Mumbai: Circa 2001. Location: Regional Cancer Centre (RCC) at Thiruvananthapuram, capital of Kerala. Twenty-six cancer patients are made test subjects for two new anti-cancer drugs by a team of doctors without approval from drug regulators of the country. The sponsor of the trials is Johns Hopkins University, he respected US medical school.
After the Johns Hopkins’ drug study at RCC, a reputed cancer research institution within India, came to light following complaints from patients, a four-month-long enquiry ordered by the state government revealed that the controversial experiments at the hospital were indeed the first human trials of these potential anti-cancer chemicals developed by Hopkins Biology Laboratory.
The real bombshell: the chemicals had not been properly tested on animals before being tried out on RCC patients, the enquiry found.
Other enquiries initiated by the state and central governments concluded that patients tested with the chemicals had indeed signed consent forms before the trials.
But, several of them said they thought the injections they received of the Johns Hopkins drugs were part of their cancer treatment.
In a country that is creating hundreds of drug development service outsourcing jobs from global and domestic pharmaceutical firms every year, such unethical testing is a daily risk, say experts.
“With the country poised to take over its Asian peers in the pharmaceutical services business, it is bound to see many more unauthorized trials risking innocent patients,” says G. Padmanabhan Nair, a lawyer and consumer activist who was one of the whistle-blowers in the RCC episode.
According to the Indian Council of Medical Research (ICMR), which is tasked with monitoring drug trials on patients, there are 300 registered patient drug tests going on in the country currently but the real number of such testing of patients could be several more.
This includes international drug trials sponsored by Indian as well as foreign drug makers. “There could be many more unregistered trials currently on in various hospitals across the country. But, at present there is no system to track them,” says Vasantha Muthuswamy, senior deputy director general, ICMR.
Often a tip-off of such trials comes from sources outside India. In 2001, for instance, it was found that illegal trials of ‘vascular endothelial growth factor’, a protein involved in boosting blood vessel formation, were conducted at the privately-run Metro Hospitals and Heart Institute in Noida. The enquiry report disclosed that Purshotam Lal, director of interventional cardiology at the hospital, has been administering the protein to patients with coronary artery disease since 1998, without due approval from regulators.
Dr Lal defended his experiments in an enquiry conducted by the Drug Controller General of India (DCGI) jointly with Medical Council, saying he used his “clinical judgment to save the life of a patient, with detailed consent of the patient and his relatives, and by informing appropriate hospital authorities.”
But, a report from a US hospital, the Medical College of Wisconsin, said it had developed a clinical protocol for ‘therapeutic angiogenesis’ (an emerging field of inducing growth of new blood vessels to supply oxygen and nutrients to damaged cardiac muscle) in patients with advanced coronary artery disease and seven patients were treated at the Metro Hospital.
Indian health administration officials are working to overhaul rules so that such incidents don’t occur.
Currently drug trials, approvals and monitoring are covered under the rules of Schedule Y of the Drugs & Cosmetics Act, 1940 but the rules don’t prescribe punitive actions against unethical trials.
ICMR had in 2000 prepared a comprehensive set of guidelines setting standards for drug trials in the country but since these are still voluntary, it has little legal binding on drug companies and investigators.
Considering the serious impact of such lax legislation, the health ministry has proposed translation of the ICMR guidelines into a law.
Key among the guidelines are that trial subjects have to fully understand the impact and risk of such research, have to be fully compensated for the risks involved in the tests, and the research has to be brought into the public domain.
Though ICMR submitted the law to the health ministry last year, it is still awaiting cabinet clearance, part of a logjam of pending legislation that isn’t being pushed for by the health ministry, including proposals to tighten policies on counterfeit drugs and creation of regulatory authorities for drug safety and recall.
Off-label use of existing drugs—the use of a drug approved for one disease or disorder for another indication—by doctors, which is again not legal under rules of the Drugs & Cosmetics Act, is another big concern.
As late as end-2003, some 435 unsuspecting young women were used as “guinea pigs” by self-styled investigators at private clinics to test if an anti-cancer drug letrozole can help childless women. The trials were conducted without DCGI permission.
The gynaecologists, who conducted the study, claimed that they had been asked to test the drug by the country’s leading drug maker Sun Pharmaceutical Industries Ltd. Legally letrozole can be sold on prescription from cancer specialists only and use of this drug for another indication amounts to a case of ‘off-label use’ of drugs.
It amounted to not just violation of drug testing rules but also contravention of ethics by using uninformed patients.
Sun declined comment on whether it had DCGI approval or if it had sponsored the letrozole trials.
“Letrozole is already approved and there’s nothing wrong for doctors to use the drug for other indications,” spokeswoman Mira Desaisaid. “No side-effects were reported after the trial.”
But, ICMR calls tests such as the letrozole trials “a blatant violation of drug law”.
Says Dr Muthuswami, “If a company want to experiment an existing drug for a different use, it is considered a new drug and the investigator has to take all the necessary approvals as in the case of a new chemical entity for the trials in human.”
The new law, experts say, will help tackle cases such as RCC or letrozole trials. And, help India emerge a destination for such tests.
Trade body Confederation of Indian Industry (CII) says more than 80 government and private hospitals in India are currently participating in international trials, a number that it predicts will almost double in two years aided by the fact that patient trials in India cost less than 60% of such trial costs in the developed world. Besides, a large population that is underexposed to drug treatments presents “drug naive” trial subjects who throw up high-quality test data for drug makers helping design better-targeted medicines.
“Clinical research is key to the discovery of latest diagnostic methods and to develop modern drugs for treatment of diseases,” says M. Venkateshwarlu, the Indian drug controller, emphasising the need of testing drugs in patients.