Lancet alert: ‘Serious scientific questions’ raised on HCQ study that led to WHO trial pause

Questions have been raised on the Lancet HCQ study over dataset and methodology. Another journal has issued similar concern over a study that used same data.

A pack of Hydroxychloroquine Sulfate medication | Photographer: John Phillips | Bloomberg

New Delhi: Prominent medical journal The Lancet has admitted to concerns on its hydroxychloroquine (HCQ) study that had linked the anti-malarial drug to higher risk of death and irregular heart rhythms in Covid-19 patients. The publication alerted its readers that “serious scientific questions” have been raised about the research published on 22 May.

“We are issuing an Expression of Concern to alert readers to the fact that serious scientific questions have been brought to our attention. We will update this notice as soon as we have further information,” it said Tuesday in an “expression of concern”.

The study, which had prompted even the World Health Organization (WHO) to pause HCQ clinical trials in Covid-19 patients last month under its giant ‘solidarity trial’, has been questioned for parsing through data in lesser-than-usual time, and has faced allegations of data fabrication too.

“Important scientific questions have been raised about data reported in the paper by Mandeep Mehra et al — Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis — published in The Lancet on May 22, 2020,” the journal said in its statement.

Mehra, a Harvard professor and medical director of the Brigham and Women’s Hospital (BWH) in Massachusetts, US, is the lead author.

The authors have commissioned an independent audit of the provenance and validity of the data and the results are expected “very shortly”, said the journal. The audit has been commissioned by authors who are not affiliated with Surgisphere, a Chicago-based healthcare data analytics and medical education company that supplied the data for the study, it added.

Surgisphere founder Sapan Desai is one of the authors of the study.

The large observational study had claimed to have analysed data from nearly 96,000 Covid-19 patients across six continents. Of these, around 15,000 patients either received HCQ alone, or in combination with some antibiotics. This was compared with the data of 81,000 control patients who did not receive the drug.

Questions on HCQ study

The Lancet statement came days after over a hundred scientists and clinicians raised doubts over the authenticity of the massive “671 hospitals” database that was the basis of the study.

The signatories of the open letter raised doubts about the peer-review process of the study, indicating that it was cleared in a short span of time despite the large dataset.

“The paper, published May 22, included data on over tens of thousands patients hospitalized through April 14, meaning that the authors analyzed the trove of data, wrote the paper and went through the journal’s peer review of its findings in just over five weeks, much faster than usual,” noted a New York Times report.

The letter also demanded details about the origin of the data and called for the study to be independently verified by either the WHO or another institution.

Statistician Peter Ellis, who is a chief data scientist at international management consultancy Nous Group, alleged on his personal blog that the peer-reviewed study probably used fabricated data. “I believe with very high probability the data behind that high profile, high consequence Lancet study are completely fabricated,” he wrote on 30 May.

“If Surgisphere can name the 671 participating hospitals or otherwise prove that the data is real I will retract that statement, delete this post or write whatever humbling apology they desire. But I think there’s nearly zero chance of that happening,” he added.

Infectious disease researchers from Australia have also raised doubts on the study after they found discrepancies in the data cited. The experts have criticised the methodology used as well as the authors’ refusal to disclose the names of the hospitals where they acquired the data, and the names of the countries they are located in.

A second journal issues similar concern

Another popular medical journal, the New England Journal of Medicine (NEJM), also issued a similar concern Tuesday for its study that had used the Surgisphere data.

Mehra is the lead author of this study as well along with Desai and others.

Published on 1 May, the study had claimed that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalised with Covid-19.

“On May 1, 2020, we published “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19,” a study of the effect of preexisting treatment with angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers on Covid-19,” the NEJM statement said.

This retrospective study used data drawn from an international database that included electronic health records from 169 hospitals on three continents, it added.

“Recently, substantive concerns have been raised about the quality of the information in that database. We have asked the authors to provide evidence that the data are reliable. In the interim and for the benefit of our readers, we are publishing this Expression of Concern about the reliability of their conclusions,” it said.