key: cord-339561-sgbxzeuh authors: Snow, Elaine K; Miller, Jane L; Kester, Linda; Mendham, Natalie A; Heydorn, Joan D; Huang, Shingyee Cindy; Leu, Lily L; Kohoutek, Lisa M; Rosanelli, Natalie C; Harves, Kaitlin M title: Creation and maintenance of a table for assessment of evolving evidence for COVID-19–related treatments date: 2020-09-21 journal: Am J Health Syst Pharm DOI: 10.1093/ajhp/zxaa334 sha: doc_id: 339561 cord_uid: sgbxzeuh DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: This report describes the development and maintenance of a table to present an assessment of evidence for treatments used in patients with coronavirus disease 2019 (COVID-19). SUMMARY: AHFS Drug Information (AHFS DI) (American Society of Health-System Pharmacists, Bethesda, MD) is ASHP’s evidence-based drug compendium that contains drug monographs written for pharmacists and other healthcare professionals. The professional editorial and analytical staff of pharmacists critically evaluate published evidence to develop drug monographs for AHFS DI. In response to the global COVID-19 pandemic, these skills were applied to assess emerging evidence for COVID-19–related treatments, and the information was compiled into a new resource for pharmacists and other healthcare professionals to use at the point of care. A list of therapies was developed and prioritized based on review of scientific and public discussions on the use of these therapies in patients with COVID-19; certain therapies used for supportive care and therapies that might theoretically be harmful to patients with COVID-19 also were considered for inclusion. Potential treatments were identified, and the evidence for use in patients with COVID-19 was assessed and summarized in a table format. Information presented for each therapy included the rationale for use, summaries of clinical trials or experience, trial registry numbers, and dosage regimens. Comments on safety and efficacy, including limitations of available data, were presented along with recommendations from recognized authorities. The editorial team continued to add new therapies to the table and update existing entries as new evidence emerged. CONCLUSION: A comprehensive table that summarized available evidence for potential treatments for patients with COVID-19 was developed. The table format enabled the drug information editorial staff to provide ongoing updates as new information emerged during the pandemic. A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t The worldwide outbreak of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a global pandemic on March 11, 2020, 1 and by the end of March more than 750,000 cases and more than 36,000 deaths had already been reported worldwide (including more than 140,000 cases and more than 2,300 deaths in the United States). 2 New information with respect to the clinical characteristics and clinical course of COVID-19 and possible strategies for management of the disease was emerging daily. At that time, treatment consisted mostly of supportive care while a variety of investigational agents and therapeutic strategies were being explored. Multiple clinical trials were already in progress and many more were being initiated to evaluate a number of potential, but unproven, therapies. 3, 4, [6] [7] [8] News media widely disseminated stories of various therapies that were being used or suggested as potential treatments; however, that information was often lacking in appropriate context and evidentiary support. 5, 8 Healthcare professionals were faced with the challenge of monitoring a rapidly expanding volume of clinical research findings that often were based on uncontrolled, unpublished, and/or non-peer-reviewed studies. There was a clear need for reliable and evidence-based information on drugs and other therapies that could be used appropriately for the management of COVID-19 and its complications. [3] [4] [5] [6] [7] [8] [9] To support pharmacists and other healthcare professionals in making informed decisions about the use of various drugs and other treatments in patients with COVID-19, the drug information staff of an evidence-based drug information compendium decided to create a concise quick-reference document that would summarize the emerging evidence. The goal was to provide a succinct compilation of the existing evidence to provide nuance and perspective to early information being disseminated from various sources. Later efforts were directed at maintaining and enhancing the summaries as new information emerged. treatments. To select drugs and biologics for inclusion in AHFS's initial Assessment of Evidence for COVID-19-Related Treatments Table that treatments, and previous treatment experience with other coronaviruses. In addition, therapies that were being discussed in the context of COVID-19 in prominent news stories from both medical and general media outlets, as well as among the members of ASHP, also were considered. Because knowledge regarding the pathogenesis and optimum management of COVID-19 was rapidly evolving, some of the therapies were prioritized for inclusion in the evidence table based only on biologically plausible, but unproven, mechanisms and/or anecdotal observations or widespread discussion. The initial list of drugs was viewed as a starting point for this new resource, and the evidence table was designed as a living document that could be updated and expanded as needed to ensure currency and relevance, reflecting the evolving changes in therapeutic perspectives. Potential therapies identified for inclusion in the initial evidence table were divided among the AHFS DI editorial team, primarily based on each individual's therapeutic areas of expertise. Each individual was given the responsibility of researching, assessing, and creating A c c e p t e d M a n u s c r i p t releases, news reports, or preliminary (non-peer-reviewed) articles and was considered acceptable for the purposes of the evidence table, such sources were replaced as soon as published studies became available. Selection of a table format for presentation of the evidence summaries enabled presentation of information succinctly while still allowing inclusion of important details about clinical trial protocols and results, including limitations; this format also facilitated creation of a living document that could be easily expanded and updated as additional evidence accrued. A 6-column format was adopted as the most efficient way to organize and present information in the evidence table. The column headings and corresponding information presented are described below. Drug (or Biologic) Name. Drugs usually were listed individually; however, some entries were for groups of drugs when a class effect was discussed (eg, angiotensinconverting enzyme inhibitors, angiotensin II receptor blockers). A c c e p t e d M a n u s c r i p t Trials or Clinical Experience. The type of information (eg, case study or series; retrospective, observational study; randomized, controlled, comparative trial) available was presented. In many cases, trials that were in the planning or recruiting stages were listed or, in some cases, described, and the trial registry number was provided. Results of trials were presented; evidence based on preliminary results or interim analysis was presented when available but identified as preliminary. Major limitations of studies were noted. If initial evidence was related to clinical experience or studies in patients with other infections, such as severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or other conditions that might provide relevant insights, such as sepsis and acute respiratory distress syndrome (ARDS), the information was described as such. Data from studies that were later retracted were identified. Dosage. Dosages presented were those used in selected clinical studies or that were being investigated in selected registered studies. Dosages used in these trials often varied. If an emergency use authorization (EUA) was issued by FDA, that dosage was included. Conclusions and other comments on safety and efficacy of the drug(s) in patients with COVID-19, including limitations of available data, were presented. Recommendations from recognized authorities, including statements from FDA (eg, MedWatch alerts, EUAs), NIH (eg, recommendations of the COVID-19 Treatment Guidelines Panel), WHO, CDC, IDSA, and the Surviving Sepsis Campaign, were included. A separate list of references for each drug or drug class was provided in each edition of the COVID-19 evidence table. When available, the citations included digital object identifiers (DOIs), PubMed IDs (PMIDs), or URLs for the published articles to enable the user to easily find and retrieve the references. Citations for early-release articles were M a n u s c r i p t updated as the articles proceeded to final publication. Articles that publishers identified as not yet having undergone peer review were noted as such in the reference citation. Articles that were later retracted were identified. The first version of the Assessment of Evidence for COVID-19-Related Treatments Because the information on COVID-19 was evolving at such a rapid pace, the AHFS DI editorial team continued to monitor the evidence on a regular basis, sometimes daily, and promptly assessed and incorporated emerging evidence. Ongoing developments and research were monitored by reviewing new information from FDA, NIH, WHO, CDC, and IDSA, as well as the PubMed database, study protocols from ClinicalTrials.gov, and other sources as detailed in the "Research and Evidence Assessment" section. Selected news media also were included in the surveillance of information to provide insights into emerging interest in other therapies that might be added to the list. In addition, queries and discussions within the membership of ASHP informed the monitoring process. The editorial team updated the evidence table as new information was identified. New therapies were added using essentially the same criteria that were used for the first iteration of the table, and existing entries were updated by the assigned editorial team member. The goal was to keep up with the current state of knowledge for each therapy as understanding of the COVID-19 disease process progressed. New information generally was A c c e p t e d M a n u s c r i p t added to an existing entry (rather than entirely replacing existing text) to provide a comprehensive narrative of the evolving evidence related to the role of the therapeutic agent in treating patients with COVID-19. Each entry included the date on which it was last revised. The most recent version of the Assessment of Evidence for COVID-19-Related Treatments table can be accessed at https://www.ashp.org/-/media/assets/pharmacypractice/resource-centers/Coronavirus/docs/ASHP-COVID-19-Evidence- Table. ashx within the ASHP COVID-19 Resource Center. As of August 20, 2020, the 34th edition of the evidence table had been published. The 34th edition included 37 table entries, compared with 15 in the original version. The median number of references per drug or drug class had increased from 5.5 (range, 1-14) in the original version to 14 (range, 3-61) in the 34th edition. A comprehensive table was developed to provide a summary of available evidence for various therapies being investigated or used in patients with COVID-19 to inform and support pharmacists and other clinicians as they make therapeutic decisions while caring for patients with the disease. The evidence table format enabled the AHFS DI staff to provide ongoing updates as new information became available during the pandemic. Given the fluid nature of the COVID-19 pandemic, the conclusion for most drugs assessed to date was that additional research is required to definitively establish the safety and efficacy of any given therapy. A c c e p t e d M a n u s c r i p t Snow was editor-in-chief of AHFS Drug Information, ASHP, and has since retired. Dr. Miller is senior associate editor of AHFS Drug Information Kohoutek is assistant editor for injectables for the Handbook on Injectable Drugs, ASHP. Dr. Rosanelli is senior drug information analyst for AHFS Drug Information World Health Organization. WHO director-general's opening remarks at the media briefing on COVID-19 -11 March 2020. www.who.int/dg/speeches/detail/who-director-generals-opening-remarks-at-the-media-briefing-on-covid World Health Organization. Coronavirus disease 2019 (COVID-19) situation report -71 for Society of Infectious Diseases Pharmacists. Coronavirus disease 2019 treatment: a review of early and emerging options Covid-19 -navigating the uncharted The urgency of care during the Covid-19 pandemic -learning as we go Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review Review of emerging pharmacotherapy for the treatment of coronavirus disease 2019 Covid-19 -a reminder to reason COVID-19 pandemic -a focused review for clinicians The authors thank Elizabeth P. Shannon, BS, Allie Berry, MS, and Lois Witkop, MBA, for their contributions to this project.