Note that this Topic Guide was produced for Debating Matters India, and looks at the issues from a specifically Indian perspective.

India has emerged as an important base for global clinical trials in recent times. Although the country had a strong indigenous pharmaceutical industry for many years, the clinical research landscape here has undergone a sea change in the last decade. Until 1995, clinical trials were mainly done in the USA, Europe, and Japan, but in the era of globalisation drug companies have been steadily outsourcing their research enterprises to the developing world. India’s signing of the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement in January 2005 gave new impetus to its medical research market. A recent study indicates that by 2010, India will host nearly a fifth of all global clinical trials, with a huge potential for financial and scientific gain. In India, clinical research is big business. Offering a large pool of patients, highly skilled medical investigators, lower drug development costs and timely completion of clinical trials, it is no wonder that India has become an attractive hub for clinical trials. All the major pharmaceutical companies now have a presence in India. With improving infrastructure and technology, industry-friendly regulations and a trained workforce, the growth is likely to increase in future.

The ‘profit over people’ controversy.
This spurt of activity has been trailed by a growing concern about the ethics of clinical trials conducted in India. Increasing global concern about unscrupulous trials has attracted adverse coverage in the media and medical journals. Pressure to increase profits, cut drug development costs and shorten regulatory approval, along with the increasing reluctance of people in developed countries to participate in clinical trials, encourages the pharmaceutical industry to outsource much of its activity to more cost-effective and less hostile environments among the world’s impoverished ill. There is no compulsory registration system for clinical trials in these countries and many do not follow European directives in their operations – though from 15 June 2009 it has become mandatory to register all clinical trials taking place in India. The industry has been calling on its host countries to adopt regulatory procedures.  However, regulatory reform and ethical practices have not kept pace with the fast and spectacular increase in research projects. Protestors argue that they amount to no more than ideological lip-service, conveniently concealing the industry’s profiteering.

Do clinical trials in India exploit people?
Studies have proved that malpractices are rampant in clinical trials in India. Recent cases include unethical testing of contraceptives, fertility drugs, cardiac treatments and cancer medicines. Analysts say as many as two million Indians may be enrolled in research trials by 2010. Just three years ago, that number was about 2,000. A major problem is that a large proportion of participants are illiterate and lured into trials by offers of free health care and financial inducements. They are often unaware of the benefits and risks of taking part in a trial, and may not even distinguish between treatment and research. The concept of informed consent is not always understood. The lack of a national ethics body with regulatory control has further hampered the establishment of a legal framework with policing powers. Other ethical debates question whether new drugs tested in India will actually benefit patients locally, and then be made available to them at reasonable prices. A case in point is the recent clinical trial of trastuzumab (Herceptin) – an expensive treatment for early breast cancer. With 25% of India’s population living below the poverty line, it is unlikely that this drug will be affordable to them. Is the outsourcing of clinical trials by the western world to India the new face of colonialism?

Do these trials offer benefits for India?
There is a counter-argument that this situation is changing. Stress is being laid on the need for international research in developing countries, focusing on drugs that are relevant to the host country, and for which plans for post-trial availability are drawn up before the trial starts. Informed voluntary consent and proper data control are being discussed, as is care for those who develop conditions in the course of the trial - whether or not they are related to the drug tested. Conducted appropriately, clinical tests can provide several benefits. The participating physicians get first-hand experience of new drugs as well as extensive training. Resource-starved public hospitals see trials as a source of funds for much-needed improvements in infrastructure. Many trials conducted in government hospitals are in fact the last resort for poor patients. It is argued that the diseased benefit since they get free, focused and more frequent medical supervision for the duration of the trial. In a diabetes trial, for example, poor patients will get blood sugar monitoring machines that they could not otherwise afford. A question that is often asked is: isn’t such medical attention better than complete neglect?

It is also important to note that a transition is underway in some Indian pharmaceutical firms as they shift from developing imitative drugs to focusing also on innovation. Consequently, it is not just multinational companies that are conducting clinical trials but Indian-based firms also. With the Indian government looking to make access to drugs more widely available to its citizens, and with a domestic pharmaceutical industry increasingly well placed to capitalise on this situation, the risk/benefit equation for the conduct of clinical trials within India may well be shifting.

Putting clinical trials to the test.
The Indian Government is also signalling positive changes with regards to regulation, including adoption of a set of internationally recognised ethical and scientific quality requirements known as Good Clinical Practice. A bill, Biomedical Research on Human Participants (Promotion and Regulation), is currently going through parliament and will ensure that all trials are reviewed by an ethics committee and follow the ethical guidelines issued by the Indian Council of Medical Research (ICMR), which oversees the formulation, coordination, and promotion of biomedical research in the country. India launched its first national online Clinical Trials Registry (CTRI) through ICMR on May 26, 2007, with a view to monitoring trials from the start, and registration has been mandatory since June 2009. This positions India among the select countries like Australia, the UK and the US that are making researchers accountable through registration and public disclosure of clinical trials. India is the first Asian country to have such a registry, and the WHO International Clinical Trials Registry (ICTR) proposes to make India an associate member. The National AIDS Research Institute (NARI) in Pune is committed to setting up community advisory bodies (CABs) with participation from field workers, patients and others concerned to disseminate awareness and information on the rights of participants in clinical trials. The Drug Controller General of India (DCGI)  is trying to bring India in line with international standards. A new agency, the Central Drug Administration, is soon to be created under the Health Ministry with its own funding, supporting the activities of the DCGI. In addition, the South East Asian Cochrane group are to get Indian medical journal editors to review their editorial policies in order to limit publishing only those trials that are in accordance with CONSORT guidelines.

What are the hurdles on the way?
However, there is a long way to go before public trust can be secured. The implementation of the CTRI remains dependent on wider awareness of the issues involved in India. The entire concept of CABs is still evolving, with insufficient information on rights or ethical principles and no mechanism for grievances to be redressed. There is a need to pin down direct responsibility for monitoring with ethics committees and for measures to be taken to revoke permanently the licence of any defaulting company. There is still no mandatory compensatory payment, or strong penalty against a defaulting company. Researchers and medical students have to be taught good clinical trial practices, with ethics forming a pivotal part of their training. As part of the regulatory mechanism, patients’ groups are required to participate in setting the research agenda and in selecting outcomes relevant to their needs. Ethics committees need to involve patient representatives in their decisions to oversee the consent process and protect patients’ rights and welfare.

A central tenet of clinical research is that it should benefit wider society. There cannot be two societies, one taking the risks whilst the other the benefits.  Will India be able to bridge this gap in order to achieve its goal of becoming the favoured destination of international clinical trials?