Clinical research industry in India is currently passing through a phase of rapid growth. According to industrial sources, the clinical trial business in India is expected to cross USD one billion by 2010. However, the sudden spurt in clinical research activity and the mushrooming of CROs have generated a lot of debate as well, among the experts in the field. The eminent cardiologist and biomedical scientist Padmavibhushan Dr M S Valiathan has his own views on the way clinical trials being conducted in India. Valiathan has been credited for the pivotal role he played in developing the indigenous 'Chitra Heart Valve' when holding charge of Director of Sri Chitra Tirunal Institute of Medical Sciences, Thiruvananthapuram. Former Vice-Chancellor of Manipal Academy for Higher Education (MAHE), Dr Valiathan is currently National Research Professor under Government of India and the Honorary Advisor of MAHE: Excerpts from an interview with Gireesh Babu

What is the current status of clinical trials segment in India?
Clinical trials as a segment, is growing very rapidly in India. Of course, the growth of the clinical trial is because the country has large genetically heterogenous population, large trained medical community who can easily use western protocols. However, our legislative regiment is not very strict. When compared to Europe or the United States, it is easier to get things done in a low cost. Many of the companies making drugs, devices and vaccines would prefer to do these trials in India provided the protocol would be acceptable to the western countries.

The business of clinical trials forcast 12 hundred to 15 hundred crore of rupees. It is difficult to say it in exact terms, but it is a very large industry. There is no way India can stay out of this as the progress in medicine can only come through trials. We cannot take the position now that we have signed the world trade agreement. A country like India with its own traditions, science and technologies and its own pharma industry, we should make sure that what is being tried on the public in the country, whether it is drugs, vaccines or devices. If all of them are developed abroad and we are only conducting the tests, that is very crucial. If you look at all these candidates which are being trialled in India, probably 90 or 95 percent of their R&D is done abroad. This does not add to the strength of the country. We are only testing and getting some money for it and becoming the testing capital of the world. That will not bring in a good reputation for a country like India.

We should have a clear vision that in 10 years 30 percent of all those trials will be on Indian products. Drugs, vaccines, devices or diagnostic kits should be developed in India for trails. There should be a clear target, on what direction we are moving. That is the first consideration. Otherwise we will end up becoming the 'clinical trial capital of the world'.

But there are some guidelines from ICMR on the clinical trials. Are they not enough to control the clinical trials in India?
ICMR guideline is only to protect our human beings. When somebody wants to test something in India, the company should obtain an approval from the institutional ethics committee. But the institutional ethics committees are very weak in India. The United States or the European countries have fool proof institutional ethics committees to protect their people. But in India, when any product is to be trailled,the concerned person or the company should abide the ICMR guideline. But it is still a guideline, we don't have a legislation which is legally enforceable. The ICMR guideline is a good set of guidelines which covers the patient's interests like informing the concerned people before you conduct a trial, or if something goes wrong, there should be a compensation for the patient including insurance coverage, the trials should be monitored and the adverse reactions must be reported etc. It contains very detailed guidelines for clinical trials. I hope that it will become a legislation. But our government takes time to do these things.

The second aspect of clinical trials isthat we are going to have hundreds and thousands of trials done here. Who are going to conduct these trials? Today any hospital can do it, which is completely deplorable. I doubt about the standards of many of these hospitals to conduct a clinical trial or whether the doctors know anything about clinical trials. They don't know how to constitute an ethics committee. Ethics committee members are not trained. Suppose you are making some retired medical superintend as ethics committee member, they will come and sit in the meeting. But he has no idea, what he is expected to do.If you allow clinical trials without any guidelines, anybody can conduct a trial. That is sure prescription for disaster, because there is a lot of money involved in this business. Suppose a company is ready to give Rs one crore for a trial, hospitals my tend to execute it, because they are struggling for money.

There is a need for the government to approve the trials on some basis. On the basis of staff, of patients, of how they keep their medical records; whether they conducted any clinical trials before, whether they published any scientific papers, we can check out.So, in this same criteria, hospitals should be recognized. It is to be made sure that these hospitals are recognised to conduct clinical trials, not only in government sector, but also in private sector atleast in the state level. There should be an objective criteria based on which hospitals are recognized to conduct the trial. And not that every body can conduct trials.The second thing is to protect our public. The institutional ethics committee members must go through regular training to ask questions to somebody who wants to try a vaccine, how they are going to do it, suppose an adverse.

ICMR guideline is only to protect our human beings. When somebody wants to test something in India, the company should obtain an approval from the institutional ethics committee. But the institutional ethics committees are very weak in India reaction is reported, what should be done etc. Everything should be trained. There must be a training programme for all the institutional ethics committee members. In that way, if a proposal comes, the institutional ethics committees will make sure that they will not be tried to the disadvantage of the people.

Can you brief about the challenges in the clinical trials sector in India at present? And what are your suggestions to tackle these challenges?
There are three things. One is the lack of technology from the domestic companies on clinical trials. The technology should be increasingly developed in our country also. The Rs 1000 crorein this business is nothing, if we look for the interest of the whole country. There should be clear target for this, like in another10 years or 15 years that 50 percent of those should be developed in this country. Secondly lack of regulations in and ranking of hospitals for conducting clinical trials. We don't have any such criteria for recognizing the hospitals which can conduct clinical trials. The hospitals must be recognized on unbiased, transparent, objective criteria like the one used in recognizing three, four or five star hotels. It lacks credibility. This ambiguity should not be there.The third challenge is that there is no criterion in selecting the institutional ethics committee and even the existing committees lack proper training on clinical trials. The institutional ethics committee should be selected and operated according to the ICMR guidelines and the members should be regularly trained, atleast in every three years. If all these are done, it is a good thing for the positive growth of the clinical trials in India.

How much is the effort of Government of India in this area?
The government is trying to control these issues on its own way. ICMR has the central ethics committee, for which I am the chairman. But that committee cannot look after all the clinical trials going on in India. All that the Central Ethics Committee does is monitoring the drug trials implemented in the public domain, for example, a national vaccine programme, in which the medicine is distributed to the public. The trials done in the institutions and hospitals should be monitored by the institution itself. ICMR can definitely play its role in the training programmes for the ethics committee members through regional training programmes, but even that department is weak in staff strength at present, and should be strengthened. ICMR can set up satellite units in four or five places in the country, where the institutional ethics committee members from the recognized hospital can get training.

You were speaking for the international standards of clinical trials in India. Kindly explain
Today, any drug, device or vaccine product developing in India, targets the global markets. The much-regulated countries like US and European countries will approve a product only after inspecting right from the R&D labs to manufacturing plant and the standards of clinical trials conducted by the company. Even we should use the international terms as per the harmonizing committee to keep the global standards.

I don't have any clear statistics to say the size of such clinical trials with international standards being done in India. The government of India has come out with a notification that any clinical trial conducted in the country should be registered with Drug Control General of India (DCGI). The editors in the top medical journals have agreed that if a clinical trial is not registered with the nation's authority, the study cannot be published in world class journals, to get the recognition of the The hospitals must be recognized on unbiased, transparent, objective criteria like the one used in recognizing three, four or five star hotels. It lacks credibility. This ambiguity should not be there global scientific community. This is a good measure for the companies to comply international standards in clinical trials.

The private participation of Clinical Research Organisations (CROs) in India are increasing rapidly. How do you feel the role of these organizations in this context?
There are around 700 to 800 CROs registered in the country. They are acting as the mediators between the foreign companies and the Indian hospitals. There must be some company law to regulate them, but I cannot suggest more on industry without studying the situation.

The CROs should have a better role in setting up standards, and it is heard that the organistions are already setting up clinical research institutes. But in India, the people are basically suspicious of the private ventures. The companies in India can form an independent autonomous affiliate, which will work with the ICMR. When it comes to developing standards and training programme, the affiliate can play its role in the whole interest of the industry. The affiliate, with independent powers and with the support of ICMR, can even offer courses on bioethics, rarely available in India, which will be helpful for the institutional ethics committee members and to win the confidence of the public.

As the man behind development of the famous 'Chitra heart valve', what is your comment on the current status of the biomaterial and medical devices sector in India?
The R&D efforts in the field are very low in the country at present. Many companies are making their contributions in low end products. Around 90 percent of the high end products, whether it is instrument or device, are imported from other countries. The R&D efforts are also miniscule, and only some centres like Sree Chithira Tirunal Institute of Medical Sciences and Technology, Thirvananthapuram, are working on it.

It is a reality that even there are some products came out from the research efforts in India, the products will soon go out of the hands of Indian companies, unless the Indian companies are aggressive and are ready to fight.There are many ideas being floated in India in the area of medical instruments, and the market size is also huge that it crossed Rs 6000 crore in 2003.

One of the possibilities being discussed to tackle the issue is that there should be a technology mission, with participa-ting national laboratories, educational institutions and private industries for making machines, may be with the help of multinational companies.

For this, we have to recognize our strengths, like many of the smart instruments coming up currently needs software, which we can provide better service than many developed countries. The software development can be handled by the earlier said consortium, may be by the educational institutions like IIT or IISc in the country. We can also accept some of the contributions from the MNCs, but there should be some IPR credit for India in the final global product. We can also ask that the product should be sold in India for a special price, but we should first of all put a target that the country should explore the field within 10 or 15 years.

The CROs should have a better role in setting up standards, and it is heard that the organistions are already setting up clinical research institutes. But in India, the people are basically suspicious of the private ventures. The companies in India can form an independent autonomous affiliate, which will work with the ICMR.

But even in instruments we are confronting some controversy like the one on medicated devices.
That is because we don't have any legislation in the country to specify the licensing authority for instruments and devices. We have encountered the same issue many years ago when we introduced thenew blood bag from Sree Chithira Thirunal Institute. The DCGI or the ICMR have no facility to test these products for license of marketing approval.

An Indian Medical Devices Regulatory Authority (IMDRA) has been notified in March 2006 by the Government of India to handle the issues related to medical devices. The guideline, the Medical Devices Regulatory Act has been under pipeline for many years, under my chairmanship, and has been published as a guideline recently. The committee's recommendation was if somebody develops a device, the classification of devices, which is according to global standards, should be tested in any of the qualified testing centres like IITs or institutions like Sree Chithira Thirunal Institute for Medical Science. With the authorization of the institution, the authority can issue the marketing approval. We found that a centralized facility like US FDA is not practical in a country like India, and a decentralized method will ensure the quality of the products.

Does it mean that we have sufficient regulatory powers in medical devices sector at present?
I cannot say that it is a mandatory legislation. The government has notified the authority and the central health ministry administers it.

If there is an MDRA, medicated devices can also get tested without controversies, as there would be skill in testing biomaterials through these institutions and the elution of drug from the device can also be tested and the certificate can be accepted by anybody from the IMDRA or the state FDAs. The institutions should be technically rich and they should have a good expert committee to look after the ISO standards and the upcoming nano materials in the devices. The committee should constantly track the standards and should update the protocols from time to time. But the phase 4 or the market surveillance study is one of the important parts, which is never done in India. We have also suggested options for this, as the act will otherwise be useless.

It is learnt that you are also heading a project in Ayurveda, named a scientific initiative in Ayurveda. Can you explain about the project?
Now a days, the R&D in Ayurveda virtually means research on herbal drugs, the testing of efficacy, standards and export oriented projects. Our project, in which some of the major scientists in the country takes part, is to explore the core concept of Ayurveda, including the scientific theories in it. There is a scope of basic science, of biology and chemistry, to be studied in the system.

The program have a selected field of five areas, including the doshaprakrithi classificationof humans, dosha-specific classification of medicinal plants, the rasayana procedure of rejuvenation therapy, the Panchakarma system of therapy and the physico-chemical characterization of the Bhasma group of drugs. The aim includes to check the genomic counterparts of doshaprakrithi, through the modern technology of gene characterization, the metabolic, immunologic profile of Panchakarma and to test the physical and chemical structures of selected bhasma candidates. We apply basic science to study questions in Ayurveda concept, process and product.

How do you find the importance of this programme in the current Ayur-vedic system?
After all, in science, we cannot predict about the results. But I can say one thing, if these studies, done by efficient scientists with novel findings, lead to publication of reports in top journals, with 10 such papers you will find that the world will look at Ayurveda differently. The study results can make a change in the mindset of foreigners on Ayurveda systems of medicine.

If there is an MDRA, medicated devices can also get tested without controversies, as there would be skill in testing biomaterials through these institutions and the elution of drug from the device can also be tested and the certificate can be accepted by anybody from the IMDRA or the state FDAs.