(Weekly Organ of the Communist Party of India (Marxist)
May 15, 2011
BRINDA WRITES TO HEALTH MINISTER
HPV Vaccine Project Marred by Companies’ Narrow Agendas
Brinda Karat, MP and member of the CPI(M) Polit Bureau, wrote on May 9 the following letter to Ghulam Nabi Azad, union minister for health and family affairs, regarding the HPV vaccine project.
is further to my correspondence with you regarding the HPV vaccine
my letter dated February 17, 2011, I had raised certain issues arising
the interim report of the enquiry committee and requested you to take
Since then, the final report has been submitted, which I have been able
recently access and study, along with the thousands of pages of
placed before the committee. These include the reports submitted by the
doctors who were consulted as experts by the committee, namely Dr Rani
(Dean, AIIMS), Dr A K Gupta (head of paediatrics,
The final report as well as the annexures substantiate not only all the issues I had raised but also raise new and disturbing issues. There has been a serious dereliction of duty by many of the institutions involved. In particular the role of the ICMR has been extremely questionable. It may be stated on the basis of the evidence available in the documents that the ICMR representative and some of its officials acted as partisans of the NGO and the interests of the manufacturing companies instead of as representatives of an institution mandated to maintain as well as ensure the implementation of the highest levels of ethical standards in research studies. The experience of this study clearly shows that it is most unwise to allow an institution like the ICMR to go in the PPP mode, as was done for this project as this gives rise to a grave conflict of interest.
For example, a perusal of the documents make it apparent that the Ministry was mistaken in appointing the very same ICMR official to assist the enquiry committee who was representing the ICMR in the Project Advisory Board (PAB) and more importantly as a partner (ICMR) in the project. As a partner, the said official was responsible for the design and implementation of the project and therefore was accountable for the violations. However, as an assistant to the committee he was able to listen in to and participate in the discussions to identify the lapses and help formulate the final report. The objectivity, impartiality of any individual in such a role is bound to be questioned. In this particular case, the ICMR representative played a proactive role as a partner in pushing for the project including persuading various committees to accept the project swiftly on the plea of “time constraints.” Thus, there was a clear conflict of interest. Indeed it may even be legitimately asked whether it was because of any such biases in the “assistance” given to the committee that the final recommendations of the committee appear as a dilution in comparison to the detailed comments made by the committee members as well as the reports of the experts which are available in the annexures and even in the main report.
A crucial aspect raised in the discussions of the enquiry committee and partially reflected in the final report is the serious ethical question of whether the entire project itself was designed to promote the interests of the companies. In its meeting on September 27, 2010 (Appendix 20.5) it is noted: “…Besides the factual information about the terms of reference the committee was greatly concerned with the aspect of commercial interests of manufacturers influencing the Government policy on this expensive vaccine. The committee observed that the study was initiated by PATH on its own having obtained funds from the Bill and Melinda Gates Foundation and supply of vaccine from the manufacturers – without any reference from the NTAGI, the official body of the GOI on vaccines..…It is not clear whether the State expenses were funded by PATH or came from their own resources. The monetary contributions of ICMR are also not clear. The committee therefore felt that it would be in the fitness of the inquiry to document the sources and magnitude of funding of the study”
Although the committee decided that collection of information on the above issues would be followed up by the ICMR scientist who functioned as the secretary of the committee, unfortunately it appears from the papers available that this crucial information was not provided to the committee and the questions remained unanswered.
this connection it is relevant to also mention that one of the roles
to ICMR in the MOU signed by the director of the ICMR is “Advising on
results dissemination to support decision making for use of the HPV
How could the ICMR have committed itself to support “the use of the HPV
vaccine” in an MOU signed in the year 2007 even before the vaccine was
for sale in
I request you to ensure that the necessary information is collected so that the issue of funds as well as whether it was wise to accept such a project by the ICMR in the first instance may be better addressed.
A related issue is the very nature of the project. This is not an issue of semantics but one which deeply concerns the rights and interests of the subjects of such a vast vaccination project, particularly when the subjects are minor girls. There are conflicting statements by the parties concerned namely the DCGI, the ICMR, the AP authorities and the NGO. The committee has unfortunately overlooked these conflicting statements, which are on record.
Appendix 20.4 it is recorded that the DCGI representative appearing
before the committee
stated, “ DCGI considers PATH’s demonstration projects as Phase IV
It had defined objectives, a plan of study, and dealt with
administration of a
drug. As such approval for carrying out the study was provided by the
DCGI. It obligates
the PI to report any SAE to DCGI within 15 days” (Dr Somani, office
The expert opinion of Dr Y K Gupta, given in his report dated September 11, 2010 and quoted in the final report of the enquiry committee (page 38) on this issue, is illuminating. He questions the PATH description of the project and quotes Schedule Y and Indian GCP guidelines. He says that since “the demonstration project is a study of a pharmaceutical product carried out on humans and since the primary objectives include the study of serious adverse effects and since the study has been carried out on “vulnerable populations,” “it is not clear” why the clinical trial protocol should not apply.
Moreover, the Committee in the Section 7 of its findings (page 73) has explicitly stated that it “is of the opinion that by whatever name you call it, the project proposal has been carried out as research on human participants. And as such it had to follow all the guidelines and statutory requirements applicable for research on human participants. Monitoring and management of AE/SAE should have been more vigorously pursued.”
Thus in the name of demonstration project and in spite of the directions of the DCGI, the said NGO got away with a flagrant violation of the norms, which should have been applied. The role of the ICMR as well as the AP Ethics Committee and the PAG is extremely questionable on this issue. It is also necessary to question why the DCGI remained a silent spectator when its own instructions were ignored.
Dr Y K Gupta in his report has been scathing in his criticism of the lack of rigour in the design regarding adverse events reporting. He has asked the most pertinent questions regarding the absence of preparedness in the event of any such occurrence. From his report it is clear that the side effects mentioned by the manufacturers themselves have been revised several times and now include serious health issues. He also asks the question that since there are contraindications for the use of the vaccine, why were there no checkups for contraindications before the girls were vaccinated. He also concludes that the design neither took the issue of SAE seriously nor was there adequate attention paid to the need for an independent monitoring agency. Precisely because of the lack of independent monitoring by the project, the reports of the deaths had an unacceptably long time gap. Dr Y K Gupta also points to the many discrepancies and gaps in the investigations of the deaths as shown in the documents available.
Expert Dr A K Gupta, in his detailed report of the deaths of the girls, while concluding that “there is no common pattern to the deaths that would suggest that they were caused by the vaccine,” is sharply critical of the delays in the reporting of the deaths in violation of the guidelines, both in AP and Gujarat, and comments that it is most unusual that there was no diary card based reporting of adverse events for assessing minor or major adverse events in the study protocol in such a large observational study. He has shown that the design of the project resulted in gross under reporting of adverse events and questioned the figures of the reported non-serious adverse events. He also comments that the insurance cover for the girls should have been ensured, which was not done.
Thus the opinions of the experts point not only to flaws within the design of the project, but also to its implementation calling into question the role of the AP authorities, the ICMR as well as the NGO.
Expert Dr Rani Kumar has gone into the question of informed consent in great detail in her two reports. She has shown the glaring discrepancies in the consent forms, for example, the fact that out of 100 forms from the AP project she was asked to study, she found the signatures of witnesses missing in 69 of the forms, in many forms there were no dates, in others the signature of one person was apparent in several forms and so on. She comments, “All the consent forms have been very carelessly filled and are incomplete and probably inaccurate.” Further, she states, “The team involved in conduct of the study on HPV had been very casual in its approach and has ignored many ethical issues.” She questions the legality of the AP circular directing all headmasters/wardens in all private/government/ashram schools to sign the consent forms on behalf of the children and their guardians. Finally, she concludes with a strong indictment, “From the above facts it is not clear how correct is it ethically to have vaccinated such girl participants.”
Thus on all counts, the serious issues I had raised about the process of gross violation of the concept and legal requirement of consent have not only been substantiated but further evidence has been marshalled by the experts which point to the extent of the violations. On this basis alone, the NGO has to be made accountable and suitable action taken.
ROLE OF ETHICS
Dr Kumar also raises the very important issue of the role of the Ethics Committees, their composition as well as the issue of registration. Neither of the two committees were registered She finds shockingly that, “Although the IEC is supposed to meet periodically to evaluate the progress of a project and review SAE reports, no such meetings were held by either of the committees in Gujarat or in AP. It was only after the reports which appeared in the media in AP, that IEC meeting was held.”
It would appear that these committees exist only as a formality and have not played the role they are designated for. This is a clear dereliction of duty. The Ministry should consider whether there should be a mechanism to take action against such irresponsibility, more so when the Ethics Committee knew that the subjects were children.
IEC material approved at various levels asserted that the government had started a vaccination programme. Thus the credibility established by the public immunization programme was used to promote private interest. It is reported in the documents that the funds from the NRHM was used for monitoring and transportation of the vaccines to the field for use in the projects (April 15th 2010, PAG meeting). Is this permitted under the rules of the NRHM? It is conveniently stated that the untied funds may be used by the State Government according to its requirements. But would this include a project of this nature involving the interests of private vaccine companies? The wrongful use of the NRHM logo for a project implemented by a private agency as well as the identification of this project with the public immunization programme does damage to the credibility of the UIP programme as well as the NRHM and should be disallowed in the future. Those responsible should be taken to task.
I have flagged only some of the additional evidences available in the related documents. I had already stated on the floor of the Parliament and I reiterate my position that my complaint is not against the HPV vaccines per se but against the gross violations in the design and implementation of the project, which have been substantiated by the reports cited above and which compromised the safety as well as the rights of the children vaccinated. I have also raised issues about the procedures followed by DCGI for giving licenses for import and sale of the products by the companies concerned, in violation of the regulations of Schedule Y of the Drugs and Cosmetics Act of India. I give details of these violations in a separate note based on the statements of DCGI officials before the enquiry committee.
I request you not to delay action on the report as well as the shocking findings of the experts about the violations in the project and the questionable lack of ethical standards. Those responsible must be held accountable. Strong action is required against officials at various levels starting with the ICMR. The project itself must be scrapped and in future no NGO should be allowed to take up such a project involving a large number of children. At the same time the children must be compensated for the grave violations of their rights, as suggested by one of the committee members, through the required insurance mechanism.
This project was proudly proclaimed as “the first of its kind project” by an ICMR official. Unfortunately, it turns out that the first of its kind project should also be the last of its kind project, if the narrow agendas of the companies pushing for the sale of their vaccines in the Indian market through access to the public immunization system, are not to be the driving force behind our research studies.
Your step to set up a committee was welcomed across the board in Parliament. I hope you will take the next logical step of taking action against those responsible for violations. It is only such action that will ensure accountability in institutions like the ICMR and the DCGI.