‘Project proposal carried out as research on human participants'

The final report of the committee appointed by the Centre to enquire into alleged irregularities in the conduct of studies using Human Papilloma Virus (HPV) vaccine has found enough evidence to suggest that there were large-scale ethical violations during the conduct of “post-licensure observational study,” be it in obtaining the consent of the young girls on whom the trial was conducted, or on issues related to safety, follow up, and reporting of adverse events.

Though the report finally does not fix the responsibility on any individual or institution despite evidence, a three-member sub-committee that assisted the main enquiry committee has clearly said that the nature and objectives of these projects make it evident that they are in fact clinical trials, wherein the projects were a “study of a pharmaceutical product carried out on human participants” and “4 of 5 primary outcome measures proposed related to evaluation of the safety in the vaccine in population study.” The principles used to define a clinical trial by the Central Drugs Standard Control Organisation (CDSCO) and the Schedule Y of the Drugs and Cosmetics Act, 1954 can be applied to the demonstration product conducted by [the non-governmental organisation] PATH.

The three-member enquiry committee comprised S.S. Aggarwal, former director of Sanjay Gandhi Post-graduate Institute of Medical Sciences; S.P. Agarwal, former director general of Health Services; and Suneeta Mittal, head of Obstetrics and Gynaecology, All India Institute of Medical Sciences (AIIMS); while the committee that assisted them included Rani Kumar, dean of AIIMS; A.K. Dutta, head of Paediatrics, Kalawati Saran Hospital; and Y.K. Gupta, head of Pharmacology, AIIMS.

The committee has said that “by whatever name you call it, the project proposal has been carried out as research on human participants. And as such, it has to follow all the guidelines and statutory requirements applicable for research on human participants. Monitoring and management of adverse events/serious adverse events should have been more vigorously pursued. There is nothing known as post-licensure demonstration project. What was done is clinical trial,” C.M. Gulati, editor of Monthly Index of Medical Specialists, told journalists here.

Dr. Y.K. Gupta has concerns over the vulnerable population (tribal) that was chosen for the project, while saying that for better understanding of the research nature of the study and its impact on cancer prevention, a better educated and better aware population inclusion might have been more desirable. It would have been better investigated to document the cause of illness even if unrelated, he said, adding that the law specifically states that “everyone shall desist from research on tribal population, unless of specific benefit to them.”

In her findings with respect to the process of obtaining consent and the inspection of the consent, Dr. Rani Kumar said the team involved in the study was casual in approach and ignored many ethical issues. The ambivalent sentences in the consent form tantamount to covert inducement and indirect coercion, she observed.

The lacunae in the adverse event reporting system has been an issue of concern for the experts as well as in the discussions of the committee. “There has been direct contact with the human participants, they have administered an intervention which is not part of a prescribed prevention, and have expected adverse events.” Dr. A.K. Dutta, in his observations, mentioned several unacceptable and prolonged delays in the reporting of adverse events and deaths due to lack of any independent monitoring system. The committee has recommended that besides issuing directions, an active programme needs to be evolved for training investigators and sensitisation of regulatory agencies to specially look for these aspects in any study involving human subjects. There is a need for specific and separate legislation covering all aspects of biomedical and health research involving human participants which should provide statutory status to Indian Council of Medical Research ethical guidelines.