Dr. Suneeta Mittal, Head of Obstetrics and Gynaecology Department, AIIMS. The brief before the Committee was to look into ‘the alleged irregularities in the conduct of studies using HPV vaccine by PATH in India’. An interim report by the Committee was made available to the media on February 21^st, 2010 at a press conference called for by the campaign. However, the Committee’s final report remains absent in the public domain till today.

The Committee’s final report also follows the trend of the interim report in exonerating the responsible parties despite providing clear evidence of misconduct and violations. The Committee was also assisted by three expert members [Dr. Rani Kumar, Dean, AIIMS; Dr. A.K Dutta, Head of Pediatrics, Kalawati Saran Hospital and Dr. Y.K. Gupta, Head of Pharmacology, AIIMS] to look into various aspects of the projects including the linkages of the deaths with the vaccine and the ethics of the implementation of the projects. While the expert members have raised pertinent questions and ethical concerns, the Committee in its final recommendations and conclusions has in most cases chosen to ignore these findings. Some of the main issues that we would like to highlight here include:

1. Nature of the Projects - Ascertained Clinical Trials Violating the Drugs and Cosmetics Act (DCA)

PATH and ICMR have reiterated several times that the Demonstration Projects could not be classified as clinical trials:  as they did not seek to evaluate the efficacy and safety of the vaccine and as no biomedical outcomes were being researched and no blood or other samples were drawn, and no therapies were tested. However, as Dr. Y. K. Gupta, observes in the Committee’s report, the nature and objectives of these projects, makes it evident that they are in fact clinical trials, wherein the projects were a “study of a pharmaceutical product carried out in human participants” and “4 of 5 primary outcome measures proposed in the study related to evaluation of the safety of the vaccine in population setting.” The very principles used to define a clinical trial by the CDSCO and the Schedule Y of the Drugs and Cosmetics Act, 1954 can be applied to the demonstration projects conducted by PATH.

Moreover, the Committee in the Section 7 of its findings [pg.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 Adverse Events/ Serious Adverse Events should have been more vigorously pursued.”

If the demonstration projects were indeed clinical trials, the non-compliance of the requirements of Schedule Y of the Drugs and Cosmetics Act raises grave ethical and legal concerns. Several   clauses of the Act have been violated. The Ministry of Health and Family Welfare (MOHFW) therefore needs to take exemplary action on those violating the law of the land: in this case the concerned officials of the ICMR, the DCGI and the NGO PATH.  

2. Selection of Study Area

Dr. Y.K. Gupta in his report to the Committee has specifically stated that the study has been carried out on “vulnerable population”. However, the report once again falls short by stating that while the stratification (urban, rural and tribal) “seems appropriate, caution is required”. The Committee in Section 7.5 (Page 75) has further stated that,  “…. for better understanding of the research nature of the study and its impact on cancer prevention a higher strata/ better educated/ better aware population inclusion might have been more desirable. The tribal and more difficult areas could have been chosen in the later round. The standard of medical care in remote areas is generally not of the same level as in the urban areas. It would have been easier to provide proper medical care at urban district level for any SAE, particularly the life threatening SAE. It would have been better investigated to document the cause of the illness even if unrelated. The adequacy of existing AEFI system to measure 4 out of 5 primary endpoints also could have been better tested in the urban area first.“

It has been categorically stressed that “everyone shall desist from research on tribal population, unless of specific benefit to them” (Pg 80:8.5). The Committee’s recommendation to apply caution and safeguards while conducting trials on marginalized populations is a necessary and welcome one. However, the Committee appears to have taken too lenient a view of the violation of this very principle in the context of these demonstration projects, wherein the Committee’s only suggestion is to undertake a review of ethics if the project was to continue.

3. Process of Obtaining Consent

In her findings, with respect to the process of obtaining consent and the inspection of the informed consent forms, Dr. Rani Kumar explicitly states “… from the numerical analysis it is obvious that the team involved in conduction (sic) of the study on HPV has been very casual in its approach and has ignored many ethical issues such as signatures of parent/guardian, witness, PI and discrepancy in the date of receiving the vaccine and date of signature (page 49).” Similarly, the Committee in its findings in Section 7.1 [Page-70] has also declared, “the most significant deficiency in the implementation of the project was the obtaining of consent”. The Committee has observed (pg 72:7.1.4) that the ambivalent sentences in the consent form are tantamount to “covert inducement and indirect coercion” especially in the light of the high cost of the vaccine (~ Rs 9000 for three doses). 

Also shocking in AP, is the Integrated Tribal Development Authority [ITDA] orders to the hostel wardens, headmasters and teachers to comply with the demands of the project and also facilitate the consent taking processes, particularly in the Ashram Paathshalas where these personnel were ordered to give mass consent (Page 51, Letter to Dr Kishore Chaudhury by Dr Rani Kumar dated 6^th September 2010). 2763 forms (out of a total of 14253) were signed by the Hostel Wardens/ Head Master in AP/.

The Committee, in section 7.1.1 [page 70] also mentions that, “this authorization runs contrary to the basic principles of obtaining consent as students cannot be considered to have full autonomy in front of their teachers/ Head Master. There is no express approval of the Institutional Ethics Committees (Ices) of MNJIO&RCC, Hyderabad for this provision, nor is there any mention of it in the consent document.”

It is extremely alarming that despite clear evidence regarding serious lacunae in such a fundamental aspect of any form of research, no action has been recommended against those involved in the designing and implementation of these projects nor against those ethics committees who approved of such a design.

4. Issues Related to Safety, Follow-up and Reporting of Adverse Events

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. The Committee in its findings in Section 7.2 [page -74] explicitly states, “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.  The Committee is of the view that in all investigational studies (irrespective of being done with non-licensed or licensed products), particularly those that deal with administration of new entities; monitoring, reporting and investigation of all adverse events – non-serious, serious or deaths – should be an integral part of the study and responsibility of the investigator. Adequate insurance cover for participants to include unforeseen/unexpected or even probable morbidity and mortality events should be a part and parcel of such studies.

In this context rule 122-e of the Drugs and Cosmetics Rules, 1945 provide that all vaccines shall be new drugs unless certified otherwise by the licensing authorities under Rule 21, and a new drug shall continue to be considered a new drug for the period of 4 years from the date of its first approval or inclusion in the Indian Pharmacopoeia, whichever is earlier.”

Moreover, Dr. A.K. Dutta in his observations has mentioned several unacceptable and prolonged delays in the reporting of adverse events and deaths due to a lack of any independent monitoring systems. Further, although his observations state an unlikely link between the deaths of 7 girls and the vaccine, in 3 of these cases no conclusive evidence in this regard could be found. Further it is shocking that the study protocols did not include a separate component for the surveillance of adverse events with solely relying on the existing State run guidelines for the reporting of Adverse Events Following Immunization (AEFI). Particularly surprising is the lack of action taken by the DCGI and ICMR in the light of these delays.

We also welcome the Committee’s recommendation: “…besides issuing directions, an active programme needs to be evolved for training investigators and sensitization of regulatory agencies to specially look for these aspects in any study involving human subjects. There is also need for specific and separate legislation covering all aspects of biomedical and health research involving human participants which should provide statutory status to ICMR ethical guidelines and harmonize separate provisions under GCP guidelines and Schedule Y of the Drugs and Cosmetics Act.” [pg 81]

Although the Committee has quite forcefully condemned the laxity and also made sound recommendations in this regard, in their section on ‘responsibilities’ [pg 81] they once again absolve all the parties involved. Moreover, the Committee does not raise the important questions related to the number of girls who have dropped out of the study and their follow up.

5. Lack of Clarity in Finances

A lack of clarity regarding the finances and the financial contributions of the different parties involved, in the projects also reflects in the Committees observations and findings. The Committee has raised certain pertinent questions in their remark in section 7.5 [page 75] that states, “On the basis of market price of Rs. 3000 per dose the approximate cost of vaccinating 25000 girls would be aprox. Rs 250 million. What was the financial investment of ICMR and State Governments in the project is not provided. The State clearly provided the cold chain and manpower for immunization. But would it have done so if the vaccine was not free. There is concern about the hidden possibility of a hidden agenda to push this prohibitively expensive vaccine into the Indian Healthcare System. It might have been more prudent if the National Technical Advisory Group on Immunization (NTAGI) has deliberated on the study prior to its implementation and given its recommendations. The Ethics Committees should have looked into this aspect as well before approving the studies and a speaking mention should have been made in their approval.”    

6. Need for Insurance Cover for Study Participants

Further the Committee states that “concerns over the Insurance No provision has been made of an insurance cover for any unforeseen event or residual, morbidity, related, or unrelated to the intervention; which is a usual practice in trials with NCE/INDs. The Committee is of the view that since the HPV vaccine is a newly developed vaccine, even though licensed, there should have been a provision of insurance coverage for study participants. The need for an Insurance cover is even more since the vaccine is administered to normal healthy individuals that too adolescent girls.” It also goes on to establish that “PATH has taken an insurance cover for itself”. The absence of any mention of such insurance cover for participants in the study protocols raises concerns regarding inadequacies of the approval process and the responsibilities of the approval bodies.

However, once again the Committee has failed to build on these concerns later in the section on ‘conclusions and recommendations’ and ‘responsibilities’.

7. Public Private Partnerships

Further, while the Committee has pointed out to the, “blurring of the distinction between the National Immunization Programme, as routine service activity versus the research nature of the HPV vaccination project” they have failed to levy any form of responsibility on either the State or PATH in this regard, merely advising caution for such partnerships in the future. Further although the Committee has commented on the role of the NRHM, it has failed to look into the other IEC material that has largely contributed to this blurring of distinction and has also in many ways mislead the parents of participants of the study.

Despite these cases of clear violations and foolproof evidence by the experts appointed, the Responsibility section of the report is the weakest with the Committee exonerating all involved in the project. Despite clearly highlighting the aspect of conflict of interest with the involvement of the two pharmaceutical companies, providing the vaccines free of cost, the Committee, fails to build upon these aspect later in the report.

Our Demands

In the light of the above, we demand that:

• The DCGI be held accountable for the approval and licensing of such a study that was severely lacking in several clinical trial protocols as is required by the Drugs and Cosmetics Act and the ICMR’s Ethical Guidelines on Biomedical Research on Human Participants.

• The multi-level violations particularly with regard to the selection of the study area, the lacunae in the research instruments, etc., – reflect the fact that the ICMR and its bioethics committees have been extremely lax in its role as technical supervisors and advisors. Furthermore it also casts doubts on the objectivity, seriousness and thoroughness of the members of the advisory group and ethics committees who gave their approval to these projects without critically examining the protocols. Immediate action should be taken against all members of these committees along with those ICMR officials who were responsible for and associated with these projects.

• Given the active engagement of the State governments and machinery in the implementation of the projects, immediate action must be taken against all those involved and further safeguards be put in place at the policy level to pre-empt such forms of exploitation in the future when similar projects run through public private partnerships.

• These projects should not be restarted and immediate action be taken against the PATH officials involved, with all research findings being treated as null and void.

• Bill and Melinda Gates Foundation the principal donor for these projects and the organization PATH, the principle investigator in this project, also largely responsible for its design and planning, take immediate onus of the various lacunae and provide compensation for all those affected by the vaccination.

• All the participants of the projects for atleast 4 years, as is prescribed by the Drugs and Cosmetics Act, for any adverse event, both serious and non-serious, with the immediate provision of any necessary treatment.

• Given, the earlier concerns raised regarding the safety, efficacy and prohibitive costs of the vaccine, these vaccines must not be introduced under any circumstances in the public universal immunization programme, with increased efforts instead to promote and provide for screening facilities in areas of high incidence of cervical cancer.

• A critical relook at the Drugs and Cosmetics Act and the ICMR’s Ethical Guidelines for Biomedical Research on Human Participants to ensure that such violations do not recur, particularly given the booming clinical trial industry.

Date: 9May 2011

In the proposed Draft Assisted Reproductive Technology (Regulation) Bill and Rules-2010, prepared by the Indian Council of Medical Research (ICMR), a substantial section is devoted towards regulating surrogacy arrangements. Though a welcome step, significant gaps in the protection of surrogate women and children still remain. The most striking of these perhaps is the provision for payment to the surrogate woman, which appears to undermine her rights by favouring instead the intended parents. According to the present Draft, payment to the surrogate is to be made in five installments instead of three (as in Draft 2008, the only previous version). The majority, i.e. 75 per cent of the payment is to be paid as the fifth installment, following the delivery of the child. This is in complete contrast to the Draft 2008, in which there was provision for the majority of the payment (i.e. 75 per cent) to be made as the first installment. This not only shows a clear priority accorded to the intended parents, but also betrays that the worth of the surrogate’s labour, pregnancy, related emotional and physical risks etc are considered reducible to and meaningless without a tangible reproductive output, the baby. The potential health risks that a surrogate might face (as a result of undergoing IVF) do not appear to be a cause of concern at all. For instance, according to the Bill, only gestational surrogacy, i.e. through IVF, will be permitted, and genetic surrogacy, i.e. through IUI, which is the less invasive option, is ruled out. While this may be to avoid any contesting claims over the custody of the baby later, it again reveals that the ‘commercial angle’ outweighs the ‘human’, and no nuanced understanding of the surrogate’s rights, who may have voluntarily entered into a contract but may also relate to the baby in emotional ways, .

The present Draft has also increased the number of permitted successful live births for a surrogate from three (in the previous Draft) to five; this is inclusive of the surrogate’s own children. This provision inadequately addresses an aspect critical to the surrogate’s health: the number of permitted cycles she can undergo. Since the number of live births is not equivalent to the number of ART cycles, to effectively ensure that the surrogate’s health is not exploited, the maximum number of permitted cycles must also be specified.

In lieu of the recent and controversial cases of international surrogacy that have resulted in legal battles for citizenship status for the child/ren, the Bill has made provisions to address this issue. The draft Bill now makes it mandatory for foreign couples to produce a certificate from their countries declaring that the respective countries permit surrogacy, and that the child will be considered a legal citizen. As an increasing number of couples from other countries access surrogacy services in India, such a provision will be a useful legal framework. The Draft Bill should take concrete measures to address the legal needs of the surrogate women.

Therefore, it can be concluded that while a legislation to regulate the untrammeled commercialism of ARTs and surrogacy in India is a much-needed step towards checking unethical medical practice, the human rights of the surrogate and the children—legal, financial, and health-related—need to be better protected.

* This post has been published in the form of an article in the Medico Friend Circle Bulletin

Shri Ghulam Nabi Azad,
Union Minister for Health and Family Welfare,
Ministry of Health and Family Welfare,
Nirman Bhavan, Maulana Azad Road,

New Delhi 110011

Date: 21^st February, 2011

Subject: Concerns regarding the Interim Report of the Committee appointed by the Government of India to enquire into “Alleged irregularities in the conduct of studies using Human Papilloma Virus (HPV) vaccine” by PATH in India.

Sir,

We, the undersigned public health organizations, health networks, medical professionals, human rights groups and women’s groups write to voice our deep concerns regarding the Interim Report of the Committee appointed by the Government of India (vide notification No. V.25011/160/2010-HR dated 15^th April, 2010) to enquire into “Alleged irregularities in the conduct of studies using HPV vaccine” by PATH in India.

While identifying several deficiencies in the planning and implementation of the project, the report, submitted to the Ministry of Health and Family Welfare, has failed to fix responsibility on any individual or agency. Rather than suggesting any punitive or disciplinary measures, the report identifies ‘minor’ deficiencies as lessons for strengthening clinical research in future.

Our questions and concerns

1. The report does not contain accounts of any interaction with the participants of the study (either in Gujarat or AP), their parents, the hostel wardens, teachers, local health workers etc, or even with the parents of the girls who died post vaccination for verbal autopsies of the deaths. These do not appear to have taken place, and may be considered a significant methodological limitation of the report.

2. In marked contradiction to the official stand of both PATH and ICMR, the report states that: “It needs to be highlighted that 4 of the 5 primary outcome measures proposed in the study relate to evaluation of the safety of the vaccine.” For instance, in an update posted by PATH on their website (accessed on 15 February 2011) following the suspension of the projects, they state,
   “It should be noted that the post-licensure observational studies in Andhra Pradesh and Gujarat do not seek to evaluate the efficacy or safety of these licensed, approved HPV vaccines. No biomedical outcomes are being researched; no blood or other samples are being drawn, and no therapies are being tested. The safety and efficacy of these vaccines have been documented in numerous studies and endorsed by numerous international and national regulatory agencies.”Similarly, in the response from Mr. A.B.Ramteke, Joint Drug Controller (I) to an RTI (dated 21.07.2010), it was clearly stated that the design and purpose of the study was i) to demonstrate suitable vaccine delivery strategy ii) to raise community awareness iii) to build the evidence base of vaccine delivery strategy for future introduction of HPV in India. However, it was not mentioned that the study outcome was to evaluate the safety of the vaccine.

   Not only does this reveal the inconsistencies in the literature made available in the public domain regarding the nature, aims and outcomes of the projects, moreover, if the safety of the vaccine is in fact being studied, it may be ascertained that the projects are clinical trials. Thus, the protocols of clinical research in India have been violated. The Committee has not dispelled this ambiguity.

3. The report states, “One of the major deficiencies of the study in retrospect was inadequacy of the preparation for tackling Serious Adverse Events (SAEs) and deaths, whether related or unrelated to the vaccine. The deaths came to notice after a long gap of their occurrence, mainly when the preparations were a foot for the next round of vaccination. And then no independent body of experts analyzed the cause of deaths.” In the absence of any mention of the follow up of deaths and serious adverse events, how did the State governments and other authorities[1] approve the study design? Further, deaths and adverse events following vaccine administration were not investigated by the DIO or DRCHO.The Drugs and Cosmetics Act clearly outlines that ethics committees are responsible for review and approval of trial protocol so as to safeguard the rights and well being of trial subjects, especially those from vulnerable sections of the population. There appears to be reluctance to hold the involved ethics committees accountable for violations.
4. We welcome the recommendation for “the need for continued pharmacovigillance of the HPV vaccine” and the reiteration of rule 122-E of the Drugs and Cosmetics Act, that “all vaccines, in particular the HPV vaccine, shall be treated as new drug for four years from the date of their approval in India. All research studies (whether a clinical trial or not) involving administration of a new drug (vaccine), even after licensing, should proactively monitor and investigate all adverse events, more so the SAE and deaths irrespective of their appearing or not appearing to be related to the vaccine.”
5. Further, while the Interim Report justifies the inclusion of girls in the age group of 9-14 years in the PATH projects as bridging the Phase III trials conducted prior to the approval of the drug for marketing, sale and import for private markets in India, it completely ignores the inadequacies and shortcomings of these pre-trials themselves.
6. While the report states that “there was no specific targeting of any particular group or class except that the plan called for including a predominantly urban, rural and tribal block in each selected district”, it goes on to say that “in hindsight the veracity of this plan can be debated… … if it was impractical to take consent of parents in predominantly tribal area such an area might have been excluded from the study.”
7. The report establishes that “The legality and morality of the circular of the Government of Andhra Pradesh authorizing the Hostel Wardens and Head Masters to sign the consent on behalf of the minor girls included in the study is questionable.” This is an absolute travesty of free and informed consent, a central and inviolable tenet of research ethics, as listed in both the DCA and ICMR’s ethical guidelines for biomedical research.
8. The report states that “no provision has been made of an insurance cover for any unforeseen event (including death) or residual morbidity related to the intervention for vaccine recipients in this study which is the usual practice for trails with NCE/ INDs”. It goes on to establish that “PATH has taken an insurance cover for itself”. In this case, why were the participants not covered? Further, the absence of any mention in the study protocols of an insurance cover for participants raises concerns regarding the inadequacies of the approval processes, and the responsibilities of the approval bodies.
9. The Committee has noted that the use of the State’s health machinery for the execution of the project “might have led to blurring of the distinction between routine, national immunization programme and research nature of the HPV vaccination study”. As such, “it is important for Public Private Partnership programmes to be extra vigilant and ensure that the Authority of the State is not misrepresented.”
10. Despite stating that “the fact that the vaccine for the study was provided by manufacturers free of cost does raise the concern about undeclared conflict of interest since the results of the study may be used to influence the decision by the Government”, the Committee fails to build upon this significant and alarming aspect.
11. The section of the report on Responsibility is the weakest, as it lets off the hook all those involved in the project, by declaring the deficiencies in the project as “minor” and not “willful or fully anticipable (sic)”, and stating that “since there does not appear to be any overt mal-intention, no responsibility can be fixed”.

Our demands

1. Since violations have occurred at all levels of the project, we demand that all involved be considered culpable, and appropriate punitive action be taken. To say that responsibility cannot be fixed with any “one” individual or organization is a dereliction of duty, and a convenient excuse for irresponsible and unethical conduct, thus setting a dangerous precedent.
2. Compensation should be provided, with immediate effect, to the families who have lost their children and to the children suffering side-effects.
3. All study participants should be provided proper medical treatment and follow up
4. The Government should place in the public domain:

• All the documents pertaining to the agreement with vaccine manufacturers and all other bodies regarding the government’s plan to introduce the HPV vaccine.
• The list and design of projects planned, proposed, approved and completed, agencies involved, and donors involved, proposed locations, and all the results of the pilot phase and clinical trials.
• All details, including names and minutes of the meetings, of all ethics committees that approved or disapproved the study plan.
• The full version of the Interim Report by the Government of India inquiry committee, as soon as it is ready.

We hope you will take cognizance of our demands, and appropriate action.

Signed By:

1. Jan Swasthya Abhiyan (Indian chapter of the People’s Health Movement)

2. Sama- Resource Group for Women and Health

3. Saheli Women’s Resource Centre

4. Low Cost Standard Therapeutics

5. All India Democratic Women’s Association

6. All India People’s Science Network

7. National Federation of Indian Women

8. Jagori

9. Haq: Centre for Child Rights

10. Gramya Resource Centre for Women

11. Dr. Imrana Qadeer

12. Dr. Indira Chakravarthi

13. Rajashri Dasgupta

14. Veena Shatrugna

In a similar project, on August 13, 2009, the Gujarat government launched a two-year ‘Demonstration Project for Cancer of the Cervix Vaccine’ in three blocks of Vadodara District – Dabhoi, Kawant and Shinor – to administer three doses of the HPV vaccine to 16,000 girls between 10 and 14 years. There were reports of deaths of four girls from Andhra Pradesh and two girls from Gujarat following the administration of the vaccine.

During March 27-30, 2010, a team of women’s and health activists visited Bhadrachalam mandal, one of the three mandals of Khammam district where the ‘demonstration project’ was undertaken to understand the ground reality; in particular, to look at the nature and procedures of taking consent and providing information to the girls and their parents, and the availability of the health infrastructure required to support cancer screening and prevention.

The children selected to participate in this project were from four social groups with poor economic background – scheduled tribes, scheduled castes, Muslims and other backward communities. Majority were tribal children, whose parents were agricultural labourers. Some girls were from families that have been displaced by the ongoing conflict in the neighbouring state of Chhattisgarh; circumstances that serve only to compound their vulnerability.

Majority of the vaccinated girls in Bhadrachalam were residents of ashram paathshalas (boarding schools). The selection of these girls for the project is striking, given that their parents, living separately, cannot monitor and respond to any adverse developments in their children’s health. Moreover, this has allowed providers to conveniently side-step the provision of parental consent.

The vaccine was administered through a camp approach in the hostels and school campuses. In many instances, the wardens of the residential schools and hostels were asked to provide consent or permission for vaccination, while parents were not informed. The very nature of this project appears to be in violation of all ethical norms as a warden, whether a legal guardian or not, be allowed to provide consent for hundreds of children without consulting their parents, who are their natural guardians;

The ‘consent form’ was used primarily in the case of non-residential schools, and children were asked to get signatures from their parents. This violates the designated protocol for obtaining informed consent, whereby the ‘researcher’ is required to directly provide information mandatory for consent to the person(s), in this case the parents.

Selected girls were given HPV Immunization Cards, which were in English – a language that neither the girls, nor their parents, were familiar with. Further, all involved (the wardens, teachers and students) believed the project to be part of the public immunization program, and had no idea that they were in fact, part of a research study. They were not even aware that they had a choice regarding participation in the study.

Many stated that they were given to understand that the government was providing free of cost an expensive vaccine that would prevent ‘uterine’ or ‘cervical cancer’. This would otherwise be unaffordable for them. Several parents brought their daughters to the vaccination camps themselves when they heard about the project. One mother said, “Since it was a vaccine being given by the government, we all trusted it blindly and considered it reliable, like any other vaccine that is given in the immunization programme”. Participants were verbally informed that the vaccine would provide life-long protection, with no side-effects or impact on fertility. The fact that the vaccine protects against only two types of the HPV virus and that regular pap screening is required even after vaccination was mentioned at all- neither verbally, nor in the written material given to some girls. Since the long term efficacy and protection by the vaccine is unknown, it cannot be claimed that even 60-70% protection will be achieved. Currently is also unclear if, when and how booster shots will be required.

Many of the vaccinated girls continue to suffer from stomachaches, headaches, giddiness and exhaustion. There have been reports of early onset of menstruation, heavy bleeding and severe menstrual cramps, extreme mood swings, irritability, and uneasiness following the vaccination. No systematic follow up or monitoring has been carried out by the vaccine providers.

While the project was being carried out under the banner of the National Rural Health Mission (NRHM) shockingly enough the Mission’s mandate does not extend to or mention any such research project. Further, the existing health infrastructure in the region is woefully inadequate. Pap smear facilities are conspicuous by their absence in all government facilities in the area. The entire tribal mandal of Bhadrachalam does not have a single gynaecologist.

The vulnerability of this these communities are thus further compounded by of the lack of access to health care, lack of access to information and absence of mechanisms for reporting adverse effects.

The state government has claimed that the deaths of the four girls post-vaccination were unrelated to the ‘project’. However, parents of Kudumula Sarita, who died in January 2010, believe that their daughter died due to the vaccination, and not by consuming pesticide, as has been officially declared by the authorities.

The trial has been suspended temporarily by the government after a strong campaign by health networks, women’s groups and by parliamentarians. A committee has been set up by the government to conduct an inquiry, the composition of the committee leaves much to be desired and is far from representative.

The Ministry of Health and Family Welfare, on 22^nd April 2010, finally conceded that the HPV vaccination project was in fact, a “post-licensure operational research study”, which on further clarification, was confirmed to be a Phase IV, post marketing, clinical trial.

On 29^th April, the ICMR admitted that their ethical guidelines had been flouted in the course of this trial.

The objective of this consultation is to orient and sensitize members of parliament and other important segments of policy planners about this very vital issue and evolve an economical and social model to ensure free treatment to all citizens of India.

Background

The total health spending in India is one of the lowest in the world, and most of it is private expenditure in the form of out of pocket payments. The majority of this payment is on the purchase of drugs and diagnostics, which are priced exorbitantly when bought individually by patients from chemist shops or pharmacies of private doctors, nursing homes, and hospitals. The same medicines are available in one tenth of the cost if bought in bulk.  It is a huge challenge that these medicines at reduced costs, which are essentially the actual prices, will reach citizens. Purchase of medicines individually:

1. Causes significant rise in the overall cost of treatment
2. Increases the load of unreasonable and unnecessary drugs, which are the causes of rising drug resistance and iatrogenic morbidities
3. Leads to higher occurrence of catastrophic illnesses, which require hospitalization because large numbers of patients do not seek treatment until it gets very serious for reasons of non-availability of money
4. Causes continuing high maternal mortality ratio and child death rates because of lesser use rate of health care services

Participation is only by invitation.

The safety and the efficacy of the two HPV vaccines Gardasil and Cervarix is highly suspect and a number of very serious side effects, including deaths have been observed across the world, in vaccinated girls.

As per the extensive documentation by a fact finding carried out by local groups in Khammam district in Andhra Pradesh (where 14000 girls in the age group if 10 – 14 years have been vaccinated with the three doses of HPV vaccine), the adverse reactions faced by over 120 girls include epileptic seizures, severe stomach aches, headaches and mood disorders. The matter has further gained grave urgency with the deaths of four girls in the area. Moreover, the very basis of the project is in direct violation of both, the Governments own Ethical Guidelines of Research on Human Subjects and the rights of children as secured by national law as well as international conventions that India is a signatory to.

Other serious issues include the unethical licensing of the two vaccines for marketing as so-called preventives against cervical cancer, and the aggressive promotion by the manufacturers in schools, residential localities and so on through pediatricians and gynaecologists.

The key findings from a fact-finding visit to Khammam district in Andhra Pradesh were also shared at the conference.

The speakers at the conference included:

Brinda Karat – Member of Parliament

Amit Sen Gupta – Jan Swasthya Abhiyaan

Sarojini N. -  Sama Resource Group for Women and Health

Kalpana Mehta -  Saheli Women’s Resource Centre

Sudha Sundararaman – All India Democratic Women’s Association

Venue: Indian Women’s Press Corps (IWPC), 5 Windsor Place, Ashoka Road, New Delhi
Date:  April 7^th, 2010
Time: 1:30 – 3:30 pm

Visit http://www.hindu.com/2010/04/08/stories/2010040857390100.htm and http://www.dnaindia.com/india/report_cancer-vaccine-programme-suspended-after-4-girls-die_1368681 to view some of the news coverage.

Press Release

April 7^th, 2010 – World Health Day

Unethical Medical Intervention to prevent HPV infection by the government in collusion with drug company and foreign NGO renders poor tribal girls dead and debilitated

Protests, representations and extensive coverage in the media against PATH-ICMR project being carried out in AP and Gujarat seem to have fallen on deaf ears and the government has gone ahead with a vaccination programme with Gardasil (HPV vaccine manufactured by Merck) leading to four deaths and 120 girls suffering from debilitating new illnesses like epilepsy, headaches, stomach disorders and early menarche.

The girls, 10-14 years old, belonging to poor families, were enrolled in a study being carried out jointly by PATH (an International NGO), Indian Council of Medical Research and the respective state governments funded by Bill and Melinda Gates Foundation. The objective of this two year study is to look into acceptability and service delivery issues of Gardasil, marketed in India by MSD Pharmaceuticals Pvt. Ltd, being misleadingly promoted as a preventive for cervical cancer.

The literature circulated in the project makes outright false statements about its safety, efficacy and duration of effectiveness. The girls and their parents have been told through the project documents that the vaccine will give life long immunity, has no side effects other than minor ones like fever and rash and will not affect future fertility of the young girls.

When deaths started getting reported local groups in Andhra Pradesh were alarmed by and carried out a fact finding to discover that no consent was taken from parents and the girls and their families have been left uncared for. Post mortem reports were also not easily accessible, and in cases of death cover up was the general dictum.

We question:

1. Why are poor girls and their families being actively misled? Who is liable for the debilitating effects of the vaccine and who will medically look after these girls and pay compensation for the damages suffered by these people?
2. How has the government embarked on this study of giving three injections to the girls when it is also planning a massive multi-centric dose determination study to see if two doses will suffice?
3. How has the Drugs Controller General granted approval to the vaccine without proper research in India? For a drug to be administered to children, it has to go through stages of clinical trial, including Phase 3 adult clinical trials. So far with Gardasil only one trial has been carried out with just a small sample of 110 girls which has followed them up for just one month after the completion of vaccination and that too only to look at the immune response post vaccination. The vaccine has also been approved for adult women till 27 years of age without doing any trials with them at all.
4. Why are these studies being carried out when at various times the concerned government officials have gone on record to say that it is not feasible for the vaccine to be introduced in the Indian Public Health system given its costs? Is it not then using these poor girls as guinea pigs for a vaccine which can be used only in the private market by well to do families? Why is a two year study being carried out with no future guarantee even for the subjects of this study to keep them protected with boosters when they actually get married by when the effect of this vaccination will wear off? The effect of the vaccine seems to wear off after 4-5 years, and will require periodic booster injections to retain claimed effectiveness.

The path of licensing of the vaccine in India raises many serious questions as time and again scientific logic and the ethical guidelines have been violated at each step. Our law clearly states that no trials of drugs can be conducted among children before trials are conducted on adults. While the other HPV vaccine, Cervarix, made by GlaxoSmithKline has also been licensed in India it has been approved for use for children without any trials among them at all. It should be remembered that last year the two drug companies had engaged in massive advertisement of these vaccines in the media and are continuing with giving incentives to doctors and holding promotional camps in schools among the paying segment of the market.

All this is being done for products which have no proven value. Even the license given by US FDA has asked Merck to actually study whether there is a reduction in the incidence of cervical cancer due to vaccination.

Even as their effectiveness and usefulness remains unproven information on the adverse effects of these vaccines are pouring in from all quarters. The tally in US alone crossed the mark of 17000 adverse effects (as reported under the voluntary adverse effects reporting system); and even the US FDA gave a hearing to health advocates to present the case against the vaccines on March 12, 2010. The adverse effects include heart, immune, blood clotting, respiratory, nervous, digestive and musculoskeletal systems and occur with far greater frequency than those observed with any other vaccines. Many experts and established medical journals have already termed it the biggest public health experiment.

In the public health system of India this vaccination will prove to be an expensive and hazardous exercise. These vaccines at best protect against two sub types among 15 which are associated with cervical cancer and hence ideally women will have to undergo pap smear tests for an effective cancer control strategy along with various hygiene and nutrition related strategies. Unfortunately, there is no investment in screening which can help the adult population today.

We demand:

1. Complete suspension of all studies and trials with Gardasil and Cervarix and suspension of their licence for marketing in India till such time that a public enquiry is held on their licensing in violation to the India law.

1. Proper enquiry in the deaths in Khammam that have been dubbed as suicides. Unless it becomes clear that the vaccine has no impact on the mental health of girls the project authorities cannot be absolved of the blame.
2. Each vaccinated girl be examined by independent authority to assess the range and incidence of side effects. While this will provide the much needed information about vaccine safety it will also detail the care that these girls require and the compensation they and their families deserve for having been actively misled.

4. Proper long term follow up of the vaccinated girls till they get married and have children and booster doses at the right time free of cost, with full informed consent for those girls who wish to continue vaccine protection.

Unless the government details a plan for cervical cancer control, with full compliment of boosters, screening and treatment this project is sheer experimentation with innocent, vulnerable and poor people of the society who can not afford this expensive vaccine. According to us the government is constitutionally bound to take care of the life of all citizens and not subject them to new medical problems at the behest of foreign NGOs.

Sama                      All India Democratic Women’s Association                   Saheli

All India People’s Science Network                  Jan Swasthya Abhiyan

To,

Shri Ghulam Nabi Azad,
Union Minister for Health and Family Welfare,
Ministry of Health and Family Welfare,
Nirman Bhavan,

Maulana Azad Road,
New Delhi 110 011

Date: April 7^th, 2010
Subject: Opposition against the unethical nature of the ‘demonstration project’ for the Human Papilloma Virus (HPV) vaccine being conducted in Andhra Pradesh and Gujarat.

Sir,

We the undersigned public health organizations, health networks, medical professionals, human rights groups and women’s groups write to voice our intense opposition to the unethical nature of the ongoing HPV vaccination ‘projects’ being conducted in Andhra Pradesh and Gujarat by PATH International, in collaboration with ICMR and the State Governments. We also strongly stand in solidarity with the local efforts initiated by groups and Networks in Andhra Pradesh following the death of 4 young, tribal girls in Khammam district following the vaccination.

As was clearly detailed in a Memorandum, dated October 1^st, 2009, signed by over 50 groups and individuals, the efficacy of the vaccines Gardasil and Cervarix is highly suspect and a number of very serious side effects, including deaths have been observed across the world, in vaccinated girls. As per the extensive documentation by a fact finding carried out by local groups in Khammam district in Andhra Pradesh (where 14000 girls in the age group if 10 – 14 years have been vaccinated with the three doses of HPV vaccine), the adverse reactions faced by over 120 girls include epileptic seizures, severe stomach ache head aches and mood swings. There have also been reports of early onset of menstruation following the vaccination, heavy bleeding and severe menstrual cramps. Moreover, the current, ‘demonstration project’ has no follow up mechanism in place for girls who suffer from adverse events following the vaccination. As a result many of the girls have had to seek treatment in the private sector and with local quacks.

The matter has further gained grave urgency with the deaths of four tribal girls in the area. The local authorities have refused to take cognizance of their probably association with the vaccine, two of the deaths have shockingly been written off as suicides, when the evidence clearly suggests otherwise! Along with sounding extremely suspicious this has also raised valid concerns of this being a massive cover up exercise.

Above all, the very nature of this project seems to be unethical and violates all norms of conducting trials on human subjects. In many Aashram Schools, a verbal consent to vaccinate girls living in the Aashram schools has been taken from the Hostel Warden/ teacher in-charge, while parents were not even informed about it. In cases of day scholars, where consent was obtained from the parents, the form given held the nomenclature of an approval form “Angikaara Patram” and only provided minimal information with no provisions for addressing in detail the need for follow. In fact, when a lady warden of a hostel objected when she was told that the vaccine was being administered on girls in the hostel, she was informed that this vaccine is mandatory! This is a travesty of the entire concept of “informed consent.”

Consent and information, reserved for only a few, is a farce and was based on provision of wrong information. Many of the girls were told that the vaccine would prevent uterine cancer and would provide life-long protection. This information is factually incorrect and provides the recipient with a false sense of security against the “dreaded” disease. As per the claims by the pharmaceutical companies themselves, the vaccine only protects against infections caused by 2 types of HPV virus (of the 13 high risk strains of HPV) that are associated with a higher risk of cancer of the cervix. Moreover, once again as claimed by the companies themselves, the protection by the vaccines is understood to last for only 4.5 years with Gardasil and 7 years with Cervarix, while, the need for a booster has not yet been established. There are reports in developed countries that this number too is an over estimation and the protection in fact may not last for more than 3-5 years.

It is also shocking and worrying that these projects are being carried out under the NRHM banner, while the existing medical facilities in the region are extremely inadequate. While Pap smear facilities are not available in Government facilities in the area (a must for even those who have been vaccinated against HPV) the absence of a Gynaecologist in the entire tribal mandal of Bhadrachalam is absolutely appalling. It is highly irresponsible and negligent of the State and Central government that such large scale exploitation of poor and tribal populations is being carried out by subjecting them to a vaccine with a dubious track record, when even the basic public health facilities are not in place.

Although, the nomenclature suggests otherwise, the secrecy regarding the non-transparent selection criteria of the area, the girls and the aim of the project has raised undeniable fears that this is a Phase IV clinical trial being carried out under the guise of a ‘demonstration project’ Moreover, there is an inexcusable lack of clarity with regards to the role and accountability of international agencies such as PATH and Bill and Melinda Gates Foundation that appear to be funding this project. It is beyond doubt the worst case of human rights violation, where young healthy girls have to die for being part of a state-endorsed experiment, initiated by a profit making private company.

This constitutes shocking criminal negligence on the part of the authorities, who have provided permission and support to this programme within the public health system. We need immediate government intervention to prevent this. No NGO should be given such permission for clinical trials/ demonstration projects, regardless of which vaccine or drug is being administered. Financial support from the industry or from an international organization should not be the criteria to introduce any vaccine, whether in a pilot project or in the universal immunization programme.

Thus, standing in solidarity with groups, parents and the girls in Andhra Pradesh, we demand that:

1. the government should make sure that all these projects are immediately brought to a halt across the country, till concerns relating to safety, efficacy and cost effectiveness of the planned interventions are reevaluated.
2. the government should set up an  inquiry:
   1. into the deaths of the tribal girls;
   2. into the side effects of the vaccine on affected girls, so that responsibility can be fixed and action taken.
3. All agencies involved in the project need to be held accountable and culpable for any ethical, legal, medical violations that emerges in such an enquiry
4. the State Government should take immediate action, including providing compensation to the families who have lost their children and to the children suffering side-effects
5. all the sufferers should be provided proper medical treatment and follow up
6. the Government place in public domain::

• All the documents pertaining to the agreement with vaccine manufacturers and all other bodies regarding the government’s plan to introduce the HPV vaccine.
• The list of projects planned, proposed, approved and completed, agencies involved, donors involved and proposed locations. and all the results of the pilot phase and  clinical trials

7.  the Government institute a national policy on this kind of medical ‘experimentation’, and  a pro-people vaccine policy based on public health needs

Signed by

1. Jan Swasthya Abhiyan (JSA)

2. All India Democratic Women’s Association (AIDWA)

3. All India Drug Action Network (AIDAN)

4. All India Peoples’ Science Network (AIPSN)

5.  Federation of Medical and Sales Representatives’ Associations of India (FMRAI)

6. Sama- Resource Group for Women and Health, Delhi

7. Action India, Delhi

8. HAQ- Centre for Child Rights, Delhi

9. KRITI, Delhi

10. Jagori, Delhi

11. Breastfeeding Promotion Network of India, Delhi

12. Centre for Women’s Development Studies (CWDS), Delhi

13. Centre for Legislative Research and Advocacy (CLRA), Delhi

14. Delhi Forum, Delhi

15. Diverse Women for Diversity, Delhi

16. RAHI Foundation, Delhi

17. SANGRAM, Maharashtra

18. Adivasi Aikya Vedika, Andhra Pradesh

19. Anthra, Hyderabad, Andhra Pradesh

20. Yakshi, Hyderabad, Andhra Pradesh

21. Asmita Collective, Secunderabad, Andhra Pradesh

22. Adarsha Women’s Society, Khammam, Andhra Pradesh

23. Koyitur Kutuva, Khammam, Andhra Pradesh

24. Adivasi Seva Samiti, Khammam, Andhra Pradesh

25. ANKURAM, Hyderabad, Andhra Pradesh

26. Girijana Deepika, East Godavari, Andhra Pradesh

27. Tholakari Adivasi Mahila Vedika, East Godavari, Andhra Pradesh

28. Adiavsi Seva Sangham, West Godavari, Andhra Pradesh

29. Arunodaya Grameen Abhivridhi Sangham, Vijayanagarm, Andhra Pradesh

30. Adivasi Chaitanya Sangham, Adilabad, Andhra Pradesh

31. Chinnayya Adivasi Vikasa Sangham, Srikakulam, Andhra Pradesh

32. Manyam Girijana Seva Sangham, Vijayangaram, Andhra Pradesh

33. Adivasi Ahara Bhadrata Sangham, Visakhapatnam, Andhra Pradesh

34. Jeevam, Visakhapatnam,  Andhra Pradesh

35. Savara mahila sangham, Srikakulam, Andhra Pradesh

36. Agricultural and Social Development society (ASDS), Khammam, Andhra Pradesh

37. Natwan Sangham (Tribal Women Federation), Khammam, Andhra Pradesh

38. Rukmini Rao, Gramya Resource Centre for Women, Hyderabad, Andhra Pradesh

39. Usha Seethalakshmi, Freelance Researcher & Consultant, Hyderabad, Andhra Pradesh

40. Kalpana.Kannabiran, Hyderabad, Andhra Pradesh

41. Vasanth Kannabiran, Hyderabad, Andhra Pradesh

42. Lalitha Kumari, Hyderabad, Andhra Pradesh

43. BHUMIKA Magazine, Andhra Pradesh

44. Anchita Ghatak, Parichiti- A Society for Empowerment of Women, West Bengal

45. Anu Gupta, Eklavya, Madhya Pradesh

46. Bimla Chandrasekar, EKTA, Tamil Nadu

47. Dr Veena Shatrugna, Hyderabad, Andhra Pradesh

48. Chinu Srinivasan, SAHAJ, Baroda, Gujarat

49. Dr Gopal Dabade, Drug Action Forum, Karnataka

50. Jaya Velankar, Women’s Rights Activist, Delhi

51. Dr. Kaveri Rajaraman

52. K R Nayar, Jawaharlal Nehru University, Delhi

53. Manisha Gupte, MASUM, Pune, Maharashtra

54. Dr Mira Shiva, Initiative for Health Equity and Society (IHES), Delhi

55. Dr Mohan Rao, Jawaharlal Nehru University, Delhi

56. Neha Madhiwala, Centre for Studies in Ethics and Rights (CSER), Mumbai, Maharashtra

57. Prof Padmini Swaminathan, Madras Institute of Development Studies, Chennai, Tamil Nadu

58. Pallavi Sobti-Rajpal, Utthan, Gujarat

59. Rajashri Dasgupta, Kolkata, West Bengal

60. Renu Khanna, Sahaj, Baroda, Gujarat

61. Dr Vandana Prasad, Delhi

62. Ranjan De, Filmmaker, Delhi

63. Dr. Ajay Kumar Khare, Madhya Pradesh Vigyan Sabha/JSA, Bhopal, Madhya Pradesh

64. Bishakha Dutta, Filmmaker, Mumbai, Maharashtra

65. Dr. Y. Madhavi, Scientist, Council of Scientific and Industrial Research (CSIR), Delhi

66. Saheli, Delhi

67. Salai Selvam, Tamil Nadu

68. CREA, Delhi

In addition, a Volume of Papers titled Making Babies- Birth Markets and ARTs in India was launched by Sama on the 23^rd January, in collaboration with Zubaan – a feminist publishing house. Sama also marked its tenth anniversary on this day, with an evening of music and poetry.

To see the programme schedule of the Consultation, click here: Programme

The print ads for these campaigns invariably feature a smiling (and presumably loving) mother-daughter pair. The latest cervical cancer ad by GSK carries sub-headings giving information and prompting action. This campaign is much more aggressive than MSD’s previous one, and is running full-page ads in leading national dailies and sending smses through country-wide networks. The ad supplies a sobering statistic on cervical cancer, putting it ahead of breast cancer as a leading killer for women. It announces the ‘Good News’ that vaccination can protect ‘our daughters’ from Cervical Cancer. The dosage required is mentioned, along with urgent slogans and affirmations such as ‘Act today!’ and ‘It’s true!’ What is missing again is the name of the vaccine, contraindications, side effects etc.

The MSD advertisements would carry on in a similar vein, asking you to know, do and give, as much as you can, to protect your loved ones from cervical cancer. The ad provided information under headings like ‘It can happen to you’, ‘Know the relation between HPV and cervical cancer’ and ‘How is HPV contracted?’ The ad concluded with a message imploring the reader to consult her doctor for protection. These also appeared on TV channels. Throughout, the name of the vaccine being so obviously promoted, was conspicuous by its absence.