Should clinical trials be allowed in India?

DEBATE

Monthly Index of Medical Specialities

Before a new drug is allowed to be sold in the market, it has to undertake a long and expensive journey, starting with tests on mice and ending with trials on men. Due to unknown and unexpected side effects of new drugs, testing them on humans can be quite dangerous, even fatal.

It is extremely difficult and expensive to find volunteers in western countries willing to participate in such trials. Developing countries such as India, with poor and illiterate patients, lax laws, obliging bureaucrats and funds-starved hospitals, have become the hunting grounds for medicine makers to test new drugs. Take a look at some recent scams involving drug trials in India.

• Three patients in Hyderabad being tested for the efficacy and safety of a heart drug called Streptokinase have died. Without any independent enquiry, the company conducting the trial has ascribed the death of "trial subjects", as they are impersonally called, to "causes other than the use" of the drug! Their families have not been compensated.
• Not long ago, Dharmesh Vasava, a 22-year-old "volunteer" from Bharuch in Gujarat died while participating in tests on Citalopram, an anti-psychotic drug. According to another participant in the same trial, the subjects were lured with money by agents working for the company that sponsored the trial.
• More recently, over 430 unsuspecting young women were used as guinea pigs by self-styled researchers to test if an anti-cancer drug Letrozole can help childless women conceive. The trials were conducted illegally at private clinics. When questioned, the doctors claimed that they had been told to test the drug by a Mumbai-based pharmaceutical company.
• In West Bengal, two self-styled investigators inserted an antibiotic, erythromycin, into the wombs of 790 women to test the contraceptive effect of the drug, without government approval and consent from the subjects.

Animals subjected to experiments in the US enjoy more protection than humans in India. Any trial done on any animal without approval from the relevant authorities is fined Rs 1 lakh ($ 2,500) under the Animal Welfare Act. In India, more than 1,200 young women have been treated worse than animals.

Such unethical and illegal trials are conducted without any fear because drug regulators, either by design or default, fail to take action. A couple of years ago, new chemicals discovered in the US were unlawfully tested on 26 oral cancer patients at the Regional Cancer Centre in Thiruvananthapuram.

Under unrelenting pressure from the media and non-governmental organisations, an unwilling government was forced to take action. But, instead of sending the guilty to jail as provided in the law, further research was stopped for just six months!

All clinical trials require Central government permission and approval by the ethics committees of the hospitals concerned. In practice, the Drugs Controller General, India (DCGI) approves clinical trials the same way as ration cards are issued. Some examples:

• A human trial on Zoniporide, a new American drug, was approved without adequate and mandatory studies on animals.
• Cilansetron, a new drug not approved anywhere in the world, was cleared for advance, large trials even though only preliminary, small trials had been conducted abroad.
• The study design of the drug Tacrolimus was cleared by the DCGI even though vital information on serious side effects was concealed, thereby misleading patients.

It appears that some documents submitted for approval are not even read by those handling drug trials in the office of the DCGI: a voluminous protocol on a new drug called Trastuzumab was approved at super-speed within five working days. It is humanly not possible to read the bulky documents in such a short period.

Most of the trials on new drugs are conducted without any arrangement for compensation in case of injury, disability or even death. Indian Council of Medical Research guidelines require that each research "shall include in-built mechanism for compensation for the human subjects...to cover all foreseeable and unforeseeable risks." Despite this requirement, trials are routinely approved even where no such undertaking is given by the sponsors.

The investigators for drug trials are chosen by the sponsoring companies. Many investigators who conduct trials are, or have been, beneficiaries of largesse from pharmaceutical manufacturers.

This could take the form of paid speaking engagements, expensive gifts, paid consultancy work or travel grants for domestic and foreign travel. Last year, a Mumbai-based company marketing a drug used in kidney dialysis had obliged some 300 senior kidney specialists with an all-expenses paid visit to Singapore.

Unless laws are honestly implemented by regulatory authorities, the current unsupervised, unethical and often illegal clinical trials will pave the way for similar trials in gene therapy that will leave many Indians diseased, deformed and even dead.

Harinder S Sikka
Senior President,
Nicholas Piramal India Limited

Much hue and cry is being raised about Indians being used as guinea pigs. Because the issue is sensitive, it grabs the immediate attention of the masses and it is the negativities that get highlighted.

Consequently, it evokes high-pitched emotions that fuel the fire in the researchers' backyard. It is, therefore, of vital importance to appreciate both sides of the story as well as the urgency of conducting clinical trials for diseases specific to our sub-continent.

Till date, the Indian industry has been reverse engineering patented drugs and supplying them at cheaper rates to the masses. While this arrangement served the purpose to a great extent, genuine research on diseases like fluorosis, malaria and tuberculosis took a back seat and no new molecule worth the name could be discovered.

Lack of infrastructure and the focus on genuine research by Indian companies was also partially responsible for the brain drain of a vast number of scientists who otherwise contributed enormously to the coffers of multinational companies overseas.

Post-2005, when the product patent comes into force, India will face challenges of a different kind. Reverse engineering of the drugs will come to naught and only those companies with a strong research base will survive.

It is in this light that the Indian pharma companies are rushing into setting up research centres and conducting clinical trials to counter diseases that are specific to the Indian subcontinent.

The situation, however, is grim. Out of 20,000 small and big pharma companies, nearly 19,950 companies produce only 40 per cent of the total $ 6 billion business. Of the remaining 50 companies, only a dozen are engaged in serious levels of research. It is, therefore, not surprising that India has lagged behind in new drug discovery.

A new drug costs up to $ 1 billion in the western world. India, however, can produce the same at one-tenth the cost. Therefore, not only can India play a major role in serving humanity, the industry can also earn precious revenue.

In fact, clinical research has the potential to be much bigger than the information technology revolution. No new drug can be marketed in any part of the world unless it is tested on animals (pre-clinical studies) and on normal, healthy humans (phased clinical trials).

Indeed, there have been instances where some fly-by-night operators have abused the system and used humans as guinea pigs. It has happened all over the world and, like any other serious crime, should be dealt with in accordance with the law of the land.

But efforts to paint ethically-conducted trials with the same brush as the unethical ones is damaging Indian research and undermining India's prowess in the field.

Ironically, globally, 95 per cent of the research and 90 per cent of funds have been focused towards research that benefited only 1 per cent of the population based in western countries.

It is, therefore, of importance for both the regulatory as well as the polity to remove the bottlenecks and unshackle research companies from undue controls.

India has Good Clinical Practices (GCPs) and Good Laboratory Practices (GLPs) at par with the US Food and Drug Administration (USFDA). Even though there are only a handful of research companies in India, they could yet open the doors for world-class clinical and contract research at cost-effective prices.

The difference between micro-electronics, biotechnology, designer material and telecommunication is rapidly thinning. Tomorrow's war is going to be fought in the knowledge market with the help of information and technology, and not with guns and bombs. That is why it is important for Indian research to seize the opportunity.

Big opportunities also pose bigger challenges. Gyan, vigyan and buddhi(knowledge, science and intellect) have been India's traditional strength. But for them to prosper, it is essential to free the mind from the clutches of narrow-minded babus.

Innovation emerges from experiments and trials. Till date India has reaped the fruits of new drugs because someone in the developed world volunteered to be a guinea pig. It is now time for the sub-continent to stand on its own two feet and deliver a safety mechanism from disease.

Banning legitimate clinical trials cannot be the answer "" just as the fact that ultrasound tests can identify the sex of an unborn child does not warrant banning the system.

The world is changing at a rapid pace. It is time for us to take a pragmatic and holistic view and strengthen our delivery system rather than take the conservative approach and block development.