Hydroxychloroquine research retracted – Expert Reaction

Authors of two studies on the use of hydroxychloroquine for treating COVID-19 have retracted the work, saying they “can no longer vouch for the veracity of the primary data sources.”

The studies, published in The Lancet and New England Journal of Medicine (NEJM), last month, found that use of chloroquine or hydroxychloroquine was linked to increased rates of mortality and heart problems among hospital patients with COVID-19. However, the authors say “serious concerns” were raised about the veracity of the data and analyses provided by US company Surgisphere.

The SMC asked experts to comment on this retraction. 

Dr Susan Morpeth, Clinical Microbiologist and Infectious Disease Physician at Middlemore Hospital, comments:

“The retraction of the observational study recently published in The Lancet by Mehta et al: “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis” was expected among the scientific community after serious concerns about the validity of the underlying data were exposed which had not been identified in the editorial and peer review process.

“Reassuringly, the RECOVERY and SOLIDARITY trials, large rigorously-conducted randomised clinical trials of potential COVID-19 treatments including hydroxychloroquine underway globally, have conducted interim analyses of their data, seen no cause for concern, and have already recommenced recruitment.

“The governance committees for the AustralaSian COVID-19 Trial (ASCOT) have unanimously agreed that ASCOT should proceed with randomising patients to the hydroxychloroquine arms of the study. This study is open in Australia and is expected to open in New Zealand in the coming weeks.

“Similarly, the governance committee of the ‘Hydroxychloroquine prophylaxis in healthcare workers study’ has advised that planning for the initiation of the study should continue.

“Also in New Zealand, the currently active REMAP-CAP trial evaluating a range of treatments for patients with severe COVID-19 is awaiting final advice from its Data and Safety Monitoring Board before re-activating the hydroxychloroquine arms.”

Conflict of interest statement: “I’ve been funded by the HRC for the NZ arm of the ASCOT study, and am a named investigator on the HRC grants for the REMAP-CAP and healthcare worker trials.”

Dr Rhian Salmon, Deputy Director, Centre for Science and Society, Te Herenga Waka – Victoria University of Wellington, comments:

“The peer review process in science is not perfect, but it’s the best mechanism that we currently have to share, interrogate and question each other’s research outputs. It relies heavily on the ethical and professional practice of all involved: authors, reviewers and publishers. While this system has clearly been under increased pressure due to the urgency of COVID-19 research, it’s very disappointing that a paper was accepted that then needed to be retracted.

“The retracted paper was an extensive study into the value of hydroxychloroquine or chloroquine in treating COVID-19, including data from over 96,000 patients. As such, it would have been an extremely important contribution to this research area and I hope they find a way to access and re-evaluate their data. The authors should have never submitted their articles if they were in any doubt about the robustness of their data. The peer-review process of the journals themselves should have also highlighted any issues.

“Both the authors and journal have definitely done the right thing, however, by retracting the paper once there were concerns. Experiences like this need to be thoroughly investigated so that we can continually improve the peer review process and sharing of critical research.”

No conflict of interest.

Dr Chris Gale, Consultant Psychiatrist and Senior Lecturer, Department of Psychological Medicine, University of Otago Medical School, Dunedin, comments:

“The journals have retracted these studies because the authors could not provide the raw data, citing confidentiality issues, which made independent confirmation of the conclusions impossible. It may be that the an undue urgency was seen to gain a definitive answer on the use of hydroxychloroquine. In my view, you cannot do this without randomized controlled trials, which are in process. Although there is considerable pressure on researchers, reviewers and editors to produce papers that will guide clinicians, we need to do any studies using good methodology. This requires that all of us are patient, and accept that we do not have definitive answers as yet. Doctors work with partial data sets and gaps in research evidence on a daily basis, and the press, policy makers and public need to understand that definitive answers will be months to years away.”

No conflict of interest.

The UK Science Media Centre gathered the following comments.

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine (LSHTM), said:

“There is little to add following the expression of concern. While concealing identifiable individual patient data is important, there are other ways to verify the integrity of the data.  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.

“It is correct to retract the paper in these circumstances. Further investigations may be required.

“It remains the case that the results from randomised trials are necessary to draw reliable conclusions. it is to be hoped that the results will be available soon.”

No conflict of interest.

Prof Chris Chambers, School of Psychology, Cardiff University Brain Research Imaging Centre, (Chair of the Registered Reports Committee, Center for Open Science and Member of the UK Reproducibility Network Steering Group) said:

“It is right that these articles were retracted. However, 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 and NEJM — ostensibly two of the world’s most prestigious medical journals. If these journals take issues of reproducibility and scientific integrity as seriously as they claim, then they should forthwith submit themselves and their internal review processes to an independent inquiry.”

Conflict of interest statement: “Registered Reports editor at BMJ Open Science, Cortex, European Journal of Neuroscience, PLOS Biology, Royal Society Open Science. Advisory Board member for Nature Human Behaviour. No other relevant interests.”