Abstract

The COVID-19 pandemic has been characterized by a lack of clear evidence to guide healthcare professionals, the public and policymakers. The resulting uncertainty, coupled with changing guidelines as additional evidence became available, added to the stress and anxiety reported by decision-makers. Research results are key to providing evidence to guide healthcare decisions. Important questions have arisen about whether various interventions are safe and effective. The evidence found guides those making treatment decisions, and influences those selecting interventions for further evaluation in research studies. As the COVID-19 pandemic intensified, the effectiveness and safety of many pharmaceuticals was queried. Ivermectin will be used to explore the ethics of how healthcare evidence must be critically appraised, even, or especially, during a pandemic. This drug is alleged to be effective in treating COVID-19, with various studies and systematic reviews finding supportive evidence. Some of these have now been linked to concerns about fraud or poor research reporting. This article will focus on the scientific literature and how apparently fraudulent studies were published and influenced treatment decisions, on-going research and public health guidelines. Research evidence is critical during emergencies like pandemics, but urgency should not overtake ethical responsibilities to critically appraise (or evaluate) studies as they become available. These responsibilities apply in various ways to editors, peer-reviewers, news media reporters, and those making treatment decisions, including clinicians, policymakers and the general public. While research article authors have the primary ethical responsibility to reject fraudulent or inaccurate claims, the readers of health research must carefully evaluate all publications. To detect and reject fraudulent healthcare claims, readers need critical appraisal skills that match their level of engagement with those articles. The core principles of critical appraisal will be described in the article, and how they can be adapted for different types of readers. Exemplar tools that develop critical appraisal skills will be noted, with reviews of ivermectin's efficacy explored as examples. As stakeholders in healthcare evidence are increasingly able to identify well-conducted and ethical research they will simultaneously be able to spot and reject fraudulent reports and prevent them from influencing healthcare decisions.

Highlights

  • The response to COVID-19 has been characterized by uncertainty

  • As the Director of the National Institute of Allergy and Infectious Disease, Anthony Fauci, the Director of the National Institutes of Health, Francis Collins, and others stated in a May 2020 commentary on COVID-19 vaccine research, “We currently know little about what constitutes a protective immune response against COVID-19” [2]

  • Specific guidelines and appraisal tools are available for every type of research study (RCT, systematic review, survey, qualitative study, etc.) and some are specific to distinct research topics

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Summary

INTRODUCTION

The response to COVID-19 has been characterized by uncertainty. This was captured early in the pandemic: “There are no antiviral drugs with proven clinical efficacy, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells” [1]. As the Director of the National Institute of Allergy and Infectious Disease, Anthony Fauci, the Director of the National Institutes of Health, Francis Collins, and others stated in a May 2020 commentary on COVID-19 vaccine research, “We currently know little about what constitutes a protective immune response against COVID-19” [2] In spite of this lack of information, decisions had to be made by clinicians, patients, and policymakers. Without reliable and trustworthy evidence, people and organizations will make different decisions and give varying recommendations, thereby compounding the confusion and frustration that exists in the midst of uncertainty This leads to two ethical imperatives that will be the focus of this article. Candidates included antimicrobial agents like hydroxychloroquine and chloroquine, ivermectin, and lopinavir, approved drugs like interferon and dexamethasone, and experimental agents like remdesivir

TIME PRESSURES
PROBLEMATIC PUBLICATIONS AND THE NEED FOR CRITICAL APPRAISAL
CRITICAL APPRAISAL
SYSTEMATIC REVIEWS AND IVERMECTIN
COMPARING SYSTEMATIC REVIEWS
Prophylaxis Trials
Outpatient Trials
Trials With Hospitalized Patients
THE WITHDRAWN IVERMECTIN STUDY
Findings
CONCLUSION
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