UPDATE: HPV VACCINES

UPDATE:

HPV VACCINES 

Newsletter May - Aug 2010

Since October 2009, various groups and individuals have been questioning and opposing the licensing, introduction, advertising and marketing of HPV vaccines in India. However, it is telling that all the memoranda, protests, representations and extensive coverage in the media fell on deaf ears, even when news of deaths among the vaccinated girls started trickling in from Andhra Pradesh. 

In March 2010, SAMA and members of AIDWA did a fact finding in Khammam district, where the PATH-ICMR project to vaccinate 14,000 girls was being carried out. They presented their report at a press conference in Delhi on April 7, World Health Day. Perhaps this report too would have been ignored, had it not been for the fact that Ms. Brinda Karat had also visited Khammam and addressed the press conference. She is not only a member of the Rajya Sabha but also on the Parliamentary Select Committee for Health and Family Welfare. The main issues highlighted at this press conference were violations with respect to the guidelines for informed consent, violations in the guidelines for approving vaccines in India, and the questionable nature of the PATH study, which came soon after the approval of the vaccines but was supposedly not intended to look into safety and efficacy issues. (See Box). 

Given that 4 girls had died in Khammam district after being vaccinated with the HPV vaccines, and another 2 had died in Vadodra district, Dr. Katoch, Director General, Indian Council of Medical Research, called a halt to the vaccination programme and set up a three member committee to look into the violations reported. The committee was to give its report in two  months time. Soon after, Ms. Karat raised the matter in Parliament, questioning the hasty approval of the vaccines by the Drugs Controller, without the necessary studies being conducted. Dr. Katoch subsequently admitted that the guidelines had been violated in that a Phase III trial had been conducted on children before a similar trial had been conducted on adults. 

While the suspension of the PATH study and the setting up of an enquiry committee were welcome steps, doubts were raised about the impartiality of such a committee and its possible role. Ms. Karat pointed out the limitations of a committee which comprised only members of the establishment, and had no independent experts. Saheli sent a set of concerns which we hoped the committee would also look into. 

In addition, we sent a letter to the Drugs Controller, giving a list of the violations that had taken place in the process of trials and approval of the vaccines and demanded a suspension of the license given to these vaccines. 

The Drugs Controller has still not answered several of our concerns: 

1.      These vaccines have been approved for age groups in which no testing has been done in India. Gardasil has been approved in India for use among 9-26 year olds, but it was tested only among 9-15 year olds. Cervarix has been approved in India for use among 10-45 year olds, but it was tested only among 18-35 year old.

 

2.      No research has been done to assess the efficacy and safety of Gardasil and Cervarix in the Indian population till date. The two trials on HPV vaccines (110 girls with Gardasil and 350 women with Cervarix) were of 7 months duration only, and ascertained only the immediate immune response and side effects.

 

3.      A Phase III trial with Gardasil (Tolerability and Immunogenicity of Gardasil in Females Between 16 and 23 Years of Age in India, on 600 women, duration 36 months) had begun recruitment of subjects. According to the Schedule Y, this trial on adults should have preceded the trial on 110 girls and it should definitely have preceded the licensing of Gardasil. What was the basis and purpose of approving this trial on 600 adult women after the vaccine was licensed for use?

 

4.      A large multicentric trial involving 20,000 girls aged 10-18 years (Trial of Two Versus Three Doses of Human Papillomavirus (HPV) Vaccine in India) is to begin soon. This has been labelled as a Phase IV trial and is of 5 years duration. 

A.      Why is a dose determination trial being done on such a large number of girls, without carrying out a phase II and III on a small number?

B.      Why is the two dose regimen not being tried on adults first? 

C.      Technically, if the dosage or form of delivery is changed for an approved drug/vaccine, Phase II and Phase III trials have to be carried out again. Why has this step been omitted?

D.     Why was the vaccine licensed for use if the dose was yet to be determined?

 

5.      Internationally, data is lacking on several aspects which can endanger the life and health of vaccine  recipients and their offsprings. Some of these are:

A.  Duration of efficacy

B. Effect of the vaccines on immuno-compromised persons (those suffering from helminthic, parasitic infection, undernutrition etc. and not just those suffering from HIV/AIDS)

C.  Effect on pregnant and lactating women

D.  Carcinogenic and mutagenic potential of the vaccines. 

With such little data available on the HPV vaccines in the Indian context, it is unconscionable that the DrugsController allowed the PATH-ICMR project to vaccinate thousands of young girls and then claim it was only a observational study, having nothing to do with aspects of efficacy and safety of the vaccines. 

In mid April, 2010 we also received a reply from the government of Andhra Pradesh, to the complaint we had sent to the Commission for Protection of Child Rights in mid November 2009, voicing our concerns about the ICMR-PATH study. In this complaint, we had urged the commission to investigate this ongoing study and prevail upon ICMR to defer any further recruitment till the concerned agencies were able to establish before the commission the rationale of this study and future plans for trials and introduction of the vaccine. The reply of the A.P. government (parts of which appeared to have been drafted by PATH), brushed aside all our concerns, and basically claimed that they were only doing a post licensure study, and the vaccines were already marketed and approved by over a 100 countries. Paradoxically, this letter came at the time when the PATH-ICMR study had been suspended and the Director General ICMR admitted a few days later that clinical trial guidleines had been violated!  

Meanwhile, news of the suspension of the PATH study in India had international repercussions in that groups which had been raising concern about the adverse effects of HPV vaccines, including several deaths among vaccinated girls, began demanding a similar halt in other countries. Women all over the world were finding similarities in the adverse effects suffered by vaccine recipients and speaking out against the vaccine. Atleast two lawsuits have already been filed in the US over the HPV vaccine. 

However, all this opposition does not seem to deter the manufacturers from finding new and novel methods of promoting and selling their vaccine. There are several reports of the vaccine being offered free to teenagers, including one that says,  “U.K. Teen girls bribed to get Gardasil vaccine with shopping vouchers”!!  And generating fear has been the key from the start. Only now it extends to men as well—“Merck and GSK Fan Fear of Cancer and Warts in Men to Sell HPV Vaccines”. 

Box 

HIGHLIGHTS FROM THE FACT-FINDING IN KHAMMAM DISTRICT 

During March 27-30, 2010, a team of women’s rights and health activists visited Bhadrachalammandal, one of the three mandals of Khammam district where the ‘demonstration project’ was undertaken. 

The team found: The children selected were from a poor economic background and were from scheduled tribes, scheduled castes, Muslims and other backward communities. The majority were tribal children, whose parents were agricultural labourers. 

The majority of the girls vaccinated in Bhadrachalam were residents of ashram paathshalas (boarding schools) in which  they lived away from their parents. Hence these parents could not monitor and respond to any adverse developments in their children’s health. 

The vaccine was administered through a camp approach in hostels and schools. 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. This violates all ethical norms as parental consent was bypassed. 

The ‘consent form’ was used primarily in non-residential schools, where 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. 

The project was carried out under the banner of the National Rural Health Mission (NRHM), which shockingly does not mention any such research project. All those involved (wardens, teachers and students) believed the project was a 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. 

Participants were verbally informed that the vaccine would provide life-long protection, with no sideeffects or impact on fertility. Each of these statements is false. 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 not mentioned at all- neither verbally, nor in the written material given to some girls. The long term efficacy of the vaccine is still unknown, and it is also unclear whether booster shots will be required. Numerous adverse effects are well documented and there is very little data on future fertility. 

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

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 state government has claimed that the deaths of the four girls post-vaccination were unrelated to the ‘project’. Post-mortem reports are not accessible. 

For the complete report, see,Trial and Error: Ethical Violations of HPV Vaccination Trials in India. Posted on May 17, 2010 by samawomenshealth, http://samawomenshealth.wordpress.com/ 

In India, private marketing has also taken new directions. We have come to know that in at least two cases the companies have approached district level officials offering huge discounts on the vaccines if these are purchased using the flexi-pool funds of NRHM. This would be a gross misuse of scarce NRHM resources and a backdoor entry into the government programme on which as yet no policy decision has been made. 

The two companies are engaging in unethical promotion of their vaccines by holding workshops in schools to generate a demand among children who know no better, and holding public medical camps misrepresenting HPV vaccines as cervical cancer vaccines. It is also being reported that the two companies are selling the vaccines to medical practitioners giving them huge discounts and using them as distribution channels. This would beviolation of trade related propriety of procedures as it is not clear as to how duties and taxes are being paid on these products, and whether giving higher than trade discounts itself is not an unfair trade practice and a way of obliging doctors, which is prohibited. 

The pressure and unseemly haste to sell these vaccines is not without good reason. The three third world countries in which PATH did similar demonstration projects did not result in the respective governments taking up the vaccine. They were waiting for the price to fall. India, with its huge potential demand could have lowered prices, but India now claims it can produce its own vaccine at a much lower cost!! Besides, several new HPV vaccines are in different stages of development, and once they hit the market, the present day HPV vaccines may be redundant. 

For women and girls in India, these developments mean more clinical trials for which they will be recruited, while the supposed benefits will remain a mirage until the government lays out a comprehensive policy for the control of cervical cancer. 

Box 

In the Press Release of April 7th, 2010 (World Health Day), issued by Sama, All India Democratic Women’s Association, Saheli, All India People’s Science Network, Jan SwasthyaAbhiyan the following demands were made: 

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 of the Indian laws.

2. Proper enquiry into the deaths in Khammam that have been dubbed as ‘suicides’. Further, 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.

3. Each vaccinated girl must be examined by an 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.