Yoga guru Baba Ramdev (right) and MD of Patanjali Ayurved Acharya Balkrishna. Photo: Reuters/Amit Dave.
Yoga guru Baba Ramdev and his FMCG company Patanjali Ayurved have recently been in the news for advancing a supposedly Ayurvedic drug named Coronil as the “first evidence-based medicine” for COVID-19. But despite the dubiety of this claim, Coronil has been approved for sale by the Government of India on the sole basis of a scientific paper, published in the journal Phytomedicine in February 2021.
A previous article discussed the wobbly assertions in the paper and their mismatch with Patanjali’s conclusion that Coronil has been properly tested or that it is efficacious. But there is another bit of detail that may disqualify the paper’s publication itself. In the paper’s ‘Declaration of Competing Interest’ section, the authors say:
“Authors declare no conflict of interests with regards to the submitted work. The medications were provided by Divya Pharmacy, Haridwar, Uttarakhand, India. Acharya Balkrishna is an honorary trustee in Divya Yog Mandir Trust. Besides, providing the medications, Divya Pharmacy was not involved in any aspect of the clinical trial reported in this study. Clinical trial was conducted at National Institute of Medical Sciences, Jaipur, India.”
There is a major discrepancy here – and to understand its significance, let’s take a brief detour.
Celebrex is a drug of the broad class of non-steroidal anti-inflammatory drugs (NSAIDs), which includes ibuprofen and naproxen. NSAIDs are commonly used to treat arthritis. Celebrex was developed in the 1990s and was considered to represent a new generation of NSAIDs, so it was marketed as an improvement over older drugs in the same class.
Results from the Celecoxib Long-term Arthritis Safety Study (CLASS), which researchers conducted to compare Celebrex with newer drugs, were published in the Journal of the American Medical Association (JAMA) in September 2000. The paper had 16 authors, six of whom were employed by Pharmacia, the manufacturer of Celebrex, and the rest were paid consultants.
The study compared patients receiving two treatments “over a period of six months”. Based on the data they obtained, the authors concluded that participants who were treated with Celebrex experienced fewer ulcers and didn’t experience a greater degree of heart attacks and stroke than those using older NSAIDs. Michael Wolfe, one of the editors of JAMA, was so impressed with the drug when the CLASS article was submitted to the journal that he co-authored a glowing editorial extolling the drug’s virtues.
However, in 2001, when Wolfe was a member of the US Food and Drug Administration’s advisory committee on arthritis, he serendipitously had a chance to examine the CLASS study dataset again. This time he found that the study had lasted for over a year, instead of the reported six months, and that a reanalysis of the data led to very different conclusions, apparently because the original analysis had been performed with a well-curated data set. Celebrex caused significantly more life-threatening adverse events than older drugs.
In a subsequent article published by The Washington Post, Wolfe was quoted as saying, “I am furious… I wrote the editorial. I looked like a fool. But … all I had available to me was the data presented in the article.”
The Celebrex study is an often quoted cautionary tale of how pharmaceutical companies can and do attempt to suppress and manipulate data and study protocols, often abetted by researchers involved with clinical trials.
Studies supported by pharmaceutical companies are also prone to methodological bias. Industry-funded clinical trials are known to yield positive results more often than studies funded by other bodies. The bias could be because of the enrolment of relatively healthy participants, inadequate sample size, inappropriate length of follow-up, misleading data presentation, use of language intended to obscure and inappropriate end points. A mix of these is already apparent in the Coronil study.
One way to increase transparency, to promote public trust in the credibility of science and to prevent industry-driven manipulation of trials is by having the authors of each paper declare any conflicts of interest. The authors owe us and science an honest declaration of how their relationships and activities, directly or indirectly related to the paper, interacted with and were handled during the planning, implementation and writing of the study.
To further transparency and to make scientific work more credible, a guild of editors came together in 2010 as the International Committee of Medical Journal Editors (ICMJE) and issued guidelines on how competing interests between the author and their work must be fully disclosed. The New England Journal of Medicine, The Lancet and JAMA – all well-regarded medical journals – are signatories to these guidelines and require their authors to comply with them. Even Phytomedicine recommends these guidelines as part of their guide to authors.
According to ICMJE guidelines: “The potential for conflict of interest and bias exists when professional judgment concerning a primary interest (such as patients’ welfare or the validity of research) may be influenced by a secondary interest (such as financial gain). Perceptions of conflict of interest are as important as actual conflicts of interest.”
But in spite of these guidelines, Acharya Balkrishna, listed as a co-author of the Coronil paper (which explicitly mentions the drug by its name), failed to disclose his role as the managing director of Patanjali Ayurved Ltd. (a title he also advertises on his Twitter bio), the company that is manufacturing and marketing the drug. Did he not think this fact deserved mention or that it described a clear conflict of interest?
Phytomedicine published the paper online in February. But the article was submitted to the journal on November 21, 2020, after Patanjali had already sold 2.5 million units of Coronil, according to India Today. That is, sale of the drug preceded the study.
In addition, the ‘author contributions’ section of the paper clearly states that Acharya Balkrishna was involved in funding, managing resources and reviewing and editing the journal article. The authors have failed to disclose the conflict of interest here too.
So the line that “Authors declare no conflict of interest with regards to the submitted work” is just absurd.
This problem is not unique to this paper. In a scientific article published online on February 28, 2020, in the journal Phytomedicine Plus, the same authors failed to declare Balkrishna’s position as the head of Patanjali Ayurved Ltd.
These declarations don’t explicitly help rule out bias or the risk of data manipulation, say, but they certainly indicate the veracity of the paper’s claim and the caveats with which it should be read and interpreted.
In addition to these transgressions, the authors have not made the raw data of their study available for public scrutiny, so there is no way to reanalyse it – like Wolfe once did – and check if we reach the same conclusions.
That the editors and reviewers of Phytomedicine failed to pick up on these issues also damages their credibility and brings into question the credibility of all the scientific work that the journal is associated with. (That the Government of India also failed to pick up on them may not merit any discussion at all.)
There is a long and healthy tradition of journals retracting published studies after establishing that authors failed to disclose financial conflicts of interest. The failure to mention major and competing conflicts of interests require – rather, demand – that for the sake of science and for the sake of its credibility, the Coronil study in Phytomedicine (in its current form) be retracted as well.
Dharamveer Tatwavedi is reading for a DPhil at the University of Oxford and works in oncology as a clinician. He tweets at @Dharam_tat.