Spaulding Physician/Researcher Shining a Light on Diversity and Inclusion in Clinical Trials
The issue of disparities in healthcare has received significant attention in recent years. Julie K. Silver, MD, physician at Spaulding Rehabilitation Hospital and associate professor/associate chair in the Department of Physical Medicine and Rehabilitation at Harvard Medical School, has been a national leader in bringing to light inequities in clinical trials and advocating for change.
Dr. Silver focuses on three key variables — sex, age, and race/ethnicity — in analyzing clinical trial participants. Whereas social constructs such as race and ethnicity are often influenced by social determinants of health, biologic variables such as sex and age may influence how individuals respond to a medication, for example.
"Older individuals may metabolize a drug differently than younger individuals due to age-related changes from decreased kidney or liver function," Dr. Silver says. "Issues like this can profoundly affect the efficacy of different interventions. If we don't study these different populations because they're not represented in the trials, then we won't understand the risks and benefits [of an intervention]."
Inclusion in Vaccine Trials Lacking
One of the first papers Dr. Silver co-wrote on this topic looked at inclusion in vaccine trials. She and her colleagues examined 230 U.S.-based vaccine trials, with nearly 220,000 participants, from July 2011 to June 2020. They found that people who are Black/African American, American Indian/Alaska Native, Hispanic/Latino, and age 65 and older were the most underrepresented groups. Adult women, in contrast, were overrepresented.
"Although we have some missing data, it is clear from the large number of studies which report this information that people who belong to racial and ethnic minority groups, as well as older individuals, are frequently not equitably represented," Dr. Silver said upon the study's publication in JAMA Network Open in 2021.
The paper has since become one of the top-cited papers on the Web of Science.
Troubling Findings in Blood Donation and Blood Transfusion Trials
So far this year, Dr. Silver has co-authored two more notable papers on diversity among trial participants.
The first of these papers, published in Transfusion and Apheresis Science in February 2023, looked at U.S.-based blood donation and blood transfusion trials. Dr. Silver and her colleagues discovered that despite FDA guidance regarding reporting requirements, researchers frequently failed to report complete demographics of trial participants.
Among the key findings were the following:
- Females were substantially underreported (29%) in blood donation trials, although females and males were equally represented in blood transfusion trials
- Only two of 24 blood transfusion trials that enrolled adults reported participation of individuals ages 65 and older
- Multiple racial and ethnic groups were consistently underrepresented in both types of trials
The study authors called for researchers to explore barriers to participation along with interventions that might guide equitable enrollment in future trials.
"Given the shortages of blood we've been seeing, it's important to understand who the donors are and how the blood supply in the U.S. is affected by the donor population," Dr. Silver says. "This is a critical issue, and one we must address to ensure we have an adequate blood supply for transfusion."
Similar Shortcomings Uncovered in Global Registries
Another study, published in Disability and Rehabilitation in July 2023 with first author Danielle Sarno, MD, a Spaulding Rehabilitation physician who is also in the Department of Neurosurgery at Brigham and Women's Hospital, entailed a comprehensive analysis of eight global registries, including 93 studies.
The researchers systematically characterized patient sex, age, race, and ethnicity in trials for rehabilitation studies worldwide. They uncovered marked differences in reporting in various countries, insufficient participant diversity, and a lack of standardized guidelines for reporting clinical research results.
For example, sex was reported in 61.3% of trials but ranged among registries from 0% to 100%. Participation among female adults showed variability from 0% to 75%. Reporting of age was not uniform, and six of the registries did not include age in all trials. Dr. Silver added that given the variable definitions of race and ethnicity globally, it was unsurprising that information about these factors was absent in most of the trials and registries.
Dr. Silver recommends steps to foster better inclusion of underrepresented groups in rehabilitation trials and beyond. "At the researcher level, there needs to be a greater commitment to reporting the identity characteristics of the participants," she says. "At the journal level, there needs to be an insistence on this type of reporting in the clinical trials they publish."
Clinical Practice Guidelines a Current Area of Focus
Dr. Silver has worked on several similar studies with clinical psychologist Helen Murray, PhD, director of the Gastrointestinal Behavioral Health Program in the Center for Neurointestinal Health at Massachusetts General Hospital, that are aimed at the intersection of physical and psychological health.
Another ongoing priority for Dr. Silver is clinical practice guidelines. "This is a critical issue in the diversity, equity, and inclusion space," she says. "Diversity among guideline authors is important in order to support underrepresented physicians' and scientists' careers, and this may also influence the content, which impacts patient care disparities."