The Union health ministry will soon initiate punitive action against violations in the clinical trial of human papilloma virus vaccines (HPV vaccines) in Andhra Pradesh and Gujarat in early 2010 in which six children were allegedly died after they were administered the controversial vaccine being marketed by MSD Pharmaceuticals (Gardasil) and GSK Pharmaceuticals (Cervarix).

Sources in the union health ministry said that the files regarding this issue are being examined by the senior officials in the ministry and there will be some action on the issue very soon.

After the alleged deaths of six children, the trials were suspended on April 7, 2010 and the Union health ministry appointed a three-member expert committee to investigate ethical issues raised in the matter.

The final report of the panel had ruled out direct linkage between the deaths and the trials held in Khammam (where 13, 791 girls were vaccinated) and Gujarat’s Vadodara (where 9,637 were vaccinated). But at the same time, it said “the reported deaths were most probably unrelated to the vaccine. However, the cause of death in all cases could not be established with certainty”.

The inquiry voiced concern over the supply of vaccines, free of cost from pharma giants GSK and Merck. It also found serious lapses in the conduct of the trials, mainly in planning and implementation of the project. It was most unusual for a large observational study not to have diary card-based reporting of serious adverse events (SAE) and for it to target “vulnerable” girls despite directions that no research would be done on tribals unless of specific use to them.  The project design didn’t take the issue of SAE seriously nor appointed an independent monitoring agency which caused unacceptable delays in the reporting of deaths. It resulted in gross under-reporting of adverse events and didn’t provide insurance to girls though PATH had a cover, according to the report.

The committee also found serious discrepancies in consent forms of the vaccinated girls. Of the 100 forms from Andhra Pradesh studied, witness signatures were missing in 69. Over 2,763 forms out of 14,253 in Andhra had been signed by wardens/principals on behalf of children (by the state government’s order).  The inquiry report also came down on the ICMR’s role as it sided with PATH to call the project an observational study and no clinical trial.

Some time back, both the Gardasil and Cervarix were allowed to undergo phase-III clinical trial in India, before granting permission to import and market authorization. For assessing the health services needs and preparedness for introducing HPV vaccines into the health services in future, an international NGO named PATH was given permission for a post licensure observational study of HPV vaccination in Khammam district in Andhra Pradresh and Vadodara district in Gujarat.

The study by PATH was recommended by the Ethics Committee and Advisory Groups at state and central government levels. The Indian Council of Medical Research (ICMR), an autonomous body under the union health ministry has been providing technical support for the development of protocols, and has been advising on ethical issues as per the government of India guidelines.

This was not the first time such suspected death occurred after the vaccination of HPV vaccine.  On September 28, 2009, the GSK was notified by the UK's Department of Health about the death of a 14-year-old girl, Natalie Morton, who was vaccinated at a school in Coventry with GSK's cervical cancer vaccine, Cervarix, as part of the national HPV immunisation programme. After the incident, which caused an alarm in many parts of the world about the efficacy of the vaccine, the GSK recalled a particular batch of Cervarix.