Thirty thousand girl-children from poor and marginalised communities have been involved in an unethical vaccine study against the HPV virus that causes cervical cancer. Why did the Gujarat and Andhra governments sanction this study? And what is the necessity for this vaccine costing Rs 9,000 when even screening tests for cervical cancer are not widespread in India despite costing between Rs 4-250?
On April 7, 2010, World Health Day, the government suspended a vaccine study in the states of Andhra Pradesh and Gujarat. That same day, a team of activists from women’s and health organisations had released the preliminary findings of an investigation that indicted the government, a drug company and international organisations for unethical practices in the controversial programme.
Starting in July 2009, a total of 30,000 girls between the ages of 10 and 14 were administered three doses of a vaccine against the human papilloma virus (HPV) that causes cervical cancer. This was in tribal, rural and semi-urban regions of Khammam district in Andhra Pradesh and Vadodara district in Gujarat. Described as “demonstration projects”, they were conducted by the state governments’ ministries of health and family welfare and the Indian Council of Medical Research, with a non-governmental organisation, PATH International. They were funded by the Bill and Melinda Gates Foundation. The HPV vaccine was provided by Merck Sharpe and Dohme.
Health advocacy organisations have protested against the HPV vaccine studies since they were first announced. In October last year, a memorandum was submitted to the health minister raising concerns about the vaccine’s safety, efficacy and public health value, and the Gujarat and AP projects.
In March this year, acting on media reports that a number of girls had suffered side-effects –and four girls had died – following vaccination, a team of women’s and health activists from Sama, Jan Swasthya Abhiyan and Antra visited Bhadrachalam, one of the mandals in Khammam district where the vaccine was being administered.
The team’s findings
The girls who were administered the vaccine were all from poor, marginalised communities – scheduled tribes, scheduled castes, Muslims and other backward communities – and extremely vulnerable. The majority were children of agricultural labourers. Some were from Chhattisgarh and their families had moved to Khammam to escape the conflict in that border state.
Most of the girls vaccinated in Bhadrachalam, where the team went, lived in ashram paathshaalas, or residential schools, They could not turn to their parents and were in no position to resist the orders of government officials, school teachers and hostel wardens. The girls with whom the team interacted said they had not been given any consent forms before the vaccination. Nor were they asked to inform their parents before the vaccination.
In other words, by choosing girls from residential schools, the authorities avoided seeking their parents’ consent.
Before the vaccination an auxiliary nurse midwife visited the school and asked for details of the girls’ birthdates. Girls whose official birthdates indicated their age as between 10 and 14 were selected for immunisation and camps were set up in the school premises for administering the vaccine. The district immunisation officer and a representative of PATH trained the primary health centre staff to administer the vaccine. The teachers or hostel wardens gave their consent for this; after all they are government employees and these orders came from a government health official. The parents’ consent was not sought. These parents believed their children to be safe in the custody of the residential school officials.
The team found that even students in day schools belonged to poor families who may not have understood the vaccine project. In many instances, the people who administered the vaccines did not visit the parents, tell them about the vaccine project and obtain their informed consent. Day students were given consent forms for their parents to read and sign. But the parents may not have been able to read the forms, let alone sign them.
Even if the girls, or their parents, or their wardens, could have refused, the information they were given was misleading. The team spoke to teachers, hostel wardens and the girls in these hostels. All of them said they were told that the vaccine would give them complete protection against ‘uterine cancer’ – a term that had no meaning for the girls –which “kills many women”. They were also told the vaccine had no side-effects and would give them life-long protection. They were told that they were lucky to receive an expensive vaccine for free. In fact, on hearing that an expensive, life-saving medicine was being given to these poor girls free of charge, a staff member at one of the schools brought her daughter in for vaccination.
The team’s findings contradict PATH’s statement that “ICMR-PATH teams conducted extensive community outreach and education prior to HPV vaccination to ensure that authorities, parents, and girls understood the purpose, uses, and potential minor side-effects of the vaccine and the purpose of the operational research project. Written consent was obtained for all vaccinations. Vaccine uptake has been very high, indicating high acceptance of the vaccine among parents.”
A total of four girls are reported to have died between one hour and some months after vaccination. According to official reports, one girl died of snakebite, another drowned in a well, and two committed suicide after consuming poison. The team interviewed the parents of one of the girls who is said to have committed suicide. They disputed the government account.
A number of unethical practices were revealed in the investigation: marginalised groups were used for the study; incorrect statements were made about the vaccine’s safety and effectiveness; and the vaccine was administered without proper informed consent and without the appropriate health service support. Finally, there was no proper follow-up of the many reported serious adverse effects, including four deaths
The government has promised an investigation into the deaths, but only to reassure the public. The ICMR seems to be distancing itself from the project, by claiming that it has provided only “technical help”. The ICMR director general is quoted as having said that “There can be no compromise, if ethical issues have been violated by any non-governmental organisation or pharmaceutical company. The government is all for the people, and genuine issues have to be addressed.” Merck has stated that its vaccine is safe and effective. The Gates Foundation has been silent on the report.
Why was a trial necessary?
What exactly was the purpose of this study? PATH is reported to have stated that the vaccine was administered in a “post-licensure observational study” of a drug that has already been approved by the DCGI. According to PATH, there is good reason to test a vaccine in India that, even at a highly discounted price, would cost more than the entire package of vaccines under the universal immunisation programme. “This is to simply keep India prepared for the day when these vaccines become affordable.” In other words, the vaccine study was to prepare the ground for introducing the HPV vaccine on a large scale in the public health system.
However, the specific details of the project are not public. What exactly was the “post-licensure observational study”? What was the study protocol? Who constituted the ethics committee that reviewed the proposal before the study started? A vaccine whose side-effects are known and whose benefits are a matter of controversy was administered to children –children belonging to a particularly vulnerable socio-economic group. What measures were to be taken to protect these children from being coerced into “consenting” for a vaccination? Were any mechanisms established to monitor the ethical conduct of this project?
The HPV vaccine and public health
Over 80% of cervical cancer deaths occur in developing countries. Some 132,000 women in India develop cervical cancer every year, and 74,000 die of cervical cancer.
But cervical cancer is 100% curable with early detection and treatment. Screening programmes can pick up conditions before symptoms appear, enabling early and effective treatment. In developed countries, screening and treatment are part of public health services, and most women will have access to regular screening with the Pap smear – an examination of cervical cells under a microscope – to detect early precancerous changes in the cervix.
In fact the debate in the UK and the US is on the age at which screening should start, and how often it should be done. The incidence of cervical cancer in these countries has dropped over the last few decades, as have deaths from cervical cancer.
However, there is no public health programme screening for cervical cancer in India. Private hospitals offer women Pap smears as part of health check-up packages. Public hospitals in cities like Mumbai offer Pap smears to patients visiting the gynaecology outpatient department. And there are some screening camps in cities like Mumbai. But there is at present no effort to inform all women about the need to get screened for cancers.
As a result, 70% of new cases of cervical cancer in India are diagnosed at stage III and higher, when treatment success rates are very, very low.
Screening for cervical cancer is simple. Dr Dhruv Mankad of the health NGO Vachan in Nashik says that health workers can be trained to run a regular screening service for cervical cancer. They can use a speculum to view the cervix after it has been stained with acetic acid or other stain. They can be trained to identify early changes in the cells of the cervix that can progress to cancer. Any suspicious cases can be referred to a gynaecologist who can do a more sophisticated test to confirm or rule out the diagnosis, and treat if necessary. Such a screening programme would be part of an integrated health service and would have to be accessible by everyone in the community. Such services are not available to the vast majority of Indians.
Visual inspection with acetic acid (VIA) costs Rs 4 per test, says Manisha Gupte of Mahila Sarvangeen Utkarsha Mandal (MASUM), a women’s health organisation working in and around Pune. Health workers at MASUM have been trained to conduct VIA and refer all suspicious cases to a gynaecologist for a Pap smear and treatment if necessary. The Pap smear costs between Rs 85 and Rs 250.
The HPV vaccine is priced at Rs 9,000.
There have been a number of studies confirming that this low-tech screening by trained health workers, when accompanied with treatment facilities when needed, can bring down precancerous changes in cervical cancer cases and the mortality from it.
Most important, the HPV vaccine does not do away with the need for regular screening for cervical cancer. The vaccine protects against the HPV types responsible for only 70% of all cervical cancers. And the vaccine is of no use to a woman who has already acquired HPV infection. Promoting the HPV vaccine for cervical cancer also bypasses other concerns such as sexuality and life skills education to protect the child from being coerced into sexual intercourse.
But screening programmes require a health system with trained staff and the right equipment and infrastructure including for treatment when necessary – and all this must be accessible and affordable to the poor.
“The HPV vaccine without screening is like focusing on the polio vaccine without providing clean water and sanitation,” says Mankad, referring to the fact that the polio virus is transmitted through faecal contamination of drinking water. It has been eradicated in rich countries but, despite massive immunisation drives, it has persisted in poor regions. In India, polio cases continue to be reported. This is what happens when medical technologies are viewed as “magic bullets” independent of the socio-economic context of a health problem.
There are many other question marks about the safety, efficacy and cost-effectiveness of the HPV vaccine. According to the manufacturer’s prescription information, the reported side-effects are both minor (pain and rash) and major (seizures, allergic reactions) and can occur months after the vaccination. The US Center for Disease Control tracks all reports of vaccine-related “adverse events” – about 15,000 as of September 2009, of which 7% were “serious events” that include a number of deaths. The CDC concludes that the deaths were unrelated to the vaccine. But this is a matter of controversy.
There are also questions about the vaccine’s efficacy: it will take decades for this to be known, as cervical cancer takes decades to develop. About the vaccine’s cost-effectiveness, it is calculated that even at a heavily discounted price, it will cost much more than existing public health programmes for conditions that are equally serious. It has also been pointed out that less than 50% of children in India receive the basic package of essential vaccines – for tuberculosis, diphtheria, pertussis, tetanus, polio and measles – and at the right time. Can we expect better immunisation coverage for the HPV vaccine?
Ethics of vaccine promotion
In addition to the PATH study, there are other studies of the HPV vaccine in India, one using GlaxoSmithKline’s vaccine Cervarix. Such vaccine studies have many purposes. One of them is to promote the vaccine’s introduction in the public health services at a later stage.
Writing in the Journal of the American Medical Association in August 2009, Sheila and David Rothman document the manner in which Merck promoted Gardasil despite the many reservations expressed on its efficacy, cost-effectiveness and public health value; how professional medical associations were bought over to promote the vaccine, and doctors were even trained in giving presentations on the vaccine; how it was promoted as a “cancer vaccine”, not one against a sexually transmitted infection; how it was extended to women at low risk of HPV infection. Merck now advises its use for boys as well.
The Rothmans note that in 2006, Gardasil was named the pharmaceutical “brand of the year” for building “a market out of thin air”.
The Indian Association of Pediatrics’ Committee on Immunisation has come out in support of the vaccine but its reasons are unclear. According to the committee, “Compliance with cervical Papanicolou (PAP) smear screening is low in India. The currently available vaccines are safe and efficacious. The HPV vaccines are thus of public health importance.” In other words, the committee advocates a vaccine because screening programmes (which it seems to acknowledge would make better sense) have not been implemented, not because the vaccine is more effective.
The committee goes on to state that “Vaccines are not 100% protective against cervical cancer and not a replacement for periodic screening. Hence screening programmes should continue as per recommendations.” In that case, why not focus on screening programmes instead of the vaccine?
The vaccine market is different from that for therapeutic drugs. For one, vaccines are meant for a healthy population to prevent their developing a condition that they don’t already have, and sometimes for relatively mild conditions for which a vaccine may not be a priority. So the market for a vaccine must be built differently from the market for a curative drug. It must focus on a possible harm, and the means of preventing that harm from occurring. For this, it may play on people’s fears, or create fears for them to imagine. The message of the HPV vaccine is: “Wouldn’t you want to protect your daughter from cervical cancer?”
To take another example, childhood chickenpox is not a life-threatening infection, and it was never viewed as more than an inconvenience. In fact, parents preferred that their children got it over and done with, especially since adult chickenpox was a more serious illness. The vaccine against chickenpox was targeted at parents: If their child fell ill with chickenpox, the parent would have to sit at home and miss work. Worse, the child could miss exams. The chickenpox vaccine could prevent such disasters. Physicians were quickly taught to promote the vaccine. But there continue to be questions asked about the long-term risks and benefits of the chickenpox vaccine.
New markets can also be created for vaccines with limited markets. Hepatitis B is a more serious infection that can cause liver cirrhosis and cancer. But 90% of the time the infection resolves within a year of infection. Hepatitis B is transmitted in the same way that HIV is. Health workers are at particularly high risk of Hepatitis B infection with serious consequences. Pregnant women with Hepatitis B can also transmit the virus to their babies, and the best way to prevent this is to test all pregnant women for Hepatitis B and give the vaccine to babies whose mothers are carrying the virus – but within 48 hours of birth.
Until 1997, the manufacturer of the Hepatitis B vaccine, GlaxoSmithKline, managed to keep prices high. Dr Anant Phadke of the Jan Arogya Abhiyan, points out that public hospitals did not provide their staff with the vaccine.
Then in the late-1990s, a number of DNA vaccines came on the market and were sold for less than half the GSK price, triggering a battle for a new Hepatitis B vaccine market and a spate of unethical promotional practices supported by these companies, including vaccination camps “for a Hepatitis B free Bombay”.
A campaign was also launched to include the vaccine in the universal immunisation programme package. As a result, the Hepatitis B vaccine is offered in the government’s immunisation package in Mumbai and a few states, and the chances are that it will eventually become a part of the childhood immunisation programme though it really is necessary for less than 2% of infants – and for these infants it must be given within 48 hours of birth. Healthcare workers are the other high-risk group, but even today, the government does not give this vaccine to all its healthcare workers. For example, in one Mumbai public hospital, health workers receive the vaccine from the government only if their department places an order for it. And medical students and residents are not assured the vaccine though they may work in situations that put them at high risk of Hepatitis B infection.
Vaccine companies’ marketing tactics can be pretty crude. Two articles published in a recent issue of the Indian Journal of Medical Ethics, one by Rakesh Lodha and Anurag Bhargava and the other by Yash Paul, reported on the industry’s promotional techniques with paediatricians. Vaccines are offered directly to doctors, at hefty discounts from the retail price; the doctors are at liberty to retain the difference between the discounted and the retail price. Naturally, some doctors will be inclined to offer their patients the brand of vaccine that gives them the biggest kickback. They may also suggest that their patients be given unnecessary vaccines.
On April 10, 2010, the newspapers reported that the Municipal Corporation of Greater Mumbai is thinking about offering the HPV vaccine to girls in this city. Two manufacturers have offered the vaccine at a subsidised rate, and there are plans to implement a “cervical cancer control programme” with the HPV vaccine.
One does not know whether to take this report seriously. But the idea is depressing: few Indian women get screened for this cancer even once in their lifetimes, but an expensive vaccine against the same cancer is promoted by the government. Maybe one should not be surprised. After all, the vaccine costs Rs 9,000 and the screening test costs between Rs 4 and 250.
Infochange News & Features, April 2010