Operation Warp Speed Research Articles

Supporting the nation in crisis: the military health system’s role in enhancing public health capacity through public–private partnerships

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic caused significant global disruptions to the healthcare system, which was forced to make rapid changes in healthcare delivery. The pandemic necessitated closer collaboration between the US civilian healthcare sector and the military health system (MHS), resulting in new and strengthened partnerships that can ultimately benefit public health and healthcare for the nation. In this study, we sought to understand the full range of partnerships in which the MHS engaged with the civilian sector during the COVID-19 pandemic and to elicit lessons for the future.MethodsWe conducted key informant interviews with MHS policymakers and advisers, program managers and providers who were affiliated with the MHS from March 2020 through December 2022. Key themes were derived using thematic analysis and open coding methods.ResultsWe conducted 28 interviews between December 2022 and March 2023. During the pandemic, the MHS collaborated with federal and local healthcare authorities and private sector entities through endeavours such as Operation Warp Speed. Lessons and recommendations for future pandemics were also identified, including investment in biosurveillance systems and integration of behavioural and social sciences.ConclusionsThe MHS rapidly established and fostered key partnerships with the public and private sectors during the COVID-19 pandemic. The pandemic experience showed that while the MHS is a useful resource for the nation, it also benefits from partnering with a variety of organizations, agencies and private companies. Continuing to develop these partnerships will be crucial for coordinated, effective responses to future pandemics.

Operation warp speed: Harbinger of American industrial innovation policies

Abstract Operation warp speed (OWS) was a crash effort from 2020 to 2021 to undertake the late-stage development, production, and distribution of vaccines for the coronavirus pandemic. The vaccines were developed, approved, and available in a record time of 8 months using an industrial policy approach. Mainstream economists have long opposed industrial policy approaches as market interference, unless they can be justified by clear market failures. The nation has long had industrial economic policies in such areas as defense, health, transport, and agriculture. However, interventionist policies on the non-defense innovation side of the economy after the research stage have generally been avoided. OWS was a departure, an industrial innovation policy. OWS built a new organization with officials from major health science, regulatory, public health, and research agencies as well as the Defense Department. Elements of its program included: supporting a portfolio of different technology platforms, guaranteed contracts that enable production to evolve alongside development, flexible contracting mechanisms that enabled rapid procurement and intervention into supply chains, rapid technology certification that assured the new vaccines of rapid market entry, mapping supply chains and filling gaps to assure rapid production and distribution, and major product distribution. The elements applied in OWS amount to a new tool kit potentially relevant to other areas, and the USA is now pursuing a series of these in other technology fields.

Can Operation Warp Speed Serve as a Model for Accelerating Innovations Beyond COVID Vaccines?

Can Operation Warp Speed Serve as a Model for Accelerating Innovations Beyond COVID Vaccines?

Preparing for Future Pandemics and Public Health Emergencies: An American College of Physicians Policy Position Paper.

The onset of the COVID-19 pandemic revealed significant gaps in the United States' pandemic and public health emergency response system. At the federal level, government responses were undercut by a lack of centralized coordination, inadequately defined responsibilities, and an under-resourced national stockpile. Contradictory and unclear guidance throughout the early months of the pandemic, along with inconsistent funding to public health agencies, also created notable variance in state and local responses. The lack of a coordinated response added pressure to an already overwhelmed health care system, which was forced to resort to rationing care and personal protective equipment, creating moral distress and trauma for health care workers and their patients. Despite these severe shortcomings, the COVID-19 pandemic also highlighted successful policies and approaches, such as Operation Warp Speed, which led to the fastest development and distribution of a vaccine in history. In this position paper, the American College of Physicians (ACP) offers several policy recommendations for enhancing federal, state, and local preparedness for future pandemic and public health emergencies. This policy paper builds on various statements produced by ACP throughout the COVID-19 pandemic, including on the ethical distribution of vaccinations and resources, conditions to resume economic and social activity, and efforts to protect the health and well-being of medical professionals, among others.

Climate Finance: An Overview

Climate Finance: An Overview

Synergistic Strategies to Accelerate the Development of Function-Promoting Therapies: Lessons From Operation Warp Speed and Oncology Drug Development.

Functional limitations and physical disabilities associated with aging and chronic disease are major concerns for human societies and expeditious development of function-promoting therapies is a public health priority. Expert panel discussion. The remarkable success of Operation Warp Speed for the rapid development of COVID-19 vaccines, COVID-19 therapeutics, and of oncology drug development programs over the past decade have taught us that complex public health problems such as the development of function-promoting therapies will require collaboration among many stakeholders, including academic investigators, the National Institutes of Health, professional societies, patients and patient advocacy organizations, the pharmaceutical and biotechnology industry, and the U.S. Food and Drug Administration. There was agreement that the success of well designed, adequately powered clinical trials will require careful definitions of indication/s, study population, and patient-important endpoints that can be reliably measured using validated instruments, commensurate resource allocation, and versatile organizational structures such as those used in Operation Warp Speed.

Maintaining Warp Speed: Policy Requirements for a Just-in-Time, Capability-Based, Scalable Medical Countermeasure Research and Development Enterprise.

Maintaining Warp Speed: Policy Requirements for a Just-in-Time, Capability-Based, Scalable Medical Countermeasure Research and Development Enterprise.

Clinical trial facilitators: A novel approach to support the execution of clinical research at the study site level

In the summer of 2020, multiple efforts were undertaken to establish safe and effective vaccines to combat the spread of the coronavirus disease (COVID-19). In the United States (U.S.), Operation Warp Speed (OWS) was the program designated to coordinate such efforts. OWS was a partnership between the Department of Health and Human Services (HHS), the Department of Defense (DOD), and the private sector, that aimed to help accelerate control of the COVID-19 pandemic by advancing development, manufacturing, and distribution of vaccines, therapeutics, and diagnostics. The U.S. Department of Veterans Affairs’ (VA) was identified as a potential collaborator in several large-scale OWS Phase III clinical trial efforts designed to evaluate the safety and efficacy of various vaccines that were in development. Given the global importance of these trials, it was recognized that there would be a need for a coordinated, centralized effort within VA to ensure that its medical centers (sites) would be ready and able to efficiently initiate, recruit, and enroll into these trials.The manuscript outlines the partnership and start-up activities led by two key divisions of the VA's Office of Research and Development's clinical research enterprise. These efforts focused on site and enterprise-level requirements for multiple trials, with one trial serving as the most prominently featured of these studies within the VA. As a result, several best practices arose that included designating clinical trial facilitators to study sites to support study initiation activities and successful study enrollment at these locations in an efficient and timely fashion.

The WTO and Vaccine Supply Chain Resilience during a Pandemic

ABSTRACT Cross-border supply chains and international trade enabled the manufacturing and delivery of billions of vaccine doses to inoculate the world against the Coronavirus disease (COVID-19). At the same time, the pandemic revealed how the World Trade Organization (WTO) must change to become more useful in the face of a public health emergency. This paper describes the market failures—especially on the supply side—justifying the domestic subsidies and contracting arrangements used to accelerate vaccine research and development and to increase the scale of vaccine production to save lives, livelihoods, and economic activity during a pandemic. It highlights the trade-offs associated with the US subsidies and the priority-rated contracts written for vaccines through the Defense Production Act under Operation Warp Speed. This case study reveals a rich environment in which cross-border supply chains exacerbate input shortages in ways that constrain vaccine production, highlighting the need for the WTO to embrace new forms of international policy coordination for pandemic preparedness and response. As part of a pandemic treaty, the paper proposes a plurilateral agreement on vaccine supply chain resilience that would include novel and enforceable disciplines for export restrictions, provisions to trigger coordinated subsidies across countries to jointly scale up vaccine output and input production capacity, and market surveillance initiatives on supply chain transparency.

Covid-19 vaccine supply chains and the Defense Production Act

Abstract In response to the Covid-19 pandemic, the US government used novel policies to accelerate research, development, and production of a diversified portfolio of new vaccines. This article begins by describing the Defense Production Act (DPA) of 1950 and the initial ‘priority-rated’ contracts agreed to under Operation Warp Speed in 2020 to expedite manufacturing and achieve scale, which succeeded in producing hundreds of millions of doses of Covid-19 vaccines by early 2021. However, a puzzle soon emerged, as the scale of US vaccine production was shortly thereafter overtaken by plants in the European Union and India. The paper investigates the trade-offs US policy-makers faced in early 2021—once much of the initial uncertainty about the safety and effectiveness of many Covid-19 vaccines had been resolved—about whether to recalibrate contracts to expand production capacity to help meet global, instead of US, vaccine demand. It also examines the emergence of input shortages and assesses whether both the price constraints implicit in the 2020 DPA contracts and business decisions made to quicken the process of bringing new vaccine plants online globally inadvertently exacerbated them. It also explores the potential need for complementary, input capacity-enhancing policies in the face of highly fragmented, cross-border Covid-19 vaccine supply chains.

The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19.

Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19. To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2. Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge. 114 centers in 10 countries. Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms. Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively. Plasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity. Plasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available. Elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients. U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Improving Care During Peacetime, War, and Disasters: A Call for Agile Military Civilian Strategic Alliances.

Improving Care During Peacetime, War, and Disasters: A Call for Agile Military Civilian Strategic Alliances.

Tixagevimab–cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial

BackgroundTixagevimab–cilgavimab is a neutralising monoclonal antibody combination hypothesised to improve outcomes for patients hospitalised with COVID-19. We aimed to compare tixagevimab–cilgavimab versus placebo, in patients receiving remdesivir and other standard care.MethodsIn a randomised, double-blind, phase 3, placebo-controlled trial, adults with symptoms for up to 12 days and hospitalised for COVID-19 at 81 sites in the USA, Europe, Uganda, and Singapore were randomly assigned in a 1:1 ratio to receive intravenous tixagevimab 300 mg–cilgavimab 300 mg or placebo, in addition to remdesivir and other standard care. Patients were excluded if they had acute organ failure including receipt of invasive mechanical ventilation, extracorporeal membrane oxygenation, vasopressor therapy, mechanical circulatory support, or new renal replacement therapy. The study drug was prepared by an unmasked pharmacist; study participants, site study staff, investigators, and clinical providers were masked to study assignment. The primary outcome was time to sustained recovery up to day 90, defined as 14 consecutive days at home after hospital discharge, with co-primary analyses for the full cohort and for participants who were neutralising antibody-negative at baseline. Efficacy and safety analyses were done in the modified intention-to-treat population, defined as participants who received a complete or partial infusion of tixagevimab–cilgavimab or placebo. This study is registered with ClinicalTrials.gov, NCT04501978 and the participant follow-up is ongoing.FindingsFrom Feb 10 to Sept 30, 2021, 1455 patients were randomly assigned and 1417 in the primary modified intention-to-treat population were infused with tixagevimab–cilgavimab (n=710) or placebo (n=707). The estimated cumulative incidence of sustained recovery was 89% for tixagevimab–cilgavimab and 86% for placebo group participants at day 90 in the full cohort (recovery rate ratio [RRR] 1·08 [95% CI 0·97–1·20]; p=0·21). Results were similar in the seronegative subgroup (RRR 1·14 [0·97–1·34]; p=0·13). Mortality was lower in the tixagevimab–cilgavimab group (61 [9%]) versus placebo group (86 [12%]; hazard ratio [HR] 0·70 [95% CI 0·50–0·97]; p=0·032). The composite safety outcome occurred in 178 (25%) tixagevimab–cilgavimab and 212 (30%) placebo group participants (HR 0·83 [0·68–1·01]; p=0·059). Serious adverse events occurred in 34 (5%) participants in the tixagevimab–cilgavimab group and 38 (5%) in the placebo group.InterpretationAmong patients hospitalised with COVID-19 receiving remdesivir and other standard care, tixagevimab–cilgavimab did not improve the primary outcome of time to sustained recovery but was safe and mortality was lower.FundingUS National Institutes of Health (NIH) and Operation Warp Speed.

Operation Warp Speed: A Legal Analysis of the Vaccine Development Process and How We Got Here

Abstract The COVID-19 Pandemic created a need for a vaccine that would need to be rapidly created, tested and approved in order to reduce the pandemic’s tremendous impact on human life and the economy. This article discusses the vaccine development process as well as Operation Warp Speed, the United States plan for emergency vaccine development in a pandemic situation. Written before the approval of the currently available COVID-19 vaccines, this article also discusses the implications of a speedier vaccine development process as well as recommendations to the standard process.

Operation Warp Speed and the Countermeasures Acceleration Group— A Twenty-first Century Manhattan Project: Preliminary Observations on the U.S. Department of Defense’s Role in the Supply, Production, and Distribution of COVID-19 Vaccines and Therapeutics

On 15 May 2020, Operation Warp Speed, later renamed the HHSDOD COVID-19 Countermeasures Acceleration Group (CAG), was a collaboration between the Department of Health and Human Services, the Department of Defense (DOD), and the private sector to accelerate development, production, and distribution of effective vaccines and therapeutics to counter COVID-19 for the American people. The CAG was the nucleus of the “whole-of-America” effort to defeat COVID-19, and DOD’s contribution was essential to the success of the CAG. This article highlights the contributions made by DOD, with a focus on innovative solutions and best practices that might apply to other DOD activities.

Accelerating clinical trial development in vaccinology: COVID-19 and beyond.

The remarkable success of the US government-backed COVID-19 vaccine development in 2020 offers several lessons on how to effectively foster rapid vaccine discovery and development. Conceptually, the formation of a public–private partnership that included innovative government and academic involvement at all levels of the program was instrumental in promulgating and overseeing the effort. Decades of NIH-sponsored research on vaccine backbones, immunogen design, and clinical trial operations enabled evaluation of vaccine candidates within months of pathogen discovery. Operation Warp Speed fostered industry participation, permitted accelerated movement from preclinical/early phase to efficacy trials, and developed structured clinical trial testing that allowed independent assessment of, yet reasonable comparison between, each vaccine platform by harmonizing protocols, endpoints, laboratories, and statistical analytical criteria for efficacy. This coordinated effort by the US government, pharmaceutical companies, regulators, and academic research institutions resulted in the streamlined, safe, and transparent development and deployment of multiple COVID-19 vaccines in under a year. Lessons learned from this collaborative endeavor should be used to advance additional vaccines of public health importance.

Covid-19 Vaccines and mRNA Technology: Not as New as Many Believe

When the mRNA COVID-19 vaccines were announced in December 2020 the world was excited that a vaccine was available to combat the coronavirus pandemic. One of the most frequent comments was a desire to wait because the vaccine technology was “so new.” This article will concentrate on the mRNA vaccines not familiar to the public and is intended to explain the developmental timeline before and after the genome of COVID-19 was announced. We discuss Operation Warp Speed and SARS-CoV-2 and specifically the development of Messenger RNA (mRNA) vaccines and concurrent other types of vaccines. Other topics of discussion include COVID-19 variants; effectiveness of mRNA vaccines; and late news about the Pfizer-BioNTech® COVID-19 vaccine. The article conclusion discusses implications for nurses as they continue to follow future developments, become competent in communicating viral epidemiology, and educate patients and families about vaccine options.

Accelerating the Pace of Innovation for the Greater Good

The COVID-19 pandemic has created the need for an accelerated drug development paradigm to bring vaccines to the masses. Several public-private partnerships, including Operation Warp Speed (OWS), helped fund an accelerated research & development (R&D) framework in which low-risk vaccines, likely to be successful, were supported via federal spending. This investment bore fruit less than a year later, with the approval of the first COVID-19 vaccines by Pfizer and OWS-supported Moderna. The collaborative problem solving and disruptive thinking demonstrated in the race to a COVID-19 vaccine has ushered in a new era of openness that has sped up global efforts. This race serves as proof-of-concept for an accelerated R&D framework. Establishing a "National Institute of Cures" could help cement this disruptive drug development process as permanent policy.

Atlas for a Warp Speed Future: Enhancing Usual Operating Modes of the U.S. Government

Operation Warp Speed (OWS) delivered new and effective vaccines to the general public in just 9 months, exploding previously held ideas about the government's role in medical countermeasure (MCM) development as well as what is possible on the timescale of vaccine development. OWS has potential to become a map for action in future pandemic crises. This article examines federal modes of governance that emerged in response to the Covid‐19 crisis, with special attention to how those modes differ from normal government operations. It is at the intersection of crisis modes of action and normal modes of operation that lessons emerge from OWS that may be worth applying in normal times – or not.In “Rules for Operating at Warp Speed,” I outlined how the leadership of OWS was able to accelerate operations under a suspension of the government's usual modes of operation (Arnold, 20201). This included suspension of rules that normally govern transparent and robust federal contracting and relaxing standards for scientific consensus‐building and expertise across government. This article draws from interviews completed in 2020 and 2021 with senior officials at the Department of Defense (DOD), Food and Drug Administration (FDA), and the White House in order to identify the key pandemic modes of action contributing to the success of OWS. It also discusses whether (and how) those modes of action might be adapted to enhance critical infrastructure preparedness in non‐crisis times.

Partisan Differences in Legislators' Discussion of Vaccination on Twitter During the COVID-19 Era: Natural Language Processing Analysis.

BackgroundThe COVID-19 era has been characterized by the politicization of health-related topics. This is especially concerning given evidence that politicized discussion of vaccination may contribute to vaccine hesitancy. No research, however, has examined the content and politicization of legislator communication with the public about vaccination during the COVID-19 era.ObjectiveThe aim of this study was to examine vaccine-related tweets produced by state and federal legislators during the COVID-19 era to (1) describe the content of vaccine-related tweets; (2) examine the differences in vaccine-related tweet content between Democrats and Republicans; and (3) quantify (and describe trends over time in) partisan differences in vaccine-related communication.MethodsWe abstracted all vaccine-related tweets produced by state and federal legislators between February 01, 2020, and December 11, 2020. We used latent Dirichlet allocation to define the tweet topics and used descriptive statistics to describe differences by party in the use of topics and changes in political polarization over time.ResultsWe included 14,519 tweets generated by 1463 state legislators and 521 federal legislators. Republicans were more likely to use words (eg, “record time,” “launched,” and “innovation”) and topics (eg, Operation Warp Speed success) that were focused on the successful development of a SARS-CoV-2 vaccine. Democrats used a broader range of words (eg, “anti-vaxxers,” “flu,” and “free”) and topics (eg, vaccine prioritization, influenza, and antivaxxers) that were more aligned with public health messaging related to the vaccine. Polarization increased over most of the study period.ConclusionsRepublican and Democratic legislators used different language in their Twitter conversations about vaccination during the COVID-19 era, leading to increased political polarization of vaccine-related tweets. These communication patterns have the potential to contribute to vaccine hesitancy.