Clinical trials in India refers to clinical research in India in which researchers test drugs and other treatments on research participants. NDCTR 2019 and section 3.7.1 to 3.7.3 of ICMR guidelines requires that all researchers conducting a clinical trial must publicly document it in the Clinical Trials Registry - India.
Various government agencies and laws regulate clinical trials. The Drugs Controller General of India grants approval for clinical trials and is the top level authority which specifically oversees clinical trials. The Drugs Controller is a part of the Central Drugs Standard Control Organisation and answers to that organization. Both of those organizations answer the Ministry of Health and Family Welfare as the highest level government agency overseeing everything related to medicine and health. The Indian Council of Medical Research governs the professional and ethical behavior of the doctors and scientists. The Pharmacovigilance Program of India tracks reports of harm from the use of drugs. Outside of the central government, each state has its own regional regulatory agencies with some input into governing trials.
Since the early 2000s there have been international discussions from science, medicine, and business sectors which observed that India is both an attractive and challenging place to conduct medical research. Favorable characteristics of India included that there are many trained workers including health professionals, there is a large and diverse population, and that the cost of research is relatively low in India in comparison to other countries capable of doing research. Challenging characteristics include lack of research capacity, evolving and uncertain government regulatory infrastructure, diversity of languages, and the need for a culture of research participant confidentiality.
In the years around 2010 there were various scandals in media and popular discussion in which companies conducted clinical trials in unethical ways. There were many discussions raising many complaints, including that researchers were not getting informed consent from research participants, and that the medical research was dismissing high rates of injury and death among research participants. Following the 2013 case Swasthya Adhikar Manch v. Union of India in the Supreme Court of India, various government agencies reformed their regulations to make clinical trials more ethical. There have been many changes with various responses. Among the responses, some say that the clinical trials are safer for participants, and others say that the new rules favor large domestic and international companies over other stakeholders.
Government regulation Since 2009 the Central Drugs Standard Control Organization has mandated that anyone conducting clinical research in India must preregister in the Clinical Trials Registry – India before enrolling any research participants.
Various government agencies and laws regulate clinical trials. The Drugs Controller General of India grants approval for clinical trials and is the top level authority which specifically oversees clinical trials. The Drugs Controller is a part of the Central Drugs Standard Control Organisation and answers to that organization. Both of those organizations answer the Ministry of Health and Family Welfare as the highest level government agency overseeing everything related to medicine and health. The Indian Council of Medical Research governs the professional and ethical behavior of the doctors and scientists. The Pharmacovigilance Program of India tracks reports of harm from the use of drugs.
Before 2005 India had a "phase lag" policy for clinical trials from foreign countries. In this policy, all clinical research in India had to begin at phase one. A 2005 change to liberalize the policy begin allowing companies to skip earlier phase trials to start with more risky trials in India, if there was prior research doing those earlier trials in another country.
Clinical trials have to be monitored by an ethics committee which registers with the government. A study examining all registered ethics committees in 2017 reported that few of them were in academic medical institutions, which is the global norm and desirable for such organizations.
Some legal commentators describe how the Constitution of India provides fundamental rights in India which apply to participants in clinical trials.
Overview of trials Various reports have discussed the number of clinical trials which the Indian government has approved per year. A theme of these reports is that the number of trials generally increases, and that changes in the rates of the number of trials approved corresponds with regulatory changes.
Count of clinical trial approvals Year Trials 2008 65 2009391 2010 500 2011 262
The government approval process for clinical trials is sporadic. A 2013 report commented that in one day, the Indian government approved 50 trials after not having approved any in the past six months. The same report noted that the rate of government approval changes by year.
A single study examining a sample of academic papers which reported the results of dentistry-related clinical trials in 2011-12 found that the reporting was poor.
Ethics Various commentators have noted that there is a conflict between the opportunity for business investors to conduct research in India and the rights and safety of the volunteer research participants who participate in these clinical trials. Discussions of this issue often propose some kind of balance where researchers do trials, but not too many or too quickly, and that the trials collectively support ethical and safety practices which community stakeholders, academic researchers, doctors, and the government all create together.
Wealthy companies in countries with strong economies routinely seek to purchase clinical trial research in India as they seek comparable results at lower cost. As the wealthy country has the power of its money, and as typical participants in clinical trials are volunteers with no understanding of the money involved or power dynamics, many ethical issues arise.
A 2018 study on informed consent found that in a set of cancer-related trials, nearly all research participants had serious misconceptions about their research participation. A common misconception was an expectation of improved health care. The study recommended improved research participant education as a way to make the management of trials more ethical.
Government talks of permitting human challenge studies in India began in 2017. The Translational Health Science and Technology Institute expressed support for allowing these trials at that time.
One 2015 audit of 5 years of trials at a single site found that the expected percentage of people invited to participate declined to do so. That study said that this rate of refusal was an indication of an appropriate level of persuasiveness in study participant recruitment.
An evaluation of about 50 clinical trials in 2007-08 found that the reported results had higher than expected rates of false positive errors due to the statistical methods the researchers used.
Comparison to other countries India's clinical research is a subject of comparison with that of China, countries in Africa, and countries with similarly sized economies. India is both an attractive and challenging place for both Indian and foreign clinical research for various reasons.
A common motivation for foreign companies doing research in India is relatively lower cost in as compared to comparable research elsewhere. India was a single nation with a large, diverse population. Many potential research participants in India had not previously had medical treatment, and clinical trials get better data from such people. India also has a well trained workforce and many research sites which met international good clinical practice standards. India's national health system provides a lot of care in large urban hospitals. This centralization is also favorable to conducting research.
One challenge to doing research is a shortage of research sites which could conduct research and expand the sector. This shortage has various causes, including lack of educational programmes leading health professionals into research as a career track, the lack of experienced administrators who could expand study capacity, and a national research environment with either insufficient quality control processes.
When researchers conduct trials in multiple countries collecting patient-reported outcomes is useful. However, to make sense of any such reports from India, then researchers have to adapt the instructions for local Indian culture.
A 2011 evaluation found that a sample of clinical trials in India complied with the Consolidated Standards of Reporting Trials.
To make India more compliant with international standards the government amended the Drugs and Cosmetics Rules, 1945 in 2005 and 2008.
At the end of 2010 India was conducting 7% of phase III and 3% of phase II trials globally. In 2019 India was hosting about 1% of the world's clinical trials.
Social awareness There was perception in the research community that the media had usefully brought public scrutiny of the ethics and conduct of clinical trials. While researchers and investors wanted trials, they also wanted a reliable research environment which the public and media could trust. Various changes in government regulation sought to make trials safer for research participants and investment in trials. The response to having changes in general was positive, although there was intense debate from stakeholders on the individual changes. The criticism tended to argue that the changes were too strict.
There was criticism that medical journals in India were publishing the results of trials without requiring that the articles describe compliance with regulatory standards including Consolidated Standards of Reporting Trials.
Injury In 2013 the Supreme Court of India ordered the Ministry of Health and Family Welfare to police and prevent multinational companies from conducting illegal clinical trials in India.
There is public information reporting how many people die during clinical trials. It is also known that when people die during trials in India, the trial organization rarely pays compensation to the family of the deceased.
The research industry has formulas for calculating how much money to pay when someone dies in a clinical trial.
Foreign influence A 2011 paper noted that low operational costs, improved government regulation, and existing business infrastructure have made India increasingly attractive as a place for foreign companies to conduct clinical trials.
Some clinical trials based in the United States also do research in India. A 2019 examination of 10 years of United States children's health research found that of about 9000 trials registered about 120 of them also included clinical trials in India. This study found that these trials were for health issues which actually affect children in India, and that consequently, the research was appropriate for India.
Some researchers study global practices for managing clinical trials and apply lessons learned to multiple countries at once, with India being among them.
When foreign companies conduct only phase III trials in India, the researchers conducting those trials tend to not publish as many scientific insights as researchers typically do in other circumstances. There is a foreign expectation that perhaps because India has relatively less regulation than foreign countries which export clinical research, then perhaps the researchers in India would have more insights. The reasons for this are not clear, but one reason may be that researchers who oversee the trial for longer periods and not just the last phase tend to care more about publishing research results.