BIPOC Underrepresented in Ketamine Clinical Trials

Black, Indigenous and People of Color Found to Be Underrepresented in Ketamine Clinical Trials

July commemorated National Minority Mental Health Awareness Month,^[1] first designated in May 2008 by the U.S. House of Representatives. The resolution was sponsored by Rep. Albert Wynn [D-MD] and co-sponsored by a large bipartisan group with its main goals to improve access to mental health treatment and promote public awareness to the unique struggles faced by racial and ethnic minority communities regarding mental illness.

Black, Indigenous and People of Color (BIPOC) experience rates of mental health disorders equal to or greater than non-Hispanic Whites, yet lack access to therapies and are underrepresented in emerging clinical research. One burgeoning area of research relates to psychedelic compounds for the treatment of mental health disorders such as depression, post-traumatic stress disorder (PTSD) and addiction. While not a traditional psychedelic, ketamine also is being studied and used for the treatment of these disorders. Although approved as an anesthetic for human use, ketamine produces a dissociative effect when administered at sub-anesthetic doses and has been associated with positive outcomes in the treatment of mental health conditions. In 2019, the U.S. Food and Drug Administration (FDA) approved an isomer of ketamine ― esketamine ― for the use along with an antidepressant in the treatment of depression. While there are many clinical studies investigating ketamine and psychedelics for the treatment of mental health disorders, the inclusion of the BIPOC population in these studies is noteworthy. Biological differences in ethnic populations may affect how a drug works in the body, including the safety and efficacy of these therapies. BIPOC already experience health disparities and access to mental health treatments, making it all the more important to ensure BIPOC populations are included in clinical studies.

A recent publication by Michaels et al.^[2] puts a spotlight on the underrepresentation of BIPOC in clinical trials. In this study, published July 19, 2022 in the Journal of Studies on Alcohol and Drugs, the authors conducted a systematic review of clinical trials investigating the use of ketamine in the treatment of mood disorders conducted in the U.S. between 1993 and 2019. This starting date is significant, as the National Institutes of Health (NIH) Revitalization Act became effective in 1993, requiring that women and minorities be included in NIH-funded research. The Act also required a valid analysis of whether the variables being studied affect women or members of minority groups differently than other trial participants.

Michaels et al. identified clinical trial studies conducted in the U.S. and published in peer-reviewed journals investigating the efficacy of ketamine in the treatment of mood disorders. The inclusion criteria for this review were limited to randomized, double-blind, placebo-controlled trial design studies, the gold standard for studying the effectiveness of an intervention. The authors then dissected these studies further to determine whether the study included and disclosed the ethnic makeup of the trial participants. In some cases, trial investigators were contacted where demographics data were missing. Some clinical trial investors did not respond and others reported that ethnicity data were not collected. Of the 972 clinical trials identified that received NIH funding, only 31 studies met the criteria for inclusion; 21 of which did not disclose ethnicity. The 10 studies that did disclose ethnicity of study participants were included in the final quantitative analysis. The small sample size presents a limitation for a robust qualitative analyses and interpretation of the study results, which the authors acknowledge. Given that the NIH Revitalization Act mandated racial inclusion, it is surprising how few of these studies disclosed ethnicity data. In the words of Michaels and colleagues, “[i]t is amazing that such studies could receive funding and have results published in peer-reviewed journals without being required to disclose the racial makeup of study participants.”^[3]

The results of the Michaels et al. study revealed that out of a combined total of 380 participants in these 10 studies, 73.7% of the participants were non-Hispanic White, 9.2% were Black, 5.0% were Hispanic/Latinx, 0.8% were Asian. Ethnicity data were not reported for 36 (9.5%) of these participants and 12 (3.2%) participants identified their race as “other.” Michaels and colleagues compared this to the 2010 U.S. Census demographic of the population: non-Hispanic White (63.7%), Blacks (12.6%), Hispanics/Latinx (16.3%) and Asians (4.8%). BIPOC clinical trial participants were significantly underrepresented in comparison. This underrepresentation remains when compared to the 2021 Census data: non-Hispanic White (60.1%), Blacks (13.4%), Hispanics/Latinx (18.5%) and Asians (5.9%).

Looking at the data, the obvious question arises: why do clinical trials, in this case for the treatment of mental health disorders using ketamine, continuously underrepresent the BIPOC population? Although the study by Michaels et al. does not provide a definitive answer, the authors suggest that implicit biases in the recruitment process can exclude racial minorities, and the location of study sites can raise access to transportation if studies are conducted in predominantly White communities. To counter those biases, the authors suggest that better community outreach and communication may improve BIPOC recruitment and retention in clinical trials, as well as allaying fears of participation in research in light of historic atrocities committed against BIPOC in the name of research. In short, efforts should be made to reduce the barriers to research participation for BIPOC and underrepresented populations.

In a move to increase diversity in clinical trials, the FDA has taken a leading role in promoting greater diversity and inclusion in clinical trials, most recently in its April 2022 draft guidance, Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Populations in Clinical Trials; Draft Guidance for Industry</em>; Availability (“2022 Draft Guidance”).^[4] It recommends that sponsors of drugs and medical devices develop and provide a Race and Ethnicity Diversity Plan to enroll more participants in clinical trials from underrepresented racial and ethnic populations in the U.S. when submitting investigational new drug (IND) applications for drugs and biologics. The NIH already mandates inclusion of BIPOC in clinical trials it supports when applying for grants. The push from the FDA to develop and submit a diversity plan may serve as a bookend on the approval side of the equation to motivate study investigators to increase diversity in clinical research.

While the recent publication by Michaels et al. shines a spotlight on the enrollment disparities among BIPOC for ketamine clinical trials, this same group also has previously published that a similar lack of diversity occurs in clinical studies related to the use of psychedelics for the treatment of mental health disorders.^[5] To fully realize the promise of psychedelic therapy for mental health conditions, industry, patient and community organizations, medical providers, policymakers and regulators should work together to address the existing challenges of racial and ethnic inequities in psychedelics research.

George Hajduczok, J.D., Ph.D., F.A.H.A., is special counsel at Phillips Lytle LLP and a member of the firm’s Psychedelics & Mental Health Therapies Practice Team. He can be reached at (716) 504-5772 or ghajduczok@phillipslytle.com.

Kyle W. Mack, J.D., Pharm.D., is special counsel at Phillips Lytle LLP and co-leader of the firm’s Psychedelics & Mental Health Therapies Practice Team. He can be reached at 716-847-7068 or kmack@phillipslytle.com.