Too bitter a pill to swallow

The Hindu, Sunday Magazine, June 12, 2011

THE OTHER HALF



Falling ill is precarious business anywhere in the world. But in India, if you are poor, or live in a village, overcoming even routine illness can sometimes become an insurmountable hurdle. First, there are few health facilities within reach. Those that exist are ill equipped. Doctors don't come. Medicines are not available. Even if you somehow make it to the nearest district hospital, there is no guarantee that you will be treated. And if you seek private care, something 80 per cent of Indians are forced to do, you will end up permanently in debt. Most Indians have no health insurance.

Better than nothing

In such a situation, if someone approaches you and says they will actually pay you if you agree to take a new treatment for an illness that you have, most poor people would agree. What harm can it do? Often doctors, in whom the majority of patients put their complete trust, endorse the trial.

But harm there can be, and is possible from participating in what are ‘clinical trials' where new drugs are tested for their efficacy on humans. And despite regulations, codes of ethics and monitoring, every now and then we hear of people who die during these trials.

Last year, an intervention by a women's health rights group, SAMA, exposed the manner in which a study, where tribal girls between the ages of 10-14 years in Andhra Pradesh and Gujarat were given the Human Papilloma Virus (HPV) vaccine that prevents cervical cancer, went horribly wrong. Seven girls who received the vaccine died. Their parents believed the reason was adverse effects of the vaccine (see The Hindu, Sunday Magazine, April 18, 2010). The SAMA report prompted the Central government to set up an inquiry committee to look into the study and in the meantime asked that it be suspended.

The report of the government committee appointed on the HPV vaccine study was released in February this year but became public only a few weeks ago. Although it concludes that the seven deaths were “most probably unrelated to the vaccine”, it also adds that “the cause of death in all the cases cannot be established with certainty.” And as for violation of ethical norms, it observes “several minor deficiencies in the planning and conduct of the study”.

However, it is these so-called “minor deficiencies” that can sometimes make the difference between life and death for people who are already vulnerable. In the case of these tribal girls in Khammam district in Andhra Pradesh and Vadodra district in Gujarat, the deficiencies included the absence of “informed consent” (the consent forms were signed by hostel wardens instead of the parents of the girls being informed and their consent sought). Furthermore, a proper procedure to monitor the health of these girls for adverse effects was not in place. This is particularly important as most of these girls were already undernourished. The committee's report notes that there was no uniform reporting system for Adverse Events Following Immunisation (AEFI), which included nausea, vomiting, diarrhoea and abdominal pain as well as giddiness, jerky movement and neurogenic shock. Worse still, the girls had no health insurance cover for treatment in case they fell ill on being vaccinated.

Consent by proxy

Although the committee does not indict either the drug company or the organisation that conducted the study, and also concludes that the inclusion of girls between the ages of 10 and 14 was justified given the nature of the drug, it has questioned the “legality and morality” of the circular from the Andhra Pradesh government permitting hostel wardens and head masters to sign the consent forms on behalf of these girls without informing their parents. It has gone further by stating: “The committee stresses that everyone shall desist from research on tribal population, unless of specific benefit to them.”

The HPV vaccine controversy draws attention to one aspect of clinical studies and trials, how vulnerable groups are roped in without proper consent and without health support in the event of problems. In this case, the connection between the vaccine and the deaths could not be conclusively established. But even where it is, the companies try and get away without paying compensation.

On June 6, newspapers reported that the Drug Controller General of India (DGCI) had summoned nine drug companies who conducted clinical trials that led to the death of 25 people. According to the DGCI records, last year, a total of 670 people who were part of clinical trials died. But the death of only 25 could be linked to the drugs. Of these, only five families were compensated within a range of Rs. 1.5 to 3 lakhs.

This news item gives us a small window into the ‘industry' of clinical trials in India that is worth millions of dollars. It has been clear for some time that these trials need to monitored much more closely. Some of this kind of scrutiny is taking place. Apart from official bodies like the DGCI, there have also been some independent studies. One of these, by Sandhya Srinivasan titled, “Ethical concerns in clinical trials in India: An investigation” for the Centre for Studies in Ethics and Rights, is particularly instructive. Ms. Srinivasan has looked at the trials of three drugs, a drug to treat breast cancer and two drugs for psychiatric conditions. Many of these drugs are expensive and it is tempting for those with terminal conditions, like cancer, to agree to be part of such trials. The report reveals the many loopholes in the rules and regulations that allow drug companies to appear to be sticking to the letter of the law while violating the spirit.

Going unnoticed

The ethics of human clinical trials is a complex subject that requires more space to discuss than is available in this column. But the two developments – the report of the government committee on the HPV vaccine and the DGCI's intervention on the question of compensation for trial related deaths – illustrates how so many things remain hidden until there is a crisis, or some independent group investigates. The problems remain hidden particularly when the people involved are the voiceless, like the young girls of Khammam district. Had it not been for groups like SAMA, perhaps no one would have ever known about what was going on.

This is not to say that new drugs should not be developed to combat disease. No one questions the need to test these on humans before they are licensed for use. But the process of certification of their safety should not lead to death or disability of those who are part of the trials. Nor should the precondition of consent be abused the way it was in Andhra Pradesh. And nor should the financial vulnerability of the majority of people in India when faced with a health crisis be cynically exploited for such trials. The onus is on the manufacturers of these drugs, who claim they are producing them to save human lives, to actually do so.

(To read the original click on the link above)

Uninformed Consent

https://www.thehindu.com/opinion/columns/Kalpana_Sharma/The-Other-Half-Uninformed-consent/article16123576.ece

The Hindu, Sunday Magazine, April 18, 2010

THE OTHER HALF

KALPANA SHARMA

What women need is basic healthcare. Not costly medical experiments involving vulnerable sections who don't know what they are getting into…

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Were they informed about adverse health impact and were these monitored and treated?

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Photo:G.N. Rao. THE HINDU

Controversial: Tribal girls treated with the cervical cancer vaccine interact with Brinda Karat.

Marie Antoinette told her people to eat cake when they needed bread. Our government encourages people to buy cars — from Rolls Royce to the Nano — when they need affordable public transport. And when people, especially women, want simple, basic health care — and clean water and sanitation — they are being urged to inject their daughters with a Rs. 9,000 vaccine against cervical cancer. If some of us conclude that the priorities of our decision makers are more than slightly skewed, we should not be blamed.

The recent controversy over the use of the Human Papilloma Virus (HPV) vaccine on tribal girls in Andhra Pradesh has once again brought into focus several ethical and gender-related issues in the arena of public health that need to be openly debated. In India, we have many recent examples of women, particularly poor women, being subjected to clinical trials for contraceptives, including injectable contraceptives. These women have suffered after-effects and not known fully what was happening to them. It is only when women's groups and health groups raised an alarm about the way these trials were being conducted did the government intervene.

Goverment intervenes

Once again, the government has intervened and stopped, for the moment, the project in three districts — Bhadrachalam, Kothagudem and Thirumalayapalem — of Khammam district in Andhra Pradesh where 14,000 girls, mostly tribal, between the ages of 10 and 14 have been given three doses of a vaccine that is supposed to protect them from cervical cancer. The project is headed by a well-known international NGO and is supported by the Indian Council for Medical Research (ICMR). The official district health authorities and health personnel have been fully involved in every aspect of the project. So it is not something that has been done clandestinely.

The alarm bells first rang when four girls died after they had received the vaccine. Whether they died due to complications caused by the vaccine, or from other factors, has not been established. Perhaps it cannot be conclusively established. But the very fact that the parents of one of the girls believes that her problems arose after she was administered the vaccine suggests that it is an issue that has to be investigated further.

Of course, there is little doubt that cervical cancer is an important health risk that millions of women face. A quarter of all deaths due to cervical cancer worldwide occur in India. The infection can lie dormant in a woman for 20 to 40 years before it manifests itself as cancer. Hence the belief that if young girls, before they become sexually active, are administered a vaccine, they might be able to avoid getting infected by HPV and thereby lower their risk of getting cervical cancer.

The first HPV vaccine came into the market in 2006 in the United States. After trials, it was declared safe for use in young women, and men. While it provided women cover against cancer and genital warts, it protected men from genital warts. However, once you were infected with HPV — of which there are at least 15 strains that can cause cancer while the vaccine protects you against only two — the vaccine was of no use. Also its efficacy in the long run has not yet been tested because the infection takes such a long time before it shows up as cancer. So young girls who have received the vaccine in the last years would have to be followed for that length of time before we can be completely sure that the vaccine actually works. Meanwhile, the best protection against cervical cancer remains regular checks — with or without the vaccine — to catch any early signs of the cancer.

So what then is the basis of the opposition to the project being conducted in Andhra Pradesh?

SAMA, a Delhi-based women's health group, has done a detailed study of the problem in Andhra Pradesh. Its members have spent time speaking to the girls who received the vaccine, to their teachers, to the health workers, to the parents and the district authorities.

What emerges is a disturbing tale of young tribal girls who are not necessarily in the best of health in the first place, given their background of poverty and under-nourishment, being given this vaccine. The information provided to them is in English, which neither they, nor their parents, nor the health worker giving them the vaccine, can read. Even the exact age of many of these girls is not certain as births are not regularly registered in large swathes of this country. Hence how were these girls chosen for the project? Were they informed about adverse health impact and were these monitored and treated? And did they really give “informed consent” to be a part of the project when they could not read the literature? In fact, many of the girls did not know the meaning of the word “cancer” or “cervix” or even “uterus”. So did they know what they were being given and why? It would appear not.

Of course, the company providing the vaccine does not deny contra-indications. Its website states: “The side effects include pain, swelling, itching, bruising, and redness at the injection site, headache, fever, nausea, dizziness, vomiting, and fainting. Fainting can happen after getting GARDASIL. Sometimes people who faint can fall and hurt themselves. For this reason, your health care professional may ask you to sit or lie down for 15 minutes after you get GARDASIL. Some people who faint might shake or become stiff. This may require evaluation or treatment by your health care professional.”

But how do you deal with all this when the girls live in a tribal hostel, or in areas where the health facilities are abysmal? In the case of 13-year-old Sarita, who is one of the four girls suspected to have died from complications connected to the vaccine, by the time her parents managed to go to the nearest big hospital in Bhadrachalam, she was dead. This is what they said to the team from SAMA:

“Our child was active and happy. We lost our child, and we know the pain and the agony of that loss. We don't want any other child to die. We don't want any other parent to suffer. Care should be taken for other children who received vaccination. Even though some girls are suffering from side effects like severe stomach pain, teachers are not letting them go home… We want the government to take immediate action. This is our only appeal. This is why we are speaking out.”

Exposing vulnerability

Fortunately, this appeal has been heard and for the moment the project has been suspended. But it has brought into focus once again, the dangers of exposing poor women, in particular, to this kind of medical experimentation. By all means, efforts should be made to try out a new technology. But not at the cost of the health of the woman. And certainly not on the basis of exploiting her ignorance. What is more important? Women's health or promoting a new vaccine? If it is the former, then there is much more that can be done at a fraction of the cost — starting with ensuring that primary health centres have gynaecologists available at all times. Women in this country urgently need basic health care and nutrition, not necessarily advanced medical interventions whose efficacy has yet to be proven.

(To read the original, click on the link above)