The Hindu Business Line : Clinical trials and good practices

IS India selling out to drug companies on clinical trials? The answer to this question has two parts. The first rests on the consideration that as the numbers establish, there is a great deal of money involved in terms of cost savings to drug companies and revenues for the intermediary enterprises which represent their interests, in "outsourcing" clinical trials to India. The second rests on the proposition that money, in sufficiently large amounts, makes for myopia.

This money-induced myopia has ensured that the authorities have not noticed reports in the media about two pharmaceutical companies — one based in Bangalore and the other in Hyderabad — which conducted Phase III trials of genetically engineered drugs apparently without the appropriate prior approval of either the Drug Controller General of India (DGCI) or the Genetic Engineering Approval Committee (GEAC). It appears that these companies applied for and obtained the DCGI permission — but they applied to the GEAC only after the commencement of the trials.

The authorities have been blind to other reports about a Mumbai-based drug company that had allegedly gone around the DCGI altogether and prevailed upon private doctors to prescribe an anti-cancer drug, Letrozole, to over 400 women for "ovulation induction."

The results were used to promote the drug for unapproved usage through medical representatives and the core issues involved in all this gets obfuscated by arcane debates about the legal and ethical right of doctors to prescribe a drug off-label — which is quite different from off-label drug research. The myopia is such that the government is now talking about the relaxation of drug testing regulations — which have not been enforced in the first place — to encourage the "outsourcing" of clinical trials to India from the West. Actually, regulations even in their present form need not be of much concern to those interested in conducting contract research and clinical trials in India as nobody has a clue about the projects underway in the absence of a central registry for medical research in India.

The public knows nothing of the clinical trials carried out in India for the past several years by multinational pharmaceutical companies, either directly or through what are known as CROs (clinical/contract research organisations) which do their work for fees the quantum of which, once again, is not in the public domain.

Whatever its other failures, the Government has apparently succeeded in its initiative to bring drug trials to India, in that well-known clinical research outfits of the West are uniformly gung-ho about the diverse advantages that this country has to offer: Staggering diversity of diseases, "drug-naïve population" (which term basically means that people have not been treated for their diseases so far), high enrolment rates, excellent patient compliance/retention, competitive costs and an increasingly accommodating regulatory environment.

How can the people of this country ensure that big business (the Confederation of Indian Industry has been making a lot of noise about how the trials outsourcing business can go up by 10 times if regulatory "hurdles" are "streamlined" and has been lobbying for the automatic approvals of all applications with the DCGI if they are not cleared within a timeframe) and government do not collude in selling them?

The introduction in India of Good Clinical Practice (GCP) norms for pharmaceutical research, based on those formulated by the WHO and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (revised 2000) and now required by the Indian Council of Medical Research (ICMR), represents a good starting point. The GCP has one problem, though: The administration of those sections dealing with informed consent, which has been pretty much left to individual investigators.

The problem here is the size and nature of the population base in India, both of which work in favour of those conducting the trials. Those who have been involved in the formulation of ethical guidelines in collaborative research is developing countries concede that securing a patient's informed consent can, indeed, be a tricky exercise, especially if the research involved is a complex one and cannot, therefore, be communicated easily. And then again, experience has proved that many of those who agree to participate in trials are often unable to distinguish between treatment and research.

But, then, that is precisely what the Government and its organisations are there for: To set the rules equitably and to enforce them — and not to drum up business as it seems to be intent upon doing in this case. For instance, the drugs being tested should be of demonstrable value to the host country and a watertight agreement on the post-trial availability of the drugs at affordable rates must be in place before trials start. The Government must, in addition, make certain that research is carried out solely on the basis of informed voluntary consent, and that trial drugs are tested only against the best available proven treatment.

A re-look at the proposed changes in the Drugs and Cosmetics Act would also be in order. Drugs are globally put through for phases of trials. Phase I trials use healthy volunteers to test a drug's safety. Phase II and III trials test a larger number of volunteers for the drug's efficacy and generate data relating to its safety, effective doses and so on. Phase IV trials are conducted after the drug is marketed in order to monitor its safety when used on a mass scale.

As matters stand, under Schedule Y of the Act, permission to conduct international clinical trials in India is given one phase behind other countries. By way of illustration, if a drug is in Phase III trial in some other country, permission will be given only for Phase II trial in India. However, the DCI can waive this if the drug that has to be tested is deemed to be of special relevance to India.

The government plans to change this system on the basis of a recommendation contained in the interim report of an expert committee which says: "Comprehensive revision of Schedule Y, that prescribes requirements of clinical trials, has been undertaken in order to harness (the) country's potential to participate in global multi-centric clinical trials." The revision, significantly, does not make any reference to a system that will ensure that the drugs tested in India will be made available to the local population at affordable rates. All that the committee has made certain is that foreign pharmacos will be able to carry out concurrent phase trials on human guinea pigs in India, putting their lives at risk. It is reliably learnt that the government is so keen on helping foreign drugs companies and their agents that the DGCI is allowing concurrent phase trials — though revisions to Schedule Y are yet to be publicly notified.

It is understood that the Government is planning to introduce the Biomedical Research on Human Subjects (Regulation, Control and Safeguards) Bill, 2004, in Parliament in the winter session. The Bill has apparently been cleared by the Union Health Ministry and is now under the scrutiny of the Law ministry. To understand this initiative in its correct perspective, one need only bear in mind the Ronald Reagan's characterisation of a government's view of the economy: "If it moves, tax it. If it keeps moving, regulate it. And if it stops moving, subsidise it." India has a tradition of pinching ideas from the West — and of then mangling them beyond recognition. The Bill under discussion, if passed into law, will merely allow the government to enhance its regulatorial powers with relation to clinical testing in such a manner that it will be able to tax certain intermediaries and subsidise the others, depending upon expediency."

Given the obvious nexus of the government, foreign drug companies, high-profile industry lobbies and opinion-makers, the people have their work cut out for them in ensuring that they are not sold as lab animals. But, in a country like India, if the people do not protect their own lives, who else will?

(Concluded)

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