IKCS 2021: Health Equity in Clinical Trials

(UroToday.com) In one of the first sessions of the 2021 International Kidney Cancer Symposium (IKCS): North America meeting focusing on multimodality perspectives on clinical trials, Dr. Lola Fashoyin-Aje presented on the critical issue of health equity in clinical trials.

She began by providing an overview of demographic representation in cancer trials. Over 7 years of clinical trials comprising more than 23,000 patients, racial minority participants are underrepresented in clinical trials compared to both the overall population, and particularly compared to those with disease.


She further emphasized that most trials (98%) that form the basis for medication approval in the United States are conducted internationally. Patients accrued from the US typically account for about one quarter of trial populations, and sometimes this is less common. Considering geographic representation, she highlighted that patients from Africa, South America, and Asia are relatively under-represented.

In addition to the importance of diversity defined by demographic factors (race, ethnicity, age, sex, and others), she highlighted the importance of diversity according to clinical characteristics. The goal of each of these is to increase the variability in the study population, evaluating differential drug responses across the heterogeneity of the population.

The benefit of diversity in clinical trials stretches to a patient benefit from accessing potentially promising drugs earlier. Further, clinical trials may provide a novel treatment option in some diseases and novel treatment options that may not be otherwise available. Further, once approved, having a diverse trial population strengthens the generalizability and external validity of the study results. Additionally, a diverse study population allows for the understanding of pharmacokinetic and safety profiles across many patient subgroups.

Dr. Fashoyin-Aje then highlighted many factors which contribute to the under-representation of certain groups in clinical trials. Many of these relate to access barriers. These may be due to societal barriers which include social determinants of health and bias. These factors may particularly affect minorities, patients at the extremes of age, and LGBTQ+ patients. The clinical research ecosystem may create further barriers to care requiring patients to be treated at major academic centers to participate. Further, global disparities contribute to barriers in access. Beyond these larger, system issues, there may be trial or protocol specific factors including eligibility criteria and the trial procedures which contribute to under-representation.

To address these issues, the Oncology Center of Excellence has a number of programmatic areas including patient and community engagement, policy development and implementation (including guidances, broadening of eligibility criteria, drug development considerations, and the use of alternative data sources such as “real-world data”), and research. These areas are manifest through projects involved in engagement and outreach including Project Community, Project Equity, and Project Facilitate. These allow the office to be flexible and nimble in addressing barriers to community involvement in clinical trials. Project Facilitate works to allow access to treatments with expanded access approval which may be difficult for many patients from under-represented groups.


The office is also involved in ongoing work with ASCO and Friends of Cancer Research to modernize eligibility criteria to expand access to trials for many patients. This work stems from issues related to overly restrictive eligibility criteria, including major protocol-level barriers to patient enrollment which are typically not based on a scientific or clinical rationale. These barriers and strict criteria limit the heterogeneity of the included patient population and reduce the generalizability of the results.

Broadening eligibility has numerous benefits including providing early access to the agent to the population, faster trial accrual, increased generalizability of results, and earlier identification of ineffective results. However, there is a risk that higher heterogeneity of the study population may lead to difficulties interpreting results or that more frequent assessment may be required.

To this end, there have been a number of guidances from the FDA, specifically addressing cancer clinical trial eligibility criteria relating to organ dysfunction, prior or concurrent malignancy, brain metastasis, age considerations, and infection with HIV, Hepatitis B, and Hepatitis C. Additionally, the Oncology Center of Excellence has worked to develop a framework for disease specific eligibility criteria which may allow for more consistency between trials in a given disease space.

She further highlighted that the COVID-19 pandemic has afforded an opportunity to examine how we can reduce trial burden. One key component of this is increasing the flexibility of study assessment and the decentralization of study procedures. To this end, we can leverage technology to allow for remote assessments and electronic consent. Further, there are opportunities to streamline data collection.

While the majority of the presentation focused on clinical trial design, she further highlighted the important role of observational real-world data. These are critical for characterizing the epidemiology of a disease, evaluating the feasibility of conducting a trial, evaluating whether a trial may yield results that would be applicable or generalizable to the population of interest, assessing outcomes of interest (eg. safety or the need for dose modification), and to identify potential trial participants (a registry-based trial enrollment).

In closing, Dr. Fashoyin-Aje highlighted the present disparities in clinical trial participation. Addressing these offers the opportunity to provide treatment to our patients earlier and generate better data to inform the safe and effective use of new treatments across the entire population. A prospective and intentional strategy is necessary to ensure diverse representation in clinical research, including specific goals across the spectrum of clinical research, a multi-disciplinary perspective, and integration into the research program.

Presented by: Lola Fashoyin-Aje, Deputy Division Director, US Food and Drug Administration (FDA)