New federal incentives for diversity in clinical trials

In June 2022, the US House of Representatives passed legislation aimed at increasing the diversity of populations participating in clinical trials of new drugs. Under this bill, trial sponsors would need to submit a diversity action plan — including goals for trial enrollment by demographic and steps to achieve those goals — for Phase 3 or pivotal trials of new drugs. These diversity provisions, part of a broader Food and Drug Administration (FDA) reauthorization of user fee funding, would codify recent FDA draft guidance recommending that clinical trial sponsors implement diversity plans for enrolling participants from historically underrepresented races and races Races evolve and submit ethnic populations.1 The legislation and draft guidelines followed an executive order by President Joe Biden directing federal agencies to review impediments and potential new guidelines to promoting equity in government actions and federal programs.

Recent controversies over the lack of diversity in pivotal clinical trials of aducanumab for Alzheimer’s disease (only 0.6% of trial participants were identified as Black) and Covid-19 vaccines have highlighted persistent gaps in clinical trial representativeness across disease areas. Between 2008 and 2018, the proportion of Black participants participating in pivotal trials for new cancer drugs increased from 2.9% to just 3.6%.2 These differences underscore the limitations of existing guidelines to ensure inclusive participation in clinical trials for new medicines. A recent report from the National Academies of Sciences, Engineering, and Medicine details the potential negative health, economic, equitable and scientific consequences of failing to reach a more diverse clinical trials enterprise.3

Since 1985, the FDA has required sponsors of new drug applications to submit efficacy and safety data for gender, age, and ethnic subgroups; In 1998, the reporting requirement for demographic data was extended to include trials of new investigational medicinal products. Since 1988, successive FDA guidance documents have called for greater inclusion of specific populations in studies; Most recently, in 2014, the FDA published an action plan to encourage study participation. However, apart from limited regulatory requirements for reporting certain demographic information, these FDA guidelines were all part of voluntary industry guidance.

Under a 1993 law, the National Institutes of Health has more explicit statutory authority to direct investigators of federally funded clinical research to ensure greater gender, racial, and ethnic representativeness. However, these NIH guidelines do not apply to private industry-led trial companies, which are responsible for most pre-market clinical trials of investigational therapies.

As a result, after decades of mostly voluntary and ambitious initiatives in pivotal trials under FDA oversight for many new drugs, there continues to be a lack of adequate proportions of participants who identify as members of historically marginalized racial and ethnic groups—as well as older adults, those with impaired functioning and those who are pregnant or breastfeeding.

The diversity provisions in recent House legislation are a welcome first step towards more systematic measurement, reporting and integration of enrollment targets in pivotal trials for new drugs. However, the legislation does not provide a mechanism to address insufficient progress in registering participants in accordance with sponsors’ diversity plans. Experience with other regulatory programs and initiatives that FDA lacked the authority and capacity to enforce, such as B. Targets for conducting studies in a timely manner after approval suggest that the actual impact of these diversity plans in practice may be suboptimal. Additionally, The new diversity provisions do not fully address the underlying causes of non-representativeness in clinical trialswhich include restrictive eligibility criteria, costs associated with participation, limited enrollment reach in marginalized racial and ethnic communities and in safety-net facilities, implicit English language requirements, and systemic inequalities in access to care.

We believe that a combination of state incentives and regulations is necessary to meaningfully promote equity in clinical trials for new drugs. Such a model would not be new: Congress had previously taken a similar approach to encourage the development of pediatric medicines.

First, as is the case with orphan drugs, the FDA could provide direct grants, including support to collaborative networks, aimed at increasing enrollment capacity and infrastructure at study sites that serve (and most likely enroll) participants from underrepresented populations. . Such support would help ensure that efforts to engage these facilities in clinical research do not place undue burdens on clinical and support staff or delay access to care, imaging and services. Regulators could also work to lower the financial barriers to study participation; For example, the FDA could clarify that certain types of expenses incurred by study participants are eligible for reimbursement. In addition, the scope of diversity action plans could be expanded to require that study eligibility criteria do not unduly restrict the participation of relevant patient populations throughout the development lifecycle.

Second, in addition to supporting study sites, Congress could offer financial incentives to drug manufacturers that are conditional on achieving sufficiently representative study recruitment in pivotal studies of their products. Incentives could take the form of a new tax credit or the repurposing of part of the existing research and development tax credit. While tax credits have some downsides (e.g. they may be cheaper for companies that are already generating revenue), they are preferable to alternative incentive measures that present other challenges – such as B. Extended market exclusivity or faster regulatory review by the FDA. Extending market exclusivity could exacerbate inequalities in post-authorisation access to new medicines by delaying the usual price reductions associated with the market entry of branded generic medicines. And forcing the FDA to quickly review drugs that would otherwise not qualify for expedited review could divert limited agency resources from reviewing drugs with greater expected public health benefits and potentially increase the risk of safety problems.4

Finally, the FDA could work to ensure that by the time a drug is approved, representative enrollment in post-approval studies as well as further studies of treatment effects and safety in representative real populations are already being conducted. In a relevant precedent, to balance the need to assess the cardiovascular safety of new diabetes drugs with a reasonable time to approval, the FDA has issued guidance requiring inclusion in cardiovascular outcomes studies prior to or at the time of regulatory approval, and demanded the timely completion of studies after admission. Although Congress would ideally clarify FDA’s legal authority to request a more representative registration, FDA could notify the appropriate advisory committee of registration differences and any remedial actions attempted in a post-marketing study without new legislation; The Agency could also promote early enrollment of target groups publicly and privately.

In the first major policy change for equity in clinical research in nearly three decades, Congress is about to pass new legislative measures aimed at improving the diversity of clinical trials. These provisions fill a gap in the FDA’s guidelines for non-government-funded research, which previously relied on voluntary guidelines. While a necessary first step, these diversity action plans are unlikely to address the underlying causes of under-representation of certain patient populations in clinical trials. With new federal incentives and regulations, policymakers and regulators can build a more sustainable infrastructure for inclusive drug development.

About Ellen Lewandowski

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