Development of the Guidelines Each section of the Guidelines is developed by a working group of Panel members with expertise in the Downloaded from https://www.covid19treatmentguidelines.nih.gov/ on 7/6/2022 COVID-19 Treatment Guidelines 9 area addressed in the section. Each working group is responsible for identifying relevant information and published scientific literature and for conducting a systematic, comprehensive review of that information and literature. The working groups propose updates to the Guidelines based on the latest published research findings and clinical information. New Guidelines sections and recommendations are reviewed and voted on by the voting members of the Panel. To be included in the Guidelines, a recommendation statement must be endorsed by a majority of voting members; this applies to recommendations for and against treatments and cases where there is insufficient evidence to recommend either for or against treatments. Updates to existing sections that do not affect the rated recommendations are approved by Panel co-chairs without a Panel vote. Panel members are required to keep all Panel deliberations and unpublished data that are evaluated during the development of the Guidelines confidential. Method of Synthesizing Data and Formulating Recommendations The working groups critically review and synthesize the available data to develop recommendations. During this process, the Panel evaluates the data, including the source of the data, the type of study (e.g., randomized controlled trial, prospective or retrospective cohort study, case series, in vitro study), the quality and suitability of the methods, the number of participants, and the effect sizes observed. The recommendations in these Guidelines are based on scientific evidence and expert opinion. Each recommendation includes 2 ratings: an uppercase letter (A, B, or C) that indicates the strength of the recommendation and a Roman numeral with or without a lowercase letter (I, IIa, IIb, or III) that indicates the quality of the evidence that supports the recommendation. Table 1. Recommendation Rating Scheme Strength of Recommendation Quality of Evidence for Recommendation A: Strong recommendation for the statement B: Moderate recommendation for the statement C: Weak recommendation for the statement I: One or more randomized trials without major limitations IIa: Other randomized trials or subgroup analyses of randomized trials IIb: Nonrandomized trials or observational cohort studies III: Expert opinion To develop the recommendations in these Guidelines, the Panel uses data from the rapidly growing body of research on COVID-19. The Panel also relies heavily on experience with other diseases, supplemented with the members’ evolving clinical experience with COVID-19. In general, the recommendations in these Guidelines fall into the following categories: • The Panel recommends using [blank] for the treatment of COVID-19 (rating). Recommendations in this category are based on evidence that the potential benefits of using this intervention outweigh the potential risks. • There is insufficient evidence for the Panel to recommend either for or against the use of [blank] for the treatment of COVID-19 (no rating). This statement is used when there are currently not enough data to support a recommendation, or the available data are conflicting. • The Panel recommends against the use of [blank] for the treatment of COVID-19, except in a clinical trial (rating). This recommendation is used for an intervention that has not clearly demonstrated efficacy in the treatment of COVID-19 and/or has potential safety concerns. More clinical trials are needed to further define the role of the intervention in treating COVID-19. Downloaded from https://www.covid19treatmentguidelines.nih.gov/ on 7/6/2022 COVID-19 Treatment Guidelines 10 • The Panel recommends against the use of [blank] for the treatment of COVID-19 (rating). This recommendation is used in cases where the available data clearly show a safety concern and/ or the data show no benefit to using this intervention for the treatment of COVID-19. Evolving Knowledge on Treatments for COVID-19 Remdesivir, an antiviral agent, is currently the only drug that is approved by the Food and Drug Administration for the treatment of COVID-19. An array of drugs that are approved for other indications and multiple investigational agents are being studied for the treatment of COVID-19 in clinical trials around the globe. These trials can be accessed at ClinicalTrials.gov. In addition, providers can access and prescribe investigational drugs or agents that are approved or licensed for other indications through various mechanisms, including Emergency Use Authorizations, Emergency Investigational New Drug applications, compassionate use or expanded access programs with drug manufacturers, and/or off-label use. Whenever possible, the Panel recommends that promising, unapproved, or unlicensed treatments for COVID-19 be studied in well-designed, controlled clinical trials. This recommendation also applies to drugs that have been approved or licensed for indications other than the treatment of COVID-19. The Panel recognizes the critical importance of clinical research in generating evidence to address unanswered questions regarding