Clinical Research in India Vital or Fatal

By Sushant Mishra Sushant_mishra1@yahoo.com Abstract The Clinical Research Industry in India is growing at a staggering pace. The potential is immense and favourable factors like huge drug nave and poor genetically diverse population along with other regulatory factors make India a favourable Clinical research haven for Pharma companies from around the world. The article seeks to bring to light the regulatory and moral discrepancies and the dangers of giving too much too soon without proper diligence and regulation to the Clinical Research industry and companies and also seeks to discuss the probable implications. Introduction The Clinical Trial Outsourcing industry in India in 2006 was $140 mn at a CAGR of 40% for 3 previous years and is expected to reach $600 mn by 2010. This rapid growth of the industry in India can be attributed to the varied, huge and genetically diverse population and the cost advantage provided by India. The Indian population of 1.109811 bn is generally drug nave and hence they prove to be excellent subjects for clinical trial studies. The people who get involved in these studies are generally poor and can be easily lured for the sake of some monetary returns to participate in such studies without fully understanding the consequences. The regulatory and administrative environment has also changed during the last few years and with the changes brought about in the Schedule Y and product patent regime has made Indians more profitable and susceptible targets. Moreover, the availability of cheap skilled manpower with no language barrier is also a primary added advantage for the Indian case.

Positive Impact of Government Policies and Product Patents on CROs The Indian government has done away with the 12.24% service tax on the clinical research industry in its budget of 2007 08
[3]

. This would add to the clinical research

services getting cheaper for the companies outsourcing their clinical trials to India. "This saving of 12.24 per cent is a big amount a saving that will now be passed onto clients." Dr. Umakant Sahoo, MD, Chiltern India [3]. This change in policy would add to the clinical trials getting cheaper in India. Comparing to the US or EU, the trials in India are upto 50% to 75% cheaper for the companies
[4]

. The further cut in costs would lead to more and more companies getting

attracted to come to India for their clinical trials. The introduction of product patents in 2005 in compliance with the TRIPS (Trade Related Aspects of Intellectual Property Rights) agreement that India signed has secured the intellectual property and would encourage the big pharma companies to start the studies on development of new molecules and entities in India. Prior to the products patents, there were process patents which led to the development of the huge generic drugs industry in India as the small firms were able to produce generic drugs quoting bioequivalence studies. The product patent regime would ensure that the rights of the intellectual property generated by a company are not violated and hence would secure knowledge in a more effective way with the parent company. There has also been a change in the Schedule Y of the Drugs and Cosmetics Act, 1945 in which the phase lag between the Indian and trials elsewhere has been eliminated and also phase 1 trials have been allowed in India India. The CTRI In view of the need for a central registration authority for clinical research trials ICMRs National Institute of Medical Statistics (NIMS) has setup Clinical Trials Registry India (CTRI).
[4][5]

. This would also attract global

companies to start trials and development of completely new drugs and molecules in

It is a body which aims to register all the clinical trials in India and even outside India and provide open information to all regarding the status of the trials. It aims to make the process of clinical trials in India more transparent and improve accountability of those responsible. It asks for the registration of the details of the trial in accordance to the 20 item dataset of the WHO International Clinical Trials Registry Program (ICTRP) and International Committee of Medical Journal Editors (ICMJE) [6]. The Implications and Shortfalls The various steps of the government and the new regulatory regime are certainly a boon for the clinical research industry but they are certainly not capable of safeguarding the Indian citizen against the vile profit bearing motives of the pharma companies. The amendment to the Schedule Y and approval to provision for conducting a phase 1 trial and removal of the phase lag would lead to Indian people getting exposed to a new threat without having any prior knowledge of the implications and consequences. The earlier rule of phase lag atleast safeguarded the people in the sense that no new entities or drugs could be administered or tried on Indians without their studies already having been conducted elsewhere in the world. So the results and side-effects if any of a particular phase of testing were already known. Moreover most of the Indian population is quite poor and not aware of their rights. They do not know of or are not capable of understanding the terms and conditions and eventualities of such trials and get involved in potentially fatal tests just to earn a little money. An example vindicating my point is the database of 2000 volunteers for clinical research maintained by Wellquest (1999) most of whom are jobless textile workers [7]. Even setting up of bodies like CTRI is of not much use until the registration and data and information providing process is made mandatory. Under the current provisions of the CTRI the registration process is voluntary and not mandatory [6].

Pharmaceutical Companies exposed December 2006 Pfizer terminated the trials of Torcetrapib (a cholesterol reducing drug). The reason cited was the high death rate among 15,000 trial subjects spread over 3 continents. No damages were claimed as the subjects had agreed to waive such rights before the trials [5]. GlaxoSmithkline withdrew its anti-depressant Seroxat and issued warnings about the diabetes drug Avandia as it increased limb fractures [5]. Merck called back its painkiller Vioxx, after it was shown that it caused increased heart attacks [5]. In 2003-04 - Biocon and Shantha Biotech started phase 3 clinical trials of Insulin and Streptokinase respectively without the prior approval of DGCI or the Genetic Engineering Approval Committee. These trials led to eight deaths
[7] [5]

2003 Sun Pharmaceuticals got private doctors to prescribe anti-cancer drug Letrozole for ovulation induction to over 400 women. No permission from the DGCI was taken [5] [7]. In 2002, Dharmesh Vasava a daily wage worker died of Pneumonia during a bioequivalence study being conducted by Sun Pharmaceuticals. It was asked by the Peoples Union of Civil Liberties, Vadodara if the involuntary informed consent of the subject had been taken before the study and whether proper measures to monitor his health before and during the study had been taken [7]. In 2002, Multicenter Phase 3 trials of the diabetes drug Ragaglitazar by Novo Nordisk were stopped when animal studies showed Urinary Bladder tumour in rats. The reports of the animal test should have been available before the human

trials were started. The drug was developed by Dr. Reddys and was licensed to Novo Nordisk. More than 2500 people across the globe were part of the study [7]. In 2002, unqualified researchers conducted trials on over 700 illiterate women in West Bengal by using antibiotic Strepromycin as a contraceptive [5][7]. Between November 1999 and April 2000, 25 patients of Regional Cancer Center, Thiruvananthpuram, Kerala had their tumours injected with tetra-Omethyl nor-dihydro-guaiaretic acid (M4N) or tetraglycinyl nor-dihydro-guaiaretic acid (G4N). Both of the entities were experimental and no prior approval obtained from the Drugs Controller [7]. During the 1980s two US based researchers, Dr Elton Kessel and Dr Stephen Mumford, led a massive illegal multicountry trial of antimalarial quinacrine as a terminal contraceptive [7]. Conclusion There is no doubt that clinical trials are a necessary evil for the development of better and newer drugs but the security and safety of the people taking part in these studies is also critical. The government should act to make stringer norms for the safety of individuals taking part in such studies. The policies should ensure that a subject is informed about the kind of study and the probable outcomes and side-effects of the trials before him getting involved in the trials. The pharma companies and other organization firms should be made accountable for concealing relevant and necessary information from the subjects and should also be made to register and divulge all the details of the clinical trials periodically. Their voluntary involvement can not be counted upon as is evident from numerous cases. Strict action should be taken against all defaulters. Without the necessary steps being taken the population of India would always be susceptible to the unknown and unimaginable side-effects of newer drugs being tested. Who knows what these new drugs might do to our genomes and physiology on a longer

time frame. It might not be wrong to say that if necessary steps are not taken we might end up as a new race or species in a few generations time or to be more pessimistic, be extinct. These are not the result of unrealistic imagination on the part of an overly hopeless author rather a pragmatic realization of the undefined possibilities. References: 1. Industry Insight Clinical Trials in India 2007. Cygnus Business Consulting and Research; May 1,2007;Pub ID: CYG1493408 http://www.marketresearch.com/product/display.asp?productid=1493408&g=1 2. WTO site on country trade profile of India as seen on 20/1/08; http://stat.wto.org/CountryProfile/WSDBCountryPFView.aspx? Language=E&Country=IN 3. Barnes, Kirsty. Clinical Trials in India just got cheaper. 28 Feb, 2007; http://www.drugresearcher.com/news/ng.asp?n=74588-chiltern-internationalindia-clinical-trial-cost 4. Gupta, S.K. and Niranjan, Galpalli D. Current Developments in Clinical Research in India. 16-31 Dec, 2007; http://www.expresspharmaonline.com/20071231/59thindianpharmaceuticalcongre ss06.shtml 5. Varma, Subodh. India a hotbed for Clinical Trials. 18 March, 2007; TNN; http://timesofindia.indiatimes.com/articleshow/1776215.cms 6. CTRI homepage as seen on 20/1/08; http://www.ctri.in/Clinicaltrials/do/login1?action=toReadMore

7. Srinivasan, Sandhya. Indian Guinea Pigs for Sale: Outsourcing Clinical Trials. 8 Sep, 2004; India Resource Center; http://www.indiaresource.org/issues/globalization/2004/indianguineapigs.html