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Lining up for Clinical Trials

Pegged at US $300 million and growing at approximately 30 per cent per annum, the clinical trials market in India is slowly becoming a focus area for many private hospitals in India, Sonal Shukla discovers

In January this year, Fortis Healthcare, the second biggest corporate healthcare chain in India, announced its plans to grab a larger slice of the expanding clinical trials market. Utilising the size and strength of its network hospitals, the group intends to conduct all phases of clinical trials.

Similarly, more than 20 clinical trials are going on in various fields in Manipal Hospital. The Apollo Hospitals Group, the largest healthcare chain in India, is involved in over 180 clinical trials across its various sites spanning the areas of cancer, cardiac, renal and neurological diseases and many others. There are plans to actively enhance these activities in the future.

According to industry experts, not just corporate healthcare, but also smaller hospitals in tier II and III cities are getting attracted to the opportunities in the clinical trials space. While not enough, there has been a significant increase in the GCP-trained consultants and more and more charitable institutions have also shown keen interest in conducting studies within the hospital setup.

These are all tell-tale signs that clinical trials are seriously on the agenda for private healthcare in India. Market value for clinical trials outsourced in India is estimated at around US $300 million. Having increased by 65 per cent in 2006, it is expected to touch US $1.5-2 billion by 2010. With such encouraging statistics, clinical trials are slowly but steadily becoming an area of focus for many private hospitals.

A few private hospitals have formed their own site management organisations which take up a large number of clinical trials. Fortis Healthcare has a separate company called Fortis Clinical Research which focuses on clinical research. Max Hospitals has a sister company called Max Neeman which focuses on clinical trials and research. Apollo Hospitals has a separate Apollo Hospitals Education and Research Foundation which has been pioneering clinical research in India for the past 10 years. "Clinical trials provide an incremental revenue stream which is complementary to the revenue stream from hospital operations. More importantly, it helps in attracting good medical professionals who are increasingly interested in research and new learning, in addition to their clinical responsibilities," shares Pradip Kanakia, Head of Healthcare Practice, PwC India.

On the Growth Trajectory

There are several clinical research projects being done in Manipal Hospital in various fields of genetics, microbiology, stem cells and teledermatology

SRMC is planning to evolve the Clinical Research Division of SRU as an independent Clinical Research Outsourcing centre of the organisation

The Apollo Hospitals Group is involved in over 180 clinical trials across its various sites

HGC Global is conducting studies which involve new chemotherapy drugs, new formulations of old drugs, biological agents and targeted therapy

Jaslok Hospital & Research center has ongoing 62 clinical trials at various faculties of medicine, which include oncology, neurology, paedia trics, stem cell research etc

During the last decade, the number of private healthcare players in India has gone up exponentially. India has emerged as a destination for global pharmaceuticals to conduct trials. With increasing demand, there is a crunch of desired patient pool and investigators who are willing to get involved in clinical trials.

Product patent protection: "The product patent protection has encouraged multinational companies to import technology into India to develop new products. These developments will open up increased opportunities for the clinical trials of biotech and medicinal products and thus in the present situation it seems to be an exciting opportunity for private hospitals to involved in clinical trials," shares Dr Pravin Potdar, Head, Department of Molecular Medicine & Biology, and Secretary, Scientific Advisory Committee, Jaslok Hospital & Research Centre, Mumbai.

Ethnic Pool: There is tough competition among pharmaceutical companies to get the drugs out as quickly as possible from the time they are 'on the bench'. This requires that the drug must be tested in various ethnic groups and markets simultaneously for the company to make profits. India offers a diverse genetic pool, which is amenable to clinical trials. "The patient population is large, diverse and therapy-naïve and is of different ethnic groups having six out of seven genetic varieties in the world. There is a large patient pool in both acute and chronic disease areas of infectious and lifestyle disorders and patients with HIV and cancers are available in large numbers in India," shares Prof SP Thyagarajan (Former Vice Chancellor, University of Madras) Pro Chancellor (Research), Sri Ramachandra University, Chennai.

Cost Advantage: In addition, India has a cost advantage for conducting clinical trials. The cost of conducting clinical trials in India vis à vis the US in a Phase I trial in India is only 50 per cent of the US $20 million in the US. Similarly, a Phase II trial would cost 60 per cent less than the US $50 million in the US and the Phase III trial again 60 per cent less expensive in India to the US $100 million cost in the US.

Preference for Private: Private hospitals are preferred over public hospitals for the trials. The follow up of patients, which is an important criterion for conduction of a trial is far better in private hospitals compared to the Government ones, feel experts. "Public hospitals in India are woefully inadequate for good patient care. Hence they cannot be relied upon to provide good care in case of adverse events during drug trials. This brings private players into focus — having good infrastructure, qualified and experienced doctors and many of them, a large pool of patients," opines Dr Nagasubramaniam, Consultant Urologist, Manipal Hospital. The Government of India has also implemented certain incentive— initiatives such as no import duty on clinical trial supplies; exemption from registration requirements for supplies of clinical trials when the clinical trials are as a whole registered in the National Clinical Trial registry; export of clinical trial related biological specimens being allowed, based on approved protocol and exemption from Service Tax on new drug testing. According to experts, the private healthcare sector is fully geared to utilise all these incentives.

Quality Manpower: Availability of high quality clinical and research manpower which is proficient in English is also a major driver for overseas players to outsource clinical trials to private hospitals in India.

Corporate Focus

Clinical research covers a wider spectrum of research activities involving patient groups for elucidation of disease patterns, their natural histories, patho-physiological differences in clinical manifestations and presentation, the management strategies for diverse diseases including the major area of newer drug development, their validation by Phase I, II, III and IV clinical trials. In view of the expertise-intensive requirements, the majority of the private hospitals refrain from taking up the entire spectrum of clinical research and restrict themselves to Phase III clinical trials only. "Today, private hospitals are interested only in conducting Phase III clinical trials, which are the final stage of drug efficacy testing in diverse patient groups. These trials, by and large, are risk free and aimed toconfirm the observations made in other part of the world and the observations made in the Phase II clinical trials," says Prof Thyagarajan.

Various Projects

"Private hospitals are interested in conducting Phase III clinical trials, which is the final stage of drug efficacy testing in diverse patient groups" - Prof SP Thyagarajan Pro Chancellor (Research) Sri Ramachandra University, Chennai

"Clinical trials provide an incremental revenue stream which is complementary to the revenue stream from hospital operations" - Pradip Kanakia Head of Healthcare Practice PwC India

Hospitals are increasingly getting interested in clinical research besides just conducting clinical trials. There are several clinical research projects being done in Manipal Hospital in various fields of genetics, microbiology, stem cells and teledermatology. Some of the projects are collaborative research projects with premier institutions like ICMR, IISc, etc. In addition to the 31 ongoing clinical trials sponsored by pharmaceutical companies, there are 51 clinical research projects funded by DST, ICMR, AYUSH, DBT etc., conducted by clinical and non-clinical investigators of the Sri Ramachandra University and its hospital. SRMC is planning to evolve the Clinical Research Division of SRU as an independent Clinical Research Outsourcing (CRO) centre of the organisation which can not only handle the projects sponsored by international sponsors and other CROs but also coordinate multicentric clinical trials and clinical research projects as a CRO directly.

The hospitals can look forward to offering their diagnostic lab service since this could generate revenues for them faster than other offerings. "A BA/BE facility with the hospital too is a lucrative option as they can quickly convert a couple of wards into BA/BE set up," believes Joseph Manoj Victor, Healthcare Industry Analyst, Frost & Sullivan. Some hospitals that are associated with teaching colleges have started courses in clinical research in order to train associates and also physicians in clinical trials management. A few hospitals have allowed clinical genomics companies to access their pathological samples to do retrospective studies. In addition to this for high-end oncology studies, hospitals are exploring possibilities of setting up tissue banks for future molecular studies of these samples which can be correlated with their clinical outcomes.

Areas of Interest

Hospitals are getting involved in diverse therapeutic areas of clinical trials according to their preference. Says Dr Rajiv Chandel, Business Development & Analyst, PD Hinduja Hospital, Mumbai, "Huge patient potential and long standing diseases have led to major trials being conducted in major therapeutic indications." Oncology, endocrinology - mainly diabetes, cardiology - hypertension, ischaemic heart disease, nephrology, infections rheumatology, chest medicine etc. are some of the areas attracting private hospitals.

Areas of clinical trials depend upon the type of hospital and its focus on different specialities. Teaching hospitals are more inclined and equipped for clinical trials. According to Dr Sita Naik, Advisor, Apollo Hospitals Education and Research Foundation, phase II and III trials of new drugs and formulations, trials of various prosthesis, assessment of interventions (lifestyle intervention in diabetes), evaluation of diagnostic and prognostic are the kind of projects which bring revenue and prestige to the hospital and their outcome has a direct bearing on the patients. Mumbai-based Jaslok Hospital & Research Centre has 62 ongoing clinical trials at various faculties of medicine, which include oncology, neurology, paediatrics, stem cell research, nuclear medicine, gastroenterology, infectious diseases etc. Over 200 trials/studies have been conducted so far in the last 11 years in Manipal Hospital and ongoing clinical trials are in the field of diabetes, epilepsy, dementia, multiple sclerosis, oncology and incontinence. A total of 18 trials are ongoing in Mumbai's PD Hinduja Hospital.

The clinical trials department in Chennai-based Madras Diabetes Research Foundation (MDRF) in concert with Dr Mohans' MV Diabetes Specialities Center (Dr Mohans' MVDSC) has been involved in national and international drug trials involving good clinical practices (GCP) in diabetes. There are several ongoing trials on antidiabetic therapy and lipid lowering drugs. MDRF has also successfully carried out various phase II and phase III trials on newer molecules anto-diabetic agents and several more are on going, utilising GCP.

Cancer and Trials

"The pie is growing larger and so better organised hospitals and groups who focus on this activity will be able to grab a larger share" - Dr Sita Naik Advisor Apollo Hospitals Education and Research Foundation

"Independent investigator initiated trials are rare as financial support is a problem" - Dr Radheshyam Nayak Head-Clinical Trials Triesta HCG

There is a distinct trend of private hospitals specially the cancer hospitals conducting clinical trials. In oncology, private hospitals are doing mostly phase II, III and IV studies. The early clinical study (Phase I) is rarely done as severe Governmental restrictions are in place. Several drug registration trials are happening in India now. Most of the studies are international and multi-centric where an Indian hospital is but a part of the overall trial. Says Dr Radheshyam Nayak, Head, Clinical Trials, Triesta, HCG, "Most of our studies are supported by the pharma companies. Independent investigator initiated trials are rare as financial support is a problem. The studies involve new chemotherapy drugs, new formulations of old drugs, biological agents and targeted therapy. A few studies involving gene therapy are also done. Several trials have supportive treatments and palliation of cancer as their aim. Trials involving surgery or radiotherapy are again rare for want of finances."

As Dr Nayak points out, generally cancer patients in a private setup are of a higher socioeconomic status along with better education and they can participate in the trials after giving a true informed consent. They are more likely to stay in the trial even if some adverse events happen in the course of the trial. Also, because of their financial status they can personally cover the cost for the items which the trial may not cover. These advantages have made the pharma companies increasingly look at private cancer hospitals to conduct theirtrials.

Several clinical research projects including numerous randomised clinical trials are currently in progress in Mumbai's Tata Memorial Hospital (TMC). The hospital is currently conducting two of the largest randomised trials in the field of early detection and prevention of cancer ever conducted in any field of cancer. The National Cancer Institute, USA is funding one of these trials through a competitive RO-1 grant and the other by Melinda and Bill Gates Foundation through the International Agency for Research in Cancer, Lyon. In addition, TMC is involved in conducting numerous trials on behalf of national multi-national industrial concerns, health agencies (DST, DBT, ICMR). It has a centralised clinical research secretariat with facilities for data collection, data management and analysis.

From Neglect to Ardour

Clinical trials were not a priority for private hospitals till 2005, since the demand for services was low. There were several reasons for that. There was a lot of confusion among hospitals regarding the safety of the participants. Lack of awareness about trials among physicians and fear about being guinea pigs among the patients were the two most important hurdles for progress. Lack of enough trained personnel and infrastructure also added to this. Many physicians, especially in tier I cities, are busy with their practice and either don't have time or inclination to participate in clinical trials. According to Dr Chandel, lack of motivation and training at UG and PG level, importance of research not being emphasised enough, unawareness for clinical research and patient safety in clinical trials were and still are few of the other concerns. However, after the amendment to the Patents Act, there has been an increase in the volume of clinical trials in India. "The quantum of clinical research as a whole in India was much smaller and many players were sharing this. Now, the pie is growing larger and so better organised hospitals and groups who focus on this activity will be able to grab a larger share," shares Dr Nayak.

Challenging Grounds

With the increasing involvement of smaller hospitals as well in this space, the emerging challenge is of managing ethical issues related to clinical trials. "The biggest challenge to conduct any clinical trial is to conduct it in an ethical manner," agrees Dr Nagasubramaniam. This automatically means that private hospitals have to develop infrastructure and mechanisms like having certain committees to look into various aspects of clinical trials (like Scientific Committee, Ethics Committee, Stem Cell Research Committee). Since the safety of the patients is paramount in any clinical trial, mechanisms have to be developed wherein patients are taken care of in the event of any adverse reactions without waiting for bills to be paid, etc. Hospitals are today also grappling with the issues of low GCP awareness, telecommunication and connectivity problems, stringent process of regulatory approvals (EC/ DCGI) and loss to follow up. "Regulatory issues, including rigorous requirements of the US and other western countries which govern clinical trials can be a major challenge to comply with, until Indian players achieve scale and become mature in this area," shares Kanakia. Maintaining data integrity, ensuring that intellectual property rights are managed and retention of subjects enrolled for clinical trials is also a challenge.

Requirements

Continuation of getting good clinical trials depends on the quality of conducting the clinical trial in a hospital, fulfilling the target number of patients promised initially to the sponsors and the quality time an investigator can give to the conduct of the trial. Several other countries including China are also in the race for trials and India can expect stiff competition in the days to come.

Good infrastructure, experienced staff, large patient pool, along with a commitment to conduct clinical trials in an ethical manner is considered a prerequisite. The other trial related infrastructure, ethics committees are to be put in place prior to starting any project. According to Dr Nayak, hospitals should organise an ethical committee to oversee the trials and have enough qualified clinical trial coordinators. The hospital also has to make commitment to store the data and original documents for about 15 years after the end of the clinical trial. As more and more auditing and inspections are being carried out by the internal and external drug authorities, hospitals should be prepared to face these events.

Future Prospects

Indian players are learning fast and gaining credibility with increasing numbers of clinical trials being done in India. At present, even if the hospitals are depending on trials outsourced by multinationals, many products are emerging from research by Indian companies which need to be tried in a scientific and safe manner. The Patents Act and more rigorous enforcement thereof, has ensured that the requirement of intellectual property rights is being increasingly respected and complied with.
The requirement in respect of data integrity and sophisticated infrastructure for conducting the trials is also being well acknowledged by recognised players and increasing investments are being made in this area. "The various stakeholders in the healthcare industry (Government, private players, investors and regulators) in India need to push the initiatives to increase the supply of good medical talent through infrastructure and capacity building. Similarly, the right focus on trials and training will ensure that the capacity of the country to undertake more clinical trials work will be significantly enhanced," concludes Kanakia.

sonal.shukla@expressindia.com