Even before the full data on these trials has been made public, the vaccine is out in four states. A petition in the Supreme Court hopes to unveil the silence over the trial data
By Meena Menon in Mumbai
A new petition in the Supreme Court has demanded that the entire segregated data on Rotavac vaccine trials held between 2011 and 2013 be made public. The government maintains secrecy over the data even as the vaccine is being administered in Haryana, Himachal Pradesh, Orissa and Andhra Pradesh since March 2016, with plans to add it to the Universal Immunization Programme.
The apex court on July 5, 2016, issued a notice to the center, Department of Biotechnology (DBT) and Christian Medical College (CMC), Vellore, on a writ petition filed by S Srinivasan seeking complete center-wise results of the clinical trial of the anti-diarrhoea vaccine, Rotavac.
Srinivasan, a health care activist and managing trustee of Locost Standard Therapeutics, demanded that the Supreme Court set aside the Delhi High Court order dismissing an earlier petition by Dr Jacob Puliyel, head of pediatrics, St Stephen’s Hospital, Delhi on October 14, 2015.
Srinivasan also demanded disclosure of the segregated results of the clinical trial of the vaccine conducted on 6,799 infants in Delhi, Pune and Vellore, and said these results be placed before the National Technical Advisory Group of Immunization (NTAGI), the expert body on immunization policy, for examination and scrutiny. DBT had failed to make available the complete de-aggregated data (centre-wise data) before launching the vaccine. The very raison d’etre of such multi-center trials is to compare results among them and without data the vaccine should not have been launched. This data should have been examined by NTAGI in public interest but such is the secrecy surrounding it that it has not been provided even to this apex advisory body, his petition contended.
While dismissing Puliyel’s petition demanding full data on the trials, the Delhi High Court ignored the fact that NTAGI also didn’t get to see the data and instead, accepted the center’s contention that the petition was motivated in private interest.
The clinical trials of Rotavac were conducted to ensure its safety in terms of the number of intussusceptions (intestinal obstruction which could need surgery to prevent death) in the two-year trial period. The vaccine has been permitted for public use despite questions on its efficacy being raised in an article in the UK journal, Vaccine. The results which were reported in this journal in August 2014 by Jacob John (a top virologist for CMC) and other investigators indicated a higher rate of intussusceptions among the children who were vaccinated. Based on this data, Puliyel said this was five to ten times higher than the risks of intussusceptions with Rotashield vaccine which was withdrawn from the market in the US and 70 times higher than Rotateq which is currently used. The incidence of intussusceptions were higher in Vellore (581/100,000 child years) than in Delhi (27.7/100,000 child years) and the regional differences could mean that it may be more risky to use the vaccine in some areas. The article did not provide the segregated data on the number of ultrasound-diagnosed intussusceptions among the vaccinated and control groups in Vellore.
The segregated data was not made public despite applications under the Right to Information (RTI) act by an NGO and online petitions, apart from emails and letters by Puliyel. The DBT and the Ministry of Science and Technology conducted Phase 3 clinical trials and of the 6,799 infants, 4,532 received the vaccine and the rest were in a control group. After the Delhi High Court dismissed Puliyel’s petition, a Special Leave Petition filed by him was also withdrawn since he was a member of the NTAGI.
Puliyel made several attempts to get the data after the Vaccine article and sent repeated emails demanding it from Sunil Chandy, director of CMC, Vellore, which was part of the trial. He also wrote to all NTAGI members and its head asking for complete data but to no avail. He then wrote a letter on June 16, 2015, to the Principal Secretary, Prime Minister’s Office (PMO), where he said that the number of potentially fatal side-effects was so high in Vellore that the data was not being released but the vaccine had been licensed for general use. He said in the letter “that phase 3 clinical trials began in 2011. However, 12 years before the trial was even started (in 1998), Bill and Melinda Gates Foundation’s PATH had already selected the manufacturer for the vaccine”.
The trial, incidentally, is funded by a grant from the Bill and Melinda Gates Foundation to PATH, USA, and others including Bharat Biotech, the company making Rotavac. PMO asked the Subject Expert Committee (SEC) of the government to examine the issue.
On June 30, 2015, according to the minutes of the meeting, the committee reviewed the submission of the vaccine-related Serious Adverse Event (SAE) during the Phase 3 clinical trial and “did not find the concerns of non-disclosure of SAE of intussusception and safety from Vellore site well authenticated”. The SEC was asked to examine the matter again and it referred to the Vaccine article (and not original data). It said that overall the percentage of intussusception in the vaccine group was 0.28% (13/4532) and the placebo group 0.26% (6/2267) and the difference is not statistically significant. None of the events of intussusception required surgical interventions and none were fatal. It suggested that further review of data at Vellore with regard to intussusceptions could be undertaken if required, based on the observations of the Delhi High Court.
However, in an order on October 14, 2015, the Delhi High Court noted that the petitioner was a member of NTAGI and it is not in dispute that NTAGI on being satisfied about the efficacy and safety of the vaccine had recommended including it for the National Immunization Programme. “The learned counsel appearing for the petitioner could not dispute the fact that the entire segregated data on the trial conducted in all these centres was available with NTAGI before making its recommendation,” the Court said, ignoring the fact that no data was shown to NTAGI.
The Court held that no case was made out to show that public disclosure of segregated data is mandatory before allowing a Phase 4 trial. The clinical trial report had been cleared by NTAGI and the vaccine was approved by the Drugs Controller General of India. The Court said that no case of violation of any statutory provision was made out in the petition and no case was also made out to show that disclosure of the segregated data is essential in public interest.
Non-disclosure of data in such a case is unethical to say the least. The revised Declaration of Helsinki in 2013 stated that researchers have a duty to make publicly available the results of their research. “Negative and inconclusive as well as positive results must be published or otherwise made publicly available,” it said. WHO too has strongly advocated public disclosure of clinical trial results.
It is a mystery why the NTAGI was not given the complete data and as Srinivasan contends in his petition, the full data is important to explain the risks that have already been seen in the Phase 3 trial before consent is taken for giving the vaccine. It is important to inform the public about the adverse effects of the vaccine as the signs and symptoms of intussusception are the same as that of dysentery (passage of blood and mucus in the stool). Unless the public is warned beforehand, it would only suspect dysentery. And that can have disastrous consequences.