The Emergency Use Authorization (EUA) of remdesivir for coronavirus disease 2019 raised questions on transparency of applied strategy, and how to equitably allocate and prioritize eligible patients given limited supply of the medication. The absence of federal oversight highlighted the critical role by states in health policymaking during a pandemic.
To identify public state-based protocols for remdesivir allocation and clinical guidance for prioritizing remdesivir use and assess approaches and inclusion of language promoting equitable access or mitigating health disparities.
We identified remdesivir allocation strategies and clinical use guidelines for all 50 states in the U.S. and the District of Columbia accessible on state health department websites or via internet searches. Public protocols dated between May 1, 2020 and September 30, 2020 were included in the study. We reviewed strategies for allocation and clinical use, including whether protocols contained explicit language on equitable access to remdesivir or mitigating health disparities.
A total of 38 states had a remdesivir allocation strategy, with 33 states (87%) making these public. States used diverse allocation strategies, and only 10 (30%) of the 33 states included language on equitable allocation. A total of 30 states had remdesivir clinical use guidelines, where all were publicly accessible. All guidelines referenced recommendations by federal agencies but varied in their presentation format. Of the 30 states, 12 (40%) had guidelines that included language on equitable use. Neither an allocation strategy or clinical use guideline were identified (public or non-public) for 10 states and the District of Columbia during the study period.
Citation: Kiptanui Z, Ghosh S, Ali S, Desai K, Harris I (2021) Transparency, health equity, and strategies in state-based protocols for remdesivir allocation and use. PLoS ONE 16(10): e0257648. https://doi.org/10.1371/journal.pone.0257648
Editor: Fernando A. Wilson, University of Utah, UNITED STATES
Received: April 30, 2021; Accepted: September 6, 2021; Published: October 18, 2021
Copyright: © 2021 Kiptanui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: Index Analytics LLC (https://index-analytics.com/) provided support for this study in the form of a salary for ZK. IMPAQ International LLC (https://impaqint.com/) provided support for this study in the form of salaries for SG, SA, KD, and IH. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have read the journal’s policy and have the following competing interests: ZK is a paid employee of Index Analytics LLC (https://index-analytics.com/). SG, SA, KD, and IH are paid employees of IMPAQ International LLC (https://impaqint.com/). This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.
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 , 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 . 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 , 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 . Also, the disproportionate impact of COVID-19 on historically marginalized communities  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 . 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.
We conducted a qualitative review of health department websites for all 50 U.S. states and the District of Columbia. We identified public information dated between May 1, 2020 and September 30, 2020 on remdesivir allocation and clinical use guidance to in-state facilities. Institutional review board review was not required, as data did not involve human subjects.
Between October 8, 2020 and November 24, 2020, we searched each state’s health department website using the search term “remdesivir”. When no relevant documents were identified from state websites, the Google internet search engine was used, with these search terms: “remdesivir”, “allocation”, “administration”, “guidelines”, and the state name. Documents were included in the study if they discussed a methodology or criteria for allocating remdesivir to in-state facilities or prioritizing eligible patients within them.
Four reviewers (S.G, S.A, K.D, Z.K) collected and reviewed state remdesivir protocols. We developed review procedures to maintain consistency of review. Each reviewer was a primary reviewer for one group of states and a secondary reviewer for another–hence a robust methodology assuring reproduceable findings. Reviewers met biweekly to discuss findings and resolve disagreements.
For each protocol, we collected details on allocation strategy and criteria for patient use. We recorded the source (state health department website or other) and whether protocols were publicly accessible (protocol details were available without user identification or additional requests). Any documented references to recommendations from federal agencies were also collected. We identified language promoting equitable access or mitigating health disparities as explicit equity-sensitive ‘remarks’ or ‘key considerations’ statements documented in the protocols.
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.
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.
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.
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.
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 . 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 .
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 . 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 .
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 . 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 . 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 . 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” . 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 . Emanuel et al. provide six ethical principle recommendations for fair resource allocation during COVID-19 . 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 .
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].
There were information gaps for some states. We did not find public protocols on remdesivir allocation or use from 10 states and the District of Columbia. Some states had public protocols on remdesivir allocation but not on patient use, or vice versa. While we chose to focus on information which was publicly available to reflect transparency, it is possible that these documents were available in non-public ways. States may have used other channels to distribute their protocols, such as via email, or in the form of a hard copy. Despite these gaps, the majority of U.S. jurisdictions were included in the study– 63% for remdesivir allocation review and 59% for remdesivir clinical use review. Another study limitation is that we focused on state-level guidance only; there may be other facility-specific protocols that have a greater influence on patient access. Notably, a survey of 66 facilities across 28 states conducted during our study period found that remdesivir use guidelines were inconsistent and did not include ethical or equitable standards . Our study findings are also limited to the data collection period; it is possible that some states may have since updated these protocols. Additionally, we based our definition of equitable access on the inclusion of explicit language promoting fair allocation in state protocols. However, our study did not further explore whether states or hospitals executed and enforced equitable allocations or if strategies were deemed equitable without explicit language. Further research can examine the different strategies to improve our understanding on fairness.
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.
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