Introduction

During the coronavirus disease 2019 (COVID-19) pandemic, individual states have had some flexibility to customize responses for their local population. Following the Emergency Use Authorization (EUA) for remdesivir in May 2020 [1], transparency concerns about the federal government’s distribution strategy emerged [2, 3]. As such, the federal government delegated allocation responsibilities to states, where each state would develop remdesivir allocation and clinical use criteria for their communities [4, 5]. It is critical that states’ flexibility in health policymaking should not exacerbate longstanding inequitable distribution of resources and health disparities.

At the time the federal government began allocating remdesivir to states, over 50,000 Americans were hospitalized for COVID-19 [6]. With the increasing number of cases, it was evident that initial remdesivir doses available through the EUA were unlikely to meet potential demand by eligible patients. Furthermore, in August 2020, the U.S. Food and Drug Administration (FDA) expanded remdesivir’s authorization by no longer limiting use to those with severe disease. As a result, all hospitalized adult and pediatric patients “with suspected or laboratory-confirmed COVID-19” met the eligibility criteria for remdesivir [7], potentially increasing demand further. Gaps in clinical knowledge of the medication were also present, including whether remdesivir reduced mortality or which patient populations would benefit most from its use [8, 9]. The federal government did not specify criteria for initial remdesivir allocation. Disorderly allocations were evident, with remdesivir sent to some hospitals that did not need it, while other hospitals significantly impacted by COVID-19 received none [8, 10, 11].

Transparent, publicly accessible protocols are essential to reassure the public about impartiality in resource allocation [12]. Also, the disproportionate impact of COVID-19 on historically marginalized communities [13] heightened the role of clinical use guidelines. In facilities with many hospitalized patients, physicians and healthcare teams must decide which patients have priority in receiving remdesivir, raising questions about how to select patients fairly and equitably [14]. Explicit considerations of health equity in development of clinical and public health protocols have become increasingly important [15, 16]. What is unknown is the extent to which states developed transparent remdesivir-related protocols with health equity considerations once the federal government delegated this responsibility to them.

This study identified publicly available remdesivir allocation and clinical guidance from all U.S. states and the District of Columbia and assessed protocols for inclusion of language promoting equitable access or mitigating health disparities.

Methods

Results

Among the 51 jurisdictions, 38 (75%) had a remdesivir allocation strategy and 30 (59%) had remdesivir clinical use guidelines. Thirty-three jurisdictions made the allocation strategy public, while all 30 clinical use guidelines were publicly available (Tables 1 and S1). Some states had a publicly available allocation strategy but no clinical use guidelines, or vice versa. Among all 51 jurisdictions, 26 (51%) developed both an allocation strategy and clinical use guidelines for remdesivir that were public. We did not find either an allocation or use protocol for 10 states and the District of Columbia. Links to the websites of the identified protocols are provided in the S1 Table.

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Table 1. Summary of remdesivir allocation strategy and clinical use guidelines by state.

https://doi.org/10.1371/journal.pone.0257648.t001

Remdesivir allocation strategies

Table 2 presents a summary of remdesivir allocation strategies for the 33 states that made these protocols public. States used varying strategies to allocate remdesivir, ranging from no systematic procedures (allocation to facilities upon request and/or on a first come, first served basis), to those strategies that use quantitative measures of COVID-19 patient burden, including number of hospitalized COVID-19 patients, number of patients meeting EUA criteria, or a formula dependent on daily average of COVID-19 hospitalizations. Some states also used multiple strategies within their allocation protocol.

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Table 2. Summary of remdesivir allocation strategies.

https://doi.org/10.1371/journal.pone.0257648.t002

Of these 33 states with public protocols, 10 states (30%) had protocols with language on equitable allocation of remdesivir. In addition to considerations of COVID-19 facility burden, these protocols highlighted the need to promote equitable remdesivir allocation to facilities within the state. Illinois, for example, included non-discrimination guiding principles, specifying that allocation decisions should not be based on race, gender, or socioeconomic status.

Remdesivir clinical use guidelines

All 30 states with guidelines for within-facility remdesivir use made these protocols publicly available. All states cited remdesivir patient use recommendations issued by the FDA, National Institutes of Health (NIH), or Centers for Disease Control and Prevention (CDC). However, as presented in Table 3, states varied in the format of presenting these strategies. Some states only included website links to these resources, while others explicitly stated and referenced federal recommendations, expanded on FDA EUA criteria, or delegated hospitals to develop their own protocols. Of the 30 states with public within-facility remdesivir use, 12 (40%) states had protocols that went further to include ethical standards or non-discrimination language. For instance, Minnesota developed a detailed framework which outlined different priority groups based on supply of remdesivir.

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Table 3. Summary of strategies in remdesivir clinical use guidelines.

https://doi.org/10.1371/journal.pone.0257648.t003

Language on equity

We further examined the states that included health equity considerations in their remdesivir protocols. Table 4 presents the narrative text promoting ethical and fair access to remdesivir developed by these states. While of varying length, wording on equity from these protocols clearly defined the disadvantaged population.

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Table 4. Language on equity from remdesivir allocation strategies and/or clinical use guidelines.

https://doi.org/10.1371/journal.pone.0257648.t004

Discussion

Despite the limited federal oversight, our review found that 33 states had a remdesivir allocation strategy and 30 states had remdesivir clinical use guidelines that were publicly accessible. However, the strategies for allocation and clinical use in these protocols varied, and fewer than half of these states included recommendations that promote fair and equal access to remdesivir.

States with public protocols used diverse strategies to allocate remdesivir to in-state facilities, potentially a reflection of ongoing debate over how best to allocate this medication [8, 9]. While we presently lack consensus on the most effective approach for allocating scarce medications during a pandemic, current research shows that COVID-19 has disproportionately affected racial and ethnic minority communities [17, 18]. Thus, the absence of language acknowledging and mitigating this disparity in a majority of the allocation protocols was concerning, particularly when employing these explicit policy statements that draw awareness and promote conscious efforts is a key characteristic of improving equity in health care systems [19]. Only 10 of 33 states (30%) with public remdesivir allocation strategies had considerations for ethical allocation approaches. Given the current disparities in COVID-19 burden of illness, regardless of the chosen allocation strategy, an ethical allocation approach for remdesivir should prioritize these communities with the greatest disease burden. Well-crafted, clear clinical guidelines promote quality of care by reducing health care variations and dissuading potentially harmful interventions [20].

All public protocols assessed cited remdesivir patient use recommendations by federal agencies but varied in their presentation format, possibly highlighting the current lack of shared methodology for guideline development [21]. Creating clinical use guidelines for a federally restricted medication would not be expected to fall within the responsibilities of the state; however, state governments should be expected to promote a standard approach for a scarce resource they are allocating. Ideally, access to remdesivir should be based on a patient’s clinical factors, as well as the likelihood and magnitude of benefit from the medication, and not based on race, age, gender, or other socioeconomic attributes. While a majority of the 30 states with public remdesivir clinical use guidelines provided specific patient use criteria, only 12 (40%) states included additional ethical standards or non-discrimination language. Guidelines that are evidence-based, avoid discrimination, and mitigate health disparities could help physicians make these difficult decisions [22].

The COVID-19 pandemic is not the first time the U.S. has faced the issue of allocating scarce resources during a public health emergency. Following issuance of an EUA for peramivir during the 2009 H1N1 influenza pandemic, the CDC managed the drug’s distribution directly to hospitals [23]. The CDC promptly provided an online portal for physicians to request peramivir for individual patients, where criteria for approval included suspected or confirmed H1N1 virus infection, and either lack of response or inability to receive oral or inhaled antiviral treatment [24]. Once approved, the medication was sent to the requesting clinician within 24 hours. The peramivir EUA provides an example of how a single designated federal agency can successfully distribute scarce resources through a transparent and clearly defined process [25]. It is important to note that the H1N1 influenza pandemic was of moderate scale compared to that from COVID-19, and other treatments were available for use in influenza. The question still remains whether the federal government could have done more to promote a cohesive response to ensure equitable remdesivir allocation across states. Multiple frameworks that include fair and equitable allocation of scarce resources in a pandemic already exist and could be customized by governments for the allocation of pharmaceutical countermeasures. In their Crisis Standards of Care, the Office of the Assistant Secretary for Preparedness and Response recommends an allocation process that is “ethically defensible, fair, and transparent” [26]. Similarly, a multidisciplinary team developed the University of Pittsburgh Guidance Model, combines clinical and ethical criteria to allocate scarce resources and to mitigate the impact of social inequities [27]. Emanuel et al. provide six ethical principle recommendations for fair resource allocation during COVID-19 [28]. A federal framework allowing for adaptation to local state context could guide allocation and use of scarce resources. Unfortunately, the process for remdesivir allocation made it difficult for the federal government to redistribute allocations based on the rapidly changing COVID-19 burden across different parts of the country. Responsibility was given to states to determine reallocation of excess remdesivir to other hospitals within their jurisdictions, or to quickly notify the federal government to reallocate their product to other states [5].

We did not find remdesivir allocation strategies or clinical use guidelines for 10 states and the District of Columbia. Lack of transparency on how scarce resources are allocated adds to the lack of public trust in allocation policies [29, 30]. Transparency also allows for modeling best practices and serving as a resource to other states; Minnesota’s remdesivir protocols were cited as a resource to create protocols in Arizona and Kansas. It is also possible that some states did not need these protocols. Oregon, for example, did not develop one and documented that the remdesivir supply was sufficient to meet the demand from hospitalized COVID-19 patients in the state. However, documenting these protocols a priori could alleviate potential triage dilemmas posed by the pandemic.

For future situations that pose a similar threat as the COVID-19 pandemic, the federal government could recommend specific evidence-based requirements for states to address in their allocation guidelines for hospitals, such as addressing how to ensure an equitable and transparent distribution process both within the state and within healthcare facilities [2, 31].

Conclusion

This review highlights the variation in strategy and, in some cases, the absence of publicly accessible state guidance for remdesivir allocation and use. Fewer than half of the states reviewed had transparent remdesivir allocation and/or clinical use protocols to guide fair and equitable access. Future research could assess the effectiveness of various strategies and models used by the states, focusing on whether equitable allocation of remdesivir was achieved. This experience with the remdesivir EUA also presents an opportunity for the federal and state governments to develop allocation and clinical use protocols promoting fair and equal access to treatments for future pandemics. Notably, both federal and state governments have issued protocols to ensure equity in distribution of COVID-19 vaccines. Further work could also assess whether these vaccination strategies were effective.

Supporting information