The below is an excerpt from my latest ebook available on Kindle, Clinical Trials in India (99 cents!!). It basically introduces some of the ethical issues regarding clinical trials and India and discusses some measures by which the Indian government has restructured its regulatory agencies. I will report much more on this in the near future, but for now check out this interview I did with a Researcher/Marketer from India from a few years ago, it is truly a MUST watch!
Could you afford to pay $100 for medication if your monthly income was only $100 or perhaps even less? Could you comprehend an Informed Consent Form if you could not even read a single word of it? What would you do if you were offered a sizeable amount of money for joining a clinical trial if you were only eating one meal a day? What would you do if you came across a new medication or treatment option if you were seriously ill and fed up with the medications already available in the market? Do these questions scare you? Most of us can’t imagine ourselves in these situations, but many people in India are facing these and participating in clinical trials every single day. Poverty is rampant in India, with the poverty line being the equivalent of 50 cents per day and roughly 29.8% of the population falls below that line.
India has been and continues to be a favorable destination for clinical trials over the years. A tremendous increase in the clinical trials market from $70 million in 2002 to $485 million in 2011, attributes to India’s strong value proposition in skilled medical professionals, low-cost services, diverse genetic pool and world-class hospitals to undertake clinical trials. In addition, India’s huge patient base in a plethora of diseases ranging from tropical to nutrition and lifestyle related, has been enticing for many Pharmaceutical companies, Contract Research Organizations (CROs) to evaluate efficacy and safety of new molecules, also safety and suitability of existing drugs before marketing them in India. As per the recent Frost & Sullivan report, the domestic contract research organization (CRO) market is set to reach $ 1 billion by 2016.
A good analogy that can help illustrate India’s clinical trial industry dilemma can be the following: you have prepared a scrumptious recipe that you cannot wait to eat. If you don’t store it under regulated conditions, what would happen? It would remain good for some time but afterwards it will begin to spoil unless you find a way to curb the growth of bacteria. Likewise, the regulatory system in India, with respect to clinical research before 2009, had no stringent rules, no compulsory registration of clinical trials and had combined with an illiterate and largely impoverished population of study participants to essentially create a cesspool of bad and unethical data. In 2006, when Netherlands-based WEMOS Foundation, also a partner of the World Health Organisation, cited 22 examples of unethical clinical trials, eight of these were found to be operating in India. These comprised Sun Pharmaceuticals and Novartis’s Letrozole for inducing ovulation, Novo Nordisk’s for diabetes treatment, Solvay Pharmaceuticals’ for treating diarrhoea, Johnson and Johnson’s for treating acute malaria, Pfizer’s for cardiac events, Otsuka’s for arterial disease and the John Hopkins’ University’s trials for treating oral cancer. These trials violated the Indian Council of Medical Research’s Ethical guidelines for biomedical research on human subjects and the World Medical Association’s Declaration of Helsinki. These trials exploited the fact that most Indians do not have access to affordable and quality care, therefore may accept offers that might provide the premise of “free treatment”. The patients were also vulnerable because they were seriously ill. In the case of psychiatric patients, they might not have been able to provide informed consent. The examples were almost endless. These trial designs do not seem to have violated regulations for the conduct of clinical research in India, but the regulatory apparatus that existed during that time permitted unethical trials that provided no benefit to Indians. The infrastructure for regulation, ethics review and monitoring was insufficient. Ethical concerns raised by these trials ignited the fire which led to drafting of compulsory registration of clinical trials in CTRI (clinical trials registry of India) mandatory by DCGI (drug controller general of India) on June 15th, 2009.
In 2010, one year after enactment of compulsory registration of clinical trials in CTRI, there was a shocking incident in Khammam district (Andhra Pradesh) and Vadodra (Gujarat) where a HPV vaccine clinical trial was conducted on nearly 23,500 girls in the 10-14 year age group. Most of their informed consents were signed by a headmaster, as the ‘guardian’. Moreover, the justification given by them was ridiculous: the parents were not easily accessible! Reporting of a death was delayed for five months, while two deaths in Khammam district were not reported. Ironically, while measuring and reporting the adverse events after vaccinations which were the “primary end points of the study,” the Principal and Co-Principal investigators failed to report all such events to the sponsor within a day, as required under the Drugs and Cosmetics Rules 1940.
The way in which human trials were being carried out within the country had become a matter of public debate for some time. Human rights activists and NGO forums kicked up more dust when arguing that the country was becoming a testing ground for a large number of therapies banned in other parts of the world. Their clamour surged soon after a couple of stories made headlines in national and international media, and forced the government to set up a committee to investigate alleged irregularities in the conduct of the clinical trial. Controversially, the final report released on the HPV vaccine issue strangely declared no relation of deaths to the vaccine. It has, however, exposed abnormalities at various levels of the conduct of clinical trials; from the informed consent to the reporting of the adverse reactions.
This incident had been a matter of debate in parliament for couple of years, soon after, registration of ethics committee associated with CROs has been made mandatory by DCGI (Drug controller general of India) in August 2012. Furthermore, ethics committees are requested to remain vigilant on clinical trials under their jurisdictions and may make surprise visits to ensure whether the trials are being conducted as per Schedule Y, GCP guidelines and to ensure the rights and safety of trial subjects are protected. To further streamline the clinical trials, union health ministry is preparing grounds to amend Schedule Y of drugs and cosmetics act, to make a provision for audio and video recording of informed consent in clinical trials.