The Consequences of Underrepresentation in Clinical Trial Design


A representative sample patient population that accurately reflects the overall population is vital to establish the safety and efficacy of a drug.

Image credit: Pixel-Shot |

Image credit: Pixel-Shot |

Clinical trials are opportunities to advance how we diagnose, treat, and prevent disease, as well as to advance medicine and improve public health, patient care, and individuals’ quality of life. But with opportunity comes responsibility, an area in which the clinical research industry has historically fallen short. As a result, we are being forced to confront the detrimental impact of lack of inclusion in clinical trials, and that impact is multi-faceted. Let’s take a closer look.

Inclusion: An ethnical obligation

We have an ethical obligation to include underrepresented minorities and other marginalized patient populations in our studies. It is impossible to ever know the safety and efficacy of a drug for ALL unless it is tested in a representative sample patient population – one that is truly reflective of the overall population. We must place intentional focus on inclusion of those most affected by respective diseases and indications, ensuring alignment with disease prevalence data. This is not the case in our industry’s current model.

To have drug options prescribed with unknown safety profiles to patient populations that were excluded from the study of that medication goes against everything that healthcare stands for. As clinical research professionals, it is our responsibility to protect our patients from ambiguity and bias. Through this lens, without true inclusion in clinical trials, we are failing the very patients we intend to serve.

Excluding select groups of patients, whether intentionally or unintentionally, may lead to unrecognized risks. The truth is that if we are not actively working to include patients of all demographics, we are actively excluding certain populations.

Without representative clinical trial participants, we will continually fail to obtain representative results. The consequence? Increased potential for risk or harm to patients.

By not including key populations in trials, our industry will continue to come up short time and time again. Studies show that from 2000 to 2020, more than 50% of trials registered on lacked any racial/ethnic enrollment data, with only “modest” improvement in minority representation over time.1

Additionally, while nearly one in four people in the United States have a disability of some kind, the research reveals that close to 75% of clinical trials still exclude individuals with intellectual and developmental disabilities.2 Certainly, lack of reporting is contributing to the imbalance of representation we see today, but social determinants and lack of access to clinical trial opportunities are also at play.

Disease prevalence data exists; we must start using it. Leaning into accessible racial and ethnic data sources early can empower us to refine inclusion and exclusion criteria to meet the needs of our patient populations more accurately.3

We have statisticians who can tell us (with a data-backed level of certainty) who is most affected by specific diseases, and how those individuals are responding (or not) to certain therapies. In spaces and indications where this information is available, why is it not being leveraged to advance our work? And in spaces where it is not, why aren’t we pushing one another to figure it out?

I believe it is our collective responsibility to act, and to do so now. As an entire industry, we must course-correct or else risk further perpetuating the massive inequalities already plaguing the clinical research space and our healthcare system.

Making the case for pursuing diverse trial enrollment and expanding eligibility requirements

Some argue that inclusive enrollment may be harder to achieve in Phase I/II or rare disease trials. While this is true, the case for pursuing inclusive enrollment and expanding eligibility requirements in all clinical trials is extensive, and it starts with extending our reach. And while addressing later stage studies may produce the most immediate results, we cannot lose sight of the relevance of improving representation in all phases and across all indications.

The reality is that we need new investigators, we need new sites, and we need new geographic reach to bring in new patient populations. Currently, only 3% of physicians and patients in the United States participate in clinical research, according to the National Institutes of Health.4

We must increase access first and foremost. Increasing access will inherently increase inclusion. To deliver clinical trial opportunities to underrepresented and geographically isolated populations, we must meet these patients where they are, and understand the vital role providers play in connecting these patient populations to research opportunities.5

In addition to expanding our reach, it is vital that we rethink enrollment criteria to achieve representative results. While it is known that we need early phase “healthy” patient volunteers to help establish a baseline for safety and efficacy profiles, I believe it is equally necessary that we work to determine safety and efficacy in more “complex” patient populations by opening some of our inclusion criteria to involve patients with more intricate medical histories.

The truth is that unfortunately, very few of us, if any, live with only one health comorbidity or diagnosis. We are all extremely complex individuals, and our health challenges are no exception.

If treatments are only studied on the “healthiest” patient populations, what does that mean for the rest of us? What if we are in a much more advanced stage of disease progression? What if we also struggle with complications from a second condition? What if we are the ones who need help most of all?

Eligibility requirements, and diverse trial enrollment, I believe, are no exception to inclusion as an ethical obligation. New legislation is helping to drive change,6 but increased diversity requires collective action.


Here are just three places you might start:

  • Improve trial enrollment through targeted community engagement and collaboration with trusted community-based partnerships.7
  • Prioritize expanding accessibility by addressing social determinants of health and supporting both emerging and experienced investigators.8
  • Evaluate ways to expand study design and inclusion criteria to increase diversity, such as by leveraging disease prevalence data early and often throughout protocol design.9

Clinical research is complex, and often overwhelming for patients. It has become increasingly clear that delivering clinical trial opportunities to patients through their trusted physician or established medical team can be the most impactful factor influencing their decision to participate. We must hold each other accountable as an industry to ensure we do not miss key opportunities to expand access and maximize inclusion.

Start anywhere; but start today.

About the Author

Ashley Moultrie, Director of DEI and Community Engagement, Javara Research.


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