FDORA and the Diversity Action Plan Requirement – Are You Prepared?

The U.S. Congress recently took action to improve diversity in clinical trials by requiring clinical trial sponsors of most drug and device studies to submit a Diversity Action Plan to the U.S. Food and Drug Administration (FDA). This requirement is a result of the Food and Drug Omnibus Reform Act (FDORA) that will apply to clinical trials that begin enrollment 180 days after the FDA finalizes its guidance on this topic.

Diversity in trials is critical because different people may have different reactions to the same treatment based on their age, gender, weight, race, ethnicity, and other factors. Since clinical trials rely on volunteers to take part, including people from diverse backgrounds can show if the treatments are safe and work well for people from all different communities.

It has taken a while for the industry to arrive at this point, so let’s look back and review how we got here.

A Brief History

In 2013, the FDA published a report on the demographic makeup of clinical trial patients that participated in pivotal trials. The report showed what many in the industry and academia already suspected – participation by racial and ethnic underrepresented populations and socially disadvantaged groups were lacking.

Since then, FDA released the “FDA Action Plan to Enhance the Collection and Availability of Demographic Subgroup Data,” and in 2016, FDA declared that year to be the “Year of Clinical Trials Diversity,” and released two guidance documents. The following year, Congress enacted the FDA Reauthorization Act of 2017 that required FDA to publish a guidance to the industry to enhance diversity in clinical trials. That guidance was finalized in 2020. In April 2022, FDA issued a draft guidance recommending sponsors to develop Diversity Action Plans to improve enrollment of racial and ethnic populations in clinical trials, which brings us up to date.

Now, under FDORA, such plans are a requirement for most drug and device studies. But there is still some ambiguity as to what should be included in the Diversity Action Plans, when and how the plans should be submitted, and best practices for patient engagement and advocacy. In this blog post, we will provide our observations and recommendations to propel your Diversity Action Plan forward.

Strategic Diversity Action Plan Components

The FDA guidance documents define a diverse population “to include all populations as defined by demographic factors such as race, ethnicity, sex, gender identity, age, socioeconomic status, disability, pregnancy status, lactation status, and co-morbidity.”

Improving racial and ethnic diversity in clinical trials can support early access to medical discoveries and innovations and improve the generalizability of results, fostering an understanding of the disease or medical product under study, and the safety and efficacy profile of medical products for patients.

The April 2022 draft guidance provides sponsors with a framework of the elements to include in their Diversity action plan. The sponsor is asked to include:

• Overview of the disease or condition
• Description of the development program inclusive but not limited to how the trial or study may address inclusion of underrepresented minority and ethnic populations
• Goals for enrollment
• Strategic operational plan for enrollment including site feasibility, community engagement, and study design optimization

FDORA provides sponsors conditions to request a waiver for submission of the Diversity Action plan. Conditions, for example, include:

• Prevalence or incidence of the condition makes it impractical to operationalize the clinical trial
• Demographic limitations of the patient population are affected by the relevant disease

Critical Timing Considerations and Communication with the FDA

Compared to the diverse population definition above, the April 2022 guidance focuses specifically on racial and ethnic demographic characteristics of study populations, recognizing broader issues regarding health disparities and health inequities and the differential experience these populations have within the social determinants of health, such as access to healthcare, housing, green space, food resources, and employment. 

The FDA will evaluate the Diversity Action Plan as an important part of the sponsor’s development program, so sponsors should define enrollment goals for underrepresented racial and ethnic participants as early as possible during clinical development. Sponsors may discuss their enrollment strategy with the FDA at any time throughout the medical product’s development.

There are some key considerations regarding planning, timing, and FDA communications as sponsors are developing their trial and study strategies.

• For drugs, sponsors should include their plan in their Investigational New Drug (IND) application as part of a milestone meeting package or on its own. Sponsors should discuss the plan as soon as practicable during drug development, which can be as early as Phase 1 and Phase 2, but no later than when a sponsor is seeking feedback regarding the applicable pivotal trial(s) for the drug, often during the end of Phase 2 (EOP2) meeting to inform the design of the Phase 3 trial.
  • If a waiver for the Diversity Action Plan is requested, this timeframe allows sponsors to discuss the likelihood of receiving a waiver or provides adequate time for the sponsor to adapt if the waiver is rejected.
• For devices, sponsors should submit their plan as part of the investigational plan included in their Investigational Device Exemption (IDE) application. To discuss a proposed enrollment strategy before submitting the plan with the IDE or for clinical studies not conducted under an IDE, a sponsor should follow the Q-submission process for obtaining feedback or requesting a meeting with the FDA. Q-submissions are feedback mechanisms used by submitters to request FDA feedback about medical device submissions; these mechanisms could be in the form of a written response or a meeting depending on the request that is made by the submitter.

In summary, it is critical to ensure early interaction with the FDA regarding Diversity Action Plans to allow adequate time to adapt and pivot throughout clinical development.

Patient Engagement and Advocacy Recommendations

To build a comprehensive assessment of a product during development, the recent FDA guidance has focused on ensuring the needs and perspectives of the patients. While the definition and exact details of patient engagement may differ, the key aspect of building trust between patients, their families and caretakers, and the healthcare providers have been a justifiable key focus as of late.

The benefits of increased patient engagement have led to instances of improved patient outcomes, faster recruitment, and even reduced time from first-patient-in (FIH) to product launch.

To aid this increased level of patient engagement, the recent FDA guidance has focused on how sponsors may collect data on the patient experience and incorporate such findings into their clinical trials. FDA has encouraged sponsors to collect data from patients regarding the signs and symptoms, how it affects their day-to-day functioning and quality of life, their experience with the treatments, and how the patient views the outcomes of the treatment and disease, among other pieces of data. Sponsors can then use this data with established clinical outcome assessments or develop their own clinical outcome assessments to design patient-driven clinical study endpoints that more truly reflect the patient experience with a disease and the potential benefit of the sponsor product.

Sponsors must be aware; however, patient-driven data and endpoints are no different than the standard clinical trial data. The data can be skewed by the population they are engaging. A comprehensive patient engagement can only be collected if sponsors consider the factors that affect the disparities in their study demographics and how that may relate to patient engagement. Factors including socioeconomic status, prohibitive study costs, geographical location, patient trust, and the study’s inclusion and exclusion criteria, in addition to criteria such race, ethnicity, sex, and gender identity.

Conclusion

Sponsors must understand their patient population’s socioeconomic status and social determinant factors and their impact on all members of their patient population to ensure equal access to the study. By interacting with all patients to ensure the study population truly reflects the real world disease demographics, sponsors are doing their part to create patient-driven endpoints that will benefit a real-world population.

Learn more about how Halloran Subject Matter Experts can help your organization with Diversity Action Plan development, clinical trial protocol design, patient engagement strategies, and Health Authority interactions and meetings.