It?s a classic case of market opportunity aplenty. The global clinical trials business is worth an estimated $50 billion at present and the thinking among the Indian regulators about allowing first in-man or phase I clinical trials in India has the potential to transform India into an outsourcing superpower in clinical research. The decision would have a positive rub-off on the sentiment of the clinical trials industry and the multinational drug companies, thus increasing business flow to India.
Recent allegations of exploitation of uneducated and illiterate subjects in India? not to mention the deaths of infants during clinical trials at the All India Institute of Medical Sciences (AIIMS)?had created a lot of concern on the maturity of the Indian society to accept clinical research as a means of advancing science and medicine for the greater benefit of the society. The fact that further investigations revealed that the trials were conducted in line with global ethical standards has managed to restore confidence to a large extent. The positive outlook of the drug controller general of India (DCGI) towards allowing phase I trials is definitely a welcome news to the beleaguered clinical research industry in India.
For one, India is the first Asian country to launch a clinical trials registry. Set up by the Indian Council of Medical Research (ICMR), it is an online register for clinical trials. The primary purpose is to make information regarding clinical trials being conducted in India freely available to anyone who desires the information. However, the registration is voluntary. Interestingly, none of the other Asian countries like South Korea, Japan, China, Malaysia, Thailand or Philippines boast of hosting such a facility.
Secondly, there is growing acceptance by the US Food and Drug Administration (USFDA) of clinical trials being undertaken in the country, thereby sending out a strong message on the growing importance of India emerging as the preferred location for clinical trials, says Arvind Lal, chairman of Dr Lal Pathlabs. Strengthened intellectual property legislation and the revision of the Schedule Y Drugs and Cosmetics Rules in 2005 have also played a crucial role, informs Lal, who is also vice-chairman of the Association of Contract Research Organisations (ACRO) India.
Now comes the move by the drug regulator on allowing global drug majors to undertake phase I trials in the country. There is broad consensus that this would not only increase contract research outsourcing business significantly, but catapult India into the big league. ?With this approval, the Indian clinical trials industry would follow global compliances, thus paving the way for new molecules,? says Krishna M Ella, chairman of Bharat Biotech.
As on date, global drug majors are only allowed to conduct phase II and III trials in India. Prior to 2005, it was not possible for them to carry out such trials in India unless those phases had already been conducted elsewhere. Radical changes to the legislation in January 2005 brought in a broad framework for trial approvals and set out standards and responsibilities for trial sponsors, investigators and ethics committees.
On the other hand, Indian companies are allowed to conduct all stages of trials on drugs including phase I and phase 0?the stage just before phase I where the drug is first tested on a few human beings. The real opportunity, however, lay in allowing global drug majors to undertake trials across the spectrum?Phase I, II, III and IV. According to Tufts Centre for Study of Drug Development, over 40% of all US-regulated clinical trials are now conducted overseas. Within the next two to three years, up to 65% of their FDA-regulated clinical trials will be conducted abroad. Therefore, the thinking among the drug regulators about allowing phase I clinical trials in India reflect an increasing maturity on their part about the need for drug research in India.
Former DCGI M Venkateswarlu says, ?The move is in the right direction, which is expected to increase the number of new drugs coming into the market. With the existing drugs gaining immunity among the prevalent diseases, the approval to conduct phase 0 and phase1 trials will take care of those diseases which are affecting the people at large.?
However, he cautions that there are still some elementary and regulatory issues which have to be implemented before the commencement of the trials. Besides, the legal structure has to be given more teeth in order to protect the clinical trial volunteers from becoming guinea pigs in the hands of MNCs.
Typically, phase 1 studies aim to determine the metabolic and pharmacologic action of the treatment. Researchers look at the safety and side effects of the treatment by testing it in low doses in a small number of healthy volunteers (about 20-80). Before a pharmaceutical company can initiate testing in humans, it must conduct extensive pre-clinical or laboratory research. This research typically involves years of experiments in animal and human cells. The compounds are also extensively tested in animals. If this stage of testing is successful, a pharmaceutical company provides this data to the regulatory authorities, requesting approval to begin testing the drug in humans. This is called an investigational new drug application (IND).
?As the Indian industry changes from being generic-led to discovery-led, phase I trials will become increasingly important and their need will grow,? says Anand Bidarkar, vice-president (business development, SIRO Clinpharm. As per Trial Trove report, a database for all clinical trials listed by therapeutic areas, locations, etc, there are currently over 3,189 phase I studies globally that are recruiting patients.
Of these, the great majority of over 2,500 are being conducted in the US. Even a small country like Singapore is currently running around 28 phase I studies, compared to around 15 studies in India.
?Therefore, the decision of the regulatory authorities in allowing phase I trials in India will definitely result in the shifting of a sizeable part of the phase I business to India in the next few years. The decision would attract a number of small scale biotech companies to conduct their phase I studies in India primarily driven by the cost advantage, faster recruitment and availability of drug naive subjects,? informs Bidarkar.
However, the financial implications of this would not be very significant initially when compared to phase II and III trials. This is because of the differences in the nature of Phase I business from the other phase trials.
Phase I trials are not driven by patient numbers, the required number is very low, around 20-80. What matters most are the requisite expertise and the sophistication of the facilities for conducting these trials. India has only a few centres that are capable of providing the requisite infrastructure and expertise currently.
?The business volume would definitely pick up once the decision is taken; we can expect many hospitals and CROs to set up dedicated phase I units, resulting in expansion in volume of studies that can be handled,? says Bidarkar.
It is important, however to consider what can be done to assure the highest ethical standards in conduct of phase I trials in India before approvals are given. This is more important as phase I trials involve healthy volunteers and patients are justly compensated for their participation and the inconvenience they have to undergo. In such a scenario, there are more chances of allegations of exploitation.
There are several measures that the industry and the regulatory authorities can adopt to ensure ethical conduct of phase I studies. CROs and hospitals conducting phase I trials should have minimum set up standards in terms of infrastructure and expertise of staff and standard operating procedures.
Phase I study listing on the Indian clinical trial registry should be made mandatory. The role of the ethics committees needs to be expanded to verify and assure a safe environment and personal safety of the volunteers participating in the phase I studies.
An industry or regulator-backed accreditation body can be set up to formulate guidelines, inspect processes and infrastructure at phase I units to prevent the incidents of unscrupulous elements tarnishing the reputation and business prospects of the industry as a whole. ?There is a need for a strong centralised regulatory regime, which can lay guidelines for high quality development of ethical capacity with extra vigilance, but an informed understanding of acceptable risk,? says Sunita Vaidyanathan, senior industry analyst?healthcare practice, Frost & Sullivan (South Asia and Middle East). She adds: ?Such a system while conforming to international standards needs to be customised to the Indian scenario. It needs to include indigenous medicine, devices, drugs and therapies, while incorporating the advent of biotechnology in general and genomics and proteomics in particular.?
Global drug firms are increasingly outsourcing their drug discovery research to low-cost destinations such as India, as these firms reel under the onslaught of generic competition and rising drug development costs. By setting its own house in order, India is making a determined bid to attract the mega-bucks riding the global clinical trials wave.