The FDA, in partnership with the American Association for Cancer Research (AACR), held a workshop on February 13, 2019 in Wardman Park, Washington D.C. to examine the under-representation of African Americans in multiple myeloma trials.1
“To address disparities in cancer care, it is important to consider the entire scope of clinical development,” Lola A. Fashoyin-Aje, MD, MPH, acting deputy director of the Division of Oncology 3 at the Office of Oncologic Diseases, said in a press release.2 “Our hope is that incorporating these recommendations early and throughout clinical development programs will lead to better outcomes for African American patients with multiple myeloma and other populations traditionally underrepresented in clinical trials.”
Recommendations were given by 3 separate working groups on how to better obtain data on racial and ethnic minorities in order to better inform the FDA’s assessment of safety and efficacy prior to the approval of new therapeutic treatments for multiple myeloma, understand the effectiveness and safety of therapies in racial and ethnic minorities, and utilize real-world data to inherently understand the outcomes.
Some of the recommendations provided by the working groups, which consisted of physicians, researchers, and industry professionals, included:
- Researchers should develop principles for promoting diversity and promote adherence to those principles through clinical trial “registration.” This could be done by:
- Setting concrete targets for trial enrollment based on disease epidemiology incidence and current evidence that addresses biological and cultural barriers.
- Considering review or publication incentives for adhering to principles.
- Sharing examples of strategies that helped to meet target enrollment.
- Study plans should include proposals for how appropriate populations will be included in trials and how these targets will be met, with the goal of the trial populations being representative of disease incidence from an early stage.
- Researchers should prespecify what subgroup analyses should be performed and the endpoints which will be assessed. To carry this out, the group suggested:
- Potentially ask for modeling on the effects of having more or fewer patients than expected for a given subgroup.
- Explore potential alternative endpoints, including minimal residual disease.
- Trials should be designed around the type and stage of disease, and subtypes most commonly seen in African Americans. For example:
- Study the genetics of multiple myeloma patients, exploring potential variables that affect differences in outcome.
- Pursue safety signals detected in African American patients or other subpopulations as thoroughly as possible.
- Collect and analyze PK/PD data and pursue signals in subpopulations to the extent that is reasonable.
- Trials should reflect U.S. clinical practice, or standard-of-care.
- Phase II and phase III clinical trials should involve a diversity officer to help design the trial and recruitment strategies, including predetermined goals for representativeness and inclusion. This role should be defined, and training should be offered to sponsors and investigators on what would constitute a qualified diversity officer.
- Grant funding should be provided that is specifically dedicated to studying subpopulation signals.
- Researchers should consider the prioritization of the inclusion of African American patients over global patients with African ancestry.
- Investigators and referring physicians should be better educated on cultural competence, and the importance of community engagement should be further stressed.
Craig E. Cole, MD, from the Michigan State University Breslin Cancer Center, who presented the first set of recommendations, added, “Editors and reviewers for papers should demand change and demand ethnicity in enrollment criteria for their papers and the idea was that if editors and reviewers demanded change, then the researchers will have to follow, so I think that’s an important point.”
Notably, Fashoyin-Aje specified that “the FDA does not have the regulatory or statutory authority to require that sponsors include demographic subgroups as participants in clinical trials.”
1. FDA-AACR Workshop to Examine Under-representation of African Americans in Multiple Myeloma Clinical Trials. Held Feb. 13, 2020. Wardman Park, Washington D.C.
2. FDA-AACR Workshop to Address Multiple Myeloma Clinical Trial Disparities [news release]. AACR. Published February 4, 2020. aacr.org/professionals/blog/fda-aacr-workshop-to-address-multiple-myeloma-clinical-trial-disparities/. Accessed February 13, 2020.