Everything you wanted to know about covid-19 treatments, in five charts3 min read . Updated: 04 Aug 2020, 01:21 PM IST
India’s official experiments with recommending drugs for treatment of covid-19 are marked with opacity around evidence
When India’s National Task Force on COVID-19 recommended against including Itolizumab, Biocon’s psoriasis drug, in its treatment guidelines, the move represented two key aspects of the global scramble for a cure for covid-19 - the problematic bar for evidence, as well as the sheer size of the challenge.
The Task Force’s decision stemmed from its members’ dissatisfaction over the adequacy of evidence generated from Biocon’s 30-person clinical trial. Similar doubts were expressed by many in the medical and scientific fraternities in the days after the Drug Controller General of India granted emergency use authorisation for the drug.
But the bar for evidence has not been uniform, or, at the very least, transparent. In the US, the recommendation by its National Institutes for Health for or against most known drugs is accompanied in its clinical guidelines with the evidence behind each such recommendation.
In India, drugs have appeared and disappeared from the protocol, which is published by the Ministry of Health and Family Welfare, with no explanation. In the second week of March, a Jaipur hospital declared “success" in treating an elderly Italian couple infected with the virus with a combination of antiretroviral drugs used in the treatment of HIV - lopinavir and ritonavir. Three days later, the drug combination had made it to the Health Ministry’s treatment guidelines. The ministry recommended Lopinavir-Ritonavir for high-risk patients including those above 60, those with diabetes, kidney failure, chronic lung disease and the immuno-compromised. By the next iteration of the treatment guidelines, this combination was gone, with no explanation, and in its place, now hydroxychloroquine was here.
Perhaps no drug candidate in the race for a cure for covid-19 has seen as much controversy as the anti-malarial drug - from being recommended heavily by US President Donald Trump who said he took it as a preventive, to being first ‘proven’ as ineffective by a major study published in the Lancet which then had to retract it for numerous problems centring opaque and implausible data. On July 4, the World Health Organisation announced that it was discontinuing the hydroxychloroquine arm of its global ‘Solidarity’ clinical trial, because little to no evidence of its effectiveness was emerging, alongside some “safety signals", meaning concerns it was instead causing harm. Yet India continues to recommend its use.
India’s clinical management protocol (as of July 3) currently focuses on supportive therapies, and directly recommends only a few types of drugs. For mild cases, it recommends hydroxychloroquine for high risk patients. For moderate cases, it also recommends anticoagulants to prevent blood clots, and corticosteroids like dexamethasone, the drug that reduced mortality by one-third in ventilated patients in the University of Oxford’s ‘Recovery’ trial. For severe cases, it recommends the same set of drugs, but not hydroxychloroquine.
India’s guidelines also suggest three “investigational therapies" for which there is limited evidence, but which can be used at the doctor’s discretion. Of these, remdesivir, the drug initially developed by Gilead for use in hepatitis C but subsequently used for the treatment of Ebola, is also recommended by the US. The second is Tocilizumab, Roche’s rheumatoid arthritis medicine which again the US did not find enough evidence to recommend for or against. The third is the non-drug convalescent plasma therapy that has been used extensively in Delhi in particular. The US has found no evidence to recommend for or against it.
Globally, over a billion dollars have been committed by governments and major philanthropies to develop drugs against covid-19, according to Policy Cures Research, a British think-tank, more than half of it from the US, followed by Canada and the United Kingdom.
Research into a cure is broadly divided into three types of drugs being investigated: antivirals such as remdesivir, anti-inflammatory drugs such as dexamethasone, and others including protein inhibitors, according to Policy Cures Research. The majority of drugs being investigated are repurposed variants of existing drugs.
The COVID-NMA project, led by an international team of researchers from the British charity Cochrane as well as from the University of Paris and other universities tracks ongoing research on covid-19. The project, backed by the World Health Organization (WHO) identifies 1236 clinical trials focused on treatment (as opposed to preventive vaccines) across the world, 52 of them in India.
Globally, the success rate of ongoing research remains low, with the NMA project raising concerns about the quality of evidence in claims put forward by most trials that are reporting data thus far.
In that respect, India’s experiments with recommending drugs to treat covid-19 are not unusual. What stands apart, however, is the opacity over its reasoning.
Rukmini S. is a Chennai-based journalist.