Dr. Vimal Sanghavi CEO Oncology services Ltd

a.) What are the business opportunities currently existing in India in concern to oncology trials? What is the total market size of oncology segment across globe and out of total how much it placed to India?
Oncology Clinical Trial business offers plethora of opportunities in the areas of conduction phase I-IV trials, offering consulting services and guidance in the area of regulatory affairs, Data Management, Quality Assurance services, Pharmacovigilance and Medical Writing. Each of this service activity has its own potential in generating substantial business for any clinical research organization.

Oncology Services (OS) offer all the above stated services under one roof. The strategic advantage OS offers is an extensive industry network that allows us to review opportunities, avoid pitfalls and mould ourselves according to the latest clinical and therapeutic trends. The complexity of clinical trials in oncology demands a high degree of experience and expertise from a CRO. We take pride in being a specialized CRO dedicated to oncology, which allows us to extend superior level of attention to study management details that others can only promise.

The global cancer market was worth $56.7 billion in 2007, growing at 16.8 percent over 2006, and is forecast to reach a value of $76.9 bn by 2013 representing a CAGR of 5.1 percent.

According to a recent market research conducted by leading consultancy firm, Clinical trial outsourcing market in India is forecasted to grow at a CAGR of over 30% during 2010-2012 to around US$ 600 million by 2012.

In order to bring more accountability and transparency in the domestic clinical trial industry, Indian government has announced making clinical trials registration, along with their auditing, compulsory in India. The main attraction for clinical trials to be held in India is the easy access to large pool of patients and faster recruitment at low cost in this segment. The country is now getting noticed for its quality of the trial site and the data generated from here.

Oncology clinical trials are complex and require a different approach than trials in many other therapeutic areas. Patient recruitment is among the most challenging obstacles-especially in the United States, where oncology trials have notoriously low participation rates among adult patients. While more than 1.2 million Americans will be newly diagnosed with cancer this year, participation in oncology trials remains very low. In fact, according to the American Society of Clinical Oncology (ASCO), only 3 percent of U.S. adults with cancer participate in clinical trials.1 Lack of participation can cause an oncology trial to recruit slowly, often lengthening the trial's timeline by months or even years.

India offers a strategic advantage to counter this major challenge. According to the latest studies based on the Indian Council of Medical Research (ICMR), cancer is the second commonest non-communicable disease in India after ischemic heart disease; almost 8.7 million disease-adjusted life years are lost due to cancers in India. An estimated 70% of the 800,000 cancers diagnosed annually in India are at an advanced stage when detected. With the improvements in technology and reporting, an ever-increasing number of cancers are being diagnosed in major metropolitan areas in India. Several cancers, e.g., gall bladder cancer, breast cancers, head and neck cancers, lung cancers, and upper aero-digestive cancers are common in special pockets in India.

• Treatment trials test new treatments (like a new cancer drug, new approaches to surgery or radiation therapy, new combinations of treatments, or new methods such as gene therapy).
• Prevention trials test new approaches, such as medicines, vitamins, minerals, or other supplements that doctors believe may lower the risk of a certain type of cancer. These trials look for the best way to prevent cancer in people who have never had cancer or to prevent cancer from coming back or a new cancer occurring in people who have already had cancer.
• Screening trials test the best way to find cancer, especially in its early stages.
• Quality of Life trials (also called Supportive Care trials) explore ways to improve comfort and quality of life for cancer patients.

The ongoing evolution of cancer therapeutics and the associated increase in survival times have prompted a re-evaluation of traditional methodology in the design and conduct of oncology clinical trials. These changes have led to increasing complexity in clinical trials as well as new operational and design challenges for researchers and drug developers.

Until recently, there were few clinical trials conducted in India by Western pharmaceutical and biotech companies, primarily because of regulatory hurdles. In January 2005, recognizing the significant advantages that India offers to multinational companies and the potential and benefits of conducting clinical trials in India, the Government of India upgraded Schedule Y of the Drugs and Cosmetics Act of India, the equivalent of the sections of the Code of Federal regulations applicable to the FDA, to harmonize it with U.S. and International Conference on Harmonization (ICH) standards. These changes removed a number of regulatory barriers to performing clinical trials in India. The changes formalized the definition and conduct of clinical trials; specified the responsibilities of the sponsor, the investigators, and the Ethics Committees; developed guidelines and procedures for importing drugs for clinical trials; instituted required compliance with GCP; specified the requirements for informed consent; and defined the structure, content and formats of clinical study reports. In addition, the Indian Government provided increased protection for intellectual property (IP).

Phase 1 trials refer to initial exploration in humans of promising cancer drugs. Drug development is a complex process but is clearly required in oncology. Several Indian companies are engaged in drug discovery and development of novel cancer therapeutics but the numbers are small compared to the situation abroad. India has a large cadre of trained investigators that have the expertise for conducting early phase clinical trials of compounds developed in India and elsewhere. However, there are still regulatory restrictions on the conduct of initial (first-in-man) trials of new therapeutics in India although later phase and repeat phase 1 trials are allowed. The Drug Controller General of India cites several reasons for this; for example, there are ethical considerations (the need to ensure that Indian patients do not become 'guinea pigs' for foreign drug companies), there is a perceived lack of expertise in India for conducting such trials, and cancer is not a major focus area in India at present, etc.

The ethical considerations in phase I trials have been closely scrutinized in Western countries. For example, the overall rate of severe toxicity to patients is very low in phase I trials. There were two large retrospective reviews published recently that have examined the toxicity and efficacy of drugs undergoing phase 1 trials. One article[s1] [s1], examined 213 studies (involving 6,474 cancer patients) published in peer-reviewed journals and found that the overall toxic death rate was 0.54%, while the overall objective response rate was 3.8%. Toxic death rates decreased over the study period, from 1.1% over the first 4 years of the study (1991-1994) to 0.06% over the last 4-year period (1999-2002); this decrease was statistically significant ( P = 0.01). It is not clear what caused this reduction in toxic death rates, but it could be related to better monitoring of patients, better patient selection, and the advent of targeted therapy. Response rates also decreased but by proportionally much less. The article excluded patients with haematological malignancies who were on phase I trials and were likely to have higher response rates. In the other study, [7] the authors analyzed 460 trials involving 11,935 participants, all of whom were assessed for toxicity and 10,402 of whom were assessed for a response to therapy. The overall response rate (i.e., both complete and partial responses) was 10.6%, while the overall rate of death due to toxic events was 0.49%.

If one compares these rates of toxicity and efficacy with that of a standard approved agent, e.g., docetaxel for treatment of second-line lung cancer, the results can be surprising: Docetaxel is associated with a 2.8% risk of treatment-related deaths. Thus, overall, the drugs used in phase 1 trials compare favourably with standard drugs as far as risk/benefit for patients with advanced cancers is concerned. Therefore, no special ethical consideration is required when conducting such trials beyond ensuring that patients clearly understand the risk-benefit equation before giving consent for participation in the trial.

Expertise is now developing in India to conduct high-quality studies. Phase 1 trials involve small numbers of select investigators around the world working to develop novel, promising agents. These trials often require a clear understanding of the scientific principles surrounding drug development and a good knowledge of oncology and the biology of disease. Participation in early phase studies like these will allow Indian investigators to publish original work on promising agents and potentially steer the development of therapies for uniquely Indian cancers.

There are potential benefits to Indian patients in these trials. Through phase 1 studies there is an opportunity for patients to get access to novel medications free of cost. These medications are likely to have very little toxicity and a reasonable chance of efficacy. In addition, with full informed consent being obtained, there is no exploitation of patients.

The total worldwide R&D spending for pharmaceutical and biotech companies (Pharma) in 2007 was $117 Billion, of which 70% represented development costs. This spending is expected to grow at 11% annually and will be $218 billion in 2013. The CRO market for Phase 1 through 4 trials represented about $7.8 Billion in 2007 and is projected to grow to $17.2 Billion in 2013.

India provides a number of significant advantages for the outsourcing of clinical trials because it offers a large patient population that facilitates faster recruitment, low trial cost per patient, a highly qualified professional medical community, plus global quality hospitals and clinical research facilities. Furthermore, with a highly developed IT and data collection capability and no language barrier, India has become an important destination for clinical trials, and exponential growth is expected in the number of trials conducted there in the near future.

• High patient numbers available
• Accessibility to specialty hospitals
• Large number of medical specialists
• Patients generally "therapy naive"
• Low cost
• No language barriers
• IT-based advantages

The cost per patient for trials in India is approximately 40 to 60% of the cost in Western nations. More importantly, patient recruitment can be greatly accelerated, and this provides a major advantage in terms of shortening the time to market for a new drug. Based on these advantages and those listed above, the number of clinical trials in India is expected to grow exponentially over the next five to ten years. It has been estimated that in 2005 only 1% of global clinical trials were conducted in India. This percentage is projected to grow to 15% of global trials by 2011. McKinsey projects that within five years, 1,500 to 2,000 GCP studies will be conducted in India per year, requiring 10,000 to 15,000 GCP-trained investigators, and supported by 50,000 clinical research professionals.

A plentiful of varied population, a greatly distributed variety of diseases, and predominant poverty: this how usually India was presented to the outside word until recent times.

Times have changed. India is a growing economy with disease patterns quite similar to the western world, with cancer, diabetes and other health problems is leading the country to an altogether different destination: the global centre of outsourcing of clinical trials.

Almost all the top names in the pharmaceutical world have concentrated on India, starting clinical trail centres and backend offices in major cities. The world is simply attracted by the infrastructure and services that India offers for pharmaceutical and biotech companies, their drug and device development plans, the most important component of which are late phase clinical trials. The pace for drug trials in the country is so fast that the Clinical Data Interchange Standards Consortium (CDISC), USA, a non-profit organization committed to the development of clinical research organizations' standards the world over, is looking at setting up its chapter in India.

CDISC is an open, multidisciplinary, organization committed to the development of industry standards to support the electronic acquisition, exchange, submission and archiving of clinical trials data and metadata for medical and biopharmaceutical product development.

The mission of CDISC is to lead the development of global, vendor-neutral, platform independent standards to improve data quality and accelerate product development in the industry.

Oncology Services is often involved in the concept phase of a clinical trial and sometimes participate in the development of client's master plan, the Constitution of the Steering Committee or Advisory Board, the outline of the study protocols and the selection of investigators. Our access to key opinion leaders in both clinical and academic practice allows us to provide conceptual input at every stage of the clinical development process. Our ready access to appropriate patients through a well developed network of clinical investigators enables us to ensure swift completion of study enrolment – a key issue in the successful study management. We have expertise in offering services, which include:

• Phase I to IV
• Data Management
• Regulatory Affairs
• Statistics
• Consulting
• Quality Assurance
• Medical Writing
• Pharmacovigilance

The pharmaceutical majors that are into breakthrough clinical trials in India are: (Update as on July 2009)

Eli Lilly: The global pharmaceutical giant has 17 large and small clinical research projects running in 40 hospitals across India. The company's clinical trials are to test if Xigris, which is indicated for reduction of mortality in adult patients, can be used for sepsis. Eli Lilly has already held clinical trials involving more than 600 patients for Human Insulin and Insulin Lispro. It is also these days conducting trials on oncology, and developing a new molecule for lung cancer.

Pfizer: The pharma giant has picked up six cities in the north-eastern states of India to conduct clinical trials on 300 patients on a new malaria 'cocktail' drug that combines chloroquine (to which Indian malarial strains have developed resistance) and azithromycin, an antibiotic. Pfizer is also carrying out clinical trials for drugs to treat osteoporosis, breast cancer and schizophrenia. Pfizer's cumulative investment on clinical research in India is believed to be $13 million.

Roche: The Swiss pharma major has set up clinical trial sites in India as part of its global trials for treatment of a particular variant of lung cancer. One of the reasons for considering India is that it has a vast patient population infected by this type of lung cancer, which is primarily triggered by use of tobacco products.

India is also being considered a prospective site for Roche's future clinical trials involving new drugs and therapies for treatment of different variants of blood cancer and colorectal diseases.

SIRO Clinpharm: SIRO is currently conducting clinical trial projects in over 30 hospitals across the country for several clients from Europe, Japan, the United States and also India.

The trials in India are mostly in different areas like oncology, endocrinology, traumatology, sports medicine, pulmonary diseases, paediatric diseases and infectious diseases.

Clinigene International: The Bangalore-based Clinigene says India's huge population allows new-drug studies to be completed much faster. Last year, when a biotechnology company from the US needed 400 diabetics for a study, Clinigene began by heading to a nearby hospital specializing in diabetes, where a dozen new patients arrive every day and more than 40,000 are in its records.

Wellquest: Wellquest, the clinical trials division of the Nicholas Piramal Group, is conducting 40 drug product tests in five cities across the country. The company has 75 beds for patients on whom clinical trials are being carried out.