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Clinical trial success hinges on a medical intervention’s ability to provide clinical benefit to all populations it is intended to serve. With that being said, diversity in studies is not just a matter of fairness; it's a critical factor in ensuring that medical research yields universally applicable and effective results.
At the end of June, the US Food & Drug Administration (FDA) released an updated draft guidance for ensuring diversity in clinical trials. More specifically, sponsors must now submit Diversity Action Plans for certain clinical trials.
Diversity Action Plans aim to increase participation from individuals of historically underrepresented groups in efforts to strengthen study data pertaining to an intervention’s ability to effectively treat its intended population. For clinical trials that necessitate a Diversity Action Plan, these requirements will take effect for studies in which enrollment will begin after 180 days from the publication of the finalized FDA guidance, which is currently to be determined.
Including a broad range of participants in clinical trials—spanning different races, ethnicities, ages, genders, and socioeconomic backgrounds—helps researchers understand how various factors influence health outcomes. This diversity is essential for identifying differences in how diseases manifest and respond to treatment across different groups. It also helps in recognizing potential side effects that might disproportionately affect specific populations.
A lack of diversity in clinical trials can lead to gaps in knowledge and ineffective treatments for underrepresented groups, perpetuating health disparities. Recruiting a clinical trial cohort that reflects the demographics (i.e. age, race, comorbidities, etc.) of the population an intervention aims to treat is crucial in ensuring the product is safe and effective for its intended use population in real-world practice. Therefore, prioritizing inclusivity in research propels healthcare systems to be more equitable and effective in providing better health outcomes for all.
Certain drugs and medical devices will require a Diversity Action Plan. Although sponsors must submit a Diversity Action Plan for clinical trials as outlined below, the FDA highly encourages sponsors to create and execute a thorough diversity strategy throughout a drug or device’s entire clinical development program, including the initial studies whenever feasible.
A Diversity Action Plan will be necessary for Phase III studies for a new drug or pivotal studies for drugs already on the market (other than those measuring bioavailability or bioequivalence).
Devices will need to include a Diversity Action Plan in their Investigational Device Exemption (IDE) applications. This exemption is required for studies that intend to use a significant risk (SR) device, studies that involve an exception from informed consent, or if the FDA simply states that an IDE is necessary for clinical investigation.
A Diversity Action Plan will also be necessary for any device where an IDE application to the FDA is not obligatory, except for those noted in 21 CFR 812.2(c), and should be relayed to the FDA in any premarket notification, request for device classification, or application for premarket approval.
Various types of clinical studies may be conducted during the premarket process, each representing different stages of development and testing. With that, the FDA will only review Diversity Action Plans for trials that are designed to collect concrete evidence surrounding a device’s safety and efficacy for its specified application. Therefore, some supporting trials may not require a plan in place.
The FDA’s guidance on this matter is not limited to clinical trials executed solely in the US – it spans to trials operating internationally as well. Studies operating in the US and other countries must have an all-encompassing Diversity Action Plan that accounts for overall study goals in both the US and all other countries in which research will take place.
During initial study planning, sponsors should take into account whether demographics such as age, race, sex, and more affect the efficacy and safety of the therapy under investigation.
The content of a Diversity Action Plan must include the following from sponsors:
As a rule of thumb, enrollment goals should be outlined based on the estimated incidence or prevalence of a medical condition in the US. For some trials, it may be beneficial to boost proportional enrollment of a specific population to accurately capture outcomes or other clinically significant factors relevant to that group. Sponsors should leverage resources such as patient registries, epidemiological surveys, and published literature to gain insights on the incidence and prevalence of a medical condition within certain demographic groups.
Some clinical development trials may involve several studies to obtain market approval that may all necessitate Diversity Action Plans. Sponsors must then note enrollment goals for each individual trial, how each trial fits into the clinical development program for a particular drug or device, and how each trial will produce the necessary data that reflects the demographic characteristics of the relevant population, based on how common the disease is in different groups.
Some indications, such as those that fall under the umbrella of rare diseases, may only warrant a small pivotal clinical study, where representative populations for each demographic group may be small. The FDA recognizes that small cohorts may not accurately detect differences in safety and efficacy, however they note these cases may present opportunities for future research.
Sponsors must also provide rationale for all enrollment goals outlined in a Diversity Action Plan. Rationale should include:
Diversity Action Plans for drugs should highlight any potential clinically relevant differences in pharmacokinetics or pharmacodynamics across different demographic groups. For devices, the rationale should describe any data on how a device may potentially impact safety and efficacy differently in the populations being studied. Sponsors should note specific characteristics (i.e. geographic location, socioeconomic status, comorbidities, etc.) that may impact clinical outcomes for a specific population as part of this rationale.
Lastly, Diversity Action Plans must detail how the enrollment goals described aim to be met. Sponsors should explain enrollment and retention strategies, and any individualized efforts based on unique demographic characteristics of a population being researched. In its draft guidance, the FDA suggests collaboration with healthcare providers and patients to strategize recruitment and retention tactics.
Some examples can include providing cultural competency and proficiency resources for research teams to more effectively work with participants, offering language assistance to enhance awareness among non-English speaking individuals, adopting a decentralized study model or consolidating study activities into as little in-person visits as possible to reduce participant burden related to travel and time commitment, and more.
While sponsors may communicate their Diversity Action Plans with the FDA at any time throughout clinical development, they must submit their plans for certain trials according to specified timelines.
The Diversity Action Plan for a trial should be submitted to the FDA no later than the date the study protocol is submitted. The FDA can review and give feedback on the Diversity Action Plan more effectively when it is discussed along with the trial design, study population, and other clinical study details. Therefore, the FDA suggests submitting the Diversity Action Plan when seeking feedback on the clinical study for the drug, typically towards the end of a Phase II trial.
Devices that mandate an IDE application must include the Diversity Action Plan upon submission of the IDE application. For studies where an IDE application is not needed, the Diversity Action Plan should be submitted alongside a 510(k) premarket notification, premarket approval (PMA) application, or De Novo classification request.
The FDA's latest draft guidance on diversity in clinical trials marks a significant step forward in ensuring that medical research is inclusive and representative of all populations. By requiring Diversity Action Plans, the FDA aims to enhance the quality and applicability of clinical trial data, ultimately leading to more effective and equitable healthcare solutions.
This guidance underscores the critical importance of including diverse demographic groups in clinical research, addressing long-standing health disparities, and ensuring that new medical interventions are safe and effective for everyone. By setting clear expectations for sponsors to create comprehensive diversity strategies, the FDA is promoting a more inclusive approach to clinical development that benefits patients across different backgrounds and communities.
Lindus Health prioritizes accurate representation among participants in clinical trials so sponsors can ensure their therapies are safe and effective for all they are intended for. Book a meeting with our team to learn more about how we enhance diversity with tailored recruitment and retention strategies for each trial we work on.
