The Missing Part of America’s Pandemic Response
Last month, Cary P. Gross and Ezekiel J. Emanuel argued that scientific advances are essential to fighting a pandemic, and they faulted America’s top medical-research agency, the renowned National Institutes of Health, for not moving faster to produce more research on COVID-19. During the coronavirus pandemic, they wrote, “the NIH has appeared more a doddering, tired institution than a robust giant bestriding the gap between science and clinical care.”
On June 5, The Atlantic published an opinion piece that does serious injustice to National Institutes of Health (NIH) frontline workers, researchers, and administrators who, in response to the COVID-19 pandemic, pivoted to achieve groundbreaking advances in vaccines, treatments, and diagnostic tests with unprecedented speed. In support of these workers, NIH strenuously objects to the article’s misguided and woefully incomplete portrayal of our COVID-19 response.
The article asserts that the NIH should “have been well positioned to create treatment guidance for doctors caring for patients hospitalized with a brand-new disease”—a claim that gives the misimpression that NIH didn’t propagate treatment information. In fact, NIH convened a panel of academic and government experts in March 2020 to critically review and synthesize available data from clinical trials and other study reports to provide clinicians with guidance on how to care for patients with COVID-19. The first NIH COVID-19 Treatment Guidelines were published on April 21, 2020, and the panel has issued more than 50 updated editions since. The guidelines have been visited more than 30 million times.
The article disparages NIH’s pursuit of therapeutic options as inadequate, but the authors seem unaware of the agency’s major efforts to seek effective treatments. In February 2020, before many Americans had realized the magnitude of the pandemic, researchers began enrolling COVID-19 patients into the Adaptive COVID-19 Treatment Trial (ACTT), a multisite clinical trial organized and supported by NIH. Less than three months later, preliminary data indicated that the antiviral drug remdesivir is safe and improved clinical outcomes, thus identifying an effective COVID-19 treatment. By May 1, 2020, the FDA authorized the drug for emergency use in hospitalized patients 12 years and older. NIH initiated three additional ACTT trials, testing various agents in combination with remdesivir, and found that the addition of the anti-inflammatory drug baricitinib reduced time to recovery for hospitalized patients.
Additionally, NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership launched in May 2020 to develop a coordinated research strategy and prioritize the most promising therapeutic agents for testing against COVID-19. ACTIV streamlined the process for adding new agents into trials and rapidly deployed existing NIH networks of more than 620 trial sites across the U.S. and internationally. The initiative has so far evaluated more than 800 therapeutic agents and prioritized 33 for inclusion in ACTIV master protocols. Twenty-seven of these agents have completed testing, and six agents have shown compelling evidence of benefit in randomized clinical trials. Fifteen agents have been shown to be ineffective against COVID-19—a finding that is equally crucial for informing clinical practice. ACTIV also includes a Tracking Resistance and Coronavirus Evolution initiative, focused on identifying emerging variants of SARS-CoV-2 and sharing data about vaccine and therapeutic resistance.
While the article recognizes NIH’s profoundly important contributions in developing the stabilized coronavirus spike protein used in the COVID-19 vaccines available in the United States, it shortchanges the accomplishment. The National Institute of Allergy and Infectious Diseases (NIAID) has spent the past 20 years working on vaccines against HIV, Ebola, influenza, respiratory syncytial virus, Zika, and other viral infections. These studies resulted in the vaccine-design approach that would allow for the development of the stabilized SARS-CoV-2 spike protein. Moreover, NIAID already had initiated pandemic-preparedness efforts that were used as the blueprint for the rapid development of the mRNA COVID-19 vaccines. Just 198 days after the novel coronavirus’s genomic sequence was released, a Phase 3 clinical trial of the Moderna COVID-19 vaccine began, supported by NIH and the Biomedical Advanced Research and Development Authority. NIH mobilized its existing clinical-research networks to enroll a diverse cohort of participants at sites across the country and provided expert clinical-trial and immunologic support for this and other Phase 3 COVID-19 vaccine trials. The vaccine candidate received FDA emergency use authorization in just 11 months, an unprecedented achievement. To put that into perspective, the first measles vaccine took 10 years to develop; the first HPV vaccine took 22 years.
The authors of the Atlantic article make no mention of NIH’s role in the swift development of COVID-19 diagnostic tests. NIH launched the Rapid Acceleration of Diagnostics (RADx) initiative in April 2020, just five days after receiving congressional appropriation. Using a Shark Tank–like approach quite different from the traditional NIH grant process, the program has sped the development and commercialization of COVID-19 tests. Notably, in only two years, companies supported by RADx have added approximately 2 billion tests and testing products to the U.S. capacity. The first at-home COVID-19 test to receive an FDA emergency use authorization was developed with RADx’s assistance, and companies supported by the initiative have now received more than 40 such authorizations.
The authors also take issue with NIH’s response to long COVID. To have a fighting chance at identifying the underlying mechanisms of that condition, NIH built a multidisciplinary research consortium to design rigorous clinical trials and longitudinal studies enrolling thousands of individuals, and to assess electronic health records and real-world data studies of more than 60 million adults and children. With $1.2 billion in backing from Congress, NIH went to work building the comprehensive infrastructure called the Researching COVID to Enhance Recovery (RECOVER) initiative. The effort involves a network of more than 30 institutions recruiting hundreds of researchers to conduct studies. The goal is to understand the full clinical spectrum of long COVID and who is at risk, and to identify potential biological targets for therapeutic intervention, which the agency plans to test in clinical trials this fall.
The authors also criticize NIH’s diversity efforts. While our agency fully agrees that diversity in biomedical research is a significant challenge, we take issue with the supposition that the agency hasn’t taken it seriously. In fact, it was NIH that shone a light on a funding gap for applications supporting Black investigators for NIH new research-project grants. Immediately following those findings, NIH launched important diversity efforts that have been associated with narrowing the funding-support gap between white and Black investigators by 75 percent since 2016. NIH leadership was dissatisfied that the gap hadn’t fully closed. In response, the agency launched the UNITE initiative to address issues of structural racism in NIH-funded biomedical research in February 2021. NIH programs also have substantially increased the number of early-stage investigators awarded first-time research-project grants from fewer than 600 in fiscal 2013 to a record high of 1,513 in fiscal 2021. We will continue to do our part to foster a diverse biomedical-research workforce that reflects the diversity of the nation.
NIH acknowledges that there is always room for improvement. We are assessing which lessons we might learn from our pandemic response and the many other research programs that we have supported. However, we are proud of the contributions our community has made to the COVID-19 pandemic response, including to the rapid development of effective diagnostic tests, treatments, and vaccines. The authors of the Atlantic article had ready access to all of the above information. Unfortunately, at a time when trust in science seems to be losing ground in the public eye, they published an essay that, through the sum of its omissions, is profoundly misleading.
Lawrence A. Tabak, D.D.S., Ph.D.
National Institutes of Health
Cary P. Gross and Ezekiel J. Emanuel respond:
We have great respect for the individual efforts of NIH scientists, clinical staff, and other frontline workers. And we recognize the agency’s important role in convening experts and synthesizing existing evidence during a time of great uncertainty. But the agency’s problem lies in the generation of new evidence. As we explained in our article, research supported by other institutions—funders that lack the NIH’s budget and stature—is getting under way faster and producing actionable findings sooner than NIH-supported research is. One study that we discussed, the United Kingdom’s RECOVERY trial, launched quickly on a modest budget and has yielded more insights into COVID treatment than any other effort. To be sure, the NIH has produced important studies in the COVID-19 era, but why not see what it can learn from investigators in other settings? Science depends on open dialogue. Our view is that the NIH could do more to strengthen America’s clinical-research enterprise, and it needs a different strategy urgently.