doi:10.1038/nindia.2013.122 Published online 11 September 2013
Pressure is mounting on the Indian government to explain the role of the Indian Council of Medical Research (ICMR) and the Drug Controller General of India (DCGI) in the case of the trial of human papilloma virus (HPV) vaccines by international charity Program for Appropriate Technology in Health (PATH).
An Indian Parliamentary panel recently accused the US-headquartered health philanthropy of having violated local government regulations while conducting clinical trials for a cervical cancer vaccine on Indian girl children three years ago. The committee also questioned ICMR's rationale for committing to support the use of HPV vaccine in the agreement it signed with PATH in 2007 even before the vaccine was approved for use in India (which happened later in 2008) and its decision to include it in the universal immunization programme — a job normally handled by the National Technical Advisory Group on Immunisation in the health ministry. The committee has accused DCGI of remaining "a silent spectator even when its own rules and regulations were being so flagrantly violated" by PATH.
A public interest litigation was filed on September 3, 2013 in the Supreme Court of India, which has now sought a detailed report on the investigations conducted by the government and the action taken on complaints of unethical clinical trials of the HPV. Political leaders of left parties have also urged the Union Health Minister Ghulam Nabi Azad to speed up probe.
In a 36-page report tabled in the Indian Parliament on August 30, 2013, the Parliamentary Standing Committee on Health called for government action against PATH for "alleged irregularities" in obtaining informed consent from trial subjects, lack of monitoring serious adverse events, and inclusion of "vulnerable and tribal population groups".
Officials of the Seattle, Washington-based non-profit agency, however, say they are "disturbed by the report's inaccurate characterization" making it clear that theirs was not a clinical trial but a "demonstration" project .
PATH, with funding from Bill and Melinda Gates Foundation, conducted the study using Human Papilloma Virus (HPV) vaccines in the Indian states of Andhra Pradesh and Gujarat in 2009-2010. Around 24,000 girls aged 10 to 14 in the two states received either Merck's Gardasil or GlaxoSmithKline's Cervarix vaccine that PATH made available for free. The Indian Council of Medical Research (ICMR) in New Delhi had approved the project in 2007 but suspended it in April 2010 following protests over deaths of seven girls — five in Andhra Pradesh and two in Gujarat — after receiving the vaccines.
The 41-member Parliamentary panel that had been investigating the issue since then says the implementation of the PATH study in both states was flawed. It says serious adverse events were not monitored and consent of trial subjects were not taken properly. For instance, many consent forms had only thumb impressions, most parents and guardians of the girls were illiterate and 69 out of 100 forms in Andhra Pradesh bore no signatures of witnesses, which was mandatory.
The committee was "surprised" that Merck's vaccine was given to children before its safety was evaluated in adults in violation of government guidelines. "Thus the safety and well-being of subjects were completely jeopardized," the report says adding that PATH should be made accountable for these ethical lapses.
Vivien Tsu, director of Cervical Cancer Prevention Project at PATH, however, denies these charges. "PATH is committed to meeting the highest ethical standards," Tsu told Nature India adding that it was for the state governments to implement the consenting process and the vaccination of the girls. Tsu said the Parliamentary report was "inaccurate in many details". For instance, witnesses were not required if the signing parent was literate. For parents who were not literate, the health workers were responsible for explaining the contents of the form.
"The report suggests that providing the vaccine for free was coercive in some way, but all vaccines in the national program are provided for free and nobody suggests that the practice is coercive," Tsu said. The project, Tsu emphasized, did not seek to evaluate the efficacy or long-term safety of the vaccines as they had already been licensed by the Drugs Controller General of India (DCGI). "Our goal was to generate the information governments would need to make their own decision about whether and how to introduce HPV vaccines" in the universal immunization programme (UIP).
The Parliamentary panel, however, says its investigation has established that PATH's exercise in India and in three other countries — Uganda, Peru, and Vietnam — appeared to be a "promotional activity for the benefit of the HPV vaccine manufacturers". The choice of countries, the diverse population groups, and the unlimited market potential in the event of the vaccine being accepted in their national programmes, "all point to a well panned scheme to commercially exploit a situation," the report says. "To achieve this end effortlessly without going through the arduous and strictly regulated route of clinical trials, PATH resorted to an element of subterfuge by calling the clinical trials an observation study or demonstration project," the report says. By so doing, PATH "has violated all laws and regulations laid down for clinical trials by the government."
Tsu emphatically denies this. "PATH is not working on behalf of any pharmaceutical company," Tsu said. "It has no financial stake in the vaccine and received no funding from the manufacturers." PATH has also assured the critics of the Indian trial that the results of similar study in Peru and Uganda has paved the way for these countries to launch national immunization programmes against HPV and contributed to the GAVI Alliance's decision to subsidize HPV vaccines for these countries.