Lessons From COVID-19 for Pandemic Preparedness: Proceedings From a Multistakeholder Think Tank

Abstract

While the coronavirus disease 2019 (COVID-19) pandemic continues to present global challenges, sufficient time has passed to reflect on lessons learned and use those insights to inform policy and approaches to prepare for the next pandemic. In May 2022, the Duke Clinical Research Institute convened a think tank with thought leaders from academia, clinical practice, the pharmaceutical industry, patient advocacy, the National Institutes of Health, the US Food and Drug Administration, and the Centers for Disease Control and Prevention to share, firsthand, expert knowledge of the insights gained from the COVID-19 pandemic and how this acquired knowledge can help inform the next pandemic response. The think tank focused on pandemic preparedness, therapeutics, vaccines, and challenges related to clinical trial design and scale-up during the early phase of a pandemic. Based on the multi-faceted discussions, we outline 10 key steps to an improved and equitable pandemic response.

The coronavirus disease 2019 pandemic showcased collaborative successes of academia, federal agencies, and industry but also mistakes and deficiencies. We highlight critical lessons and necessary steps toward a more effective response to ensure the United States and the world are prepared for the next pandemic.

By 5 August 2022, 550 million documented coronavirus disease 2019 (COVID-19) infections had resulted in 6.4 million deaths globally [1]. The pandemic heralded unprecedented scientific discovery with thousands of clinical trials that resulted in new vaccines; novel vaccine platforms; and new and repurposed treatments, diagnostic testing, and clinical care approaches. In May 2022, the Duke Clinical Research Institute convened a think tank of stakeholders from academia, clinical practice, the pharmaceutical industry, patient advocacy, the National Institutes of Health (NIH), the US Food and Drug Administration (FDA), and the Centers for Disease Control and Prevention (CDC) to discuss the strategies applied and lessons learned from the COVID-19 pandemic in the United States and determine how these insights can inform future pandemics. The leadership of Duke Clinical Research Institute and the think tank chairs selected representatives and stakeholders from academia, public health, government, and industry based on their involvement and leadership in the COVID response. All participants provided information on potential conflicts of interest, which are included in the Notes section. We acknowledge the limitation of not including bioethicists and community representatives and view this as a priority for future think tanks.

STRATEGIES TO IMPROVE PANDEMIC RESPONSIVENESS

The think tank focused on the response to the early pandemic by US public health agencies, academic institutions, health systems, and industry and on developing accurate and reliable diagnostic tests, which are critical in the healthcare response. They also considered the history of FDA emergency use authorizations (EUAs; Supplementary Table 1), the primary mechanism by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics, vaccines, and treatments were initially made available in the United States (Figure 1), as well as trials and subsequent approvals for therapeutics and vaccines (Table 1, Figure 2).

Figure 1.

Timeline of key events in emergency use authorization for in vitro diagnostic tests. Abbreviations: COVID-19, coronavirus disease 2019; EUA, emergency use authorization; HHS, US Department of Health and Human Services; ITAP, Independent Test Assessment Program; IVD, in vitro diagnostics; LDT, laboratory-developed test; OTC, over the counter; POC, point of care; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Table 1.

Level of Evidence for Severe Acute Respiratory Syndrome Coronavirus 2 Therapeutics and Vaccines at the Time of Emergency Use Authorization Issuance

Drug/Vaccine	Description	Level of Evidence at Emergency Use Authorization Issuance
Chloroquine and hydroxychloroquine	Antimalarial/immunomodulator	Observational data
Remdesivir (Veklury)	SARS-CoV-2 nucleotide analog RNA polymerase inhibitor	Phase 3
Coronavirus disease 2019 convalescent plasma	Pooled human plasma with high titers of anti-SARS-CoV-2 antibodies	Observational data
Bamlanivimab	Spike protein receptor-neutralizing IgG1 monoclonal antibody	Phase 2
Baricitinib (Olumiant)	Janus kinase inhibitor	Phase 3
Casirivimab/Imdevimab (REGEN-COV)	Recombinant human IgG1 monoclonal antibodies targeting receptor-binding domain of the spike protein	Phase 1/2
Bamlanivimab/Etesevimab	Spike protein receptor-neutralizing IgG1 monoclonal antibodies; distinct but overlapping epitopes	Phase 2/3
Sotrovimab (Xevudy)	Spike protein receptor-binding recombinant human IgG1κ monoclonal antibody	Phase 1/2/3
Tocilizumab (Actrema)	Interleukin-6 inhibitor; recombinant humanized monoclonal antibody	Phase 3
Tixagevimab/Cilgavimab (Evusheld)	Spike protein receptor-neutralizing IgG1 monoclonal antibodies; distinct but nonoverlapping epitopes	Phase 3
Nirmatrelvir/Ritonavir (Paxlovid)	Nirmatrelvir: SARS-CoV-2 main protease inhibitor Ritonavir: human immunodeficiency virus type 1 protease inhibitor and CYP3A inhibitor	Phase 2/3
Molnupiravir (Lagerivo)	Nucleoside analogue that inhibits SARS-CoV-2 replication by viral mutagenesis	Phase 2/3
Bebtelovimab	Spike protein receptor-neutralizing IgG1 monoclonal antibody	Phase 1/2
Pfizer-BioNTech vaccine (Comirnaty)	Messenger RNA vaccine	Phase 3
Moderna vaccine (Spikevax)	Messenger RNA vaccine	Phase 3
Janssen vaccine	Adenovirus vector vaccine	Phase 3
Novavax vaccine (Nuvaxovid)	Subunit protein vaccine	Phase 3

Abbreviations: Ig, immunoglobulin; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

Timeline of COVID-19 emergency use authorization and approved therapeutics (A) and vaccines (B). Revisions noted only include major amendments to EUAs. Abbreviations: CCRT, continuous renal replacement therapy; COVID-19, coronavirus disease 2019; EUA, emergency use authorization; yo, year old.

The discussion highlighted the lack of a coordinated response that resulted in testing disparities during the pandemic's early phase. Access to testing was concentrated at large health centers, which was later replicated as point-of-care tests became available. Similarly, the challenges of rapid clinical trial start-up resulted in thousands of patients being treated with unproven therapies without the opportunity to contribute to high-quality trials to confirm the efficacy and safety of these products [2].

10 STEPS TO AN IMPROVED AND EQUITABLE PANDEMIC RESPONSE

The think tank participants focused on the most informative challenges, shortcomings, and successes from the COVID-19 response to develop high-level recommendations for future pandemic preparedness. Ten themes emerged as essential to improving future pandemic responses (Table 2). Here, we summarize these insights with the goal of affecting policy change to proactively prepare for the next pandemic and optimize an equitable response to future public health emergencies.

Table 2.

10 Steps to an Improved and Equitable Pandemic Response

Step	Description
Increase collaboration and coordination among academia, government, and industry	Leverage successful links among academia, government, and industry established during the coronavirus disease 2019 pandemic to prepare swiftly for future pandemics
2. Enhance regulatory flexibility and consumer advice around diagnostic tests	Develop a federal panel for evidence-based guidelines for diagnostic tests for future pandemic pathogens
3. Enhance coordination of clinical trials through a national trials network	A federally funded national clinical trials network capitalizes on the large US population and widespread electronic health records systems to coordinate and prioritize trials to answer pressing clinical management questions with harmonized and robust end points
4. Invest in “warm” clinical trials infrastructure	“Warm” clinical trials infrastructure with a “disease agnostic” approach includes supply chain readiness for scale-up, fungible trials and diagnostics staff, and equipment and devices that can be rapidly reassigned in a public health emergency
5. Diversify trial center locations, workforce capacity, and recruitment	A federal trials network should include non-academic and safety-net hospitals, pharmacies, and public health departments to ensure equity in access to trials and diversify trial recruitment
6. Use pragmatic trial and “direct-to-participant” trials capabilities	Increasing capacity for e-consent, remote monitoring, and patient-reported outcomes will increase trial diversity and equity by allowing for broader community engagement
7. Develop robust real-world data sources and a pandemic “early watch” system	A national trials network could facilitate reporting of real-world evidence for novel pathogen outcomes, test performance, and treatment and vaccine effectiveness and help to drive policy and public health efforts
8. Establish a framework for a globally uniform regulatory response	International regulatory harmonization and the global coordination of drug safety reporting systems would alleviate the burden on industry and facilitate swifter global access to diagnostics, therapeutics, and vaccines
9. Achieve global equity in access to diagnostics, therapeutics, and vaccines during pandemic response	Interpandemic investment in multiple global sites for drug and diagnostic manufacturing capabilities may circumvent nationalism and global protectionism for future pandemics
10. Address disinformation, misinformation, and mistrust in science	Decentralization of scientific knowledge and public health activity and collaboration with diverse messengers are essential to pandemic preparedness and should be prioritized and fostered during interpandemic periods

Increase Collaboration and Coordination Among Academia, Government, and Industry

Collaboration among academia, government, and industry was critical to the COVID-19 pandemic response. Operation Warp Speed, the Adaptive COVID-19 Treatment Trial (ACTT), and the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Trial highlighted the synergy in public–private partnerships to fast-track scientific discovery and successfully moved linear clinical trials to a safe parallel process. Outside of the United States, primarily in countries where universal healthcare eliminated some of the barriers faced in the United States, large trials rolled out quickly, impacting the care of people with COVID-19, particularly in the inpatient setting. The US-based approach of leveraging existing clinical trial networks and collaborations between NIH and industry accelerated the timeline and feasibility of trials.

Early in 2020, the FDA issued guidance for clinical laboratories regarding the pathway to diagnostic EUAs, providing urgent flexibility to develop diagnostic tests with a lower threshold of analytical data [3]. Federal economic incentives provided diagnostic manufacturers security to produce large volumes of tests. Yet, diagnostic test development and validation were concentrated mainly in academic health systems and industry with little preexisting process for collaboration with smaller or rural hospital laboratories, delaying access to testing in these communities. Industry limited sharing of viral strains and clinical samples to preexisting relationships, delaying the development and validation of diagnostic tests.

Successful links among and within academia, government, and industry established during the COVID-19 pandemic are essential for early response to emerging public health threats, such as the timely sharing of global clinical samples for rapid development of diagnostics, therapeutics, and vaccines. Creating these contracts and agreements now and formalizing diverse networks from the partnerships that developed over the past 2 years are key to accelerating the rapid scale-up of discovery needed to respond early and swiftly to the next pandemic. The US approach of harnessing existing clinical trial networks and forging rapid public–private collaborations and industry-sponsored clinical trials led to discoveries of new COVID-19 vaccines and treatments.

Enhance Regulatory Flexibility and Consumer Advice Around Diagnostic Tests

During the COVID-19 pandemic, it was critical for the validation and rollout of laboratory-developed tests (LDTs) to be expedited in order to meet clinical needs and expand access to testing and diagnosis. The FDA facilitated this by permitting the use of LDTs while awaiting EUA determinations and simplifying the test validation process [3]. As a result, hundreds of diagnostic tests were authorized quickly. Yet, there were delays and gaps in access to testing early in the pandemic due to regulatory hurdles related to deploying or revising LDTs and supply chain bottlenecks. A degree of regulatory flexibility is essential to expedite testing access, such as permitting selected substitutions when LDTs are revised (eg, minor alterations in swabs and transport media). In addition, rapid and reliable information on the quality and accuracy of each diagnostic test is critical to guide clinical care and treatments. Facilitating the federal government's ability to maintain and mobilize stockpiles is also important to alleviate supply chain bottlenecks experienced during COVID-19 due to “just-in-time” imperatives.

Once tests were available under EUA, consumer advice was not readily provided on test quality, accuracy, and appropriate use. Consumers received messaging from the lay press, social media communication, and local test availability for guidance, which was not based on peer-reviewed studies. This resulted in tests being used outside of EUA-authorized indications and settings, weakening consumer confidence in tests [4].

To address these issues, a comprehensive community education and outreach plan is critical to ensure individuals have access to reliable information from a central, trustworthy source. This plan should address the specific needs and concerns of the public to limit confusion and improve access to testing and, ultimately, diagnosis. In addition, a federal panel for diagnostic guidelines, similar to the NIH COVID-19 Treatment Guidelines Panel, should address consumer use of tests by creating evidence-based recommendations.

Enhance Coordination of Clinical Trials Through a National Trials Network

The United States led the world in COVID-19 cases and mortality but not in clinical trial enrollment and development of clinical evidence. Estimates suggest that <10% of hospitalized patients in the United States participated in clinical trials for COVID-19 [5]. Globally, only 5% of trials were adequately randomized and powered, representing 26% of patient enrollment [2]. The international World Health Organization Solidarity Trial for COVID-19 Treatments and the United Kingdom's Randomised Evaluation of COVID-19 Therapy trials demonstrated the success of coordinated clinical research networks to enroll trials quickly with lean protocols, large sample sizes, and robust end points by using innovative and pragmatic designs that capitalized on national health databases [6]. In the United States, by contrast, there were initially many small, underpowered trials for COVID-19 therapeutics. However, large-platform trials, such as ACTT, that were conducted to allow for experimental therapies to be added and dropped adaptively were pivotal to creating an evidence base for novel and repurposed COVID-19 therapeutics [7]. In addition, some industry-sponsored trials for monoclonal antibodies and antiviral treatments were rapidly launched, recruited, and completed, leading to early EUAs and authorizations. However, too many clinical trials failed because of slow or incomplete accrual, a potential consequence of uncoordinated competition among parallel trials.

Learning from the impact of the ACTT and ACTIV NIH-led programs, a more centralized approach that engages academia, regulatory bodies, and industry simultaneously should be a best practice for future pandemics. Large-platform trials that leverage the country's sizeable population and widespread electronic health records (EHRs) system to answer vital clinical questions are essential for public health emergencies. To prepare for this, development of a single national system of trial participants, drawing from linked EHRs, would allow rapid randomization of large numbers of participants into definitive clinical trials. The National COVID Cohort Collaborative (N3C), an open science community that aims to aggregate and harmonize EHR data across clinical organizations in the United States, is an example of a novel partnership for collaborative data sharing that could be used to address key clinical questions in future health emergencies [8]. Trials could be conducted through a federally funded clinical trials network, the Patient Centered Outcomes Research Institute's PCORnet [9], or facilitated through data-sharing platforms such as N3C, with a primary objective of prioritizing and addressing the most pressing clinical management questions and emphasizing harmonized end points to provide a robust evidence base for EUA applications and FDA authorizations. Lessons can also be learned from the National Emerging Special Pathogens Training and Education Center's Special Pathogens Research Network, which uses a central, rapid-response institutional review board to support research in special pathogens across their multiple research partners [10]. A unified clinical trials network would also incentivize companies with candidate drugs and biologics to participate through the ease of centralized laboratories, data and safety monitoring boards, access to large participant numbers, and increasing statistical power for definitive end points.

Invest in “Warm” Clinical Trials Infrastructure

During the COVID-19 pandemic, the NIH developed a clinical trial inventory of federally funded sites to identify where the country had capacity [11]. Despite this initiative, there was a lag time in scaling up trial enrollment in areas where cases were high, resulting in use of unproven treatments and little to no ability to contribute to high-quality clinical studies. Investing in and maintaining operational “warm” clinical trials infrastructure, diagnostic capabilities, manufacturing capacity, and supply chains maximizes the readiness to enroll participants in clinical trials and allows agile trial networks to respond quickly to changing incidence of infection.

Warm clinical trials infrastructure ranges from laboratory workforce capacity [12] to supply chain readiness for scale-up and predefined funding for a few well-designed and validated diagnostic tests that can run on high throughput platforms. Pandemic preparedness infrastructure requires a “disease agnostic” approach and maintenance during interpandemic activities. To achieve this, critical elements of the clinical trials infrastructure must be fungible, including trials and diagnostic staff, supply chains, equipment, and devices, so that it can be devoted to studies in other disease areas between pandemics but then be rapidly reassigned in a public health emergency.

Diversify Trial Center Locations, Workforce Capacity, and Recruitment

In the United States, clinical trials are typically run from academic medical centers or commercial clinical research firms with established trial infrastructure. During the COVID-19 pandemic, the fault lines in this model became evident as academic medical centers were overwhelmed with clinical care responsibilities and struggled to staff trials and support clinical research. Outside of academic medical centers, the responsibility of clinical trials often fell on medical staff who had little infrastructure to conduct quality trials.

Clinical trials during future pandemics and nonpandemic periods should ensure broad representation, including nonacademic and community hospitals, and recruitment should emphasize participant diversity. Creating community trial networks that include nonacademic and safety-net hospitals, pharmacies, and public health departments is key to diversification, and members should be trained, supported, and sustained during interpandemic times as an essential component of the warm trials infrastructure. Community trial sites provide opportunities to embed clinical research with clinical care, strengthening community infrastructure and supporting long-term sustainability. Community-based clinicians and federally qualified health centers often have established and trusting relationships with patients, which increases the likelihood of trial participation among underserved populations and improves equity in access to trials [13].

Use Pragmatic Trial Designs and “Direct-to-Participant” Trials Capabilities

A major barrier to trial participation is accessibility of the study site. The COVID-19 pandemic prompted more “direct-to-participant” (remote) trials due to concerns about virus transmissibility and the logistic challenges of public health restrictions. Trials such as ACTIV-6 (COVID-19 Study of Repurposed Medications) leveraged telemedicine, direct-to-participant delivery of study drugs and materials to patients’ homes, and remote collection of participant-reported outcomes, limiting the need for in-person contact between the study team and the participant. These methods center the participant in clinical trial design and reduce patient participation burden while allowing for the attainment of robust outcomes [14].

Improving rapid response requires a more pragmatic, simplified, and streamlined trial study design that draws data from EHRs and uses remote monitoring and e-consent to allow individuals to participate in trials without leaving their homes. While this approach is best suited to drugs with understood safety profiles (eg, repurposed drugs), even in studies of novel drugs, streamlined trial designs that focus on collecting the most critical information are essential. Direct-to-participant trials lower barriers to trial access and allow for broader community involvement in clinical trials, potentially increasing recruitment diversity and equity [15] and engaging a greater proportion of the public in generating scientific data that, in turn, enhances generalizability of the results. Greater investment in and early initiation of pragmatic and direct-to-participant trials will be critical to future pandemic responses.

Develop Robust Real-World Data Sources and a Pandemic “Early Watch” System

Real-world data sources are vital to monitoring a novel infection, particularly when the pathogen is rapidly evolving. During the COVID-19 pandemic, much of the data on vaccine effectiveness, persistence of immunity, and viral variants were captured through established national health system databases, for example, in the United Kingdom, Israel, and Qatar. These sources of real-world evidence were essential to regulatory decisions and guided scientific inquiry and public health advice. A national trials network in the United States that aggregates EHR data could have a dual purpose of trial coordination and a data repository to facilitate reporting of real-world evidence for emerging pathogens and variants, informing clinical trial designs, test performance, treatment and vaccine effectiveness, safety monitoring, and implementation assessments. In addition, establishing multinational collaborations and infrastructure is essential to more effective collection of real-world data to guide pandemic responses. This resource would provide timely evidence to support the value of interventions, specifically among the diverse US population, to drive policy efforts and public health guidelines.

The SARS-CoV-2 genetic sequence was shared early in the pandemic. However, for test developers, this information was insufficient to understand how the test might perform in the presence of viral mutations; clinical samples were needed for this. Surveillance for new pathogens, both in the United States and globally, gives diagnostic, treatment, and vaccine development a head start on preparedness. Early warning, even a few weeks, for diseases of pandemic potential provides public health and other authorities critical time to prepare, collaborate with global partners, and share early specimens for diagnostic and treatment development. A “pandemic watch” system should monitor diseases of pandemic potential and identify when a disease that is capable of human-to-human transmission is at risk of zoonotic spillover that necessitates a global response [16]. This surveillance system would prioritize pathogens of pandemic potential for investment and research, providing opportunities for prospective technological innovation and novel treatments for diseases that often receive little funding.

Establish a Framework for a Globally Uniform Regulatory Response

The COVID-19 pandemic demonstrated many challenges and inefficiencies in the global regulatory requirements for pharmaceutical authorizations and safety monitoring procedures. Manufacturers of vaccines and therapeutics received multiple information requests and had meetings with national regulatory authorities, at times with contradictory requirements, placing a significant burden on industry at a critical time. Additionally, regulatory differences across countries, from study design, trial end points, chemistry manufacturing and control expectations, and product label requirements, delayed access to essential drugs and vaccines.

As therapeutics and vaccines for pandemic pathogens often have less robust data available, addressing standard and universal international regulatory requirements for pandemic treatments and vaccines should be prioritized by international collaborations such as the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use [17]. International regulatory harmonization should also include the centralization and coordination of drug safety systems across national networks so that adverse event signals might be seen and analyzed earlier. Global harmonization of regulatory and safety requirements would alleviate some barriers in access to pandemic treatments and vaccines, increase efficiency within industry, and ensure timely delivery of the supply to patients.

Achieve Global Equity in Access to Diagnostics, Therapeutics, and Vaccines During Pandemic Response

Diagnostics, therapeutics, and vaccine equity must be central to future pandemic responses. Efforts for global diagnostics, therapeutics, and vaccine distribution attempted during the COVID-19 pandemic did not have all the intended results. Global collaborations were established early in the pandemic to ensure equity in access; however, they were insufficient to combat vaccine and diagnostic nationalism and global protectionism. The successes in access to diagnostics and vaccines during the COVID-19 pandemic leveraged preexisting global partnerships and existing programs (eg, human immunodeficiency virus and tuberculosis) to pivot to COVID-19.

Investing in infrastructure and partnerships to distribute global public goods is needed during interpandemic times, rather than waiting for the next public health threat. Infrastructure development, such as establishing drug and diagnostic manufacturing capability in each geographic region, takes significant investment and time and will be crucial for interpandemic efforts. Building up these national public health capacities allows countries to pivot rapidly to respond to a broad swathe of public health emergencies. These investments in global health diagnostic, therapeutic, and vaccine infrastructure and surveillance should be considered essential to preparing the world for the emergence of pandemic pathogens.

Address Disinformation, Misinformation, and Mistrust in Science

The benefits of public health advice, therapeutics, and vaccines during a pandemic are limited by individual uptake [18]. With every COVID-19 vaccine booster recommended in the United States, uptake has declined, with fewer eligible individuals vaccinated with each serial dose [19]. The inconsistent use of public health advice in the United States has not just affected vaccinations but also adherence to behavioral measures and the use of SARS-CoV-2 therapeutics. The COVID-19 pandemic propelled the scientific method into the public arena. The processes of generating, interpreting, and iterating evidence and of modifying recommendations based on new evidence became a matter of public scrutiny and, ultimately, distrust. Instead of coordinated communication, advice was fragmented across government and political sources, health authorities, social media, a flood of non–peer-reviewed preprints [20], and the lay press. The rapid, unfiltered flow of information allowed the uninformed, misinformed, and bad actors to build stories that harmed good public health practices and diminished the value of trusted information sources.

It is imperative to find solutions to combat mistrust in science. Even the best science cannot be implemented without clear, simple, and consistent messages from trusted sources. Two key strategies to rebuilding public trust in science are summarized below.

Decentralization of Scientific Knowledge and Public Health Activity

The production of scientific knowledge is currently concentrated in academic medical centers, biomedical agencies (eg, the NIH, FDA, and CDC), and biomedical and pharmaceutical companies. Generation of scientific knowledge needs to have community input. Community-based trial initiatives, such as Rapid Acceleration of Diagnostics—Underserved Populations, have demonstrated that the presence of local trusted voices is critical to encouraging COVID-19 testing and vaccination. As such, local public health authorities and community-based organizations are integral to public health efforts, and long-term investment in developing and sustaining deep, enduring partnerships with these individuals and organizations is crucial to ensuring the public is engaged and invested in scientific discovery.

Collaboration With Diverse Messengers and Creative Communication

Strengthening partnerships between the CDC, local health departments, and community-based organizations is critical to engaging local messengers for creative, nontraditional communication strategies to reach individuals who are less exposed or less receptive to traditional forms of public health messaging. These partnerships should be established for routine public health messaging and can be leveraged during public health emergencies. Social media is a primary method for consumption of information with broad reach; a focus on combatting misinformation and disinformation directly on these platforms is critical. Although complete elimination of misinformation and disinformation is not possible, increasing the confidence in our public health institutions, both local and national, by disseminating clear public health information through trusted and educated messengers is a priority for future pandemics.

The think tank discussions did not explore the ethical or health-adjacent considerations of pandemic planning, such as economic, educational, and cultural considerations. Assessing the values and preferences of individuals and communities, particularly with regard to balancing individual rights and community well-being, were not addressed in detail. The tension between public health restrictions (eg, mask mandates, vaccine mandates, stay-at-home orders) and their potential population health benefits in reducing morbidity and mortality, as well as the impact of individual restrictions on mental health, children, education, economic welfare, and the perceived limitations on individual liberties, were central to many of the challenges during the pandemic. There is still a lack of guidance on how to approach future pandemics and public health emergencies in terms of balancing the relative benefits and harms of public health interventions; understanding who should be tasked with those decisions (eg, local health departments, state health departments, federal agencies, politicians/elected representatives, public health practitioners, or community groups); and how these decisions should be made, whether on a community, national, or global level.

CONCLUSIONS

The COVID-19 pandemic highlighted many collaborative successes of academia, federal agencies, and industry to work together for the good of the global community. Diagnostics, therapeutics, and vaccines were developed rapidly and at scale, often through public–private partnerships. Scientific and public health communication with the public became more direct; trial design became more streamlined and participant-centered; and protocol finalization and operational setup succeeded more swiftly. The EUA process was tested in a global pandemic for the first time and was found to be an agile tool, largely fit for purpose. On the other hand, the lack of an early comprehensive federal response, driven in part by the breakdown of public health infrastructure over decades, the inherent limitations of a centralized trial infrastructure, the absence of global regulatory harmonization, and the increasing mistrust in science highlighted by COVID-19, require immediate attention. Maintaining the excellent progress that has been made in pandemic responsiveness while investing in areas where further work is needed, will be critical to ensure the United States is prepared for the next pandemic.

Supplementary Data

Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.

Notes

Author Contributions. All authors take responsibility for the accuracy of the discussion and had authority over manuscript preparation and the decision to submit the manuscript for publication. Concept and design: S. N., Sh. N., R. T. G. Drafting of the manuscript: S. N., Sh. N., R. T. G. Critical revision of the manuscript for important intellectual content: All authors. Administrative, technical, or material support: All authors. Supervision: S. N., R. T. G.

Acknowledgments. The authors thank Jennifer Gloc for assistance in organizing the think tank and supporting manuscript preparation. The authors also thank the think tank speakers and participants and Dr Warren Kibbe for his support with manuscript preparation.

Disclaimer. This article reflects the authors’ views and should not be construed to represent the US Food and Drug Administration (FDA) or the National Institutes of Health (NIH) views or policies. The Duke Clinical Research Institute had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and the decision to submit the manuscript for publication.

Financial support. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Creation of the manuscript was funded internally by the Duke Clinical Research Institute (DCRI). M. S. reports support for this work from DCRI (travel/hotel) and K24DA034621. B. L. reports support for this work as an employee of Moderna.