A few years ago, Renuka, a social worker in the Khammam district of Andhra Pradesh, discovered that around 14,000 girls, between 10 and 14 years of age, living in various hostels across the district, were enrolled in a study for a cervical cancer vaccine. “In most cases we found that the consent forms were signed by the hostel warden without any permission or knowledge of parents of those young girls,” says Jyoti who heads the All India Democratic Women’s Association in Khammam and under whom Renuka works.
The matter came to notice only when the vaccine allegedly led to the death of a few girls and various others developed new illnesses like epilepsy, headaches, depressions, stomach disorders, irritations and early menarche or irregular menstrual cycles. “We took up the matter with various authorities, even filed complaints with the police and district collector, but everything fell on deaf ears,” say Jyoti and Renuka.
It is only now that there is outrage over the methods used by drug makers, hospitals and doctors in clinical trials. According to government data, as many as 2,242 people have died during clinical trials in the country since 2008. Data also shows that most of the deaths have happened during studies conducted by multinational pharmaceutical companies. Recently, the Supreme Court expressed concerns over illegal clinical trials of drugs in the country, saying it’s “unfortunate” that humans were being treated as “guinea pigs”. A recent report of the Parliamentary Committee on Health and Family Welfare, tabled in the Rajya Sabha, said the Drug Controller General’s office doesn’t have the wherewithal to keep such activities under check. Now, at long last, the Union health ministry and the Drug Controller General’s office have started drafting legislative guidelines to regulate the sector. The issues under discussion include compensation to the families of those who die during the trials or suffer after-effects, inspection of trial sites and ethical best practices.
|2,242 deaths during clinical trials in India since 2008|
|2011: Of 438 deaths, compensation paid in 15 cases|
|2010: Of 668 deaths, compensation paid in 22 cases|
Drug makers need to try their new drugs on patients for efficacy before launching them in the market. Availability of a large, easy-to-access, treatment-naive population makes India attractive for drug makers, local as well as multinational, to do clinical research. There are significant savings in costs also. According to a recent report by Frost & Sullivan, India offers a cost advantage of up to 50 per cent over developed countries like the US. The market, the report says, is growing at 11-13 per cent per annum. According to a statement by the government in the Lok Sabha, 2,376 clinical trials were registered with the Clinical Trials Registry of India at the Indian Council of Medical Research site during 2009 to March 2012.
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The biggest draw for the drug makers is the loose regulatory environment here. While villages and small towns are easy pickings, there is no stringent monitoring even in large cities like Delhi, Mumbai and Kolkata. A medical practitioner in Delhi points out that pharmaceutical companies often look for doctors who get more patients and are willing to complete the study faster — this cuts the go-to-market time. The money paid by drug makers to hospitals and doctors varies according to the company, the drug and the duration of the trial. For instance, a multinational company conducting trials for a premier drug may pay Rs 2-3 lakh per patient, whereas the lower limit starts from Rs 50,000-60,000 for each patient. This is a neat sum of money for small doctors and hospitals. While companies involved in these trials insist they follow global best practices, concerns are rife that trial participants are often not fully aware about the possible consequences. Many blame it on the lack of regulatory guidelines, norms and legislation. While the country’s drug related laws are outlined in the Drugs and Cosmetics Act, it talks little on clinical trials. There are no set guidelines or structure to be followed by companies, clinical research organisations or doctors who administer these trials in India.
There are no means to ensure that those who enroll in these studies have been made aware of the risks of the treatment and have given their informed consent. Besides, clinical trials can be conducted anywhere with medical supervision — there are no basic criteria for a trial site. Even a doctor in his private clinic is eligible to do a trial. These sites are not even mandatorily required to have an intensive care unit. “The system is totally arbitrary,” says Anoop Mishra, chairman, Fortis-C-DOC centre for diabetes and metabolic diseases.
While it is mandatory for a clinical trial site to get approval from an ethics committee (while large hospitals have their own committee, smaller ones can go to independent committees; the Indian Council for Medical Research lay down guidelines for their conduct), experts say that in reality it is merely a formality. “These independent ethics committees are often situated far away from the trial site,” says C M Gulati, a health expert and editor of Monthly Index of Medical Specialties. So, it is easy to escape their prying eyes. According to Mishra, site selection for clinical trial also depends on how soon it can get the ethics committee’s approval — those which manage to get the nod quickly, by hook or by crook, are favoured by the drug makers. For instance, a government-run institution like All India Institute of Medical Sciences would hardly be commissioned a clinical trial study by a company because it takes three or four months to get an ethics committee nod.
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A bigger issue is compensation: there is very little on offer in the event of death, injury or serious after-effects. Government data shows that in 2011, compensation ranging from Rs 50,000 to Rs 300,000 was paid only in 15 cases of the 438 deaths reported during clinical trials. In 2010, compensation was paid only in 22 cases of the 668 deaths, that too as low as Rs 1.5 lakh. So why would anyone participate in these trials? Experts point out that in a country with a population of 1.22 billion, of which around 30 per cent are poor, there is no dearth of volunteers. “Most of these trial participants are poor, illiterate or tribal,” says Gulati. Many of these subjects suffer from serious diseases and do not have money to go for treatment or buy medicines. Becoming a part of a clinical trial means free medication for such people.
Pharmaceutical companies and research organisations say that mostly serious illness and old age are the reasons for deaths during trials and the company conducting the trials should not be held responsible. “Most patients die due to the natural progression of their disease and causes unrelated to the medicine being tested. In many trials in terminal illnesses such as cancer, death is the primary endpoint and the trial is geared to measure the duration of survival or the quality of life during the period of survival. In such trials, all patients will eventually die and be counted among those who died in the course of a clinical trial. It would be incorrect to suggest that these deaths were due to the clinical trial,” says Shoibal Mukherjee, chief medical officer, Quintiles India, a US-based contract research organisation which is carrying out clinical trials in India.
However, health activists and social service groups trash the argument saying this is not reason enough for a company to not compensate a participant. According to an official working with the Drug Controller General’s office, a company has up to 30 days to prove that death during the trial hasn’t happened because of the medicine being tested. If this is proved, the drug maker need not pay any compensation to the family of the deceased.
Other issues too have come up. Indian law does not require any company conducting trials in India to mandatorily launch the drug in the country, Gulati points out. “And even if the company decides to launch, it may not be affordable and accessible to people of the country. Then what is the logic and advantage for us to allow foreign companies to conduct trials on patients of our country?” asks Gulati. “Reliability and consumer confidence in Indian clinical trials data is lacking, greatly impacting the contract research market,” says a Frost & Sullivan research analyst. “This is the result of a number of small-scale contract research organisations having compromised on the standard of their studies in their bid to compete.”