Health and Medicines

http://www.businessworld.in/
GINA S. KRISHNAN AND GAURI KAMATH

Seated in his spanking new office, with tall windows and plenty of natural light, Vasudeo Ginde, 42, has the air of a man who has overcome many odds. In the short span of a decade, this doctor has western drug manufacturers trusting him with their bread and butter —new drugs. DiagnoSearch (now renamed iGate Clinical Research), the company that Ginde created and then sold off to a US company, iGate Corp., manages clinical tests of experimental drugs on humans in India. At the time Ginde started his outfit in 1996, India’s drug patenting regime was lax, and a track record in human testing or clinical trials was absent. Not any more.

In 2005 the government passed the Patents (Amendment) Act, which gave new protections to patents held by foreign companies and, thus, emboldened them to invest in India. By 2006, global pharmaceutical companies had already begun discovering the advantages of India as a destination for clinical testing of drugs under development. The same year A.T. Kearney listed India second in a study that rated 15 countries for their attractiveness as clinical trials centres on parameters such as availability of patient population and cost efficiency.

And there is the potential size of the Indian pharmaceutical market itself. Consumer spending on healthcare went up from 4 per cent of GDP in 1995 to 7 per cent in 2005. That number is expected to go up to as high as 13 per cent of GDP by 2015. According to a recent McKinsey report, that will turn India into a $20-billion pharmaceutical market.

By one estimate, the number of trials done in India to fulfil approvals need for the US Federal Drug Administration (FDA) has almost quintupled, from around 60 in 2003 to about 260 today. These trials account for most of the money — about a billion dollars — that western companies spend on getting a new drug to market, according to a report by the US’s Tufts University’s Centre for the Study of Drug Development.

But success has bred a new and imposing set of challenges for what is a complex business with many moving parts. First, there is a shortage of doctors who can carry out the trials on patients. By one estimate, there are only about 600 such doctors, called principal investigators, India. Stories of doctors bargaining for more money are common. Second, monitors — experienced people trained to ensure that trials are performed according to laid down procedures or protocols — are scarce. CRO officials say that poaching of talent is rampant — by competitors and by companies doing their own clinical trials. On an average, monitors may spend just about a year with one organisation. Third, there is the issue of patient recruitment and safety. Laws and ethics dictate that only patients who fully understand the risks of participating in the testing of new drugs can be included in clinical trials. But its unclear how diligently this principle is followed in India, and regulatory oversight on the issue is thin.


Alarm Bells

Proposals to run clinical trials in a hospital usually have to be cleared by its IEC, which ensures that neither the patients nor doctors participating in the trials have been induced by money or other incentives. The IEC, which usually includes doctors, lawyers and other professionals, is also responsible for patient safety during the trials.

The A.T. Kearney Report says the world’s 12 largest pharmaceutical companies sponsored 26 trials in India in 2005. In March 2006, the number had jumped to 40. But the capacity Indian IECs, whose members serve voluntarily, to study and approve these trials has not increased proportionately.

To be fair, the pharmaceutical industry and the CROs are just as concerned and even recognise that they have to be part of the solution. “It has to be a shared role, equal among all stakeholders,” says Chandrashekhar Potkar, director of medical and regulatory affairs at the Mumbai affiliate of the world’s leading drug maker Pfizer. “We aren’t there as yet.” Pfizer should know. In Nigeria, it faces a $7-billion (Rs 28,700-crore) lawsuit over an allegedly botched clinical trial of an antibiotic, partly on account of a local hospital administration’s failure to put in place international standard procedures for ethical testing. The Nigerian hospital allegedly did not have an IEC at the time the trial began. It was formed a little later.

And there is the issue of patient recruitment. Guljit Chaudhri, senior adviser with 3i, a Gurgaon-based international manpower firm catering to the testing industry, is surprised that India’s speedy patient recruitment rates are not attracting more scrutiny. “Anywhere else in the world, faster recruitment means tighter scrutiny,” she says.




What is the regulatory framework for clinical trials? The Drugs Controller General of India (DGCI) — at whose door the buck stops — is handicapped. It is the last word on anything to do with drugs and even medical devices — from testing to marketing. Yet only half its 81 sanctioned posts are reportedly filled. As a result, the staff to do on-site inspections is lacking, and there is heavy reliance on IECs in the hospitals to do the job.

“By ourselves, we cannot ensure responsible behaviour,” says Vasantha Muthuswamy, deputy director general of the Delhi-based Indian Council of Medical Research (ICMR), referring to the excessive load on the system. The ICMR frames guidelines for drug testing. Jesani, though, thinks this is too much to expect from the industry. “If business has to survive, it has to multiply,” he says. “That is its only driving force.”

Do It Yourself

The obvious strategy, then, is to develop more hospitals and investigators: a geographical expansion from the metros of Mumbai and New Delhi to smaller cities such as Indore, Coimbatore and Nashik. The other, riskier option that some CROs, such as SIRO Clinpharm and Reliance Life Sciences, are exploring is to expand outside the country.

Despite this, the pace at which other investments in testing infrastructure are being made is slower pace than preferable. When a drug company or CRO invests in a new ‘site’, it does several things: invest in hospital infrastructure such as diagnostics, train IECs on international guidelines, and hand-hold doctors who do the trials. Ultimately, all of this should add to the healthcare system’s capacity to handle the growth.

“We track doctors (in the newer sites) on the phone every other day to make sure they understand the gravity and seriousness of what they are doing,” says Chetan Tamhankar, chief operating officer of SIRO Clinpharm. The hand-holding involves explaining international laws, the drug company’s requirements, and ensuring that everything is extensively documented. Training involves 3-4 people on-site from SIRO. This may be a luxury for CROs and companies in a talent crunch, but there is no other way that companies can scale up.

In the meanwhile, using newly trained doctors as investigators can be stressful. With, say, 15 new investigators or sites in any trial, CROs are confident of managing the trial process. But when that number goes up as a proportion of the total number of investigators in a trial, some nervousness sets in. If the number gets to beyond 65 per cent, it can get scary, and ethics can skate on thin ice.

Estimates suggest that India still accounts for just 1 per cent of all trials done globally, and aspires to grow at least fourfold by 2010.


Big Brother Is Also Watching

To be fair, the Indian government is making a valiant attempt to keep pace. It recently released a set of tightened guidelines for the conduct of trials that includes issues such as conflict of interest — investigators have to declare their interest in doing a trial, whether monetary or otherwise (some do it to be on the cutting edge of research). They also spell out the roles and responsibilities of IECs. Urmila Thatte, who heads the clinical pharmacology department in Mumbai’s BYL Nair Charitable Hospital says, “Right now, no one knows what happens when the law is violated. Do you get jailed? Or fined?”

Last month, ICMR also unveiled an online registry of trials accessible to everyone for the first time in 13 years of new drug testing. Registration is currently voluntary but would eventually be mandatory. Despite the registration being voluntary, many CROs have done so. “They know that if they don’t toe the line, the government could also come down heavily on them,” says Abha Aggarwal, the website coordinator who reports receiving 40 separate queries on the registration process. “One incorrect move and it could affect the industry adversely. It makes sense for them to police it themselves.” But even now, there is a great deal that needs to be done, says Muthuswamy. Presently, no drug discovered outside the country can be tested for the first time on Indians. These studies, called ‘first-in-man’, are used to assess a drug’s safety. They can be repeated on Indians once they have been performed elsewhere. That said, the DGCI has said that the government has been thinking allowing first-in-man tests too.

In any other industry, these constraints can be explained away as the pangs of growth —– growth that is gaining momentum. But experts warn that the growth has to go hand in hand with adequate capacity building; they advocate a number of checks and balances to moderate unbridled growth without regard for the cost that such growth may impose on patients and the system. But this is easier said than done. “The legal, regulatory and ethical framework pertaining to clinical trials is still evolving in nature,” says Rao. This poses a challenge for all stakeholders. And if not addressed fast, these could seriously undermine a lot of what iGate and others have achieved.

For months, Mumbai-based Reliance Life Sciences has been scouring the West for potential clinical research organisation or CRO acquisitions. It’s a tall order. Such an acquisition can alter a CRO’s cost profile drastically. The other problem is post-acquisition attrition — if employees leave and take their clients with them, little value is left behind. But Indian CROs have little choice. They are up against strong global competition…..

Kishan Lal (name changed), 77, a retired bureaucrat, is part of a six-month trial to test a new drug for Parkinson’s Disease in a private hospital in New Delhi. Mathur has been suffering for 12 years, and says he is aware that the condition cannot be cured. “I will probably never get better,” he says. “But if there is a chance that this medicine works, I would have helped humanity.”

In the overcrowded out-patient departments of public hospitals, patients who are part of a clinical trial get the attention others are denied. There is no queue, and the doctor spends 15 minutes with you, rather than the standard 5. Doctors spend more time on trial subjects since protocols call for extensive documentation of how the patient is doing on a drug. Plus, the gamut of tests is paid for. The economics are compelling, as for many Indians, such quality healthcare is an unaffordable dream.

“I suspect many participate because they get the drugs free,” says Urmila Thatte, who heads the clinical pharmacology department at Mumbai’s BYL Nair Charitable Hospital. There is currently no publicly-available information on the quality of informed consent taken from patients enrolled in new drug trials in the country…..


Last month, Artemis, a super-specialty hospital promoted by Apollo Tyres, opened its first multi-specialty tertiary care hospital in Gurgaon. It has two clear goals, to provide clinical care to patients and conduct research.

On the other hand, Apollo Hospitals has reconstituted its clinical trials division Spectra into Apollo Hospitals Educational and Research Foundation (AHERF) to offer Apollo Hospitals to pharma companies and clinical research organisations (CROs) to conduct trials. The reason to do this is compelling. The doctors who practise at Apollo are already conducting trials in the business. The hospital wants to give it structure, provide the doctors with resource people and pathology services.

With centres in six locations, Apollo is aggressive about getting clinical trials into its sites. According to Anvita Pandiya, who manages the clinical trials division at AHERF, the group prefers all the trials to happen in its hospitals. “That is the advantage we want to offer CROs.” When a principal investigator gets a trial proposal or a CRO approaches Apollo, a circular is sent out to the concerned departments. Principal investigators who are interested can contact AHERF and take it forward from there. “The fee, which is budgeted, comes to the hospital instead of going to other vendors,” says Pandiya.

For now, this could be the ideal testing model for hospitals involved in clinical trials.

# posted by Airavat @ 4:46 AM