Developing Treatment Guidelines During a Pandemic Health Crisis: Lessons Learned From COVID-19

Abstract

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.

Figure 1.. NIH COVID-19 treatment guidelines: the first year.

BAM = bamlanivimab; CAS = casirivimab; CQ = chloroquine; DEX = dexamethasone; EAP = Expanded Access Program; ETE = etesevimab; EUA = emergency use authorization; FDA = Food and Drug Administration; HCQ = hydroxychloroquine; IL-6 = interleukin-6; IMD = imdevimab; IVM = ivermectin; NIH = National Institutes of Health; RDV = remdesivir; TCZ = tocilizumab.

Appendix Figure.. COVID-19 treatment publications on PubMed.

For a detailed explanation of the search strategy, please see the Supplement.

Figure 2.. Key clinical studies for developing treatment recommendations for COVID-19.

This figure is not inclusive of all studies that informed recommendation statements or of all drugs for which there are recommendation statements. For published articles, dates reflect e-publication if applicable. For unpublished reports, dates reflect the posted date at the time of Panel review. Size of symbol corresponds to approximate study size. AZM = azithromycin; IL-6 = interleukin-6; mAbs = monoclonal antibodies. * Proportional to the log₁₀ of the number of participants in the target drug group.

Figure 3.. NIH COVID-19 treatment guidelines weekly page views and new U.S. COVID-19 cases.

The data on new COVID-19 cases were downloaded from the Centers for Disease Control and Prevention COVID Data Tracker on 19 April 2021. Domestic and international weekly page views through 19 April 2021 were obtained from Google Analytics on 4 May 2021. NIH = National Institutes of Health.