Abstract
IntroductionIn early 2020, the coronavirus disease 2019 (COVID-19) pandemic spread worldwide, overwhelming hospitals with severely ill patients and posing the urgent need for clinical evidence to guide patient care. First treatment options available were repurposed drugs to fight inflammation, coagulopathy, and viral replication. A vast number of clinical studies were launched globally to test their efficacy and safety. Our analysis describes the development of global evidence on repurposed drugs, in particular corticosteroids, anticoagulants, and (hydroxy)chloroquine in hospitalized COVID-19 patients based on different study types. We track the incorporation of clinical data in international and national treatment guidelines and identify factors that characterize studies and analyses with the greatest impact on treatment recommendations.MethodsA literature search in MEDLINE was conducted to assess the clinical evidence on treatment with corticosteroids, anticoagulants, and (hydroxy)chloroquine in hospitalized COVID-19 patients during the first year of the pandemic. Adoption of the evidence from this clinical data in treatment guidelines of the World Health Organization (WHO), Germany, and United States (US) was evaluated over time.ResultsWe identified 106 studies on corticosteroids, 141 studies on anticoagulants, and 115 studies on (hydroxy)chloroquine. Most studies were retrospective cohort studies; some were randomized clinical trials (RCTs), and a few were platform trials. These studies were compared to studies directly and indirectly referred to in WHO (7 versions), German (5 versions), and US (21 versions) guidelines. We found that initially large, well-adjusted, mainly retrospective cohort studies and ultimately large platform trials or coordinated meta-analyses of RCTs provided best available clinical evidence supporting treatment recommendations.DiscussionParticularly early in the pandemic, evidence for the efficacy and safety of repurposed drugs was of low quality, since time and scientific rigor seemed to be competing factors. Pandemic preparedness, coordinated efforts, and combined analyses were crucial to generating timely and robust clinical evidence that informed national and international treatment guidelines on corticosteroids, anticoagulants, and (hydroxy)chloroquine. Multi-arm platform trials with master protocols and coordinated meta-analyses proved particularly successful, with researchers joining forces to answer the most pressing questions as quickly as possible.
Highlights
In early 2020, the coronavirus disease 2019 (COVID-19) pandemic spread worldwide, overwhelming hospitals with severely ill patients and posing the urgent need for clinical evidence to guide patient care
In our literature search covering the first year of the COVID-19 pandemic, we identified 333 publications reporting results on observational and interventional studies of patients hospitalized for COVID-19 that were treated with corticosteroids (106 studies), anticoagulants (141 studies), and/orchloroquine (115 studies) (Figure 1)
Results on mortality from the New York cohort study by Nadkarni et al based on evidence from a living review provided by the American Society of Hematology (ASH) [53] have been included by WHO in their considerations [13] January 25, 2021
Summary
In early 2020, the coronavirus disease 2019 (COVID-19) pandemic spread worldwide, overwhelming hospitals with severely ill patients and posing the urgent need for clinical evidence to guide patient care. Our analysis describes the development of global evidence on repurposed drugs, in particular corticosteroids, anticoagulants, and (hydroxy)chloroquine in hospitalized COVID-19 patients based on different study types. Given the rapid increase in infections— more than 1 million confirmed COVID-19 cases and more than 60,000 deaths within the first 3 months of the pandemic in 2020 [1]—and the lack of specific treatments for COVID19—repurposing widely available drugs was the obvious choice in immediate response to the urgent medical need. Since repurposed drugs were readily available to physicians, cohort studies examining various treatment approaches have contributed a large volume of clinical data from patient care. Platform trials are a form of RCT often based on a pragmatic master protocol with adaptive features that facilitates collaborative and streamlined efforts to test multiple different treatments in a large patient population while using a single control arm [4]
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