India: HPV vaccine & other medical trials fail notions of consent & primum non nocere Print E-mail

Sunday Magazine / June 12 2011

THE OTHER HALF

Too bitter a pill to swallow

By KALPANA SHARMA

In rural India, where medical facilities are few and health insurance non-existent, marginalised groups like tribals are especially vulnerable to clinical trials.

Inadequate: Where rural hospitals are within reach, they are woefully under equipped (LINGARAJ PANDA)

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.
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 Tuesday, May 10, 2011

HPV vaccine: A.P. issued orders to educational institutions

Special Correspondent
For smooth implementation of the ‘cancer cervix vaccination programme' in Khammam district; Panel report pointed to casual approach, says Brinda
23,000 girls in Andhra Pradesh and Gujarat were vaccinated
‘Ambivalent sentences in the consent form amount to indirect coercion'

Rajya Sabha member and CPI(M) leader Brinda Karat addresses a press conference on recent developments with the HPV vaccine demonstration projects, in New Delhi on Monday (V.V.Krishnan)

NEW DELHI: The Andhra Pradesh government had issued an order for the smooth implementation of the ‘cancer cervix vaccination programme' in Khammam district. It had ordered all educational institutions to support the efforts of the Health Department in implementing the Human Papilloma Virus (HPV) vaccine programme.

The Deputy District Medical and Health Officer of Bhadrachalam, P. Mohan Rao, had written on June 2, 2009 to the Project Officer of the Integrated Tribal Development Authority (ITDA) instructing him to issue orders to all the “hostel wardens and ashram schools to sign the consent forms on behalf of the adolescent girls to have the vaccine, as contacting parents will be difficult in agency area (Bhadrachalam area).”

Teachers to help
“Teachers will help guide in consent process for the day scholars, by inviting the parents to attend the parent teacher meeting if needed. Teachers will support health officials to monitor the vaccination campaign in schools,” he said, further instructing the project officer to issue orders to private school coordinators to support the initiative and participate in the HPV project and provide necessary support to the officials.

As many as 23,000 girls in Andhra Pradesh and Gujarat were vaccinated under the ‘Post-licensure observational study of HPV vaccination Demonstration Project,' carried out by an international non-governmental organisation, PATH, for two American pharmaceutical companies.

However, the Centre suspended the programme following the death of seven girls who had been vaccinated and allegations of violation of ethics in conducting the trial.

‘Ethical issues ignored'
Talking to reporters here on Monday, Rajya Sabha member Brinda Karat said the final report of the committee, appointed by the Centre in April last to look into “alleged irregularities in the conduct of studies using Human Papilloma Virus (HPV) vaccine” by PATH in India, had stated that “from the numerical analysis it is obvious that the team involved in conducting the study on HPV has been very casual in its approach and has ignored many ethical issues such as signatures of parents/guardians, witness and there are discrepancies in the date of receiving the vaccine and date of signature.”

Significant deficiency
A three-member expert committee set up to assist the main committee has, in its report, said that the most significant deficiency in the implementation of the project was obtaining the consent. “The ambivalent sentences in the consent form tantamount to covert inducement and indirect coercion especially in the light of the high cost of the vaccine,” Rani Kumar, Dean of All-India Institute of Medical Sciences, has said in her observation. “This authorisation runs contrary to the basic principles of obtaining consent as students cannot be considered to have full autonomy in front of their teachers.”

“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,” Ms. Karat said at the press conference which was attended by representatives of Jan Swasthya Abhiya, Sama­Resource Group for Women and Health and Human Rights Law Network among others.

Ms. Karat further pointed out that that one of the roles assigned to the Indian Council of Medical Research (ICMR) in the memorandum of understanding with PATH was to “advise on plans for results dissemination to support decision-making in the use of the HPV vaccine.''

“How could the ICMR have committed itself to support the use of the HPV vaccine in an MoU signed in 2007, even before the vaccine was licensed for sale in India which actually happened in 2008,” she asked.
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 Friday, May 13, 2011

HPV vaccine: AIDWA for action against rights violators

Special Correspondent
Consent forms signed by higher authorities on behalf of adolescent girls
‘Interests of NGO, business prioritised over that of people'
Due attention was not paid to the adverse side effects and vaccine-related problems
NEW DELHI: Expressing concern over the “shocking” irregularities and violation of medical ethics in the Human Papilloma Virus (HPV) vaccine trial, revealed by the final HPV enquiry report and its findings, the All-India Democratic Women's Association (AIDWA) has demanded fixing accountability and ensuring action against those at fault.

In a statement issued here on Thursday, AIDWA said the three-member expert sub-committee that assisted the inquiry ordered by the Health and Family Welfare Ministry into complaints against the HPV project has clearly underscored the widespread violation of ethical norms. It is indeed disturbing that despite glaring evidence of rights violations, collated in detail by the experts, the report has neither apportioned responsibility nor recommended any action against those responsible for the lapses. The AIDWA demanded that the government examine the expert findings seriously.

Questioning the collaboration between a private body and the Indian Council of Medical Research in a project with questionable objectives, AIDWA said PATH ­ an international NGO ­ had undertaken a study for two American pharmaceutical companies, producing/marketing the expensive HPV vaccine. Evidently, the ICMR guidelines and protocols designed to provide safeguards for research subjects were breached right from the inception stage.

“It is a matter of concern that the interests of the NGO, and the business interests of the companies that it represented, received greater priority, while the interests of the Indian people were marginalised. The report brings out the facts clearly. The so called ‘post-licensure observation study,' has been found to be no less than ‘a clinical trial on human participants' by the experts,” the statement said.

The second alarming aspect relates to how the project was implemented and consent obtained from the “human” objects of the study. In June 2009, an official circular issued by the Andhra Pradesh government instructed the authorities to sign the consent forms on behalf of the adolescent girls. The vaccination of as many as 23,000 girls ­ mainly tribals ­ in Andhra Pradesh and Gujarat, with the consent forms duly signed by the hostel wardens, represents a gross violation of rights as students could not possibly have objected to the higher authorities' instructions, the AIDWA statement said.

Due attention was not paid to the adverse side effects and vaccine-related problems while conducting the trials.