Baba Ramdev sitting in front of a display of Patanjali products. Photo: Reuters/Adnan Abidi.
On February 19, Patanjali Ayurved, the FMCG company owned by yoga guru Baba Ramdev and known for its line of ‘Ayurvedic’ products, organised a product launch event at New Delhi’s Constitution Club. On the podium, flanking Ramdev on the right was Union health minister Harsh Vardhan and on his left was Nitin Gadkari, the minister for micro, small and medium enterprises.
It was a considerable might of the state thrown behind a supposedly Ayurvedic drug called Coronil, whose maker Patanjali had claimed it was the first “evidence-based medicine” for COVID-19 and that it had been “approved by the WHO” – both of which were also written in red print on the backdrop. Once again, science – or claims of it – was freely waltzing with politics, not for the first time nor the last.
Was it right for public representatives to be present at the launch of a private drug, their presence being its greatest endorsement? And was it right for Patanjali to advertise false claims of WHO approval, only to be speedily debunked by a tweet from the WHO? The answer to these questions is obviously ‘no’. But what is not obvious is the science behind these claims.
Patanjali has responded to questions about Coronil’s efficacy by pointing to a paper it published in a journal called Phytomedicine. In this paper, Acharya Balkrishna, the chairman of Patanjali, is listed as co-author. A summary of its contents could help if we are to understand the problems with this paper’s claims.
The paper speaks about a study conducted with 100 people: 45 of them are asymptomatic and receive nasal drops (anu taila) and oral medicine (swasari ras powder, giloy ghanvati, ashwagandha and tulsi ghanvati); 50 of them receive a placebo. Both groups are followed up for seven days in the hospital, and are monitored with a panel of tests, including RT-PCR.
According to the paper, the treatment group reported 100% recovery by day 7, compared to only 60% in the placebo group. But on closer analysis of data, the percentage of recovery by day 7 in the placebo group was found to be 80%, which is 20% more than what the paper claims, by use of some clever language in its abstract.
There are many problems with this study.
First, the numbers. Remdesivir, the first treatment approved for COVID-19, was okayed by the US Food and Drug Administration based on evidence collected from three studies conducted with 1,361 participants in all. Dexamethasone, another drug known to be lifesaving against severe COVID-19, was recognised as treatment after researchers studied its effects with 6,425 participants in the UK-based RECOVERY clinical trial.
In contrast, Coronil was supposedly approved after a study in a hundred patients. Biology can be cluttered with variability, and the only way studies can demonstrate their robustness and generalisability is through trials with large cohorts – where there is a real chance of picking up a drug’s true efficacy and rarer side-effects. Absurdly enough, even the study paper uses the word “pilot” to describe itself.
Second, the age and gender bias of the study population. We know that age and gender can play a major role in the natural history of COVID-19, and can become major determinants of its progression. The average age of participants in the treatment group and the placebo group was 33 years and 35 years, respectively. There are only four participants aged more than 55 years, a group we know to be the most vulnerable to death by COVID-19.
In addition, there are only 18 women in the cohort, rendering the study not generalisable.
So in effect, the study has very little to say on how the drug works in women or anyone above the age of 55 years.
Third, the drug’s side-effects. After having prematurely assumed the safety of ‘Ayurvedic’ drugs, and without ever having conducted phase 1 and phase 2 clinical trials to clarify the drug’s safety, the current study talks about how haematological parameters and liver-kidney function tests remain unchanged after Coronil administration, and points to a table for more data: ‘table 1’ in the paper.
Sadly, ‘table 1’ has no data on differences in these parameters. No such data was to be found in the paper’s supplementary materials section either. So your guess about the side-effects is as good as mine.
Fourth, and most important, an intricate point about what the study treats as ‘recovery’. We must remember that the study only involves asymptomatic patients who have tested positive with RT-PCR tests for COVID-19. In asymptomatic patients, we rarely know the day of probable infection.
Now say person A and person B both get infected with the novel coronavirus and both are asymptomatic. We know that the viral load in our body usually goes down to negligible levels sometime around day 10-14, and a continuous decline after the first 3-4 days. If person A happens to get infected a few days earlier than person B, and both persons undergo RT-PCR tests on day 7, there is a good chance that person A has cleared the virus and will test negative and person B might test positive.
Does this mean that person B won’t clear the virus? No – it only means that we will have to give person B a few more days to catch up with person A.
Can we ever correct for the discrepancy between the two people to study them better? Yes – we can do that by examining the viral load. The viral load is a measurable quantity of the virus, whereas RT-PCR tests can only tell us if the virus is present in the individual or not.
However, the study cleverly measures recovery by RT-PCR and has nothing to say about the viral load in the treatment and placebo groups on day 0. Therefore, there is a possibility that the difference in RT-PCR positivity – 100% v. 80% in the treatment and placebo groups – is simply because the group that received Coronil had a lower viral load to begin with, and their test results have little to do with the drug. The study also fails to eliminate this possibility until the end.
Fifth, any study can only be extrapolated to the population it studies. And Coronil has only been shown to have mild efficacy (which is also contestable) in clearing the virus in 30-year-old men who have no symptoms for COVID-19.
While the use of modern scientific methods to prove claims by alternative systems of medicine is impressive, it is sorely inadequate in this case. As for Coronil’s approval, the waltz continues.
Dharamveer Tatwavedi is reading for a DPhil at the University of Oxford and works in oncology as a clinician. He tweets at @Dharam_tat.