CHENNAI, India — India's huge population, many of whom have hardly been exposed to medication, makes it one of the world's most promising markets for drug research.
But as the $400 million business accelerates, critics say it is exposing the dark side of the country's health-care sector.
"The regulations are weak, implementation is nonexistent, and ethics seem to be taken very lightly," said Anjali Shenoi, a researcher with a New Delhi-based women's health advocacy group called Sama.
"We feel like it is a growing problem, especially with India growing as a clinical trial hub, and more and more research being conducted by CROs [contract research organizations]."
Last week, the drug controller general of India — the top industry regulator — officially censured nine firms for failing to compensate the families of patients who died during clinical trials over the past year. But critics say the real story lies in the overall numbers, and the drug controller's tardiness in taking action.
According to the official figures, more than 1,500 Indians have died in the course of clinical trials since 2008 — 670 last year alone. And even though few of those deaths were reported to be treatment-related, there is no independent audit system to investigate the fatalities that occur during clinical trials.
Some see the booming industry as a ticking bomb.
Indians are desperate for affordable medical treatment. The government accounts for only 15 percent of health spending, and some two-thirds of patients pay the entire cost of care out of pocket. More than half of the poorest 20 percent of the population must sell property or borrow money to pay their medical bills, and yet, government spending on health care has declined.
Meanwhile, and instead of national health insurance or more widely subsidized health care, the government is promoting clinical research — the target of which is its poorest people.
Since India amended its laws governing drug research in 2005 to allow companies to conduct clinical trials in India at the same time as they are being conducted abroad, the research industry has expanded dramatically. Clinical trials are up to 60 percent cheaper to conduct in India than in developed countries, and companies are cashing in.
According to the drug controller, the number of Indian contract research organizations registered with the U.S. Food and Drug Administration has nearly tripled since the early 2000s, from 60-odd to 150. And more than 1,000 clinical trials are officially registered with the Indian Council of Medical Research, though that number is low compared with the number of trials underway in the United States.
As high as Indian authorities are on the industry, critics say that the method of oversight — which relies on decentralized, independent ethics committees — is woefully inadequate.
Thousands of institutions are involved in drug testing, not only in major cities but in small provincial towns across the country, according to Amar Jesani of the Indian Journal of Medical Ethics. But while companies are required to register the trials themselves, there is no comparable system for registering the ethics committees charged with evaluating their research protocols.
Only a handful of the hundreds of ethics committees have any official accreditation, which means that most of the supposed watchdogs have never been evaluated or audited by any outside agency themselves. Most of them do not publish any details about the number of clinical trials they have evaluated or what methods are used to monitor drug testing.
"There's a complete mystery about how they function," Jesani said.
But they aren't functioning very well, a trickle of press reports suggests.
Last year, after seven young girls died during testing of a new vaccine for the Human Papillomavirus (HPV), a sexually transmitted disease that can cause cervical cancer, Sama and Jan Swasthya Abhiyan, another non-governmental organization (NGO), conducted a fact finding study. The NGO probe allegedly found evidence of serious ethical violations in the design and execution of the project — which was funded by the Bill and Melinda Gates Foundation and carried out by PATH, an internationally respected nonprofit.
Sama and Jan Swasthya Abhiyan alleged that for "informed consent" researchers routinely relied on school officials, for example, claiming the parents of the research subjects were not available. Parents and girls who participated in the study said they were told that the vaccine would prevent uterine cancer — though they were not clear about what that meant.
Some may not have understood the nature of the project, as the NGO report quotes one mother as saying, "Since it was a vaccine being given by the government, we all trusted it blindly and considered it reliable, like any other vaccine that was given as part of the immunization program."
A subsequent government investigation found that the seven deaths were “most probably unrelated to the vaccine." And though it upheld most of the NGOs' findings in its report, the government described the ethical violations as "minor deficiencies" — downplaying the importance of informed consent, the most vital aspect of medical ethics for clinical trials.
PATH defended the way the study was conducted.
"PATH and its Indian collaborators worked with two ethical review committees in India and one in the United States to design study protocols and informed consent materials," Dr. Christopher Elias, president and CEO of PATH, said in statement following the controversy. "PATH is confident that these procedural safeguards informed and guided all aspects of study implementation and conduct."
Similarly, an independent study of clinical research sponsored by the Mumbai-based Center for Studies in Ethics and Rights, found that multinationals like GlaxoSmithKline, Johnson & Johnson and AstraZeneca also skirted the boundaries of medical ethics.
Evaluating clinical trials of drugs for breast cancer, acute mania and schizophrenia, journalist Sandhya Srinivasan and researcher Sachin Nikarge found that the pharmaceutical companies took advantage of patients who were desperate for any kind of medical care and, in the case of psychiatric patients, probably incapable of providing genuine informed consent.
While AstraZeneca did not respond to the journalists' inquiries, Johnson & Johnson and GlaxoSmithKline defended their research practices.
"We have well trained physicians and scientists to explain protocols to patients and answer any questions to obtain and document informed consent ... with particular attention to relevant language, literacy, cultural and societal issues," Johnson & Johnson said in response to questions emailed by Srinivasan and Nikarge. "Our trials are open to internal and external audit. We don't enroll anyone for whom appropriate consent is not given."
"Global study protocols are ... designed to ensure appropriate local standards of care are provided to eligible participating patients," GlaxoSmithKline said in a similar statement.
Yet in each of the trials that Srinivasan and Nikarge investigated, they had concerns about whether some patients were denied effective treatments for their illnesses because of their participation in the research project.
For instance, the Center for Studies in Ethics and Rights report claims that psychiatric patients suffering from mania and schizophrenia were denied the normal treatment for their diseases and given placebos during clinical trials — likely because placebo-controlled studies are faster and more conclusive than studies that compare the experimental drug to an existing treatment.
And, though the company concluded it was “not considered treatment related," one schizophrenic patient in the placebo group committed suicide during the trial of an anti-psychotic manufactured by AstraZeneca, the report says.
"The moral of the whole story is the regulators are sleeping," Jesani said. "They are doing nothing."