Clinical trials are the critical steppingstone for drugs or medical devices to become available for use by health care practitioners.  These products must be thoroughly tested in humans for safety and efficacy before approval by the FDA in the United States (1).  Most other countries have similar processes. It can be a long process.

Beyond gender and age, humans are obviously of different racial or ethnic backgrounds. There are differences in health-related behaviors as well as socioeconomic and educational experiences.  In a nutshell, people are different from each other in many ways.  In clinical practice, “one shoe SHOULD not fit all” in most practice.

Unfortunately, for many years clinical trials were conducted with a more homogeneous population of subjects that did not represent the patients targeted by the experimental drug or treatment.  As a struggling young graduate student, I participated in several of these studies. Typically, test subjects were healthy younger White males with no bad habits!  Women and children were generally excluded from trials, as were smokers and others who met a long list of “criteria for exclusion”.  Some of the logic was that you cannot work around female hormonal cycles and who wants to try and do “controlled experiments” with children or people with a variety of “bad habits” or other complicating health conditions.  As a result, study subjects represented a relatively homogeneous population, but the resulting data from the studies led to conclusions and clinical treatments applied to a wide spectrum patient population.  For example. drugs or devices tested in healthy young White males were later used in older Black females who had complex underlying conditions.  A recent study has shown that the commonly used pulse oximetry device that is placed in a fingertip to determine the level of oxygen carried in the blood does not detect a hypoxic condition in Blacks and this leads to a dangerous underestimate of the patient’s health (2). Fortunately, this situation is continuing to change, though slowly (3).

Early sets of Guidelines regarding gender, age and racial subgroups were published by the FDA almost 25 years ago (4, 5).  Slightly more recently, a revised set of Guidelines was developed in 2003 (6) but those guidelines were somewhat controversial. At that time, the FDA used the race and ethnicity categories established by the Office of Management and Budget (OMB).  This allowed only five categories of race based on skin color and/or country of origin and two categories for ethnicity (7). It is well established that the Asian American and Pacific Islander (AAPI) as well as the Hispanic and Latin American populations are incredibly diverse within those groups (8, 9).  It also has been shown that there is as much or more genetic diversity within groups compared to between groups (10).  The most recent set of Guidelines was released in April 2022 (11).  These Guidelines recognize the longstanding obstacles to increasing diversity in such trials.

“Barriers to participation among racial and ethnic groups may include mistrust of the clinical research system due to historical abuses, aspects of the trial design such as inadequate recruitment and retention efforts, frequency of study visits, time and resource constraints for participants, transportation and participation conflicting with caregiver or family responsibilities. In addition, language and cultural differences, health literacy, religion, limited access within the health care system and a lack of awareness and knowledge about what a clinical trial is and what it means to participate may impact clinical trial participation among racial and ethnic minority populations. (11)”

Despite these barriers, the FDA, NIH, universities and pharmaceutical companies are making concerted efforts to increase participation and inclusion of, and data collection from, diverse populations in clinical trials (12, 13, 14, 15).  The outcome from a major multistakeholder conference (FDA, NIH, clinicians, pharma and device representatives, community organizations, patient advocacy groups, etc.) resulted in proposed “actionable steps to support a lasting change. (16)” The most important among these are community engagement of underrepresented groups, use of digital tools, and improving diversity among clinical investigators and research staff.  That document is publicly available and very worth reading!

References

  1. NIH Clinical Research Trials and You:  The Basics | National Institutes of Health (NIH)
  2. Racial bias in pulse oximetry (April 2022):  Racial Bias in Pulse Oximetry Measurement Among Patients About to Undergo Extracorporeal Membrane Oxygenation in 2019-2020: A Retrospective Cohort Study – ScienceDirect
  3. Nature Comment on Clinical Trial Diversity: When will clinical trials finally reflect diversity? (nature.com)
  4. FDA Guidance for collecting data regarding gender, age and ethnicity (September 8 1995): 95-22297.pdf (govinfo.gov)
  5. FDA Guidance on collecting data regarding gender, age and racial subgroups (February 11, 1998): 98-3422.pdf (govinfo.gov)
  6. FDA Draft Guidance for data collection by race and ethnicity (January 2003): Federal Register :: Draft Guidance for Industry on the Collection of Race and Ethnicity Data in Clinical Trials for FDA Regulated Products; Availability
  7. Science Policy Forum on FDA and Diversity policy (July 2003): science.1087004.pdf
  8. AAPI diversity: Understanding Diversity Within AAPI: Disaggregating Data and Other Inclusive Practices – Paradigm (paradigmiq.com)
  9. Hispanic and Latino diversity: Facts about U.S. Latinos and their diverse origins | Pew Research Center
  10. NIH Genetics: Genetic Similarities Within and Between Human Populations – PMC (nih.gov)
  11. FDA Press Release on new guidance for diversity in clinical trials (April 13, 2022): FDA Takes Important Steps to Increase Racial and Ethnic Diversity in Clinical Trials | FDA
  12. NIH Diversity policy and plan: Diversity & Inclusion in Clinical Trials (nih.gov)
  13. FDA Draft Guidance document (April 2022) Diversity Plans to Improve Enrollment of Participants From Underrepresented Racial and Ethnic Populations in Clinical Trials; Draft Guidance for Industry; Availability (fda.gov)
  14. Pfizer diversity plan: Doing Better: Increasing Diversity in Clinical Trials | Pfizer
  15. PhRMA diversity initiative: Clinical Trial Diversity (phrma.org)
  16. Outcome plan from multistakeholder conference (FDA, NIH, clinicians, pharma and device representatives, community organizations, advocacy groups, etc.: Inclusion and diversity in clinical trials: Actionable steps to drive lasting change – ScienceDirect