Killugudi Jayaraman responds:

Seth Berkley ignores the central point of the controversy: the launching of a phase 1 trial in India after the results of the Belgian study had already shown that the vaccine was not sufficiently immunogenic. Critics think that IAVI's argument that the vaccine would have fared better in Indians because of their different genetic factors is scientifically weak. Although clearly phase 1 studies are used primarily to assess safety, Berkley notes that an immune response was found in 17% of all pooled trial volunteers at the highest dose tested. This means that when the Indian trial was launched, there was at least a possibility that some individuals in the Indian arm could potentially have mounted an antibody response to HIV and thus become exposed to the potential discrimination on the basis of their HIV-positive status. The information that none of the volunteers in India actually tested positive to HIV is beside the point.

In terms of the Indian legislative framework, phase 1 trials are covered by Schedule Y of the Drugs and Cosmetics Rules, which allows phase 1 trials to be approved for molecules and vaccines discovered outside India only in exceptional circumstances. Even when such permission is granted, it is usually given only after the results of a phase 1 trial conducted abroad are made available; the cases where the Indian government permits a phase 1 trial of a foreign product in the absence of a phase 1 trial conducted abroad are even more rare. In this last case (e.g., applicable to the IAVI vaccine example), sponsors are obligated to notify the Drugs Controller General, India (DCGI; New Delhi) of all important developments in clinical trials. In India, DCGI is the regulatory body for clinical trials and not the Indian Council of Medical Research (ICMR), which has a mandate to promote research only and, as a co-sponsor of the IAVI trial, was an interested party. In the case of IAVI's AIDS vaccine, then, the results of the trials in Belgium and Germany, once available, should have been officially communicated to the DCGI so that the permission to conduct a phase 1 trial as an exception could be reviewed. This apparently was not done, although IAVI has stated the information was given to trial subjects and fresh consent obtained.

There are other reasons why the trial was ethically controversial. When the permission to conduct the trial was given by DCGI, members of civil society in India expressed two major concerns. First, it was hoped that trial volunteers would be restricted to well-educated, affluent individuals and that the enrollment of poor, illiterate persons avoided—a suggestion that was not accepted by the trial sponsors. And second, it was suggested that “since volunteers could test positive for antibodies to HIV after the trial,” the sponsors should outline compensatory measures.

The issue relates not only to potential discrimination by employers concerning HIV-positive status but also to the families of prospective brides. As is well known in India, marriage partners are mostly selected by parents. Given the low literacy rate and fear of AIDS, issuance of certificates by sponsors is certainly not the answer.

It is also argued that trials were conducted in India to determine the specific response to environmental and genetic factors. India is a vast country and there is not one but several diverse, entirely different ethnic groups, such as Indo-Aryans, Dravidas, Mongols and indigenous tribes. There is no ethnic entity called 'Indian'. As far as I am aware, the protocol in India did not make obligatory the enrollment of volunteers from all the ethnic groups.

Finally, it is widely known that the office of DCGI in India lacks expertise, is grossly understaffed (not a single medically qualified expert on its staff) and inexperienced in handling clinical trials. Furthermore, according to ICMRs' own study, no more than 40 hospitals in the whole country have functioning Institutional Review Boards (called Ethics Committees in India). Both the Indian (e.g., Indian Journal of Medical Ethics, Monthly Index of Medical Specialities, TV and newspapers) and foreign media (e.g., The New England Journal of Medicine, BBC, ABC) have drawn attention to these general shortcomings, which has led to a lack of protection of trial subjects in the past.