Drug alert

-REUTERS

FOR almost a fortnight in December 2009, leading newspapers and private television and radio channels kept warning the public about the dangers of ignoring cervical cancer. The advertisements in the newspapers, targeted at young girls and their mothers, highlighted the need to get vaccinated against cervical cancer but did not mention the name of the vaccine. Its true! Vaccination can now protect your daughter from cervical cancer, screamed a headline, with the sub-head saying that 200 women died in India every day from cervical cancer, a bigger cause of death than breast cancer.

The advertisements, which showed a mother and daughter in a loving clasp, were issued by a multinational pharmaceutical company in the form of a public awareness initiative. They advised readers to act today and contact their gynaecologist or paediatrician for vaccination. They clearly hinted that it was young women who were at the highest risk of contracting the infection that might lead to cervical cancer.

In the advertisement, it was explained that for the best response, the vaccine should be taken by adolescent girls as early as possible. But nowhere did the advertisements mention anything about the possible side-effects of the unnamed vaccine.

Predictably, the advertisement blitz caught the attention of women and health groups. They felt that the studied silence of the Ministry of Health and Family Welfare over the advertisements was grossly misleading. The advertisements were brought to the notice of the Drugs Controller General of India (DCGI), whose office pulled up the pharma major for its unlawful propagation of the vaccine Cervarix.

The Drugs and Cosmetics Act, 1940, and the Drugs and Magic Remedies Act, 1954, do not allow any claim to prevent or cure diseases that include cancer. And drugs sold under prescription, which include vaccines, cannot be advertised. Even though Cervarixs maker had not mentioned it by name, it still fell foul of the existing legislation. The advertisements soon stopped appearing.

Apart from Cervarix, which secured approval from the United States Food and Drug Administration in October 2009 (the advertisements in India started soon after), Gardasil, a version of the vaccine, was launched by another pharmaceutical major in the Indian market.

It was in December 2005 that Gardasils manufacturer and the Union Ministry of Health and Family Welfare, through the Indian Council of Medical Research (ICMR), announced their collaboration to assess the use of Gardasil. Under the agreement, the manufacturer would supply Gardasil for the study.

The manufacturers press release includes forward-looking statements, which are about product development, product potential or financial performance. These statements are defined in the Private Securities Litigation Reform Act, 1995. The press release, issued in 2005, cautioned that no forward-looking statement can be guaranteed and actual results may differ materially from those projected. This essentially means that Gardasils maker has no obligation to update publicly any forward-looking statement, whether as a result of new information or future events, or for other reasons.

It is interesting to note that even though the Union Ministry and the State Health Departments play a key role in vaccine introduction policies, it is the National Technical Advisory Group on Immunisation that finally advises the Central government on the feasibility of introducing a vaccine in India. The introduction also needs clearance from the National Drug Authority and a licence from the DCGI. However, State governments can introduce any vaccine that is not part of the national immunisation programme.

The international campaign around the human papillomavirus (HPV) is not very old. It began essentially three years ago following the development of vaccines against two types of HPV, which accounted for 70 per cent of cervical cancer cases worldwide. It was claimed that clinical trials had shown the vaccines to be 90 per cent effective in preventing persistent HPV infection and 100 per cent effective in preventing type-specific cervical lesions.

Even sources that push for the vaccines appeared to suggest that cervical cancer can be prevented if the precancerous lesions are detected and treated early on.

The international non-governmental organisation (NGO) PATH claims in recently published literature on the subject that along with other organisations such as the Bill and Melinda Gates Foundation, it is seeking to help developing countries understand the HPV disease burden and determine how best to introduce the new vaccines and says that cervical cancer rates are highest among the poor, in large part because effective screening and treatment programmes often are not available, and most women with cervical cancer only reach health centres when their disease is advanced and incurable.

This is precisely what women and health groups in India are arguing that it is screening that is required and not mass vaccination of adolescent girls.

According to the literature, PATH is working closely with ministries of health and civil society organisations to conduct clinical and operations research in India, Peru, Uganda and Vietnam. By its own admission in June 2006, it was given a major grant to strengthen the capacity of developing countries to prevent cervical cancer. A document titled Shaping a strategy to introduce HPV Vaccines in India details formative research results from the project, HPV Vaccines: Evidence for Impact Project, a collaborative effort of PATH and the National AIDS Research Institute (NARI).

The project was initiated in 2006 and the research undertaken in two States, Andhra Pradesh and Gujarat. The research was carried out by NARI of the ICMR with technical and financial support from PATH. The research concluded that policymakers, health care providers, parents and adolescents would accept vaccination against cancer of the cervix as long it was safe, effective, affordable and accessible.

Interestingly, PATHs strategy report, of which Frontline has a copy, mentions right in its introduction that the incidence and mortality rates of cervical cancer have gradually decreased in developed countries, thanks largely to screening programmes (traditionally using Pap smears) that can spot the signs of precancer and treat them early.

It is strange that this line of prevention is not being explored in the developing world. The argument given is that in developing countries, however, many women cannot access screening services or do not receive necessary treatment for precancer.

The only reason that women do not have access to these services is that they are not there, and if present they are not affordable or easily accessible. With a public health system thus far focussed on controlling the fertility of women, rather than addressing problems relating to their reproductive health, screening is the last thing on the minds of policymakers.

Instead of arguing for more investment to strengthen the public health system with more accessible and better-quality screening services, including Pap smear tests, the study is pushing for the HPV vaccine.

In July 2009, it was from news reports that health groups in India got to know that two demonstration projects for vaccination were under way, in Andhra Pradesh and Gujarat. These were not private initiatives. They were carried out in association with the ICMR, PATH and the State governments concerned.

In both the States, 16,000 girls between 10 and 14 years were to be administered the vaccine in selected blocks of Khammam in Andhra Pradesh and Vadodara in Gujarat. In each case, three doses of Gardasil would be administered over a period of six months. The Gujarat project was longer; it was for two years.

PATHs publicity material, which Frontline has accessed through some sources, has slogans like Our protection is in our hands; vaccinate 10-14 years girl child to protect against cervical cancer. Strangely, the same material states that sexually active women are more susceptible to this infection and that HPV spreads through sexual contact. It also says that the vaccine is not effective fully and that is why pre-pubertal girls are required to take it urgently.

It claims that the vaccine is very potent, that it is being promoted by the Indian government and the governments of other developed countries where millions of girls have been vaccinated without any adverse effects. It also asserts that the vaccine does not lead to infertility or other health problems, that there will be no difficulty in conceiving or delivering healthy babies. It says that health workers like auxiliary nurse midwives, anganwadi workers and accredited social health activists (ASHA) will be trained to vaccinate and that free and voluntary consent will be taken from girls and their parents.

More than 50 women and health activists groups and many individuals across the country have written to the Union Health Minister expressing their concerns on the introduction of Gardasil. They have said that first, information about the efficacy of Gardasil is uncertain; and that it is admitted by the service providers themselves that the vaccine only prevents infections resulting from two HPV subtypes and another two subtypes that can lead to genital warts.

Secondly, they say, there are more than 100 HPV subtypes and that if the vaccine is successful in blocking two subtypes, then the other carcinogenic subtypes can become dominant. Thirdly, they point out, there is a lack of conclusive data regarding the duration of immunologic protection conferred by the vaccine.

Quoting a follow-up study of vaccinated subjects (Lippman A., Melynk R. et al, 2007) published in Canadian Medical Association Journal, the signatories to the memorandum have said that the vaccine offers protection only up to five years. Its long-term efficacy is therefore in doubt. They also point out that as cervical cancer in India occurs among women over 35 years, there is a lack of clarity on whether a three-dose schedule can provide long-lasting immunity or whether booster doses are required.

Vaccination, it is argued, cannot be a substitute for screening as even those who are vaccinated are required to undergo regular Pap smear tests as the vaccines preventive effect on cancer has not yet been demonstrated. Quoting another June 2007 study on HPV published in Prescrire International, the letter to the Union Minister points out that it is rare that HPV infection has led to a progression to cancer.

More importantly, critics of the vaccine point to its side-effects, of which there is no mention in the advertisements. According to the U.S.-based Centres for Disease Control and Prevention, 12,424 adverse events have been reported by the Federal Vaccine Adverse Reporting System.

Says Kalpana Mehta from Saheli, a womens group: Gardasil itself doesnt declare that it may protect everyone. She points out that the official website states that it does not treat cervical cancer or genital warts.

The website also lists side-effects such as pain, swelling, itching, bruising and redness at the injection site, headache, fever, nausea, dizziness, vomiting and fainting. Sometimes fainting is accompanied by falling, as well as shaking or stiffening and other seizure-like activity. Cervarixs website also lists side-effects, which, not surprisingly, were missing in the advertisements.

The other important argument posed by the drugs critics is the cost of the vaccines themselves. The current cost is Rs.3,000 a dose, so the total cost of three doses (Rs.9,000) and booster shots every five years would be around Rs.33,000. Public health activists are wondering whether the Ministry can afford an injection that will cost Rs.9,000 for every woman in the country where the system has failed to give the basic DPT vaccine to almost 50 per cent of the population. Independent studies have shown that the cost-effectiveness of the vaccine is yet to be proved.

Critics say the advertisements themselves create fear and the feeling that there is a public health emergency. The letter has demanded that the government review its decision to conduct an HPV vaccine demonstration project in its mass immunisation programmes in the absence of sufficient evidence of the vaccines long-term effectiveness.

The focus, the writers of the letter correctly argue, should be more on preventive health care, such as Pap smear tests, population-based outreach screening for women in rural and tribal areas, measures to promote awareness, and measures to detect cervical cancer at an early stage. Of paramount importance, they say, is making public health services available to all, with stress on womens health through measures such as filling vacancies of gynaecologists and paramedical workers.

The organisations have also expressed concern that there is no information available about the status of the trials that have been under way as a result of the memorandum of understanding (MoU) between the Health Ministry and the makers of Gardasil. They have categorically rejected the idea that financial support from industry or an international organisation should be the criterion to introduce a vaccine either in the pilot phase or in the Universal Immunisation Programme.

The organisations are awaiting a response. None has come as yet. One public health activist put it: Earlier, they used to show some interest in what we had to say. They used to come to our meetings and express their point of view, right or wrong. Even that doesnt seem to be happening now.

The question here is one of priority, of cost, of the health of lakhs of girls and women, and, more importantly of transparency.