Assessing the feasibility to conduct efficacy trials in India

The implementation of clinical trials to test the vaccine efficacy is one of the major difficulties of clinical development for any vaccine, in particular for AIDS vaccines. Such implementation represents a tremendous scientific and organisational challenge that must be anticipated years in advance. An important step is therefore to define the feasibility of such trials in India. In this regard, assessments of various infrastructures and organisations working with different communities and their epidemiological characteristics were conducted to provide recommendations for the conduct of site and community preparedness studies.

A team comprising of several national and international experts visited select scientific institutions and non-governmental organisations in Tamil Nadu, Andhra Pradesh, and Maharashtra in July 2003. In January 2004, similar visits were made to West Bengal, Assam, Manipur and Nagaland in cooperation with the National Institute for Communicable and Enteric Diseases, Kolkata. A complete report has been handed over to ICMR and NACO. Recommendations included the need to work with groups at higher risk for HIV infection including men who have sex with men, intravenous drug users, sex workers and sexually transmitted disease clinic attendees. Feasibility studies estimating HIV prevalence and incidence in these groups are under consideration.

Involving the Community

IAVI's programme in India is based on transparency and accountability. To ensure that the trials are ethical and safe, broad-based community support is required. To achieve this, several mechanisms have been put in place.

Informed Consent Group

A 15-member expert committee of scientists, academicians, lawyers, activists, gender experts, researchers and members of non-governmental organisations (NGO’s) was constituted to develop a template for the Informed Consent documents used in the Phase I trials. The aim was to ensure that documents comply with the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines, are scientifically relevant, culture-sensitive, and ethically sound, and that the volunteers would have a full understanding of the risks and benefits involved in trial participation.

The Screening and Enrolment consent forms, the Volunteer’s Information Brochure and the Test of Understanding for the Phase I trials have been created using the approved templates.

Gender Advisory Board and Training

Composed of a small group of experts, the Board oversees and guides the programme’s efforts to incorporate gender concerns into AIDS vaccine trials. The Board has assisted in developing training modules and a framework for implementing gender training for trial staff. The group aims to encourage recruitment and retention of women in AIDS vaccine trails conducted by NACO-ICMR-IAVI, setting standards for other vaccine trials in the country.

A gender training workshop for the NARI trial team staff was conducted in August, 2004 to help the staff develop an understanding of the gender issues in AIDS vaccine trials. Similar training will be conducted for the trial staff at TRC. An IAVI report “Addressing Gender Concerns in AIDS Vaccine Trials in India” is now available at http://www.iavi.org.in/indprog_files/IAVI Gender Report 2004.pdf

National Consultation on HIV Care and Treatment in AIDS Vaccine Trials

Safety of AIDS vaccine trial participants is of prime concern for IAVI. Although counseling to avoid risk of HIV infection will be provided all through the clinical trial, it may be possible that some volunteers do not follow these recommendations and indulge in high risk behaviour leading to HIV infection. The vaccine cannot in any circumstances cause HIV infection. This situation would be particularly acute in efficacy trials that recruit people at high risk for HIV infection. Should a volunteer become infected during the course of the trial, the provision of appropriate care and treatment for trial participants is a significant part of an AIDS vaccine development programme. The IAVI policy is to offer free of charge HIV care and treatment including anti-retroviral drugs to volunteers who would become HIV-infected during the course of the trial for the duration of five years from the time of treatment initiation.

In March 2004, an informal consultation was held in New Delhi to clarify the responsibilities of research sponsors and the host country (India) in providing appropriate care and treatment for trial participants. The consultation helped define the policy and technical guidelines for the care and treatment of trial participants, including those who become HIV-infected, during the course of AIDS vaccine clinical trials, within the larger framework of the NACO HIV/AIDS care and treatment policy guidelines. The recommendations have been accepted by the participants and incorporated into the Phase I trial informed consent documents.

Next steps: While the launch of the first Phase I clinical trial of a preventive AIDS vaccine candidate is a significant moment for India, there will be several such Phase I trials before the most promising candidate for Phase IIb and III clinical trials is selected.

Other AIDS vaccine candidates that have been short listed for clinical trials in India include the above-mentioned vaccines or their improved versions as well as DNA and adenovirus-based vaccines. Decisions to proceed depend on the safety and immunogenicity data generated in pre-clinical studies as well as in Phase I trials in humans in India and in other countries.

In addition, IAVI has entered into a partnership with Department of Biotechnology aimed at conducting research towards the design and development of the next generation of AIDS vaccines.