'Clinical trials should promote health care'

Dr. M.S. Valiathan, now Honorary Adviser to and formerly Vice-Chancellor of the Manipal Academy of Higher Education (MAHE), was for 20 years Professor of Cardiac Surgery and simultaneously Director of the Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, the premier institution under the Department of Science and Technology, Government of India. It was under his directorship that one of the earliest institutional ethics committees in the country, with a retired High Court Judge as its chairman, was established at the Sree Chitra Tirunal Institute. The institute needed to ensure strict ethical compliance in order to be commercially successful when it became the first such institute in India to engage in the development of biomaterials and medical devices including the Chitra heart valve. In an e-mail interview he gave R. Krishnakumar, Dr. Valiathan spoke about the various aspects of clinical trials in the context of the RCC-Hopkins drug trial controversy. Excerpts:

Is India really ready for clinical trials?

Whether India is ready for clinical trials is a vague question. Many institutions are ready and have, in fact, been conducting clinical trials quite well and as per international norms. For example, domiciliary treatment of tuberculosis at TRC (Tuberculosis Research Centre), Chennai. Readiness must be assessed for institutions, not countries.

Do you think that India is increasingly becoming a favoured destination for human trials? What are the reasons for this?

Yes, the developing world including India is becoming a favoured destination for clinical trials. You may recall the recent U.S. House legislation which puts restraints on U.S. drug firms conducting clinical trials in the developing countries. The reasons for the popularity of the developing world are the following:

(a) Large population (b) Low cost (c) Legislative vacuum or infirmities (d) Ignorance about the legal and ethical issues of human trials among the public and even health care professionals and (e) Craze among the developing countries to link up with Western institutions unthinkingly and at any cost.

What do you think is a more serious problem today in India - unethical practices involving the kind of first-time trials of chemicals in human beings (as it happened at the RCC) or trials of new or me-too drugs by pharmaceutical companies? Is the latter a pardonable offence?

A serious problem arises when medical investigators and companies go about clinical trials without paying the slightest attention to the Ethical Guidelines for Biomedical Research on Human Subjects issued by the Indian Council for Medical Research (ICMR). The ICMR document emerged through the effort of the Justice Venkatachaliah Committee which held extensive consultations at the national level. I cannot understand why this document is ignored by investigators and companies. Between the rules of the Drugs Controller General (India) and the ICMR guidelines, the issues of the trial of new chemical entities and that of me-too drugs are fully covered.

Cannot Indian institutions, researchers and doctors say no to unethical trials and still "survive"? What do you think are the incentives that make institutions agree to unethical practices?

Indian institutions can certainly survive the refusal to take part in unethical trials. The reasons for institutions adopting unethical conduct are no different from those which tempt individuals to become corrupt.

Is there a general lack of awareness among Indian medical professionals about ethical requirements? How effective are Indian guidelines and laws?

Yes, there is a serious lack of awareness of ethical guidelines among health care professionals - not doctors alone, administrators, politicians, media, etc. Apart from the ICMR guidelines, the DBT (Department of Biotechnology) has set up a separate set of admirable guidelines on human genome research which is in its infancy in India. Therefore, one cannot claim that we have no guidelines. Of course, guidelines are not laws, but legislation on the basis of guidelines will emerge soon. However, it is a fact that in practice the guidelines are not often observed. This is no more than another illustration of our scant regard for laws and guidelines in India.

Is getting "informed consent" a difficult task in the case of a majority of patients here? What has been your experience? In that case should such people be made "participants" in drug trials at all? Is getting "volunteers" a difficult task here?

It is not difficult to get informed consent - on the basis of my Kerala experience. It is true that when patients are illiterate and uneducated (not the same thing) and look upon doctors as gods, informed consent would become difficult. Getting volunteers by giving financial incentives is, of course, unethical. Ultimately, the inclusion criteria for subjects, including their ability to give informed consent, should be determined by the principal investigator and his colleagues. Incidentally, the rights of the subjects in a trial are spelt out in the ICMR guidelines.

There is a new breed of contract research organisations which act as a sort of "event managers" for the drug companies, organising clinical trials. Do you think they are good or bad for the Indian scene?

Clinical trials are essential for making progress on many fronts - drugs, devices, vaccines, diagnostic kits, etc. If the trials are restricted too rigidly, there would be little scope for innovation; if unrestricted, there would be chaos and human exploitation. One has to adopt the middle path by sticking to the national guidelines and keeping oneself posted on what is happening in biomedical research at the international level. The human trial should be planned on the basis of an MoU (Memorandum of Understanding) between the firm which developed the product and the medical institution, which would obviously take the approval of its own ethics committee and other approvals as necessary. There is no place for third parties or middlemen in this exercise.

What should the country be cautious about and what needs to be done at the practical level when trials involve researchers and resources from developed countries and multinational companies? Are Indian companies and research institutions comparatively better in the matter of sticking to ethical rules?

As I mentioned earlier, clinical trials are necessary insofar as they promote the interests of health care. The problem is a mismatch between the interests of the group which developed the product and those evaluating it in human subjects. Firms in India and abroad who spend millions on developing products would want to maximise profits; ethics in business is a controversial subject. On the other hand, the evaluating institutions need money and must also protect the interests of patients and subjects. Medical investigators who are approached to take up clinical trials therefore face serious ethical dilemmas. This is true as much in the affluent countries as it is in India. In the last few years, this issue has become pressing because medical investigators have themselves promoted firms. It is now mandatory for authors of papers for top journals to indicate any direct or indirect links they may have with the firms/industry where the product/process being reported on were developed. In fact, the affiliation is published with the paper.

Lastly, it is no use blaming institutions and firms in affluent countries for exploiting us. We are grown up and should look after our own interests. If we are upright and do a thorough job no one stops us in this and all would be well.