Operationalizing A Diversity Action Plan That Makes An Impact

By Devra Densmore, founder and principal consultant, Elevate Advocacy

Although creating an ecosystem of support for a diversity action plan (DAP) is a critical first step, it is paramount that the plan drive representation within clinical research by its operationalization. No amount of infrastructure can fix a plan that is not a clear map detailing how a sponsor and its partners will attempt to reach articulated enrollment goals that align with epidemiology and the disproportional impact some populations experience within that disease state. Therefore, every DAP should use the following statement from the revised guidance to influence its development, measurement, and improvement and every program team should anchor to this standard.

A DAP is "[i]ntended to increase enrollment of participants who are members of historically underrepresented populations in clinical studies to help improve the strength and generalizability of the evidence for the intended use population."

If your DAP is not being written or executed in service of the objective to improve the strength and generalizability of your product’s evidence for the intended use population, then your DAP and your study will fail to meet the FDA’s expectations and your program may be at risk.

After The Ecosystem Of Support Is Established

Once a study sponsor has the environment and infrastructure in place in which its program can thrive, the cross-functional team will need to assess if and how a DAP can support the success of its studies. The following are the key considerations and questions to explore before the program team drafts at DAP.

1. Assessing if a DAP is required (this is also part of the ecosystem)

• Does your company plan to commercialize the investigational product in the U.S.? If yes, a DAP will most likely be required.
• Will enrollment for your Phase 3 or pivotal study commence at any time 180 days after the FDA finalizes the guidance? A conservative timeline for the requirement could be as early as March 27, 2025. If yes, a DAP will most likely be required.

As a program team considers these questions, it is important to remember that DAP waivers, while available, will be the exception, even in cases of rare disease studies. Discussions with the FDA about the possibility of a waiver should start as early as possible and with the assumption that your program will most likely not be granted one.

2. Integrating the program team to collectively write the DAP (this is also part of the ecosystem)

• Ideally, the program team will begin this step before Phase 3 or pivotal study so that they can design earlier-phase studies to collect vital data (e.g., PK/PD and safety data) from the same historically underrepresented groups critical for later-stage studies.
• If your program team is already in the process of designing its Phase 3 or pivotal study, it will need to look back on the data it has to assess whether there are gaps in data, and if the program can confidently move forward without that data or if it will need to conduct another study to collect missing data.

It is critical when assessing what data is available and what data is missing to remember what the guidance says: "Sponsors should consider whether certain groups (older patients, pediatric patients) may have a different response to the product due to differential presentation of the disease or condition.” To best assess, program teams would be wise to use the following points and evaluate risk exposure.

Do you have:

• PK/PD data that is representative?
• Safety data that is representative?
• Strong epidemiological data about the patient population in the United States (and globally if you will be conducting a global study)?
• Have you exhausted the different public and non-public data sources to defend your population assumptions (including claims data, registries, patient advocacy group mapping, and literature reviews)?

If you have not met the above thresholds, it is imperative to assess whether the absence of that data exposes the program to vulnerability when defending the strength and generalizability of the product’s evidence.

3. Assessing your resources

Have you appropriately budgeted for:

• Community engagement before your study start (this includes identifying and collaborating with community partners)?
• Study materials and collateral to be influenced by patient insights and co-developed with advocacy and community groups (advisory boards, sponsorships)?
• Community education initiatives co-developed with advocacy and community groups, including disease state education, company awareness, and the importance of clinical research?

It is important to remember that building relationships in communities that have been historically underrepresented in research requires an appropriate amount of time – sometimes years. Without realistic expectations that are supported by appropriate staff and budget, community and patient engagement will be slow, costly, and ineffective.

4. Assessing your partners

Have you selected partners to help:

• Determine the best sites to improve enrollment?
• Engage community members via in-person and digital campaigns to reach communities that are historically underrepresented in research?
• Develop patient-facing, site-facing, and HCP-facing information, materials, tools, and platforms that empower CROs, sites, and others to fulfill the DAP?
• Conduct training (if needed)?
• Lessen burden on sites and patients?

A sponsor must be vigilant in identifying partners that can adroitly execute a DAP. To help evaluate potential partners, sponsors may wish to develop criteria specific to community engagement. Potential criteria could include:

• Does the vendor/partner have experience with community engagement and DAP planning and implementation? Can they share case studies or client and community testimonials?
• Is the vendor/partner owned and operated by members of historically underrepresented communities, particularly those communities the sponsor wishes to engage?

Assuming that previous partners can successfully parlay traditional recruitment and retention practices into community engagement in historically underrepresented communities is flawed. Different communities have different mores and ways of engaging, which require bespoke plans. Any vendor that cannot demonstrate actual community engagement with specific examples should be viewed skeptically Not finding the right partners to support DAP implementation may require a sponsor to seek another vendor to rescue a study that has not been appropriately targeted and focused. Much like other rescue interventions, these are costly and often require new and extended timelines and budgets. Moreover, seeking a rescue is often entirely preventable if vendor selection has been based on proven successes.

Inclusive Programs Yield Successful DAPs

The FDA has demonstrated a preference for patient-focused drug development, and sponsors would do well to incorporate that same philosophy into the DAP process. Therefore, as a DAP is being conceptualized, program teams should assess whether other areas of trial design are patient-focused to ensure no unintended negative consequences create barriers to DAP execution. Key considerations and questions include:

1. Has your study design been reviewed by patients living with that condition who are from historically underrepresented populations —assessing if the number of site visits, mode of administration, formulation, procedures, patient-reported outcomes (PROs), questionnaires, and other key requirements make sense for potential trial participants? Not doing this exposes the study to risks that may make a DAP harder or impossible to successfully execute, because the study may require participants to do things (or have things done to them) that are too difficult, burdensome, or scary.

2. Have your inclusion and exclusion (I/E) criteria been evaluated by both KOLs and patients to determine if they may create barriers to participation for patients who may have more comorbid conditions, yet who may be a significant portion of the generalizable intended use population? If your program believes that including patients with comorbid conditions may bias or weaken your evidence, a clear rationale as to why these decisions were made must be collected and a narrative created. This will be important for both the FDA and other key stakeholders, including payors, patients, and providers. Not doing so may put study enrollment at risk, should the most disproportionately impacted patient community, the very one a sponsor may wish to engage, be eliminated from consideration because there is a high likelihood that many, most, or all people within that community would have that condition or situation.

3. Has your informed consent form (ICF) been reviewed by patients living with the condition from underrepresented populations (both trial naïve and trial savvy) to ensure the ICF is written in a way that is understandable to people who are considering volunteering for the study and anyone they may share the document with (including family, friends, personal doctor, or community leaders)? Not doing so exposes the study to risks, because people who are not familiar with clinical research, and who may have a history of medical traumas or mistrust, could find the trial’s requirements too confusing or perceive the study as unsafe and not engage.

Writing Impactful DAPs

Once the aforementioned considerations and questions have been applied to the program’s data and study design to determine potential risks and subsequent mitigation plans, the program team can go into the DAP writing process with greater confidence.

Ultimately, a DAP’s purpose is to ensure a new drug or device is safe and effective for anyone living with the health condition the drug or device is intended to help treat or diagnose. Integral to that purpose is identifying the people who are impacted by the health condition the drug or device would be used for. Therefore, the DAP must focus on articulating the following four aspects of drug development within the context of the program:

• What – the hypothesis
• Who – the patient population intended to be treated
• How (this includes when, where, and measures) – the actual plan or map
• Why – the rationale behind the what, who, and how

When evaluating the “who,” sponsors must evaluate their enrollment goals to assess if those goals are reflective of the "product's intended use population." According to the FDA, factors to consider when setting goals include

• Demographic characteristics (e.g., race, ethnicity, sex, age)
• Clinical characteristics (e.g., presence of comorbidities, disease etiology)
• Other characteristics (e.g., access to standard preventative and diagnostic care, access to standard treatments of the clinically relevant population)

Additionally, sponsors should also consider the following criteria as part of “historically underrepresented:”

• Geographic location
• Pregnancy or lactating status
• Gender identity
• Sexual orientation
• Socioeconomic status
• Physical and mental disabilities
• Comorbidities

When considering these characteristics, implementing the same inclusive approach as detailed earlier for the ICF, protocol design, and I/E criteria can help sponsors ensure that the very populations it needs to include in its studies have been identified and engaged in ways to improve both the study’s and DAP’s design(s). Without the insights and input from these historically under-engaged and underrepresented communities, the likelihood of wrong assumptions being made and unintended negative outcomes happening increases significantly.

Additionally, if a sponsor chooses to default to census data, it may expose the sponsor to risk if there is no publicly available data, or even non-publicly available data, that can be found. A sponsor will need to be prepared to defend their decision with the same rigor they may choose to defend a study's design if the FDA challenges it.

As a sponsor develops the “how,” it should detail the clear steps it plans to take to meet the enrollment goals.

• Identify, select, prepare, and train the best sites to engage the historically underrepresented patient community.
• Select community, advocacy, faith, and DEI partners and vendors to engage potential patients and by what means, as well as how and by whom those tactics were influenced.

• Determine what interventions, strategies, and tactics the sponsor, its CRO, and partners will implement to minimize or eliminate potential barriers participants could encounter, particularly those from historically underrepresented communities.
• Decide what the sponsor will do to measure progress and assess if changes to the DAP need to be made to improve the DAP’s goals (i.e., what does success look like and how will the sponsor assess if it needs to adjust the plan throughout the study?).

If a clear line cannot be connected between the intervention, the intended outcome, and how that line will be measured, as well as why the sponsor has chosen to include this information in its DAP, then a sponsor has not created a strong DAP, and it should be ready to receive challenges by the FDA and the public. Feedback from the FDA can be helpful to sponsors, but only when the FDA sees a strategic and well-reasoned approach to drug development. A DAP should have the same rigor applied to its development as the other aspects of a program.

Once Your DAP Is Created

Remember that DAPs will be viewed by the FDA and by the public, as sponsors will be required to post their DAP to clinicaltrials.gov, the study’s website (if created), and/or the sponsor’s pipeline webpage. DAPs will not be private documents shrouded in secrecy; rather, they will be transparent plans that allow regulatory bodies, legislators and policymakers, patient advocacy groups, payors, investors, and the public to see firsthand a company’s commitment to ethical and inclusive drug development. Therefore, careful and intentional planning and execution of a DAP will serve a sponsor well to meet both its near-term enrollment goals and long-term reputational ambitions.

Ultimately, a thoughtful and intentional DAP should take these myriad factors into account to ensure the sponsor meets the FDA’s soon-to-be codified mandate to “increase enrollment of participants who are members of historically underrepresented populations in clinical studies to help improve the strength and generalizability of the evidence for the intended use population."

About The Author:

Devra Densmore is the founder and principal consultant at Elevate Advocacy. Over her 20 years of patient advocacy and engagement experience, Devra has helped center diverse patient insights to improve health literacy and education initiatives, clinical trials in rare and common disorders, and treatment algorithms in hospitals inside and outside the United States. She and the team at Elevate Advocacy partner with drug and device sponsors to create effective and successful engagement strategies and DAPs. With decades of experience engaging diverse communities around health education and clinical research, Elevate Advocacy advises sponsors in DAP creation and execution while building meaningful, lasting, and differentiated relationships with these important community and DEI partners.