Use of Ebola Vaccines - Worldwide, 2021-2023.

Ebola virus disease (Ebola) is a rare but severe illness in humans, with an average case fatality rate of approximately 50%. Two licensed vaccines are currently available against Orthoebolavirus zairense, the virus that causes Ebola: the 1-dose rVSVΔG-ZEBOV-GP (ERVEBO [Merck]) and the 2-dose regimen of Ad26.ZEBOV and MVA-BN-Filo (Zabdeno/Mvabea [Johnson & Johnson]). The Strategic Advisory Group of Experts on Immunization recommends the use of 1-dose ERVEBO during Ebola outbreaks, and in 2021, a global stockpile of ERVEBO was established to ensure equitable, timely, and targeted access to vaccine doses for future Ebola outbreaks. This report describes the use of Ebola vaccines and the role of the stockpile developed and managed by the International Coordinating Group (ICG) on Vaccine Provision during 2021-2023. A total of 145,690 doses have been shipped from the ICG stockpile since 2021. However, because outbreaks since 2021 have been limited and rapidly contained, most doses (139,120; 95%) shipped from the ICG stockpile have been repurposed for preventive vaccination of high-risk groups, compared with 6,570 (5%) used for outbreak response. Repurposing doses for preventive vaccination could be prioritized in the absence of Ebola outbreaks to prevent transmission and maximize the cost-efficiency and benefits of the stockpile.

The Strategic National Stockpile: identification, support, and acquisition of medical countermeasures for CBRN incidents.

The Strategic National Stockpile (SNS) serves as a repository of materiel, including medical countermeasures (MCMs), that would be used to support the national health security response to a chemical, biological, radiological, or nuclear (CBRN) incident, either natural or terrorism-related. To support and advance the SNS, the National Institutes of Health (NIH) manages targeted investigatory research portfolios, such as Countermeasures Against Chemical Terrorism (CounterACT) for chemical agents, that coordinate projects covering basic research, drug discovery, and preclinical studies. Project BioShield, managed by the Biomedical Advanced Research and Development Agency (BARDA), guides and supports academia and industry with potential MCMs through the Food & Drug Administration's approval process and ultimately supports the acquisition of successful products into the SNS. Public health emergencies such as the COVID-19 pandemic and the ever-increasing number of MCMs in the SNS present logistical and financial challenges to its maintenance. While MCMs for biological agents have been readily adopted, those for chemical agents have required sustained investments. This paper reviews the methods by which MCMs are identified and supported for inclusion in the SNS, the current status of MCMs for CBRN threats, and challenges with SNS maintenance as well as identifies persistent obstacles for MCM development and acquisition, particularly for ones focused on chemical weapons.

Estimating Shortages in Capacity to Deliver Continuous Kidney Replacement Therapy During the COVID-19 Pandemic in the United States.

RATIONALE & OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, New York encountered shortages in continuous kidney replacement therapy (CKRT) capacity for critically ill patients with acute kidney injury stage 3 requiring dialysis. To inform planning for current and future crises, we estimated CKRT demand and capacity during the initial wave of the US COVID-19 pandemic. STUDY DESIGN: We developed mathematical models to project nationwide and statewide CKRT demand and capacity. Data sources included the Institute for Health Metrics and Evaluation model, the Harvard Global Health Institute model, and published literature. SETTING & POPULATION: US patients hospitalized during the initial wave of the COVID-19 pandemic (February 6, 2020, to August 4, 2020). INTERVENTION: CKRT. OUTCOMES: CKRT demand and capacity at peak resource use; number of states projected to encounter CKRT shortages. MODEL, PERSPECTIVE, & TIMEFRAME: Health sector perspective with a 6-month time horizon. RESULTS: Under base-case model assumptions, there was a nationwide CKRT capacity of 7,032 machines, an estimated shortage of 1,088 (95% uncertainty interval, 910-1,568) machines, and shortages in 6 states at peak resource use. In sensitivity analyses, varying assumptions around: (1) the number of pre-COVID-19 surplus CKRT machines available and (2) the incidence of acute kidney injury stage 3 requiring dialysis requiring CKRT among hospitalized patients with COVID-19 resulted in projected shortages in 3 to 8 states (933-1,282 machines) and 4 to 8 states (945-1,723 machines), respectively. In the best- and worst-case scenarios, there were shortages in 3 and 26 states (614 and 4,540 machines). LIMITATIONS: Parameter estimates are influenced by assumptions made in the absence of published data for CKRT capacity and by the Institute for Health Metrics and Evaluation model's limitations. CONCLUSIONS: Several US states are projected to encounter CKRT shortages during the COVID-19 pandemic. These findings, although based on limited data for CKRT demand and capacity, suggest there being value during health care crises such as the COVID-19 pandemic in establishing an inpatient kidney replacement therapy national registry and maintaining a national stockpile of CKRT equipment.

A Commons for a Supply Chain in the Post-COVID-19 Era: The Case for a Reformed Strategic National Stockpile.

Policy Points Reflecting on current response deficiencies, we offer a model for a national contingency supply chain cell (NCSCC) construct to manage the medical materials supply chain in support of emergencies, such as COVID-19. We develop the following: a framework for governance and response to enable a globally independent supply chain; a flexible structure to accommodate the requirements of state and county health systems for receiving and distributing materials; and a national material "control tower" to improve transparency and real-time access to material status and location. CONTEXT: Much of the discussion about the failure of the COVID-19 supply chain has centered on personal protective equipment (PPE) and the degree of vulnerability of care. Prior research on supply chain risks have focused on mitigating the risk of disruptions of specific purchased materials within a bounded region or on the shifting status of cross-border export restrictions. But COVID-19 has impacted every purchase category, region, and border. This paper is responsive to the National Academies of Sciences, Engineering and Medicine recommendation to study and monitor disasters and to provide governments with course of action to satisfy legislative mandates. METHODS: Our analysis draws on our observations of the responses to COVID-19 in regard to acquisition and contracting problem-solving, our review of field discussions and interactions with experts, a critique of existing proposals for managing the strategic national stockpile in the United States a mapping of the responses to national contingency planning phases, and the identification of gaps in current national healthcare response policy frameworks and proposals. FINDINGS: Current proposals call for augmenting a system that has failed to deliver the needed response to COVID-19. These proposals do not address the key attributes for pandemic plan renewal: flexibility, traceability and transparency, persistence and responsiveness, global independence, and equitable access. We offer a commons-based framework for achieving the opportunities and risks which are responsive to a constellation of intelligence assets working in and across focal targets of global supply chain risk. CONCLUSIONS: The United States needs a "commons-based strategy" that is not simply a stockpile repository but instead is a network of repositories, fluid inventories, and analytic monitoring governed by the experts. We need a coordinated effort, a "commons" that will direct both conventional and new suppliers to meet demands and to eliminate hoarding and other behaviors.

Surge activation by the emergency department for COVID-19.

In March 2020, the American College of Emergency Physicians (ACEP) published a national strategic plan for COVID-19, which provides general guidelines yet leaves logistical details for institutions to determine. Key capabilities from this plan provided a crucial foundation for a 16-day Emergency Department (ED) surge planning process at one pediatric institution. This paper describes critical milestones and lessons learned during this brief period, including derivation of criteria for ED surge activation, a full-scale surge drill, and the resultant ED surge protocol. The framework of real-time evaluation was used throughout the planning process and involved constant and iterative synthesis of real-time feedback from multidisciplinary stakeholders for responsive decision-making. Ultimately, the objective of this paper is to provide timely and readily actionable information to other institutions seeking guidance to apply the ACEP strategic plan for COVID-19.

Investing in antibiotics to alleviate future catastrophic outcomes: What is the value of having an effective antibiotic to mitigate pandemic influenza?

Over 95% of post-mortem samples from the 1918 pandemic, which caused 50 to 100 million deaths, showed bacterial infection complications. The introduction of antibiotics in the 1940s has since reduced the risk of bacterial infections, but growing resistance to antibiotics could increase the toll from future influenza pandemics if secondary bacterial infections are as serious as in 1918, or even if they are less severe. We develop a valuation model of the option to withhold wide use of an antibiotic until significant outbreaks such as pandemic influenza or foodborne diseases are identified. Using real options theory, we derive conditions under which withholding wide use is beneficial, and calculate the option value for influenza pandemic scenarios that lead to secondary infections with a resistant Staphylococcus aureus strain. We find that the value of withholding an effective novel oral antibiotic can be positive and significant unless the pandemic is mild and causes few secondary infections with the resistant strain or if most patients can be treated intravenously. Although the option value is sensitive to parameter uncertainty, our results suggest that further analysis on a case-by-case basis could guide investment in novel agents as well as strategies on how to use them.

Planning Considerations for State, Local, Tribal, and Territorial Partners to Receive Medical Countermeasures From CDC's Strategic National Stockpile During a Public Health Emergency.

The Centers for Disease Control and Prevention's Strategic National Stockpile is a national repository of potentially life-saving medical countermeasures including pharmaceuticals and medical supplies for use in a public health emergency severe enough to cause local, regional, and state supplies to run out. Several planning considerations can assist state, local, tribal, and territorial jurisdictions in preparing to receive, distribute, dispense, and administer medical countermeasures from the Strategic National Stockpile. These considerations include, but are not limited to, issues surrounding regulatory requirements, controlled substances, cold chain management, and ancillary supply needs. Multiple aspects to consider for each of these functions are discussed here to assist partners in their planning efforts.

Pharmaceutical lobbying and pandemic stockpiling of Tamiflu: a qualitative study of arguments and tactics.

Background: Little is known about how pharmaceutical companies lobby authorities or experts regarding procurement or the use of vaccines and antivirals. This paper investigates how members of Denmark's pandemic planning committee experienced lobbying efforts by Roche, manufacturer of Tamiflu, the antiviral that was stockpiled before the 2009 A(H1N1) pandemic. Methods: Analysis of interviews with six of seven members of the Danish core pandemic committee, supplemented with documentary analysis. We sought to identify (1) arguments and (2) tactics used in lobbying, and to characterize interviewees' views on the impact of (3) lobbying and (4) scientific evidence on the decision to stockpile Tamiflu. Results: Roche lobbied directly (in its own name) and through a seemingly independent third party. Roche used two arguments: (1) the procurement agreement had to be signed quickly because the drug would be delivered on a first-come, first-served basis and (2) Denmark was especially vulnerable to an influenza crisis because it had smaller Tamiflu stocks than other countries. Most interviewees suspected that lobbying had an impact on Tamiflu procurement. Conclusions: Our study highlights risks posed by pharmaceutical lobbying. Arguments and tactics deployed by Roche are likely to be repeated whenever many countries are negotiating drug procurements in a monopolistic market.

Choice of Antiviral Allocation Scheme for Pandemic Influenza Depends on Strain Transmissibility, Delivery Delay and Stockpile Size.

Recently, pandemic response has involved the use of antivirals. These antivirals are often allocated to households dynamically throughout the pandemic with the aim being to retard the spread of infection. A drawback of this is that there is a delay until infection is confirmed and antivirals are delivered. Here an alternative allocation scheme is considered, where antivirals are instead preallocated to households at the start of a pandemic, thus reducing this delay. To compare these two schemes, a deterministic approximation to a novel stochastic household model is derived, which allows efficient computation of key quantities such as the expected epidemic final size, expected early growth rate, expected peak size and expected peak time of the epidemic. It is found that the theoretical best choice of allocation scheme depends on strain transmissibility, the delay in delivering antivirals under a dynamic allocation scheme and the stockpile size. A broad summary is that for realistic stockpile sizes, a dynamic allocation scheme is superior with the important exception of the epidemic final size under a severe pandemic scenario. Our results, viewed in conjunction with the practical considerations of implementing a preallocation scheme, support a focus on attempting to reduce the delay in delivering antivirals under a dynamic allocation scheme during a future pandemic.