This pandemic is a time for clinical research to help humanity out of the crisis, and scientists are scrambling to find a COVID-19 vaccine.
It is urgent because if they do not do human trials during the pandemic, the infection rate may decline and the vaccine will not be well-tested enough to prevent this disease.
This lack of cases and the resulting inability to test a strong candidate vaccine is exactly what happened to the zika virus vaccine. Zika may have run its course even as the vaccine study was getting underway. But there is every likelihood it may return with a vengeance without an effective vaccine in place.
Many big pharma including Astra Zenca, Pfizer, Merck, and Johnson and Johnson are involved in the testing and manufacture of the COVID-19 vaccine. Companies in India, China, and Japan are also ramping up their efforts.
Unfortunately, no promising drug treatment is on the horizon. Remdesivir, convalescent plasma, interleukin inhibitors like tocilizumab, chloroquin are certainly not the silver bullets they are made out to be. But every bit of hope is useful.
Last week, a riveting scandal rocked the medical world that involved a team of doctors whose research into choloroquine and the journals that published the result.
This antimalarial drug, discovered in 1934 and introduced generally in 1947, is one which humans have been most exposed to. Chloroquine is inexpensive and simple to administer. It remains a first-line treatment for non-falciparum malaria and is on the World Health Organisation (WHO) List of Essential Medicines.
It has been used extensively as a continuous prophylaxis against malaria for individual periods often exceeding five years, and has been the prophylactic drug of choice in pregnancy in order to avoid non-falciparum malaria. In addition to its antimalarial use both chloroquine, and the closely related hydroxychloroquine, are used in continuous daily dosing for common joint diseases like rheumatoid arthritis and lupus.
Cholorquine in viral culture cells in research laboratory has been shown to suppress the novel betacoronavirus SARS-CoV-2, the cause of the COVID-19 infection. This effect occurred when the drug was given either before or immediately after viral inoculation, not after a long lag period.
An observational study purporting to use data from a multi-country registry was recently published in The Lancet, revealing that regardless of any benefit chloroquine may (or may not) have for the treatment of COVID-19, there were unacceptable side-effects on the heart leading to decreased survival of the patients.
But there was a problem with the study. Sapan Desai, one of the authors and owner of Surgisphere Corporation based in Chicago from where this registry data was obtained, was, when requested, unable to share the dubious list.
Desai’s colleague, Mandeep Mehra, the lead author, and other co-authors including Amit Patel have now retracted the article from The Lancet. But the story does not end there.
This same group of authors, some of whom work in prestigious institutions like Harvard (Mehra), also retracted a recent New England Journal of Medicine (NEJM) article regarding COVID-19 where they had used data from Surgisphere Corporation, and when requested, were unable to share it.
These retractions by the same set of authors (one of whom owns the data collection corporation) from two of the highest impact medical journals could suggest possible fraud. In addition, the editors of both the NEJM and The Lancet were caught with their pants down in the rush to publish data.
Finally, a proper randomised controlled trial named the Recovery Trial from the UK that utilised large numbers of patients who were treated with hydroxychloroquine revealed this week that the drug does not work in the treatment of COVID-19 patients.
But whether chloroquin works in prevention (as opposed to treatment) of COVID-19, especially in the vulnerable group of health workers, is not known and studies are continuing regarding pre-exposure to the virus. Medical science can be tricky. A drug not useful for treatment can often be useful for prevention.
Potentially fraudulent studies notwithstanding, it is beneficial for countries like Nepal, after proper examination, to collaborate in international observational or randomised controlled trials like the WHO’s Solidarity Trials for COVID-19 antidotes — especially because it will help with capacity building in our region without desperately having to look for funding.
The Nepal Health Research Council has been doing an excellent job of reviewing manuscripts and usually providing prompt feedback to the researchers in the region. However, what we medical researchers in South Asia lack is an appreciation of equipoise.
‘Equipoise’ means curiosity, but it also has an element of humility. A true state of equipoise exists in research when there is no good basis for a choice between two or more options. In fact, the state of equipoise is the reason for doing research using RCTs.
Unfortunately, many health care professionals in South Asia do not make room for this quality. For example, some institutions have turned down doing potentially useful, well-written and well-grounded multilateral studies in the mistaken belief that we know better that the drug or treatment in question does not work. How can this be assumed?
This narrow belief may shut useful research out which ultimately could inform clinical treatment and help the patient. Helping the patient, at the end of the day, is what we all are trying to do.
Buddha Basnyat is a clinical researcher at Patan Academy of Health Sciences and writes this frequent health column Dhanvantari for Nepali Times.