Study dismissing benefits of malaria drugs under lens
The review has put the spotlight on Surgisphere, a Chicago-based company that owns the questionable database that has been used in studies published in The Lancet and also New England Journal of Medicine, the world’s two most highly-cited medical journals.Updated: Jun 04, 2020 00:05 IST
The Lancet has alerted its readers that it is reviewing the data and methods of a study published in it that claimed the malaria drugs, hydroxychloroquine and chloroquine, provided coronavirus disease (Covid-19) patients no benefits while raising the risk of abnormal heart rhythms and death after scientists, clinicians and governments questioned its validity.
The review has put the spotlight on Surgisphere, a Chicago-based company that owns the questionable database that has been used in studies published in The Lancet and also New England Journal of Medicine, the world’s two most highly-cited medical journals.
An investigation by the The Guardian revealed that Surgisphere has a sci-fi author and an adult-content model among its handful of employees; that employees have little or no data or scientific training; and that it has provided data for multiple studies on Covid-19 co-authored by its chief executive Sapan Desai. The investigation further shows that the company has consistently failed to adequately explain its data source or methodology. Desai has been named in three medical malpractice suits, unrelated to the Surgisphere database, according to The Guardian.
The study, published by The Lancet on May 22, drew flak for using questionable data and flawed methodology and refusing to share data sources, including the names of participating hospitals or countries. Last week, around 120 leading scientists and clinicians wrote an open letter to the study’s authors and The Lancet asking for details about the provenance of the data and called for the study to be independently validated by the World Health Organization (WHO) or another independent body.
“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. Although an independent audit of the provenance and validity of the data has been commissioned by the authors not affiliated with Surgisphere and is ongoing, with results expected very shortly, 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,” said a statement issued by The Lancet on Wednesday.
The Lancet’s editor-in-chief Richard Horton tweeted The Guardian link, calling it “an important investigation---Governments and WHO changed Covid-19 policy based on suspect data from US company,” which led to angry responses questioning the quality of peer review in medical journals.
“The key concerns for us were that the data was questionable and there were clear differences in the hydroxychloroquine or chloroquine treated group that made analysis unreliable and any results misleading. If not for the name of the journal, the paper would have not have been taken as seriously. I do not think there is any lasting harm. What you see is the scientific process of self-correction. There was a questionable paper, questions were asked, The Lancet has put out an expression of concern regarding the paper. Let us wait and see. The truth will come out by this process,” said Dr Anurag Agrawal, director, CSIR-Institute of Genomics and Integrative Biology, New Delhi.
Dr Agrawal is among India’s top scientists who have also written to WHO chief scientist Soumya Swaminathan questioning the health agency’s decision to suspend hydroxychloroquine or chloroquine part of the multi-country Solidarity Trial following The Lancet study. The letter said the WHO decision to pause trial is “knee-jerk” because the database is flawed and the malaria drugs were given to the sickest patients.
“We are not saying that hydroxychloroquine or chloroquine are totally safe or that there is any certain benefit. Nobody knows. All we are saying is that the risks and benefit of hydroxychloroquine or chloroquine are open questions that need to be answered. Being inexpensive and potentially available worldwide, trials must continue. Until good evidence comes, national regulatory bodies should take decisions based on their context,” said Dr Agrawal.
In a statement on Friday, The Lancet study’s author Dr Mandeep R. Mehra, professor of medicine at Harvard Medical School and executive director of the Brigham and Women’s Hospital Center for Advanced Heart Disease in Boston, said this group’s study “leveraged the data available through Surgisphere to provide observational guidance to inform the care of hospitalized Covid-19 patients” because the results of randomized clinical trials would not be available for some time”. He said the study’s authors have asked for an independent academic audit.
Scientists who wrote and signed the letter criticising the study included clinicians, researchers, statisticians and ethicists from universities and medical institutes, including Harvard T.H. Chan School of Public Health, University of Pennsylvania, Vanderbilt University and Duke University.
France’s health minister Olivier Veran wrote to the scientific journal with questions about the underlying data after it was criticized for the data used in the study, French government spokeswoman Sibeth Ndiaye said after a Cabinet meeting on Wednesday.
In the absence of a treatment or vaccine, two of the major drugs being repurposed to treat Covid-19 are the tried and tested malarial drugs hydoxychloroquine and chloroquine, which US President Donald Trump told White House reporters he has been having prevent infection.
India is the world’s biggest producer of hydroxychloroquine, which is approved for use as a prophylaxis and given to asymptomatic health workers and contacts of Covid-19 patients since March 23. This was expanded to include frontline workers from May 22 on the basis of a study by Indian Council Of Medical Research that found that having four or more doses of hydroxychloroquine lowers the odds of getting infected with Sars-CoV-2, the virus that causes the coronavirus disease. The study, published in Indian Journal of Respiratory Research earlier this week, said the malaria drug lowered the risk of infection by 80% if taken as recommended. The National Task Force for coronavirus in India recommended a once a week maintenance dose for seven weeks -- 400 mg once every week, following the loading dose of 400 mg.
A cheap, safe and widely available drug that has been used to treat malaria for at least a century, hydroxychloroquine is also approved to treat lupus and rheumatoid arthritis.