How Rotovac vaccine controversy questions the transparency of clinical trials

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Amid much fanfare in March this year, Prime Minister Narendra Modi launched Rotavac, an antidiarrhoeal vaccine. Manufactured by the Hyderabad-based Bharat Biotech, the vaccine has been developed by Indian institutions in partnership with the National Institute of Health, USA. Much of the media attention that the launch has received is due to its branding as an indigenous vaccine which, the government announced, would be available at an affordable cost of Rs60 per dose ($1). However, the non-disclosure of site-specific data about the result of phase III of the clinical trial of the vaccine, conducted at three sites (Delhi, Pune and Vellore) that preceded the approval and subsequent launch of Rotavac, has raised important questions about the ethics of clinical research, and the obligation to publish complete trial results for further examination by the medical and research community.

A vaccine trial aims at establishing the safety and efficacy of a vaccine prior to it securing the stamp of official license. According to the World Health Organization (WHO), the clinical evaluation of a vaccine is a critical factor in supporting it. Clinical trials are conducted to assess the safety, immunogenicity and efficacy of the vaccine before approving it for licensure.
In consonance with the protocol of licensing the rotavirus vaccine, the clinical trial of Rotavac was registered with the Clinical Trial Registry. Its aim was to assess the safety of the vaccine in terms of the number of intussusceptions over a two-year trial period. Intussusception, in lay terms, is a medical condition where part of the intestine folds into another part of the intestine which leads to obstruction that could need urgent surgery in order to prevent death from occurring. The particular kind of medical condition is diagnosed with ultrasound examination. The Rotavac trial was meant to test the risks triggered by the potentially fatal side-effects of the vaccine.

Without disclosing the segregated data from all the three centres where the clinical trial was conducted on infants, the government is now planning to escalate the research to Phase IV in which the vaccine will be administered to another 100000 infants. The withholding of data is in clear violation of international ethics of medical research and global norms governing clinical trials.

The government has not even shared the data with its own advisory body – the National Technical Advisory Group on Immunisation (NTAGI). A NTAGI member, also an expert on immunisation policy, repeatedly requested the government for access to the segregated data and the trial results from the different centres — especially Vellore. But the government has repeatedly stonewalled all information in this regard.

A writ petition seeking the data has subsequently been filed in the Delhi high court. Rattled by the petition, the government appeared before the high court on the very first day, pleading its inability to share the data. The government, as well as the Christian Medical College, Vellore, which conducted the clinical trial in the Vellore limb of the study, argued that the “site specific data on safety is inappropriate for release as per protocol and its inappropriate interpretation or publication would lead to disinformation about the product (that has been) developed by government with great effort and expense, and will give unfair advantage to multinational products which were never tested in India, (and) yet (were) licensed.”

In its March 2014 issue, The Lancet published a paper on the results of Rotavac clinic trials, vouching the vaccine to be safe with a 53.6 per cent efficacy in the first year against severe rotavirus gastroenteritis (diarrhoea). The peer-reviewed, scientific, UK medical journal Vaccine reported an efficacy of 48.90 per cent against severe rotavirus gastroenteritis. The paper published in Vaccine stated that a decisive assessment of the risk of intussusceptions has been left to phase IV post-marketing studies. However, neither of these papers has furnished complete segregated data from different clinical trial centres.

According to the trial findings so far, the number of intussusception cases in the Vellore centre is almost 20 times the corresponding figure computed at the Delhi centre. This is 5-10 times higher than the risk of intussusception triggered by the Rotashield vaccine which has been withdrawn from the market in the US, and nearly 70 times higher than the risk of intussusception that could be caused by the current, internationally licensed vaccine — RotaTeq.

Whether such a huge difference in numbers can be attributed to an innocuous mistake on part of the Vellore centre, or whether it is a case of a particular population being more susceptible to the side-effects of the vaccine, cannot be gauged without the site-specific data. The government’s insistence on withholding this important data from even its members of NTAGI has understandably heightened the speculation about the efficacy of the Rotavac vaccine. Last but not least, it is indeed ironic that the government has invested almost Rs300 million in developing this controversial vaccine which now seems to be in the eye of a storm.

The author practises law in Supreme Court