Strong Medicine

Hirani fits the description to the T. Last year, he signed an Informed Consent Document to ease a costly battle with Type II Diabetes for two global glucose monitoring trials. He doesn’t know the sponsor names and is quite indifferent to the fact. ‘‘Look, I didn’t have a stable job, insulin costs Rs 1,700 a month,’’ the 43-year-old says. ‘‘I have two daughters. And I weighed 49 kgs.’’

Impressed with four cellphone numbers of doctors he can dial anytime to report adverse reactions, the frail man allowed two sensors to be implanted in his abdomen. In return, he adds triumphantly, ‘‘I got free insulin, tablets, and Rs 4,000 in monthly compensation.’’

In dingy civil hospitals and upscale private clinics alike, visits to the doctor are rapidly becoming akin to state secrets. The stakes are higher than patient privacy, the risks greater than life and death.

The happy hunting ground for the drug developers are the hospital OPDs, where millions throng every day. At least some are happy to swallow free medicine, ideal candidates for swift, low-cost clinical trials. A far cry from Europe and the US (see graphics).

HOW to prevent mystery deaths and adverse reactions suffered by patients is still a fuzzy area.

‘‘Due to lack of drug penetration, India has a huge patient population that’s never been subjected to any drug,’’ says a Rabo India 2003 study. ‘‘This gives a critical pool of naive or uncontaminated patients important in conducting clinical trials’’.

Some time ago, Dharmesh Vasava, a 22-year-old volunteer from Bharuch in Gujarat died, reportedly during tests for citalopram, an anti-psychotic drug sponsored by Mumbai-based Sun Pharmaceuticals.

More recently, some 400 unsuspecting young women in small towns across the country were reportedly illegally used as guinea pigs by self-styled researchers at private clinics to test if anti-cancer drug Letrozole — again, a Sun Pharma product — can aid ovulation. The drug is considered toxic for the foetus or embryo.

When contacted, Sun Pharma spokesperson Mira Desai would only say: ‘‘The company cannot speak on the issue’’.

‘‘Even animals subjected to experiments in USA enjoy more protection than humans in India,’’ says former WHO drug expert Dr C M Gulhati, editor of Monthly Index of Medical Specialities. ‘‘Unethical and illegal trials are conducted with impunity because the regulatory authorities, either by default or design, fail to take action.’’

Legally, all clinical trials require clearance from the Drugs Controller-General, India, and the approval of the ethics committee of the hospital concerned. Research is supposed to be conducted only at recognised centres by duly qualified and experienced investigators (see box overleaf).

But the lapses, and their number, are alarming.

DEAN of KEM Hospital, Mumbai, Dr Nilima Kshirsagar, is visited every week by global contract research organisations (CRO). They are nosy about the civic hospital’s disease patterns and eye its massive OPD turnout.

‘‘We ensure the volunteers get some support during and after trials,’’ she says. This year, KEM’s ethics committee received 150-200 applications for clinical trials, 10-50 of them from global players. Such applications are cleared quickly, after one or two meetings.

Last year, Pfizer’s clinical research spendings in India added up to $3 million, double the usual outlay. ‘‘These investments are a fraction of what’s possible,’’ Dr Shekhar Potkar, director, clinical research, Pfizer, told The Sunday Express in Mumbai.

Every three to six months, a long line of short schoolchildren heads inside KEM Hospital. Escorted to hospital because they are the shortest in class, the children are part of a 40-country genetic mapping study to discover the gene responsible for short stature. Each child will get free growth therapy and counselling till they attain just the right height.

Nearby, the psychiatry department is busy, a site for four global drug trials for schizophrenia and mania.

‘‘India’s potential for clinical research is unmatched,’’ says Narges Mahaluxmiwala, president, clinical development services, of Quintiles, the largest CRO in the country. She has a sweeping trial field for Phase II and Phase III trials nationwide: psychiatry, oncology, neurology, anti-infectives, gastroenterology, diabetes, ophthalmology, cardiovascular indications and internal medicine.

The world ‘unethical’ is swiftly rejected. ‘‘If we listen to activists complaining of exploitation, we’ll remain at the lowest level of drug development, unable to develop globally relevant new drugs,’’ says Kiran Mazumdar-Shaw, chairman and MD of the Bangalore-based Biocon and chairperson of Karnataka’s vision group on biotechnology. ‘‘Surely, taking care of bioethics and biosafety, we can ensure patients get access to new therapies?’’

The problem, as M V Shrishyla, medical director, Novo Nordisk, a leader in diabetic-care, says, is that ‘‘We have excellent clinicians, but few trained in good clinical practices. There are plenty of quality issues to be addressed at all stages.’’

There is also a long list of to-do reforms. ‘‘Our regulatory infrastructure is inadequate,’’ admits Shaw. ‘‘There is no specialist knowledge of biotech products and animal trials are clouded by unresolved issues’’.

Dr Gulhati, on his part, is certain of the exploitation factor. ‘‘Most clinical trials in India are conducted without organising any compensation in case of study-related injury, disability or death. ICMR guidelines specifically require each project to incorporate a compensation mechanism for all eventualities,’’ he says.

At the Indian Council of Medical Research (ICMR), the nodal agency for conducting and monitoring trials, director-general N K Ganguly asserts that on paper, at least, the checks are in place.

‘‘Only four per cent of drugs tested on animals go in for human trials. We have monitors for adverse drug reactions, and make sure there are no monetary or other pressures in human trials,’’ he says. ‘‘We also inform the volunteers extensively about the nature of the trials. The most important criterion is the DALYS burden — the disability-adjusted life years.’’

BUT it’s unlikely that the global applications flooding Mumbai’s best hospitals have these criteria as their guiding light. Tata Memorial Centre, with 32,000 annual patients — numbers unmatched by most South Asian hospitals — receives so many global applications, they often reject some.

Dr Arun B Shah, head of neurology at Nair Hospital, recently had discreet visitors from England. ‘‘They told me they’re exhausting US and European patient pools, often enrolling only 40-50 per cent of required numbers’’.

Shah says in the last two-three years global collaborations (the likes of Mayo Clinic) have increased. His latest project is a two-year trial on Parkinson’s Disease with a French sponsor.

During planning, execution and closure of trials, India’s advantage is execution, thanks to speedy patient recruitment. ‘‘If we address IPR protection, data exclusivity and public awareness, investments can increase manifold,’’ Potkar says, adding that Pfizer currently has ‘‘no particular interest’’ in conducting Phase I studies for under-development drugs in India.

CMC’s principal investigator and endocrinologist Dr Nadeem Rais — with three new trials for US sponsors on hand — insists it’s untrue that only the unemployed and illiterate are enrolled for drug testing.

‘‘We recently completed a 12-month trial for a drug for erectile dysfunction,’’ he says. ‘‘All patients were A-class.’’

MAHARASHTRA is leading a flurry of activity to invite global drug majors to avail of a vast patient pool streaming into civil hospitals.

Global presence is also expected to buck up statewide biotech parks. ‘‘We’re speaking to hospital deans about clinical trials,’’ Vishwas Dhumal, principal secretary, industries, told The Sunday Express. ‘‘Once it’s clear how public hospitals can retain revenue, we’ll conduct training for hospital staff’’.

Ethics committees of bigger hospitals are offering to guide Mumbai’s smaller, peripheral civic hospitals who don’t want to be left out of global trials.

Returns are rich. A civil hospital recently received medical equipment worth Rs 40 lakh — for keeps — from sponsors of an osteoporosis trial.

Of course, there is a catch. Tata Memorial Centre director K T Dinshaw admits that the global majors dictate research. ‘‘We have no control over information we collect. Now we want to dictate the terms’’.

So, with a fat grant from the Department of Atomic Energy, this year the Tata Memorial Centre set up a Clinical Trials Centre linking major hospitals, and launched it with a new trial on head and neck, and cervical cancer.

The mandate: ‘‘To bring the clinical trials culture to India.’’