Authors retract divisive hydroxychloroquine study as WHO restarts trial

After more than a week of debate questioning the integrity of data underpinning a controversial study that found hydroxychloroquine or chloroquine treatment for COVID-19 not safe or effective, three out of the four authors behind the paper have voluntarily requested it be retracted. Meanwhile, results have been published from the first randomized clinical trial testing the treatment, suggesting it is no better than placebo at preventing COVID-19.

The research published last week in The Lancet, one of the world’s most prestigious medical journals, presented the first large-scale epidemiological review of hydroxychloroquine or chloroquine treatment for COVID-19. Data from 671 hospitals spanning six continents were analyzed, comprising nearly 15,000 patients with COVID-19 treated with some form of either hydroxychloroquine or chloroquine.

Soon after the study was published questions were raised over the veracity of the data. The hospital records evaluated in the study were supplied by a company named Surgisphere and, although the company defended the integrity of its data, independent reviewers were unable to effectively audit the full dataset.

“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis as such transfer would violate client agreements and confidentiality requirements,” write three of the authors behind the original study in their recent retraction statement. “As such, our reviewers were not able to conduct an independent and private peer review and therefore notified us of their withdrawal from the peer-review process.”

Sandap Desai, the fourth author credited in the study and CEO of Surgisphere, is not listed on the retraction notice. Recent statements from both Desai and Surgisphere claim the overall dataset is accurate, and the findings in the original paper are correct.

Chris Chambers, from Cardiff University and chair of the Registered Reports Committee at the Center for Open Science, says it was correct to retract this paper. He suggests this situation raises serious questions about the integrity of the peer-review process at one of the world’s most prestigious medical journals.

“… the failure to resolve such basic concerns about the data during the course of normal peer review raises serious questions about the standard of editing at the Lancet,” says Chambers.

Stephen Evans, from the London School of Hygiene & Tropical Medicine, also agrees with the retraction, and suggests while it is important to respect patient privacy, there are plenty of ways the Surgisphere data could be verified without violating confidentiality.

“While concealing identifiable individual patient data is important, there are other ways to verify the integrity of the data,” says Evans. “For example, data providers should be able to confirm that they have provided data with at the very least, the approximate numbers of patients involved.”

Evans also reiterated the need for clear randomized clinical trial data to better answer the question of whether hydroxychloroquine or chloroquine is effective at treating, or preventing, COVID-19.

In a timely release, researchers from the University of Minnesota published the first results from a clinical trial trying to answer that very question. The study, published in The New England Journal of Medicine, did not explore the efficacy of hydroxychloroquine as a COVID-19 treatment, but instead investigated whether the drug protected against infection from the virus if administered as a prophylactic.

To test this, the researchers recruited 831 subjects who were exposed to COVID-19, either as a healthcare worker or simply by living in the same household as a confirmed case. Within four days of confirmed exposure the subjects blindly received either a short course of hydroxychloroquine or placebo.

After a two-week follow-up the researchers found there to be no statistical difference in the number of COVID-19 infections between the hydroxychloroquine and placebo groups. Over a third of the hydroxychloroquine cohort did report minor side effects (nausea or diarrhea) but no serious adverse effects, such as cardiovascular complications, were detected.

“Our objective was to answer the question of whether hydroxychloroquine worked to prevent disease or did not work,” says David Boulware, senior investigator on the trial. “While we are disappointed that this did not prevent COVID-19, we are pleased that we were able to provide a conclusive answer. Our objective was to find an answer.”

The results of this trial certainly are not the final word on hydroxychloroquine and COVID-19. More clinical trials will be necessary to establish whether the drug is useful in combination with other treatments. The World Health Organization has recommenced its hydroxychloroquine trial, following a temporary suspension and review by an independent safety board.