The importance of recruiting diverse patients for clinical trials in pharmaceutical development and approval has been highlighted by various stakeholders. Regulatory agencies have been proactive in establishing policies and providing guidelines. These promote practices which support diversity in clinical trials to ensure greater population representation.
An example is the US FDA’s Racial and Ethnic Diversity Plan, hereon referred to as Diversity Plan, which aims to enroll participants from underrepresented racial and ethnic groups in the US like Black or African American, Hispanic/Latino, Indigenous and Native American, Asians, Native Hawaiian and other Pacific Islanders and other persons of color in clinical studies. The guidance document for the Diversity Plan is structured on FDA’s guidance “Collection of Race and Ethnicity Data in Clinical Trials” which provides a standardized approach for collection and presentation of race & ethnicity data in submissions to the FDA and recommends that sponsors produce and submit a plan to address incorporation of clinically relevant population.
Goals of the Diversity Plan
- Enrollment of underrepresented racial and ethnic groups in clinical trials.
- Helps to identify safety and efficacy data among these populations upon using medical products.
- Also include other underrepresented groups defined by demographics like sex, gender, identity, age, socioeconomic status, disability, pregnancy & lactation status, and co-morbidity in their clinical trials.
Clinical trials measure the safety and efficacy of medicinal products and participation in these trials is crucial to ensure the product’s safety and efficacy. Investigational New Drug (IND) holders must incorporate the total number of subjects planned for clinical study and how many of them participated in clinical study. New Drug Applications (NDAs) should also provide safety and efficacy data and determine whether any modifications are needed regarding dose or dose interval in specific subgroups.
The US FDA recommends many ways that help in improving the diversity in clinical trials; indeed diverse populations are characterized by race and ethnicity which are important for evaluating medicinal products with respect to their safety profile. This is attributed to correlations that have been observed between race, ancestry, genetic variations/ethnicity and response. The US FDA recommends addressing certain aspects in helping improve clinical trial diversity including: 1) collection & analysis of racial and ethnic data, 2) steps that improve diversity in clinical trials and 3) expanding the eligibility criteria. Also, sponsors should develop a plan that provides information on the operational steps that will be executed to assure diverse clinical trials participations to improve the development of safety and efficacy data across the whole population i.e., reimbursement, language translations provisions, partnering with community-based entities that support trial/study participants, etc.
Though the US FDA, in its guidance documents, includes all populations based on their age, gender, sex, race, ethnicity, pregnancy & lactation status, and also multiple comorbidities, several people are underrepresented in clinical studies which could lead to an incomplete generation of safety and efficacy data, so FDA makes sure to prioritize them in trials too. Although, FDA is aiming to enhance registration of individuals from underrepresented racial and ethnic groups because underrepresentation of these groups in clinical studies reflects a concern regarding unequal health care access, including access to clinical research centers for new treatments and awareness regarding clinical trials. The US FDA also says that children from racial and ethnic minority backgrounds should also be included in clinicals studies where studies are designed for pediatrics populations. To speed up the development and approval process of medicinal products, especially for rare diseases and serious and life-threatening conditions, there has been an increase in dependency on small studies, intermediate endpoints, and innovative study design.
When is a Diversity Plan recommended?
FDA advises sponsors to submit a Diversity Plan for medical products for which an IND submission is required, and/or for clinical studies that are to support a BLA, or under 505(b)(1) or 505(b)(2) for an NDA. A plan is also advised for medical products for which an IDE submission is required and/or for which clinical studies are intended.to support a 510(k), PMA, De Novo classification request, or HDE application (for devices).
What is the procedure for submitting a Diversity Plan?
- Drugs: submission of Diversity Plan to the IND application from sponsors at the earliest but much before than when a sponsor wishes to seek feedback on the applicable pivotal trials for those that occur at the End of Phase 2 (EOP2) meeting.
- Medical Devices: FDA recommends sponsors to submit their Diversity Plan as part of the investigational plan contained IDE application. Sponsors need to use the Q-submission process to get feedback or request a meeting with FDA about their plan for enrolling participants in clinical study of a medical device.
- IND, IDE, or Q submissions containing a plan, sponsors must make aware the FDA by writing “RACE AND ETHNICITY DIVERSITY PLAN” in large and bold letter.
Sponsors must include the Diversity Plan including the description of successes and challenges related to its implementation in the product’s marketing application.
What should a Diversity Plan contain?
In accordance with the draft document, a Diversity Plan should address the following:
- Enrollment goals for underrepresented racial and ethnic participants for each indication as early as possible in clinical development.
- For drug, the collection of pharmacokinetics, pharmacodynamic, and pharmacogenomic data from diverse populations, and for medical devices, data on factors for device performance, like phenotypic, anatomical, or biological need to be collected.
- The plan should address how the sponsor will evaluate safety and efficacy of medical products on race and ethnicity, as well as those factors which are not the part of the study but can influence the outcome of the study.
- The plan should define the study design features if the data obtained signifies that the medicinal products may act differentially among the population. FDA identifies that the enrollment based on only epidemiology may not be enough to observe any differences in safety and efficacy of the medical products.
- The plan must define the sponsors plan to gather the data to investigate if there’s any possibility for differences in safety and efficacy throughout the medical product development lifecycle.
- The race and ethnicity diversity plan should also include pediatric studies.
The plan should include:
- Summary of the disease or condition:
- Detailed data on pathophysiology of disease/conditions in underrepresented racial and ethnic groups.
- Analyzing the current scenario in any similarities or differences in the disease/conditions that are related with the underrepresented racial and ethnic groups.
- Scope of medical product development program:
- Study design and population, endpoints, geographic locations of the trials.
- Synopsis of PK, PD, and pharmacogenomics data.
- Goals for enrollment of underrepresented racial and ethnic participants:
- Define goals, but in some cases, an increased number of populations may need to demonstrate the potential important differences.
- Specific plan of action to enroll and retain diverse participants:
- Explaining steps to enroll and retain underrepresented participants.
- Site location & access, sustained community engagement and lessened the burden due to study trials.
- Status of meeting enrollment goals:
- The sponsor should discuss the status of enrollment goals as the FDA updates the diversity plan. The sponsor should discuss a plan and reason for collection of data in the post marketing setting.
Conclusion
The racial and ethnic diversity plan aims to enroll participants from underrepresented racial and ethnic populations in clinical studies. The generation of safety and efficacy data, PK, PD, and pharmacogenomics data from clinical trials helps to study the effect of medical products in these populations. Inclusion of these populations in clinical trials helps to study the diseases, medical products and also opens the door to access health care system.
References and Further Reading
- US FDA. Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Populations in Clinical Trials. United States Food and Drug Administration. 2022
- US FDA. Collection of Race and Ethnicity in Clinical Trials. United States Food and Drug Administration. 2016