The new article describes in detail the applicability scope and also outlines specific considerations for certain groups of patients that require special attention in order to ensure they are properly represented among study participants.
Table of content
The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a draft guidance document dedicated to Diversity Action Plans to improve the enrolment of participants from underrepresented populations in clinical studies. Once finalized, the document will provide information about the applicable regulatory requirements, as well as additional clarifications and recommendations to be taken into consideration by the parties responsible for clinical trials.
At the same time, provisions of the guidance are non-binding in their legal nature, nor are they intended to introduce new rules or impose new obligations. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the existing legal framework and has been agreed with the authority in advance.
Clinical Studies Requiring Diversity Action Plans
Under sections 505(z) and 520(g)(9) of the FD&C Act, certain clinical studies related to drugs, biological products, and devices are mandated to submit a Diversity Action Plan. This requirement applies to studies under sections 505, 515, 510(k), 513(f)(2), or 520(g) of the FD&C Act, and section 351(a) of the Public Health Service Act.
For instance, for drug studies, a Diversity Action Plan is necessary for phase 3 clinical investigations or other pivotal clinical studies, excluding bioavailability or bioequivalence studies. According to 21 CFR 312.21, phase 3 studies are typically conducted to gather additional information on the effectiveness and safety of a drug, which is critical for regulatory approval.
For device studies, sponsors must include a Diversity Action Plan in their Investigational Device Exemption (IDE) application. This requirement applies if the sponsor plans to use a significant risk (SR) device, as defined in 21 CFR 812.3(m), in an investigation, intends to conduct a study with an exception from informed consent under 21 CFR 50.24, or if FDA mandates an IDE application.
For devices not requiring an IDE application, except those studied under 21 CFR 812.2(c), section 520(g)(9)(A)(ii) requires sponsors to develop a Diversity Action Plan for any clinical study related to the device. These plans must be submitted with any premarket notification, request for classification, or premarket approval application under sections 510(k), 513(f)(2), or 515 of the FD&C Act, respectively.
Considerations for Device Studies
As further explained by the FDA, device studies vary in type and purpose throughout the premarket process. Not all device studies necessitate an IDE application; for instance, nonsignificant risk (NSR) studies complying with 21 CFR 812.2(b)(1)(i)-(vii) or studies conducted entirely outside the US without the need for an IDE application.
The FDA also recognizes that a Diversity Action Plan may be less relevant for exploratory stage small studies. However, the FDA expects a Diversity Action Plan for studies intended as the primary basis for evaluating the device’s safety and effectiveness and benefit-risk determination.
The FDA does not require Diversity Action Plans for studies exempt from IDE regulations under 21 CFR 812.2(c), even if they are intended as the primary basis for FDA’s evaluation.
Comprehensive Diversity Strategy
While it is obligatory for sponsors to submit Diversity Action Plans for the specified studies, the FDA strongly advises developing and implementing a diversity strategy across the entire clinical development program, including early-phase studies when feasible. This approach can ensure consistent representation and enhance the overall applicability of the clinical findings.
Sections 505(z) and 520(g)(9) of the FD&C Act necessitate that sponsors’ Diversity Action Plans outline specific enrollment goals disaggregated by race, ethnicity, sex, and age group demographics. These goals should reflect the distribution of the intended use population.
Consideration of Demographic Factors
According to the recommendations provided in the document, sponsors should evaluate whether certain demographic groups, such as older patients, pediatric patients, females, or specific racial or ethnic groups, might exhibit differential responses to the medical product. This consideration could be based on varying effectiveness, safety profiles, differential pharmacokinetics (PK) and pharmacodynamics (PD), or susceptibility to specific adverse events.
In some cases, it may be essential to increase the enrollment proportion of a particular demographic to thoroughly assess outcomes or other clinically relevant factors in that group. In addition to the above, sponsors developing Diversity Action Plans should refer to additional FDA guidance documents for recommendations pertinent to sex and age considerations in clinical study enrollment.
These documents provide detailed instructions and best practices for achieving diverse and representative clinical study populations, thereby enhancing the robustness and generalizability of the study findings.
Conclusion
In summary, the present draft guidance document issued by the FDA is intended to clarify the approach to be followed by the parties responsible for clinical trials in order to ensure the scope of the study covers a wide enough range of patients, ensuring the accuracy and reliability of the results. The document highlights the key points to be taken into consideration when determining whether a Diversity Action Plan is needed for a specific study, as well as other specific aspects pertaining thereto.
How Can RegDesk Help?
RegDesk is an AI-powered Regulatory Information Management System that provides medical device companies with regulatory intelligence for over 120 markets worldwide. It can help you prepare and publish global applications, manage standards, run change assessments, and obtain real-time alerts on regulatory changes through a centralized platform. Global expansion has never been this simple.
