India, with second largest population in the world, and with every sixth patient in the world being an Indian, is going through an upheaval economically, socially and scientifically. Increasing globalization has brought about fundamental changes in the way clinical trials are conducted here.
Increased awareness of GCP requirements, stronger desire of international acceptability of research done in India has brought favourable changes in the attitude of clinicians in India towards participation in clinical trials.
Investigators are eager to take part in GCP clinical trials and are also wiling to adhere to constraints of the protocol.
Indian Health System
Matters of health and medicine in India are under the control of Ministry of Health. Currently, health insurance schemes cover only a miniscule portion of the population and most of the patients are treated in government-funded, subsidized large general hospitals. These hospitals are more than often attached to teaching institutions.
Nevertheless these institutions provide the best of facilities, and state-of-art techniques and equipment to needy patients in India.
These institutions often offer hundreds of in patient beds with most of the treatment, laboratory facility and medicines in almost all therapeutic fields at very low cost.
Apart from above a large group of private practitioners, GPs and specialists run their private consulting and nursing homes. For higher social strata there are corporate higher-end hospitals in almost all major metropolitan cities across India.
Moreover, with opening of the economy, more and more foreign insurance companies are setting up their operations in India. The large urban and semi-rural middle class is expected to be covered for medical insurance by these new players along with Indian insurance companies.
Pharmaceutical Industry in India
Over 2,400 registered pharmaceutical manufacturers exist in the country. The multinational pharmaceutical companies enjoy a market share of around 35% while the share of Indian companies is nearly 65%.
The annual pharmaceuticals industry output exceeds US$ 4.4 billion. Of this around 83% are formulations and 17% is bulk drugs.
Bulk drugs: Over 60% of India''s bulk drug production is exported.
Formulations: More than 85% of the formulation production in the country is sold in the domestic market. India is largely self sufficient in case of formulations. Some life saving, new generation under-patent formulations continue to be imported, especially by multinational companies, which then market them in India. Overall, the size of the domestic formulations market is around US$ 35 billion and it is growing at 15-16% per annum.
The pharmaceutical industry shows a healthy picture with annual industrial out put exceeding US$ 4.4 Billion that is growing at 15-16% per annum.
Until recently the government controlled the pharmaceutical industry. Indian Patents Act, Drug Price
Control Order and Foreign Exchange Regulation Act were the pivotal rules controlling pharmaceutical industry in India. The Drugs Controller General of India''s office (DCGI) is the nodal office responsible for approvals of manufacture and marketing of new products in India. It is also responsible for approvals of clinical trails application. However, with opening of the economy and implementation of
WTO agreement from the year 2005 AD, India will grant product patent recognition to all new chemical entities. This will also lead to relaxation of government controls over the industry.
Morbidity, Mortality and Diagnoses
Infectious diseases are still the major cause of morbidity and mortality with over 51% deaths reported due to infectious diseases and parasitoses. With fears of HIV endemic in Indian subcontinent, the problem appears to be aggravating. Tuberculosis, malaria, tetanus, diarrhoeal diseases form the major component of morbidity due to infectious origin.
Cancer and other life style diseases like cardiovascular ailments, hypertension, diabetes mellitus are also an important cause of morbidity in India.
India has an estimated 2 million cases of cancer with 500,000 new cases detected every year. Annual deaths due to cancer total around 300,000. The most common malignancies are cancers of the oral cavity, cervix and breast. Cardiovascular diseases are a major health problem with over 35 million people suffering.
A major tertiary centre recently reported an increment in proportion of coronary heart disease from 4% to 30% in past 30 years.
High blood pressure (defined as 160/90 mm of Hg) ranges from 4.3 to 21.1% in different parts of India. A recent survey in urban Delhi reported a prevalence of 17.4% in persons of age group 35-64 years (using a threshold of 140/90 mm Hg). An estimated 2 million people die annually due to cardiovascular diseases. The incidence of type II diabetes is rising fast in India - so fast that it is estimated that by 2005, there will be 30 to 35 million diabetics in the country meaning that one out of every five diabetics will live in India. Diabetes is expected to come with all complications including macrovascular, microvascular and neuropathic diseases. Accelerated atherosclerosis causes the macrovascular abnormalities, which include cerebrovascular, cardiovascular and peripheral vascular disease. The risk of stroke and myocardial infarct is increased 2 to 3.5 times in diabetic patients. Diabetic retinopathy, nephropathies are also important disease complications that diabetic patients in India would suffer from. Apart form various diseases, trauma, road accidents, and fire are important reasons for morbidity in India.
The recent census revealed that Indians live an average of 65 years with age at death going to as high as 75-85 years in urban India. India is ageing with a large proportion of the population crossing 60 years of age. Many geriatric conditions not prevalent until recently are expected to come to the forefront as India''s life expectancy increases further.
Clinical research in India
The clinical trials legislative requirements are guided by specifications of schedule Y of Drugs and Cosmetics Act in India. Recently the Ministry of Health, along with DCGI and Indian Council for Medical Research (ICMR) has come out with draft guidelines for research in human subjects. These are essentially based on Declaration of Helsinki, WHO guidelines and ICH requirements for GCP.
The Department of Science and Technology has taken initiative for establishing quality requirements by setting up National Board for Accreditation of Testing and Calibration Laboratories for clinical and diagnostic laboratories ( NABL).
Legal prerequisite for the conduct of clinical trails
DCGI acts as nodal office for approval of clinical trial applications. Schedule Y of Drugs and Cosmetics Act is the guiding principle for requirements of submissions. All phases of trials could be approved, though the DCGI office would be keen to know status of test product elsewhere in the world. It is easier to obtain approvals for next phase of clinical study with respect to already completed phase elsewhere in the world.
More than often, DCGI office would seek clarification from the sponsors, which are typically done by personal presentation of scientific data by the sponsor person with technical staff in DCGI office.
The timeframes could be anywhere between 45 days to 90 days for completion of entire process. However, applications of drugs on infectious diseases, especially related to HIV may take longer. This could happen as DCGI office may refer such protocols to ICMR or other government bodies for consultation or advice.
Ethics committee approval
Most teaching hospitals now have well constituted ethics committees that comply with ICH requirements for composition. All the protocols require approvals form institutional ethics committees before they are initiated. Currently there could be some lacunae in compliance to most of the ICH GCP requirements as regard functioning and SOPs for ethics committees, but a conscious effort is being put in to comply with operational requirements of GCP by many institutions. The investigator usually submits the protocols, consent documents in English and their translated versions in local languages, along with any other necessary information including investigator''s brochure. Ethics committee approvals could generally take-up to 60 days and occasionally, the approval coming in as fast as in two weeks. There are no currently functional central ethics committees in India, though some pharmaceutical companies have taken initiative for formation of such committees to facilitate clinical trials with general practitioners.
Insurance coverage
The ethics committees expect that the sponsor provide insurance cover to clinical trial subjects for trial related injuries and "no fault compensation" to investigators and institutions against any legal proceedings. The amount of insurance ploy is not specified. No insurance companies in India offer clinical trial insurance currently and the covers are almost always sought from insurance companies aboard.
The India Advantage
- Patient pollution
- Speed
- English language
- Quality
- Responsiveness
Patients population
Unfortunately though, large patient population in a spectrum of diseases, including those in advanced stage is available in India. Poorer patients benefit form participation in trials as it helps them gain access to latest treatments.
Speed
Although fraught with the usual amount of bureaucratic red tape in government offices, including those of DCGI, import licensing and clearances and local ethics committees, the system allows the setting up of multi-centric trials in not more than six months. With the right local contacts, this time frame can be reduced further.
English Language
The entire education in modern medicine in India is in English making investigators comfortable with usage of English. All the source documents, hospitals papers, laboratory reports, clinical notes are generally written, printed in English, avoiding need of translation of documents that arises in countries like China or Japan for auditors form the West.
The monitors and other project management staff are also generally fluent in both English and the local language enabling building of easy and quick rapport with sties.
Quality
Clinicians are highly motivated and committed to comply with the protocols and are willing and eager to work to international standards. Many investigators have already participated in international trials with a few exposed to international audits for protocol and ICH GCP compliance.
Responsiveness
Communication infrastructure in India is well developed in most urban areas where clinical trials are conducted. All investigators have access to dedicated telephones, facsimiles and email / internet facilities.
Expedited telephone connections can be sought is most cites if not available with the investigators.
- The author is general manager, Siro Clinpharm Pvt Ltd, Mumbai.