Background

Despite widespread understanding and acknowledgement of diversity shortcomings among clinical trials, persistent difficulties exist. This issue is highlighted in the Food and Drug Administration’s 2022 Centre for Drug Evaluation and Research’s (CDER’s) Drug Trials Snapshots Summary Report. The approved therapies span a wide range of medical conditions including ones that largely affect paediatric patients, diseases affecting only males or only females, common diseases that affect a large proportion of the population in the United States, and rare (or orphan) diseases with a smaller number of patients in the United States and around the world. Given the varied diseases being targeted, including in men’s and women’s health issues, looking at patient populations by individual drug or therapeutic area gives the clearest insight into patient diversity in clinical trials specific to a disease, rather than summary statistics of all approved therapies combined.

The CDER drug Trial Snapshot summary report sanctioned 37 new therapies that cater to a wide array of diseases. The success can be attributed to the significant contribution made by more than 27,000 patients who participated in key studies that were instrumental in these approvals. This yearly report provides a comprehensive summary of demographic data from the different populations studied.

Of great significance in the report are nine innovative therapies approved for the treatment of 10 prevalent diseases in the U.S. The information about these approvals is sourced from publicly accessible FDA reviews. It’s important to note that all the decisive trials backing each of these highlighted approvals were multinational.
In the programs where patient numbers were reported by country, the proportion of patients from the U.S. varied from 8% to 69%. While, for programs reporting the number of study locations by country, the U.S. accounted for 29% to 55% of all sites. It is also significant to highlight that, in diseases impacting both sexes, the percentage of females evaluated varied from 25% to 68%. This annual report continues to offer invaluable insights into the field of science and medicine.

In the majority of crucial trials endorsing 37 new therapies, the predominant demographic was White patients. This was then followed by Asian and Black patients. Some programs, however, had significant admissions of Asian patients – notably Lytgobi (29%), Spevigo (55%), Ztalmy (45%), Imjudo (49%), and Omlonti (33%). Similarly, Black patients represented a notable proportion in programs such as Omlonti (19%), Vivjoa (17%), and Sunlenca (38%).

Understanding the prevalence within racial subgroups for these diseases and identifying factors that led to greater inclusion of these two racial categories in these clinical trials may guide strategies in other therapeutic areas with lower representation from key demographic groups. Nevertheless, the racial categories of Native American or Alaska Native, and Native Hawaiian or Pacific Islander have overall representation that remains low.

Nonetheless, in the five critical trials that led to the approval of a new diabetes drug (Mounjaro), 25% and 11% of the patients enlisted were from the Native American or Alaska Native race group. Historically, this racial group typically accounts for a mere 1–3% of trial participants in diabetes drug testing programs. A deeper inspection of the Mounjaro program could uncover strategies that can boost the enrolment of patients from this racial group in future trials.

Key Points

In the draft guidance for diversity plans, outlined in April 2022, the FDA advises that industry sponsors should create a comprehensive diversity plan. This plan should be included in the investigational new drug (IND) application before or concurrently with the time sponsors request feedback from the agency. This feedback usually pertains to the key trials for the drug, frequently in the End of Phase 2 (EOP2) meeting.

Specifically, it’s crucial for sponsors to set target levels for the enrolment of underrepresented racial and ethnic participants as early as feasibly possible during the course of clinical development for a particular indication. This should be based partly on the predetermined protocol objectives.

In terms of timing, sponsors are advised to engage with the Agency regarding their plan at their earliest convenience during the medical product development process. This should occur at the very latest when the sponsor is seeking FDA feedback concerning the suggested pivotal trials, these are typically phase 3 trials.
Furthermore, Food and Drug Omnibus Reform Act (FDORA) of 2022 illustrate what is expected of sponsors to prospectively plan to increase diversity in clinical trials, and it also outlines many additional requirements to increase accountability of both sponsors and the Agency.

Summary

Addressing the death of diversity in clinical trials to conform to the Diversity Plan stipulations outlined in the FDORA regulations, it is crucial for pharmaceutical firms and leading researchers to allocate suitable resources towards studies incorporating diverse groups. Here are some strategies to achieve this:

• Employing researchers and staff from diverse backgrounds enhances cultural understanding when dealing with patients and their families, helping eliminate unconscious or implicit bias.
• Atypical locations should be utilized for patient recruitment.
• It is essential to expand the eligibility criteria and circumvent unnecessary exclusions that affect specific communities in clinical trials.
• Enhancing transparency, involving study participants throughout the medication development process for informed trial design, endpoint selection, and results communication is crucial.
• Continuous engagement with the patient community is imperative to foster trust.
• Demonstrating the commitment of sponsors and researchers to better health outcomes for patients, irrespective of their background, needs clear communication.

The establishment of FDORA’s regulations reflects the organization’s dedication to guaranteeing all pertinent patient groups, regardless of their race, sex, or ethnicity, are included in clinical trials. The aim is to assess the safety and effectiveness of therapies. This is a significant advance towards the realization of genuinely representative clinical trials.

List of References

For a copy of the FDA draft guidance document please click here FDA Draft Guidance – Diversity Plans to Improve Enrolment of Participants from Underrepresented Racial & Ethnic Populations in Clinical Trials

For more information on our Regulatory Consulting and Compliance Services please click here https://www.spgl.eu/services/regulatory-consulting-compliance