Photo: Gustavo Fring.
“The office of the scholar is to cheer, to raise, and to guide men by showing them facts amidst appearances. He plies the slow, unhonoured and unpaid task of observation.” – Ralph Waldo Emerson, 1837
I entered medical school 25 years ago. Back then, I’d picked medical science over a career in the pure sciences, but many years later I can only confess to being tepid about the path taken. Most of my peers in rank or scholarship are far ahead in terms of research output or citation metrics. Nevertheless, life in Indian medicine has its thrills. It is often about improvising perpetually with technology or medicines in a resource-poor environment and in describing these meanderings as published ‘research’. This is contextually relevant.
The current novel coronavirus pandemic is the first healthcare crisis my generation has seen. It has wrought clinical, ethical and economic uncertainty on a scale that we are fully yet to realise. From the research point of view, the pandemic has been characterised by an infodemic: it has a mix of authentic and false information, both improved and worsened in different ways by the social media and internet search engines.
In India, the infodemic has some other attributes. For one, the official face of the pandemic is a member of the Indian Administrative Service (IAS). From all perspectives, this method of scientific declamation fails the philosophy of Karl Popper absolutely. A Popperian attribute of true science is that it must led itself to being disproved. But here, an IAS officer peddles faulty takes on case fatality, testing approaches and the tenuous links of an outbreak to congregations. None of his assertions are backed by data for qualified assessors to assess and critique. Another attribute of course is the overall lack of data.
As on date, researchers worldwide have published more than 20,000 papers on COVID-19. An Indian bibliographic study of COVID-19 in May 2020 showed Indian researchers contribution to this effort was a mere 89 – despite India now being the fourth most affected country. An article on the clinical management of COVID-19 from the Indian Journal of Medical Research, the flagship journal of the Indian Council of Medical Research (ICMR), has no Indian evidentiary citation. The advisories from the ICMR or even from well-performing states like Kerala have made away with the niceties of adducing evidence altogether, although they are targeted at physicians.
Altogether, this is an egregious example of authority bias. Confirmation and authority bias are anathema to any science and retard any hope of progress or debunking of myths. This applies to scientific medicine as well. As an example, the intrinsic madness of Ignaz Semmelweis (1818-1865) and his struggle against authority is the reason hand-washing is the foremost public health measure against the spread of viruses today.
Of lockdowns and ventilators
COVID-19 is, at its heart, a severe acute respiratory infection, a.k.a. SARI. WHO has estimated that about 5% of patients with COVID-19 will become sick enough to need supportive ventilation. But as predictions on the size of the pandemic have gone awry, so have these estimates. Even so, according to official figures, about 0.33% of those infected will need this therapy in India. Officials cited ventilators as one of the justifications for a lockdown. But it seems obvious now that Indian planners didn’t make room for the possibility of COVID-19 being severe in India to a different extent than it has been found to be elsewhere, not least because India’s at-risk population is younger than in other cohorts.
Severe lung disease is often the most challenging clinical scenario for ventilator and clinician performance. It’s inexplicable that we have allowed fly-by-night versions, such as the ‘Dhaman 1’ unit, to be used in this setting or how primitive some of the initiatives have been in design. Equally importantly, it’s unfathomable that health systems think the lack of clinical expertise can be overcome by machines. If this is true, it could explain how Ahmedabad comes out with its ignominious performance.
Given the nature of SARI, it’s also impossible to deliver these therapies without advanced clinical monitoring and adjunct intensive care therapies. India already has an endemic shortage of critical care beds (2.3 beds/1,000 people) and should have understood this was a myopic approach when even the muscled US (34.7/1000) and Italian systems (12.5/1000) were overwhelmed at the peak of their COVID-19 outbreaks.
Pioneers in this area describe COVID-19 phenotypes that actually respond poorly to mechanical ventilation. There has been no systematic effort to investigate non-ventilatory therapies that offer opportunities of scale, and sometimes potential to avoid less available and more expensive treatments as well. This is and should have been a key area of investigation in India, particularly as regional demands spiked and outran supply in Mumbai and now in Delhi. Critical-care planning for COVID-19 in India hasn’t been and still isn’t about reallocating resources between regions and from bloated private to burdened public health systems.
The drug episode
As I write this article, favipiravir has been approved to treat ‘moderate’ COVID-19 in India, promising a windfall for its manufacturer. In a clinical trial in China, researchers studied all of 80 patients, 35 of whom received this drug. From the stables of Japanese Fujifilm, it is a parody that favipiravir hasn’t yet been approved for clinical use in Japan! The professed reason is that the drug isn’t efficacious enough.
If this is stranger than fiction, consider: ICMR first approved the use of hydroxychloroquine (HCQ) has a prophylactic for healthcare workers based on a smaller dataset and one dubious study. And it still doesn’t seem to matter to ICMR that a randomised controlled trial showed it to be ineffective even at much higher doses.
Its own investigation couldn’t distinguish the effect of wearing protective equipment as a guard against infection from any effect of HCQ. Stranger still, this study seemed to suggest that lower doses of the drug increased the risk of infection. This is lamely ascribed to physicians being less careful – a concept known as risk homeostasis. ICMR is its own sceptic in any case: as its latest missive states, self-administration of HCQ should not “instil a false sense of security”.
Remdesivir, the other sought-after molecule, is not yet proven to be magical. In fact, the molecule found to improve COVID-19 survivability thus far is the common steroid dexamethasone. According to preliminary results, it cut mortality by 20% among those with severe COVID-19 needing oxygen care, and by a third among those with severe COVID-19 needing ventilator support. As the drug seems suited for a stressed system, its success may not translate to a triumph at the population level.
India needs to set up a large, collaborative research network to confront this pandemic. Its research response has been pathetic and this is a legacy problem. To blame are ICMR and its stranglehold on biomedical research and the collective apathy of the medical community at large. To quote Shakespeare in remonstration:
There is a tide in the affairs of men
Which, taken at the flood, leads on to fortune
Aveek Jayant MD DM is a clinical professor (cardiac anaesthesiology and ICU services) at the Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham. The views here are the author’s own.