With a steep growth in the economy, urbanization, and more affluent lifestyles for some, Western-type diseases have begun to emerge in India. The increasing prevalence of oncologic, cardiovascular, respiratory, and diabetic disorders, central nervous system degenerative diseases, and psychiatric conditions among some parts of the population, alongside the tropical and infectious diseases, provide an opportunity for the pharmaceutical industry to work with clinicians in India to improve health care both within India and globally. The rationale for running clinical trials in India is a much-debated topic in both local and national media within India. The benefits of participating in clinical research are always considered on behalf of the patient who could receive, free of charge, a potentially effective treatment and/or medical attention that may not otherwise be given or available. The investigator benefits by learning new clinical research skills and by being in contact with a global medical research community with the possibility of contributing to a new medical therapy. The benefit for India is in social, public health, and economic development terms, while the potential benefits for the global pharmaceutical industry in terms of medical advances are clear.

It is expected that investment by pharmaceutical companies in clinical trials in India will rise from its current levels of approximately 0 million to .5 – billion by 2010. Many of the trials conducted in India will be run as part of global studies, bringing together patient data across a number of countries. The FDA, EMEA, and other regulatory agencies are already prepared to consider clinical data generated in India for the purpose of regulatory submissions. The foundations for clinical research clearly exist in India, and the regulatory agency, having issued the Indian GCP guidelines in December 2001 and the Schedule Y in January 2005 (requirements and guidelines for conducting a Clinical Trial in India), is determined, under the leadership of the new Drug Controller General of India (DCGI), to enhance the operations of the agency and deliver timely, robust, and quality medical advice and decisions.

In addition, the Indian Council of Medical Research (ICMR) issued the Ethical Guidelines for Biomedical Research on Human Subjects in 2000 and works with the DCGI to improve the processes and procedures for clinical research and development in India. A Clinical Trial Registry is already operational in conformity with the suggestions of  the World Health Organization, and guidelines for research and therapy are being placed on the website. Successful applications to the DCGI for a new trial are those that focus on patient safety and the potential overall benefit and those that have all documentation correctly submitted. The new Drug Controller General of India has continued the two-track system (effective from December 2006) for regulatory approval of clinical trials such that those clinical trials that have already gained approval by the regulatory bodies in the US, Germany, UK, Switzerland, Australia, Japan, South Africa, Europe, or Canada (Category A) are likely to be approved within a timeframe of approximately three months, whereas applications for trials that are not already approved by another recognized regulatory agency (Category B) go through the normal review process and may take up to six months for approval.

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Ethics committees can be approached in parallel to the submission to the DCGI at most sites. In the granting of a license from the Director General of Foreign Trade (DGFT) for the import and/or export of blood samples/investigational products or bi-products, delays are inevitable if partial, or inaccurate, documentation is submitted. Particular attention should also be paid to the labeling of the Investigational Medicinal Product (IMP). Import/export licenses are issued subsequent to approval from DCGI and may take two to three weeks. Understanding the bureaucracy and working through it rather than against it achieves greater success. According to PAREXEL’s bio/pharmaceutical R&D Statistical Source Book 2008/2009, India rose to claim the eighth spot in the world with regard to the number of clinical investigators signing on to conduct FDA-regulated clinical trials in 2007. The number of clinical investigators rose by 29% to 395 in 2007 and represented 1.8% of all investigators around the world signing on to conduct FDA regulated trials (up from 1.3% in 2006). The opportunity exists for universities

(over 220 medical colleges in India), hospitals (more than 16,000 hospitals and more than 700,000 specialty hospital beds), pharmaceutical companies, and government agencies to work together to provide world class, ethical clinical research capabilities in a sustainable economic and politically stable environment.

The challenge now is to continue to train significant numbers of clinicians in semi-urban and rural areas to become investigators, and other study staff to ICH GCP to consistently deliver quality during a high-growth phase and that can be achieved in one of India’s fastest growing Clinical Research Institute, Avigna Learning Academy. There is an obvious advantage that India has the second largest English-speaking population in the world and while informed consent documents and patient-related documents may need to be translated into other languages such as Hindi, Marathi, Telugu, Bengali, Tamil, Urdu, the vast majority of patient notes and source documents are written in English. A cautionary note should, however, be sounded as real cultural differences and preferences can be missed because of the large English-speaking population and particularly so because many legal and business constructs, due to historical legacy, seem to be familiar. Care also needs to be taken however, as not all corporate constructs and processes will translate instinctively or immediately.

Regarding the conduct of a clinical trial, it is clear that quality control is the key to success. While there is a large pool of talented and enthusiastic graduates, there are fewer skilled and experienced clinical research associates (CRAs). Sponsors should focus on effective training in worldwide standard operating procedures (SOPs) both in an academy style teaching course and through on-the-job training, mentoring, and follow-up testing. In such a competitive resource market, retention of key employees is an essential management focal point and requires attention to individualized personal development plans. Regarding SOPs, it is important to appreciate the value of Indian innovation, procedures, and contributions to process improvement, understanding that the British or the American way is not the only way.

However, at the same time, it should be noted that training to work with standardized processes, clear communications, and awareness of escalation routes, are imperative for CRAs and investigational site staff alike, particularly regarding patient inclusion/exclusion, serious adverse events reporting, use of code breaks, etc. Some of the challenges expressed by clinicians in India include issues around informed consent and real choice for the patient, patient compliance (although new tracking technologies may help here), concomitant unknown, unapproved, local medications and treatments, and finally the impact on the effectiveness and safety of the IMP based upon the underlying nutritional status and genetic variations within the Indian patient population. Technology-enabled processes and operations are well accepted and expected in Indian clinical research, and applications can be very advanced and readily applied, often limited in the quality of the deliverables only by the lack of consistent basic utilities such as electricity and water. The same erratic availability of power can lead to issues in the clinical setting, and attention needs to be paid to back-up systems for any electronic diagnostic and reporting procedures and even something as routine as refrigerating the IMP or samples.

Other areas which are enhanced by setting clear boundaries and management focus are logistics and vendor management. A combination of global and local distributors tried, tested and tightly managed, can work well. Likewise, local procurement managers clearly benefit from any global or corporate guidelines. Foreign companies in India need to be aware that a western-style management matrix structure is not necessarily well understood and can seem confusing within a more familiar hierarchical structure of governance in India. Also, there is an expectation, which is generally fulfilled, that large local companies and international companies will manifest corporate social responsibility through social, educational and/or medical non-profit making programs in the community. At the same time, from an industry perspective, we should consider India as high value, not low cost.

Labor costs in India are in fact on the rise, spurred by growing international demand for skilled India-based staff; the high value is derived from the abundance of highly skilled scientific, medical, and technical staff in India. While significant investment in both human resources and the infrastructure is required, there are financial incentives in the form of either local or national tax benefits for certain types of research or businesses. Issues around protection of data and intellectual property rights are high profile and continue to be addressed between global pharmaceutical companies and the Indian government agencies. The expectation is for significant growth of outsourcing of clinical research to India, anticipating an enhanced regulatory environment with more resources, facilitating faster clinical trial set-up and quality deliverables.