A new report from the National Academy of Medicine (NAM)-part of the National Academy of Sciences-highlights the pressing need to include more minority and female participants in clinical trials. The National Institutes of Health (NIH) requested and sponsored the report, titled "Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups." NAM held a webinar to release findings of the new report.
For the last 30 years, progress has "largely stalled" in inclusion of underrepresented Americans in clinical trials, said report committee chair Kirsten Bibbins-Domingo, PhD, MD, MAS, Professor and Chair of the Department of Epidemiology and Biostatistics; the Lee Goldman, MD Endowed Professor of Medicine; and the inaugural Vice Dean for Population Health and Health Equity at the University of California at San Francisco School of Medicine. She said improving diversity in clinical trial participants is "urgent," and that "purposeful and deliberate change is needed." What needs to happen, she noted, is a paradigm shift which moves the balance of power from the institution and puts the priorities, interests, and voices of the community at the center.
Bibbins-Domingo said that this lack of representation in clinical trials compromises the generalizability of research findings to the U.S. population; costs billions of dollars in terms of life-years lost; may hinder innovation in research and development of new therapies; may compound the low accrual that causes many clinical trials to fail; can lead to lack of access to effective medical interventions for groups of patients; can undermine the trust of Americans in the U.S. research enterprise; and compounds existing U.S. health disparities laid bare by the pandemic.
She believes the report's findings apply broadly to different minority populations, noting that, while women now represent more than 50 percent of clinical trial participants, they are overwhelmingly White.
As previously reported by Oncology Times, cancer organizations are taking specific steps to ensure that cancer clinical trials reflect more diversity. On May 19, 2022, the American Society of Clinical Oncology (ASCO) and the Association of Community Cancer Centers (ACCC) published online a joint research statement addressing the need to increase racial and ethnic diversity in cancer clinical trials (J Clin Oncol 2022; doi: 10.1200/JCO.22.00754). That joint statement recommends better access to clinical trials; equity-focused trial designs; partnerships among stakeholder groups; continuous education and training; specific investment in equity, diversity and inclusion; and the sharing of data and strategies.
"This report is all about heterogeneity in clinical trial responses," said NAM committee member Dana Goldman, PhD, of the new NAM report on the need for a more diverse representation in U.S. trial participants. Goldman is Dean of the Sol Price School of Public Policy; C. Erwin and Ione L. Piper Chair; and Leonard D. Schaeffer Director's Chair at the Schaeffer Center for Health Policy and Economics at the University of Southern California. He said the NAM committee used the Future Elderly Model to value how chronic conditions differentially affect the lives of older Americans in terms of life expectancy. The model examined non-Hispanic Black females and males; Hispanic females and males; and non-Hispanic females.
The model examined three common chronic conditions: diabetes, heart disease, and hypertension. Goldman said use of this model showed that eliminating disparities in these health conditions would increase life expectancy by 1-1.5 years, thus adding billions of dollars in value in terms of life-years saved. He said that even a modest reduction in health disparities equates to billions of dollars. Goldman said U.S. COVID-19 clinical trials demonstrated the need to move quickly during a public health emergency, but he noted these trials also showed that the U.S. lacks the research infrastructure in place to ensure adequate population inclusion and representation in clinical trials.
"You can't be invited [to be a trial participant] if you're not known," said NAM committee member Arleen Brown, MD, PhD, Professor of Medicine at the University of California at Los Angeles (UCLA) and Chief of General Internal Medicine and Health Services Research at UCLA Medical Center. The new NAM report shows that mistrust is not a cause of lack of participation by minority groups in clinical trials. Rather, evidence reveals that Asian, Black, Latinx Americans, and American Indian/Alaska native people are no less likely-and in some cases more likely-to participate in research if asked.
Brown said the coronavirus pandemic forced the U.S. to focus on underrepresented populations, which have too long been overlooked in clinical trials. She noted that barriers to trial participation by minorities include the following:
* engaging underrepresented populations is often not aligned with academic institutional incentives;
* institutional review boards (IRBs) lack incentives for increasing diversity and inclusion;
* community health centers face financial and infrastructure challenges in terms of trial enrollment of minorities;
* sources of research funding are often not focused on achieving health equity; and
* lack of representation of minorities on the editorial boards and publishing staff of medical journals.
Brown said that because the NIH sponsored the new report on diversity, there should be an increased interest in its content.
NAM committee member Amelia Knopf, PhD, MPH, RN, Assistant Professor of Nursing at Indiana University's School of Nursing, agreed with Brown that the coronavirus pandemic has put a spotlight on underrepresented Americans. "Today there is a willingness to recognize racism as a public health problem," she said.
Knopf also noted that achieving better representation in clinical trial enrollees is possible when: an institution makes a commitment to diverse representation; the institution establishes a foundation of trust with trial participants and the community at large; barriers to participation-such as lack of child care and transportation-are anticipated and removed; a flexible approach to recruitment and data collection is established; a robust network is built with all stakeholders; the trial study team is chosen to ensure alignment with research goals; and adequate resources and support have been obtained to achieve diverse representation.
Among the committee's specific recommendations to achieve better diversity and inclusion in clinical trials are the following:
* There is a need to develop increased reporting on who is actually participating in clinical trials. Bibbens-Domingo noted that data collection is "never a sexy thing," but it is necessary. She said the poor collection of data on COVID-19 testing amply demonstrated the need for better reporting.
* To achieve better accountability, the FDA should require study sponsors to submit a detailed recruitment plan no later than at the time of submission of the Investigational New Drug or Investigational New Device application. This plan should explain how the trial population will reflect the demographics on the disease under study as part of the process for FDA approval.
* There should be federal incentives for clinical trials that achieve diversity enrollment goals. Specifically, Congress should direct the FDA to not only enforce existing accountability measures but also to establish a task force to study new incentives for trials proposed in new drug and new device applications that achieve representative enrollment. These might include tax incentives, fast-track criteria and exemption from some FDA drug application fees, and extended market exclusivity.
* The Office of Human Research Protections (OHRP) and the FDA should direct local IRBs to assess and report the representativeness of clinical trials as one measure of sound research design that it requires for the protection of human subjects.
* In grant proposal review, the NIH should formally incorporate consideration of trial enrollee representativeness in the score-driving criteria that assess the scientific integrity and overall impact of a grant proposal.
* Journal editors, publishers, and the International Committee on Medical Journal Editors should require information on the representativeness of trials and studies for submissions to their journals, especially related to the affected population; should consider this information in accepting submissions; and should publish this information for accepted manuscripts.
* There should be remuneration for research participants and their caregivers, and clinical trial participants should receive reimbursement for the routine medical costs of participating in a clinical trial. Remuneration can be controversial since some IRBs might consider it coercion.
* Education, workforce development, and partnerships related to the clinical trial enterprise should be diverse and inclusive.
* The government should place a high priority on investing in the infrastructure of community research centers.
In 2013, the National Academy of Sciences published a report called "Implementing a National Cancer Clinical Trials System for the 21st Century." That report noted that the National Cancer Institute's NCI Community Oncology Research Program has been "promoting the participation of underserved populations and incorporating disparities research questions into clinical trials and cancer care delivery research." But that 2013 report also stated there is a lack of data on how best to enhance research participation and improve health care for underserved communities.
Peggy Eastman is a contributing writer.