Goans Now ‘LAB’ Rats!
In 2010 as many as 462 people have died on account of clinical trials in India. Goa, however, officially reported no death over clinical trials; yet over the past years clinical research, as an industry has been growing in Goa with consent from the Directorate of Health Services bringing with it the fear of local Goans becoming laboratory rats sometimes with their consent and sometimes without… GoaChronicle.com investigates into the yet unforeseen danger.
In 2008 it was reported that at the All India Institute of Medical Sciences (AIIMS) in New Delhi, 49 babies died on account of clinical trials conducted. Of the 4,142 babies used for the trials – 2,278 were below the age of one. The clinical trial was conducted to test two drugs – olmesartan and valsartan – meant for reducing blood pressure. Interestingly it was never tried on patients above the age of 10 before even though the drug was meant for adults aged above 18 years. The Pharma Company was trying to determine the drug efficacy and safety on children.
There was this incident where 200 adolescent students from an elite school in Delhi were stripped and examined (without permission from their parents). All this was done by a private research group called Health Care and Research Association for Adolescents (Noida-based). Other Indian companies like Bangalore-based Biocon and Hyderabad-based Shantha Biotechnic as well as Mumbai-based Sun Pharmaceutical Industries have come under a cloud for conducting medical testing of drugs without following proper procedures.
Oral cancer patients at the Regional Cancer Centre, Thiruvananthapuram were also subjected to testing and there is also the case of Indian diabetic patients who were used in a clinical trial by a European pharmaceutical company with a drug that was “subsequently found to cause cancer in rats and mice.”
For years since the early 1980s, a pair of US-based ‘barefoot researchers’ Dr Elton Kessel and Dr Stephen Mumford, led a massive, illegal multi-country trial of the potentially hazardous anti-malarial drug quinacrine as a terminal contraceptive without legal approval. Trials had been halted in the West. They smuggled the drug into India and distributed it directly to practitioners in West Bengal and elsewhere. They went underground after a petition was filed in the Supreme Court in 1997. Another illegal ‘contraceptive trial’, this time with the antibiotic erythromycin came to light in 2004.
Multi-center Phase III clinical trials of the diabetes drug Ragaglitazar by the multi-national corporation Novo Nordisk were suspended when animal studies reported urinary bladder tumors in rats. The results of these studies should have been available before the human trials started. The drug was developed by Dr Reddy’s Laboratories, Hyderabad, and licensed to Novo Nordisk which conducted the trials. 130 people in eight centers from India were part of the trial, of which half would have received the experimental drug. Novo Nordisk refused to give further details on the centers that conducted the trials in 2002.
Goa too has had its share of clinical trials; a trial was conducted by the Department of Pediatrics, Goa Medical College from July 1971 to June 1974 to assess the effects of the Liv 52 drug in cases of infectious hepatitis children. They were 50 children taken for the clinical trial 30 males and 20 females from the age of five months to 12 years.
Novo Nordisk – a company already under question for its clinical trials practices – under permission from the Directorate of Health Services has been conducting a three-year diabetic survey in Goa to determine to growing rise of diabetes in the state. In fact it had reportedly paid the government a grant of Rs 1 crore to do the test and the clinical tests were not conducted by members of the Novo Nordisk Company but representatives were to be hired by the Directorate of Health Services, Goa. 400 untrained youth were employed to conduct this survey. Reports by senior doctors that attended these Diabetes camp at Panjim, Margao, Vasco and Mapusa were disappointing about the hygiene standards followed during these camps. In fact, at one place, nearly 40 volunteers blood sample was extracted using the same needle! More importantly, sources revealed that while Novo Nordisk conducts such health camps in different parts of the world, it is interesting to note that while the company sponsored the survey, the Goa government did spend a considerable amount to purchase their products as part of the arrangement.
Like the above mentioned illustrations; over the past couple of years there has been a tremendous rise in clinical trials across India and Goa is being considered as one of the preferred destination for these exercises. One most commonly used clinical trial in Goa is being done for anti-depressant drugs as an effort to treat Common Mental Disorders. A project known has the MANAS Project funded by the Wellcome Trust has been conducting its clinical trials in Goa since 2005; here is what the reasons were for conducting the research in Goa as mentioned in their research paper, “Goa is relatively wealthy by Indian standards. But most of its three million residents earn a few dollars a day, not enough to afford much medical care. Public health officials say that poverty can lead to alcoholism, domestic abuse and stress, all contributors to depression and anxiety.”
India is the world leader when it comes to bagging outsourcing jobs in clinical research. It has double the market share of its nearest competitor, Italy, and nearly four times as much as the next in line, Spain. In 2005 contract research in India was valued at USD 100-120 million and growing at a rate of 20-25 per cent each year as per Chemical Pharmaceutical Generic Association report. Other projections (McKinsey report) say that clinical research in India will be a USD 1 billion industry during the current financial year.
The average cost of running a US-based clinical trial per patient is USD 19577. In India it can cost up to 60 per cent less than in the US. Getting trials done in India also saves time as not only are more people available, they are easier to convince. In the US patients with decent healthcare and health insurance will be reluctant to participate as they see few benefits. Time is money for the companies, particularly as patents are given to drug companies for limited periods.
The Ugly Truth
There is no effective monitoring mechanism for research, and existing regulations are to be relaxed shortly as India encourages the outsourcing of clinical trials from the West. A huge population with a diversity of diseases that are untreated – yes, that is the “India Advantage” identified by Igate Clinical Research International, (www.igatecorp.com/icri/html/aboutus/tia.htm), commenting that India represents a largely untapped resource for clinical trials. Besides the fact that the ill in India are largely “drug naïve”, the company also lists high enrolment rates, good patient compliance/retention, “competitive costs”, and an “increasingly accommodating regulatory environment” as the other benefits of conducting clinical research in India.
Multinational drug companies have been conducting clinical trials in India for years, directly or through clinical/contract research organizations (CROs) which conduct the trials for a fee. In some cases, local pharmaceutical companies are setting up CROs to collaborate with the international ones. For instance, in 1999, Nicholas Piramal set up a joint venture with a UK-based health care firm in central Mumbai, site of a once-thriving textile industry. Promoted as a center for genome research, Wellquest maintains a database of over 2,000 healthy volunteers for such studies. It is reported that many of the research subjects are jobless textile workers.
Trials are apparently on-going by various CROs on drugs for diabetes, blood pressure, cancer and other diseases of interest to the international drug market. Quintiles Transnational is reported to have recruited more than 13,000 Indian patients for various clinical trials since it came to India in 1997. The Indian CRO SIRO Clinpharm claims to have done 22 studies involving more than 2,000 patients. These organizations can enroll sufficient patients for their studies in a fraction of the time it takes their counterparts to do so in the West. CROs offer to do everything for the drug company, from designing trial protocols for all stages and types of trials; getting regulatory permissions and ethics committee (EC) approval, conducting studies after obtaining written informed consent of subjects, analyzing the data, and writing up the results.
Significantly, many trials are conducted in government hospitals which are largely the only resort of poor patients. Resource-starved public hospitals see trials as a source of funds and equipment. It is worth noting a parallel phenomenon as public health services deteriorate without funds and the private health sector is being developed to meet other needs. The combination of low costs, trained personnel, medical and communications infrastructures also make India a competitive source of high quality health services internationally.
The Good Clinical Practice guidelines drawn up by India are required by the ICMR and are based on those formulated by the WHO and the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. The question though is how many clinical trial practioners stay true to their guidelines in light of the money made in the clinical trials.
A medical director notes that GCP guidelines will make a marked improvement in the quality of informed consent expected in a trial. “But how effectively informed consent is actually administered is for you to guess. It will depend on individual investigators, and the type of study.” For example, a trial for chronic hepatitis has a limited number of potential subjects so there is more pressure to get consent from patients eligible for the study. Since there are a limited number of drugs currently available and they are expensive, it is always possible for the investigator to persuade the patient that the trial is the only or best option. “In other cases, such as a trial for antibiotics or drugs for diabetes, patient refusal is fine,” because there are plenty of people to choose from who need antibiotics or diabetes drugs. “The population base is an advantage.”
The Law Side
Before 2005, the Indian law was designed to actively discourage the use of Indians as mere subjects for experimentation by foreign companies. The law required that if a foreign company wished to conduct trials in India, it needed to repeat the trials from the same phase in India as had already been conducted in locations outside India. Thus if a company had already conducted phase I trials outside India, it could not directly start phase II trials in India – it would have to conduct phase I trials again in India, before permission was conducted to conduct phase II trials in the country. This allowed Indian regulatory agencies greater control over the kind of trials being conducted in India and was a vital tool for protection of trial subjects against unethical trials. In 2005, however, this requirement was waived (by an amendment to schedule Y of the Drugs and Cosmetic Rules) and concurrent phase II and III trials were allowed. This means that a phase II or III trial can be conducted concurrently in India, along with similar trials in other centers in the world, even if the drug has not undergone a phase I or II trial in India.
The result of this change in the law has been spectacular. In 1997-98, less than a 100 trials were conducted in India. The number jumped to over 250 by 2005 and is projected to exceed a 1000 by the end of 2010.