The failure of drug repurposing for COVID-19 as an effect of excessive hypothesis testing and weak mechanistic evidence

Abstract

The current strategy of searching for an effective treatment for COVID-19 relies mainly on repurposing existing therapies developed to target other diseases. Conflicting results have emerged in regard to the efficacy of several tested compounds but later results were negative. The number of conducted and ongoing trials and the urgent need for a treatment pose the risk that false-positive results will be incorrectly interpreted as evidence for treatments' efficacy and a ground for drug approval. Our purpose is twofold. First, we show that the number of drug-repurposing trials can explain the false-positive results. Second, we assess the evidence for treatments' efficacy from the perspective of evidential pluralism and argue that considering mechanistic evidence is particularly needed in cases when the evidence from clinical trials is conflicting or of low quality. Our analysis is an application of the program of Evidence Based Medicine Plus (EBM+) to the drug repurposing trials for COVID. Our study shows that if decision-makers applied EBM+, authorizing the use of ineffective treatments would be less likely. We analyze the example of trials assessing the efficacy of hydroxychloroquine as a treatment for COVID-19 and mechanistic evidence in favor of and against its therapeutic power to draw a lesson for decision-makers and drug agencies on how excessive hypothesis testing can lead to spurious findings and how studying negative mechanistic evidence can be helpful in discriminating genuine from spurious results.

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