can contribute significantly to clinical trials that are designed to meet their unique, unmet needs and priorities. By involving patients early in the research process, they can help solve more than just clinical challenges. They can share their real-world experience on patient preferences and patient-relevant outcomes, such as the need for flexible dosing and treatment, and the burden of disease on everyday life and mental well-being, which can inform clinical trial design and help meaningfully address the holistic needs of those living with the disease. Additionally, providing counseling and psychosocial support throughout the clinical trial process is a necessary component of a complete plan to support treatment adherence and help people change how they think, cope, react, and acquire the skills and confidence necessary for recovery.

By expanding access to treatment, people living with OUD may have a chance to more effectively manage this chronic brain disease and begin their journey to long-term recovery.⁴

References:

1. Ahmad FB, Cisewski JA, Rossen LM, Sutton P. Provisional drug overdose death counts. National Center for Health Statistics. 2023.
2. Tanz LJ, Dinwiddie AT, Snodgrass S, O’Donnell J, Mattson CL, Davis NL. A qualitative assessment of circumstances surrounding drug overdose deaths during the early stages of the COVID-19 pandemic. SUDORS Data Brief, No 2. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services; 2022.
3. Zipp R. 3 in 10 Americans Say They Know Someone Affected by Opioid Addiction Amid Surge in U.S. Drug Overdose Deaths. Morning Consult. May 2, 2023. Available at: https://pro.morningconsult.com/trend-setters/opioid-addiction-overdose-data-stats.
4. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Sciences Policy; Committee on Medication-Assisted Treatment for Opioid Use Disorder; Mancher M, Leshner AI, editors. Medications for Opioid Use Disorder Save Lives. Washington (DC): National Academies Press (US); 2019 Mar 30. 5, Barriers to Broader Use of Medications to Treat Opioid Use Disorder. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541389/.
5. Substance Abuse and Mental Health Services Administration. The Facts About Buprenorphine for Treatment of Opioid Addiction. Available from: https://store.samhsa.gov/sites/default/files/d7/priv/sma14-4442.pdf.
6. NIDA. 2020, July 13. Drug Misuse and Addiction. Available from https://nida.nih.gov/publications/drugs-brains-behavior-science-addiction/drug-misuse-addiction.
7. Substance Abuse and Mental Health Services Administration. Medications for Opioid Use Disorder. Treatment Improvement Protocol (TIP) Series 63 Publication No. PEP21-02-01-002. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2021. https://store.samhsa.gov/sites/default/files/SAMHSA_Digital_Download/PEP21-02-01-002.pdf.
8. Substance Abuse and Mental Health Services Administration. Medications for Substance Use Disorders. Available from: https://www.samhsa.gov/medications-substance-use-disorders.
9. Krawczyk N, Rivera BD, Jent V, Keyes KM, Jones CM, Cerdá M. Has the treatment gap for opioid use disorder narrowed in the U.S.?: A yearly assessment from 2010 to 2019". Int J Drug Policy. 2022;110:103786. doi:10.1016/j.drugpo.2022.103786.
10. Feyman Y, Provenzano F, David FS. Disparities in Clinical Trial Access Across U.S. Urban Areas. JAMA Netw Open. 2020;3(2):e200172. doi:10.1001/jamanetworkopen.2020.0172.
11. Seidler EM, Heshaviah A, Brown  C,  et al. Geographic distribution of clinical trials may lead to inequities in access. Clin Investig. 2014;4(4):376-380. doi:10.4155/cli.14.2110.4155/cli.14.21.
12. Zweben A, Fucito LM, O'Malley SS. Effective Strategies for Maintaining Research Participation in Clinical Trials. Drug Inf J. 2009;43(4):10.1177/009286150904300411. doi:10.1177/00928615090430041.
13. Svendsen, T.S., Veseth, M., McKay, J.R. et al. Securing Participant Engagement in Longitudinal Substance Use Disorder Recovery Research: A Qualitative Exploration of Key Retention Factors. J. Psychosoc. Rehabil. Ment. Health 8, 247–259 (2021). https://doi.org/10.1007/s40737-021-00222-y

About The Author:

Joshua M. Cohen, MD, MPH, FAHS is the chief medical officer at Braeburn. He completed board certification in neurology and headache medicine. He was chosen as a Super Doctors 2013 and 2014 New York Rising Stars™ and was selected as a Castle Connolly America’s Top Doctors™ in 2015.

Josh completed undergraduate training at Harvard University, medical school at the New York University School of Medicine, and neurology residency at Columbia University’s Neurological Institute. At the Columbia Mailman School of Public Health, he received his Master of Public Health, and he completed his headache fellowship at The Headache Institute. Prior to Braeburn, Josh served as the global medical therapeutic area lead for migraine & headache at Teva, where he provided dynamic leadership for the global launches, leading a matrix team of medical directors, scientific communications, health economics and outcomes research, and other global and regional functions.