Use of hydroxychloroquine and chloroquine in COVID-19: How good is the quality of randomized controlled trials?

Research output: Contribution to journalReview articlepeer-review

Authors

  • Faizan Mazhar
  • Chia Siang Kow
  • Albaraa Mohammed N Marran
  • Hamid A Merchant
  • Syed Shahzad Hasan

Colleges, School and Institutes

External organisations

  • University of Milan
  • Prince Mohammed Bin Nasser Hospital
  • University of Huddersfield

Abstract

OBJECTIVES: We critically evaluated the quality of evidence and quality of harm reporting in clinical trials that evaluated the effectiveness of hydroxychloroquine (HCQ) or chloroquine (CQ) for the treatment of coronavirus disease 2019 (COVID-19).

STUDY DESIGN AND SETTING: Scientific databases were systematically searched to identify relevant trials of HCQ/CQ for the treatment of COVID-19 published up to 10 September 2020. The Cochrane risk-of-bias tools for randomized trials and non-randomized trials of interventions were used to assess risk of bias in the included studies. A 10-item Consolidated Standards of Reporting Trials (CONSORT) harm extension was used to assess quality of harm reporting in the included trials.

RESULTS: Sixteen trials, including fourteen randomized trials and two non-randomized trials, met the inclusion criteria. The results from the included trials were conflicting and lacked effect estimates adjusted for baseline disease severity or comorbidities in many cases, and most of the trials recruited a fairly small cohort of patients. None of the clinical trials met the CONSORT criteria in full for reporting harm data in clinical trials. None of the 16 trials had an overall 'low' risk of bias, while four of the trials had a 'high', 'critical', or 'serious' risk of bias. Biases observed in these trials arise from the randomization process, potential deviation from intended interventions, outcome measurements, selective reporting, confounding, participant selection, and/or classification of interventions.

CONCLUSION: In general, the quality of currently available evidence for the effectiveness of CQ/HCQ in patients with COVID-19 is suboptimal. The importance of a properly designed and reported clinical trial cannot be overemphasized amid the COVID-19 pandemic, and its dismissal could lead to poorer clinical and policy decisions, resulting in wastage of already stretched invaluable health care resources.

Details

Original languageEnglish
Pages (from-to)107-120
Number of pages14
JournalInternational Journal of Infectious Diseases
Volume101
Early online date28 Sep 2020
Publication statusPublished - 1 Dec 2020

Keywords

  • COVID-19/drug therapy, Chloroquine/therapeutic use, Humans, Hydroxychloroquine/therapeutic use, Randomized Controlled Trials as Topic/standards, SARS-CoV-2