HOME     CONTACT     BACK

 
 
 
THE PHARMA REVIEW (SEPTEMBER - OCTOBER 2010)

Present Status of Clinical Trials in India: Unfolding The Truth

Dr. Papiya Bigoniya, Alok Shukla, Chandra Shekhar Singh

Abstract
 

Clinical trials are conducted on human volunteers to access the safety and efficacy of new drugs, treatments, therapies, surgical procedures and new medical devices before making it publicly available. India proved to be one of the hottest destinations for conducting global clinical trials with a remarkable growth of more than 30%, owing to a huge patient pool representing both chronic and infectious diseases, easy recruitment of patients, and high cost savings. Moreover, the market is getting boost from improved IPR protection and also from reduced taxes and duties on CROs engaged with clinical trials. Every opportunity comes along with great responsibility, as it a challenge for regulatory body to keep pace with need and requirements of fast growing trial industry.
 
Unethical practices, falsified data, frauding trial subjects, noncompliance of GCP guidelines and more over conduction of trials without DCGI approval are some the discrepancies going on converting the boon to a bane. There are several reports of exploitation of poor illiterate Indian citizens as guinea pigs for clinical trials with increasing reports of trial participant fatalities alarming the need of strict vigilance. Conducting trial in India is easier than in North America or Europe due to strict legislation and the patients are well aware of their rights. In India exploitation of trial participants are happening because of illiteracy, poverty and unaware of common rights making the poor needy people as experimental guinea pigs. To favor the promotion of clinical trial in India, restrictions are necessary to ensure safety and well being of the trial subjects providing adequate health insurance and compensations. CDSCO has taken noteworthy step by launching online clinical trial registry (CTRI) ensuring accountability, transparency and information sharing on clinical trials making it a public domain. This review aims to provide a comprehensive and critical overview of the national and global clinical trials registered in CTRI providing the actual picture of trial parameters.
 
Introduction
Clinical research is an indispensable part of the drug discovery process to ensure the safety and efficacy of any new drug. In today’s global scientific era, clinical trials are the mainstay for bringing newer and better drugs to market. Although a set of robust guidelines is available to govern the conduct of clinical trials in any country, the conduct of clinical research is also looked upon as an area of humanitarian concern. Clinical trials are one form of clinical research that involves a researcher or researchers who directly observe a person or people, and/or collect data to answer a scientific or medical question about the safety or potential benefit of an intervention such as a medication, device, teaching concept, training method or behavioral changes.1
 
James Lind is considered as the father of clinical trials, since he was the first to introduce control groups into his experiments. In this manner, he documented the fact that citrus fruits in the diet could prevent scurvy. Lind carried out trials while at sea on board the Salisbury in 1747. All scurvy patients were given the same general diet but this was supplemented with various additional items, including cider, elixir vitriol, vinegar, seawater, nutmeg and (crucially) oranges and lemons. In just six days, those patients taking citrus fruits were fit for duty. Although the results were clear, Lind hesitated to recommend the use of oranges and lemons because they were too expensive. It was nearly 50 years before the Navy eventually made lemon juice a compulsory part of the seafarer’s diet and this was soon replaced by lime juice because it was cheaper. This is why British sailors, and later the British in general, were called ‘limeys’ by the Americans.2
 
From 1800 onwards, clinical trials began to proliferate and more attention was paid to study design. Placebos were first used in 1863 and the idea of randomization was introduced in 1923. The first modern clinical trial was conducted in 1946. British epidemiologist, Sir Austin Bradford Hill put patients into experimental and control groups at random. This eliminated any bias - only the test medicine would account for differences seen in the health of the two groups. With the establishment of guidelines for ethical clinical trial conduct and regulations for drug development, more than 1019 novel drug therapies have been approved by the Food and Drug Administration – that’s virtually all the medicines used today. The first trial using properly randomized treatment and control groups was carried out in 1948 by the Medical Research Council, and involved the use of streptomycin to treat pulmonary tuberculosis. This trial also featured blind assessment (where neither the researchers nor the patients knew which treatment group each patient was in at the time of the study) enabling unbiased analysis of the results.
 

 
Since 1945, the ethical impact of clinical trials has become increasingly important, resulting in strict regulation of medical experiments on human subjects. These regulations have been enshrined in documents such as the Nuremburg Codex (1947), Declaration of Helsinki (1964, amended in 1975, 1983, 1989, 1996, 2000 and 2001) and Ethical Principles for Medical Research Involving Human Subjects. Clinical trials have thus evolved into a standard procedure, focusing on patient safety and requiring informed consent from all participants. There will always be a balance between medical progress and patient safety, and the regulation of clinical trials helps to ensure that this balance is acceptable.3
 
Clinical Trials Market Value in India
Clinical trials market in India has recorded significant growth trends in the recent past. Clinical research experienced over 84% growth during 2006-2008 and it has its own merit in regards to further prospect considering that global clinical market is growing at 12% rate. Clinical research industry in India touched US$ 320 million in 2009, up from US$ 140 million in 2006. An estimate shows that clinical research in India is expected to be US$ 320 million by 20094. According to the Associated Chambers of Commerce and Industry, an influential national industry association, India is set to grab clinical trials business valued at approximately US$ 1 billion by 2010, making the subcontinent one of the world’s most preferred destinations for clinical trials.5
 
The Facts Behind Clinical Trial Boom in India
India presently occupies only a small quiche of the global market. The total numbers of clinical trials conducted in India were 221 in 2007 and had increased to just over 700 trials in 2008. Although there was an increase of 65%, it associates to only single digit percentage of the global clinical trial market. The country is projected to conduct nearly 50% of the global clinical trials by 2012. Clinical trials and research is now a major business in India. Over 100 companies are currently conducting the clinical trials in India. Top multinational pharmaceutical companies like Pfizer, Glaxo Smith Kline, Aventis, Novartis, Novo Nordisk, Astra Zenica, Eli Lilly are conducting clinical trials in India apart from the Indian companies like Dr. Reddys, Nicholas Piramal, Cipla and Lupin.6
 
The clinical trial market in India looks very lucrative. The country promises to be one of the hottest destinations for conducting global clinical trials, owing to a huge patient pool representing both chronic and infectious diseases, easy recruitment of patients, and high cost savings. The availability of a large drug native patient population and well-trained medical professionals, coupled with sophisticated technological infrastructure have made India an attractive destination for conducting global clinical trials. Moreover, the market is getting boost from improved IPR protection with changed rules and also from reduced taxes and duties. According to “Booming Clinical Trials Market in India” a report, the clinical trial outsourced market in India is forecasted to grow at a CAGR of around 31% during 2010-2012. Presently, the market is characterized by the dominance of phase III and phase II trials, which currently hold more than 80% of the market. This scenario is expected to remain intact in future as well. In terms of competitive landscape, the market is characterized by many small CROs, with certain companies like Syngene, Quintiles, Lambda therapeutics, Vimta labs etc doing better in comparison of the rest.7
 

 
According to IGATE Clinical Research, the “India Advantage” includes the following qualities: large numbers of people with a diverse range of diseases, relatively low costs, availability of trained human power and infrastructure, high enrolment rates (higher than in the West), good patient compliance / retention, and an “increasingly accommodating regulatory environment”. IGATE also mentions that India has diverse categories of ‘treatment naive’ patients who are unable to afford treatment – so they are ideal for testing new drugs. IGATE specifies that apparently India have 40 million asthmatic patients, about 34 million diabetic patients, 8-10 million people with HIV, 8 million epileptic patients, 3 million cancer patients, more than 2 million cardiac-related patients, 1.5 million people with Alzheimer’s disease, 15% of the population is hypertensive, and 1% suffers from schizophrenia.
 
The government policies are also enclosing to encourage India as a site for clinical trials, for example:
 

 
The government bowed to the drug industry’s lobbying to announce limits for the time taken for drug trial applications to be cleared – 90 days for phase I trials, 45 days for phase II trials and 45 days for phase III trials. If the Drug Controller General of India (DCGI) does not reply within the given period, the application is taken to have been approved.
 
According to the drug industry the amended Indian Patent Act will remove barriers to foreign research in India. The Indian Patent Act’s amendments in March 2005 give foreign companies the assurance that data collected in trials of their drugs in India will not be used by local companies to manufacture and market cheap generic versions. European and US regulatory authorities now permit the use of data from clinical trials in India for approval purposes.6
 
Import of pharmaceutical reference standards and drugs for clinical trial were made duty free as per notification no. 26/2003-custom dated 1st March 2003. Total exemption from service tax is being provided to technical testing and analysis for testing of new drugs, vaccines and herbal remedies, on human participants by a CRO approved to conduct clinical trials by the Drugs Controller General of India. Identifying huge potential and growing employability in Indian clinical trial field a tax exemption on all services carried out by contract research organization and clinical trial industry – a saving of 12.24 % starting from financial year 1st April 2007. The decision removes a previous stumbling block that international pharmaceutical sponsors faced when considering contract research organisations (CROs) in India and is designed to give a boost to this budding market.
 
Elimination of restrictions on concurrent trials has also boost up the out sourcing of trial from western countries breaking the phase lag barrier. Now parallel global clinical trials in concomitant phase II and phase III are permitted. India now become part of global trials but even then phase I have to be repeated for safety.
 
India as Clinical Trial Hot Spot

  • Tax incentive to CROs.

  • Indian clinical trials market is expected to grow at a CAGR of nearly 36% between 2006 and 2011 to register revenues worth US$ 546 Million in future. India by 2011 will be conducting more than 15% of the total global clinical trials.

  • One of the biggest advantages of conducting clinical trials in India is the availability of a large patient pool that can be recruited at much shorter time then it takes to recruit patients in the west.

  • India becomes a more obvious choice because this is home to over 16,000 hospitals and 500,000 doctors, making it an ideal country, in which to conduct clinical trials.

  • India presently lacks in GCP trained investigators (which are less than 1000). Their demand is projected to reach upto 6000 by 2010.

  • India does not provide “Data Exclusivity” in clinical trials unlike the US and EU members.

  • The salaries of a clinical data specialist and medical writer in India are around 15 % and 9 % less respectively in comparison to US.

  • The clinical trials market growth will drive to the growth of diagnostics and pathology industry in India.

  • According to the Drugs Controller General of India (DCGI), India will be a preferred site for clinical trials because, in addition to its medical infrastructure and trained, English speaking human power. It has a large, diverse and treatment-naive (not exposed to any form of treatment) population with six out of the seven genetic varieties of the human race.

  • Huge patient base with diversity of diseases, at risk from diseases of poverty and underdevelopment as well as the so called life style diseases.

  • The average cost of drug discovery in US is estimated at US$ 800 million. Research conducted for comparing the drug development cost in India versus other developed countries has clearly spelt that the cost of conducting clinical research in India is much lower as compared to the developed countries.

  • Clinical trials in India are economic. Drug companies can save up to two - third of overall cost of conducting trials in India compared to the west.

  • English-speaking technical workforce, Good IT infrastructure, low infrastructure costs, which can reduce expenditures for clinical trials by as much as 60 percent.7

 

Well Known Trial Conduction Sites in India
1.    Central Drug Research Institute (CDRI) Chattar Manzil Palace, Lucknow – 226001, Uttar Pradesh
2.    Centre for Cellular & Molecular Biology (CCMB) Hyderabad – 500007, Andhra Pradesh
3.    Indian Institute of Chemical Biology (IICB) Calcutta – 700032, West Bengal
4.    Institute of Microbial Technology (IMT) Chandigarh - 160036
5.    Quintiles Spectral Limited Ahmadabad 380 015, Gujarat
6.    Specialty Ranbaxy Limited Mumbai - 400 093, Maharashtra
7.    Metropolis Health Services (India) Pvt. Ltd. Mumbai - 400 030, Maharashtra
 
Clinical Trial Indications

  • Assess the safety and effectiveness of a new medication or device on a specific kind of patient.

  • Assess the safety and effectiveness of a different dose of a medication than is commonly used (e.g., 10 mg dose instead of 5 mg dose).

  • Assess the safety and effectiveness of an already marketed medication or device for a new indication (i.e. a disease for which the drug is not specifically approved).

  • Assess whether the new medication or device is more effective for the patient’s condition than the already used, standard medication or device (“the gold standard” or “standard therapy”).

  • Compare the effectiveness in patients with a specific disease of two or more already approved or common interventions for that disease (e.g., Device A vs. Device B, Therapy A vs. Therapy B).9

 

Regulatory Control: Clinical Trial Approval
Clinical trials in India are regulated by Schedule Y of the Drugs and Cosmetics Act and Rules. The Rules are enforced by the office of the DCGI also responsible for monitoring all clinical trials. For new drugs being developed in India clinical trials have to be conducted in India from phase I. For marketing approval of drugs already approved in other countries, a phase III clinical trial is required on about 100 patients in three or more centers in order to establish the drug’s impact on the Indian ethnic population. An application for a new indication of an already approved drug is treated as an application for a new drug’s approval. New formulations of approved drugs may be subjected to bioequivalence studies. Till January 2005, clinical trials of new drugs being developed outside India were permitted only with a “phase lag”: a phase II trial could be conducted in India only after phase III trials were completed elsewhere.10 Phase I trials of foreign drugs are not permitted, except for drugs of special relevance to India and phase 0 trials are not permitted. This clause enabled, for example, phase 1 trial of HIV vaccines in India. In fact, international multicentre trials have been conducted in India since the mid-1990s.11
 
Central Drug Standard Control Organization (CDSCO) on 4th Aug 2010 recommends new guide line for clinical trials in India. According to new guideline application in Form 44 is required for grant of permission to import or manufacture a new drug to undertake clinical trial. The prescribed fee for the proposed trials should be submitted through challan TR 5 and TR 6. The fee for phase I is Rs. 50,000/ and for pivot study (safe study) i.e. phase II and III is Rs. 25,000/.12
 
Problem Encountered During Trial: Unseen Concern and Challenges

  • Failure to obtain informed consent.

  • Falsified data.

  • Ethics unawareness.

  • Inadequate source documentation.

  • Protocol noncompliance.      

  • Delinquent or inaccurate data submission.

  • In the field of rare diseases sometimes the number of patients might be the limiting factor for a clinical trial.

  • For clinical trials involving a seasonal indication (such as airborne allergies, seasonal affective disorder, influenza), the study can only be done during a limited part of the year (such as spring season for pollen allergies), when the drug can be tested. This can be an additional complication on the length of the study.

  • Physicians are not as familiar with the clinical trial process as they are in the West.

  • Work with local industry, there is a danger of supplies being contaminated because standards are not adopted.

  • The DCGI and Food and Drug Administration (FDA) are understaffed and lack the expertise professionals to evaluate clinical trial protocols.

  • The sponsors do not guarantee that new drugs tested in India will be made available here at affordable prices.

  • DCGI gives approval to carry out trials, but there are few examples also of doing trials without regulatory approvals.13

Clinical Trial in India: A Boom or Bane
Amendment of Indian Patent Act 2005 showed a clear spurt in clinical study outsourcing in India by U.S. and European firms but with many drawbacks e.g. exposure of Indian people to the danger of being experimented with toxic drugs. To overcome these drawbacks and avoid exploitation of poor illiterate Indian citizens as guinea pigs for clinical trials, few compensatory models and suggestions are to be implemented.
 


 
There was no compulsory registration system for clinical trials in India until 2006. WEMOS foundation and the Centre for Research on Multinational Corporations (Netherlands) prepared an overview of 22 known examples of unethical clinical trials, eight of which were operating in India.
 
Inclusion of patients in clinical trial without permission or consent is coming out as devastating problem of clinical trials in India making it a hot discussion topic in political circle. Central Health and Family Welfare minister Mr. Dinesh Trivedi quoted death of 1,519 persons in last three years (2007-2009) in a Parliament session in response to a question raised by Chhattisgarh M.P, Mr. Charan Das Mohant.14
 
Another matter of concern is that some principal investigators are involved with trial of specific drug for which they are not actually authorized. Doctors of Allopathic discipline are engaged with trial of Ayurvedic medicines and in some cases retired doctors are also involved in trial of drugs carried out in government hospitals. Cases are reported for conduction of trial over cancer patients without active component (placebo only) making them vulnerable to lethality.15
 
After a four month long enquiry the Johns Hopkins University admits that the illegal nature of anti-cancer trial conducted (samples developed at the Hopkins Biology Laboratory, U.S) at Regional Cancer Centre (RCC), Thiruvanthapuram, Kerala was not been properly tested on in animal before they were tried out in human. The investigator involved was not qualified or authorized to do experiments on human subjects and started experiment without mandatory ethical IRB (Independent Review Board) clearance, without approval from DCGI and US government approval for export of chemicals. No clearance from Health Ministry was obtained for collaboration with a foreign institute. Patients signed the informed consent in language other than their native language. Neither ICH-GCP nor the ICMR guidelines for biomedical research on human subjects were followed resulting which the clinical trials was suspended at RCC for 6 month.16
 
There are cases of trial on children on drugs that have never been formally studied in children because of many ethical concerns. Many drugs work differently in children. Reye’s syndrome, for example, is a potentially fatal complication of aspirin therapy in children that is very rare in adults. The death of 49 babies in clinical trial at the All India Institute of Medical Sciences (AIIMS), New Delhi, has opened a Pandora’s box as two of the trial drugs have never been tried on patients below 18 years. The AIIMS pediatrics department conducted 42 sets of trials of hypotensive drug olmesartan and valsartan on 4142 babies out of which 2728 was below the age of one, which was not registered in CTRI website. These unethical practices can be justified on the ground of safety on a particular age group as well prevalence and incidence rates conducting trials on a rare disease condition put the children at risk without any benefit. Phase III clinical trials are normally conducted as pre-approval requirement for marketing a new drug, but in this case studies were conducted when foreign company has not applied for marketing in India. This incidence has bought in to public notice through a Right to Information action filed by a non-government organization.17
 
A fatality was reported in a trial conducted by GVK Bio conducted on pneumonia vaccine in infants developed by Wyeth Pharmaceutical at St John’s Hospital, Bangalore. Healthy babies between 42 to 72 days were recruited for the trial which points to the callous manner of clinical trial subject recruitment. There are reports of participating in different bioequivalence studies in various CROs simultaneously by the ‘professional’ subjects only due to monetary incentives. This is not only unethical but also dangerous given the cocktail of different drug to which such a participant would be exposed giving rise to falsified results.18 All the types of issues have raised a concern against clinical trial creating hatred against the trial among the common man making it a low prestige value between the doctors and principal investigators.
 
The phase III clinical trials are the final phase of research needed before a drug receives FDA approval. Two fairly large-scale studies are needed and they need to show the drug is both safe and effective on the subjects tested. There’s been a long-standing problem with such clinical studies, however, one that the FDA has long been aware of but powerless to fix. They are purposely designed to employ stringent inclusion and exclusion criteria that may exclude a substantial portion of the population. In other words, the participants on whom the drugs are studied on are not representative of the people that will actually be receiving the drugs once approved.19
 
Death occurring during clinical trials may be due to unrelated health problems, but the number is steadily increasing alarming the situation. In 2010 alone (till June), 462 people died who were a part of clinical trial. Deaths occurring due to negligence of companies during trial are rare according to officials, such instances should come to light. Conducting trial in India is easier than in North America or Europe due to strict legislation and the patients are well aware of their rights. In India exploitation of trial participants are happening because of illiteracy, poverty and unaware of common rights making the poor needy people as experimental guinea pigs.20
 
The phenomenal growth in clinical trial unfortunately has created a situation where regulatory mechanism cannot keep pace. Ethical review in now mandatory for clinical trial but there is little review of the functioning of the ethics committee by the DCGI. There is little interaction between ethics committees in different locations, thereby allowing the practice of ‘ethics committee shopping’, sponsors whose trials are rejected by one ethics committee approach a different centre for approval.21
 
Measures to Counteract the Problems
a)    DCGI needs to generate effective monitoring mechanism for continuous evaluation of trials throughout the study period ensuring rregular and periodic scientific            and ethical review. Strategies should be developed to prevent fudging the data.
b)    Studies should follow strict adherence to ethical guidelines.
c)    All persons involved in study should undergo basic training concerning counselling and preventive strategies.
d)    All persons should be recruited in any study after ensuring receipt of proper informed consent for participation.
e)    Adequate care and protection should be provided to vulnerable groups.
f)     Community involvement at all stages of the studies.
g)    Sharing results with all persons involved in research.
h)    Ensure global justice, narrowing gap between developed and developing worlds.
i)     Prior agreements to ensure that proven interventions will be made to cases of trial discrepancies to prevent exploitation of study participants.
j)    Research ethics should be integral part of every biomedical research and into psyche of every stake holder that research participants who are central players in               every trial should be protected from any harm.
k)   All the legislations should be implemented strictly.22, 23
l)    To favor the promotion of clinical trial in India, restrictions are necessary to ensure that the health of the trial subjects is adequately protected in case of any contingency. It must be assured that the trial subjects are volunteers in true sense not enrolled due to monetary or other incentives, explicitly informed that they are part of a clinical trial. Comprehensive health insurance for all the participant volunteers must be provided by the sponsor in the form of a viable bank guarantee ensuring the obligation of any direct / indirect consequences. In the United States the sponsor or institutions are not legally bound to provide either free medical care or compensation for research related injuries to trial participants, which they made clear to the subjects before enrolling. Many European countries mandate the provision of ‘no fault’ clinical trial insurance. The vulnerability of clinical trial subjects in India must be provided with insurance cover and compensation in case of injury or death due to underprivileged conditions of most of the population.22, 23
 

Clinical Trial Registry (CTRI) - India
Clinical Trial Registry-India (CTRI) was launched 20th July 2007. With the launch of clinical trial registry, India became Asia’s first country to have online registry of clinical trials. This is a welcome step seeing the growing business of clinical trials in India and a major step towards accountability, transparency and information sharing on clinical trials. The mission of the Clinical Trials Registry- India (CTRI) is to encourage all clinical trials conducted in India to be prospectively registered before the enrollment of the first participant and to disclose details of the 20 mandatory items of the WHO International Clinical Trials Registry Platform (ICTRP) dataset.
 
Now it is compulsory to take registration in CDSCO office before starting of any clinical trial. As per the registration and their detail on the official website of CTRI the following are the facts which are discussed below.
 
The clinical trials registry-India is a free and searchable on-line register of all clinical trials being undertaken in India. Other countries, which do not have the facilities of such registration, may also register their clinical trials here. Though the registry, information of all clinical trials taking place across the country in all areas of health- new drugs, treatments, therapies, surgical procedures and new medical devices will become publicly available. Further it promotes greater trust and public confidence in clinical research. Trial registration also helps to prevent bias generated by selective reporting of only “positive” findings as well as reduce unnecessary duplication of research through greater awareness of existing trials and results. Further, prior registration is now a condition of publishing clinical trial data. From 1st July 2005 the International Committee of Medical Journal Editors (ICMJE) has declared that their journals will not publish the results of any clinical trials not included on an authorized register at the trials inception.
 
All interventional clinical trials conducted in India and involving Indian participants need to be registered. Trials should be registered before the enrollment of the first patient. The “Responsible Registrant” for a trial is either the principal investigator (PI) or the primary sponsor, to be decided by an agreement between the parties. For multi-center and multi-sponsor trials, it is the lead PI or lead sponsor who should take responsibility for registration. However, in case of muti-country trials, the Indian PI should also get the trial registered in CTRI quoting any other Registration number as its secondary ID. UTRN or Unique Trial Reference Number is a number assigned by the WHO by giving some preliminary information. To get this number, one has to click on the link given alongside the UTRN icon, which will take the registrant to the designated WHO site.
9
 

 
Truth of Clinical Trial in India
Untill June 2010 permissions has been obtained for 117 international trial and 134 Indian trial. In 2009, 258 global and 195 local trials took place in India21. In the official website of CTRI the reported trials for Phase I, II, III and IV were 109, 290, 636 and 171 respectively till 7 Sep 2010.
All the trials register in CTRI website was studied in detail to have comparative picture of parameters like; trial distribution site, regulatory approval status, trial allocation methods and diversification of age group, trial centre, disease and drug therapy was compiled for all four phases. The most happening clinical trial destination site in India is Maharashtra, Delhi comes under 2nd choice and Karnataka third. A total 69 DCGI approval were taken for phase I, 83 for phase II, 139 for phase II and 42 for phase IV. A total of 221 trails in all phases were noted as approval ‘not applicable’ the reason for which was not clear. Only for 01 trial in phase II and 03 trials in phase III for which DCGI approval is awaited.
 
Review of trial design method revealed maximum use of computer generated randomization sequence (261 trials). Centralized allocation concealment method adopted for highest 138 trials, coded identical and sequential numbered sealed opaque containers were also used for 70 and 77 trials respectively. Open level blinding and masking was applied for 173 trials, and participant, investigator and outcome assessor blinding was adopted for 125 trials. The trial method compilation showed the use of terms not applicable (105 for randomization sequence, 125 for allocation concealment and 82 for blinding and masking), no sign (43 for randomization sequence), not specified (57 for allocation concealment) and not mentioned (33 for blinding and masking) in the CTRI online data format.

 
The maximum clinical trials in India are targeting in the age group of 18-70. The least are in infants. There are many trials undergoing in age group above 65 in which, maximum 34 trials are in registered in phase IV. A total of 122 trials were found collectively in all phases where the age group was not specified. There are 105 trials with completed status out of which 12 for phase I, 21 for phase II, 40 for phase III and 33 for phase IV. The numbers of terminated trials in phase I, II and III are total 12 without any specified reason.
 
In India single as well as multicentred clinical trials are going on. The number of single centred studies was 58, 43, 62 and 80 for phase I, phase II, phase III and phase IV respectively. The number of multicentre study for all phases (I, II, III and IV) are 36, 74, 131 and 74 respectively.
 
Clinical trials are going on not only in Allopathic or Ayurvedic medicines but a good number of trials are on move on Homeopathic, Unani medicines along with naturopathy, surgical and diagnostic devices. The traditional treatment systems like yoga is also under study in different phases for diabetes and other diseases. Highest numbers of clinical trials are registered for anti cancer drugs for pancreatic, breast, bladder and prostate cancers (a total of 89 collectively in all four phases). Trials in children are under process for diarrhoea, asthma and jaundice. A total of 56 studies are in progress on diabetes and 31 trials are ongoing for antibacterial/antibiotic. Stem cell transplantation studies on ischemic stroke and obstructive pulmonary disease are total 10. Nine trial on Siddha and Homeopathic anti-HIV drugs are on progress. A very good number (total 22) of studies are registered on vaccines for HIV, swine flu, rabies, malaria and hepatitis.24
 
The Way Ahead

  • Proper planning and the use of trial sites in the southern as well as northern hemispheres allows for year-round trials can reduce the length of the studies.

  • Selecting the right CRO, tools and techniques.

  • Good contract negotiation between sponsor, hospitals and principal investigators and equal sharing of responsibilities.

  • Strict adoption of Good Clinical Practices (GCP) guidelines rectifying the hurdles.

  • System of prioritizing clinical trials of medications or techniques based on national interests, approving drug trials providing benefits to a substantial segment of the Indian population and for diseases relevant to Indian population.

  • Leverage of private and public resources.

  • Capacity building activities

  • Smart Regulatory system: strengthening ethical review mechanism and accreditation of IECs

  • Allowing phase I and phase 0 trials for drugs developed outside India.

  • Compulsory registration of all CROs with DCGI.

  • Discontinuation or termination of trials with reimbursement to participants should be implemented for fraud and misconduct.22

Conclusion
The outcome of clinical trials has major impact on the manufacturer’s interests and efforts and also on prognosis of disease. Thus clinical trials are not only important to a drug company and patients but also to government, regulators, media, different advocacy groups, ethical police, media, and the general public. Drug companies, pharmaceuticals and medical-device manufacturers have gradually realized the benefits of outsourcing clinical research.
 
In the last 10 years, skyrocketing costs of R&D have led to a growth explosion in the clinical services industry as pharma companies scramble to cut costs. Cost-savings are a significant draw card for many pharmaceutical companies when deciding to outsource clinical research to countries in emerging markets such as India and Latin America. The average cost of running a US-based clinical trial per patient is $5,404 for Phase I, $6,538 for Phase II and $7,635 for Phase III. According to an analysis last year by Rabo India Finance, conducting a clinical trial in a lower-cost destination such as India, for example, can cost up to 60 per cent less than in the US.
 
Strengthening and designing an appropriate evaluation method will definitely check misconduct. Forming Bioethics Centers in different states or at least in all metropolitan cites can improve the vigilance system on the ongoing trials. Adequate formal training of all the investigators, supervisors and data management staff will help in integrating ethical concerns in a better way and there is also need of introducing courses in government institutions tailoring the shortfalls. Networking between national and international trial centers help in reduction of mishaps in a way by prompt exchange of reports and data. It is the high time that health ministry should adopt hard steps to strong the regulatory mechanism to promote India a clinical trial heaven.
 
References

  1. Julka, P. K., Clinical Trials in India, Dilemmas for Developing Countries. Monitor, April, 2007.

  2. A History of Clinical Research. Available online: http://www.clinicalresearch.com/Research/Pages/HistoryofClinicalResearch.aspx. Accessed on 28th Aug 2010.

  3. Twyman, R., A Brief History of Clinical Trials. Available online: http://genome.wellcome.ac.uk/doc_WTD020948.html. Accessed on 28th Aug 2010.

  4. Industry Insight - Clinical Trials, A Report by Cygnus Business Consulting & Research, Hyderabad, Feb 2010.

  5. Clinical Trials in India: Ethical Concerns. Bulletin of the World Health Organization. August 2008, 86 (8):581.

  6. Booming Clinical Trials Market in India, Market Research Reports, Marketing and Business Research, Industry Analysis. Available online http://www.marketsmonitor.com/Booming-Clinical-Trials-Market-in-India-Report/IM564.htm. Accessed on 16 Aug 2010.

  7. Srinivas, S., Open House on Drug Trials: News on Social Justice and Development Issuses in India. Infochange Health. Available online http://infochangeindia.org/20051110275/Health/Features/Open-house-on-drug-trials-in-India.html. Accessed on 16 Aug 2010.

  8. Clinical Trial Laboratories in India. Available online http://www.indiaonestop.com/clinicaltrials.htm#Status of clincial trials in India. Accessed on 20th Aug 2010.

  9. Malik, V., Law Relating to Drugs & Cosmetics. 20th ed., Eastern Book Company. Lucknow, India, 2009 pp. 570-580 and 1006-1009.

  10. Gulhati, C.M., MIMS, India, Interviewed by e-mail, November 15, 2008.

  11. Khanna S., CliniRx Research, Delhi, Interviewed in Delhi, October 1, 2008.

  12. Requirements for Conducting Clinical Trial(s) of Medical Devices in India, Guidance Document, Central Drugs Standard Control Organization Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India. Dated 04.08.2010, pp. 4.

  13. Norrby, S.R., Clinical Trials of Antimicrobial. University of Lund, Sweden. Available online http://www.isap.org/2000/Bangalore/norrby/sld004.htm. Accessed on 28th Aug 2010.

  14. Indore Drug Trial. India Today, 1st Sep 2010, 27.

  15. Medical Research: The Truth of the ‘Drug’ Trials. Frontline India’s National Magazine. 2001, 18(24). Available online: http://www.hinduonnet.com/fline/fl1824/18241140.htm. Accessed on 6 Sep 2010.

  16. Ethical problems using children in clinical trials. Available online: http://en.wikipedia.org/wiki/Ethical_problems_using_children_in_clinical_trials. Accessed on 2nd Sep 2010.

  17. Jayaraman, K., AIIMS Clinical Trial Deaths: A Blow to Medi-ethics. Available online: http://www.igovernment.in/site/AIIMS-clinical-trial-deaths-a-blow-to-medi-ethics/. Accessed on 4th Sep. 2010.

  18. Ramana, K. V., Clinical Drug-Test Claims Volunteer’s Life in Hyderabad. Available online: http://www.dnaindia.com/india/report_clinical-drug-test-claims-volunteer-s-life-in-hyderabad_1212047. Accessed on 7th Sep 2010.

  19. Grohol, J. M., The problem with Phase III Clinical Trials. Available online: http://psychcentral.com/blog/archives/2009/05/06/the-problem-with-phase-iii-clinical-trials/. Accessed on 18th Aug 2010.

  20. Thacker, T., Data Suggests Clinical Trial Deaths on Rise. Available online: http://www.indianexpress.com/news/data-suggests-clinical-trial-deaths-on-rise/657844/. Accessed on 31th Aug 2010.

  21. Pandeya, R., Infant’s Death Leads DCGI to Allege Aesting Rules were Violated for Vaccine. Available online: http://www.livemint.com/2008/11/15001216/Wyeth-drug-tests-fall-foul-of.html. Accessed on 7th Sep 2010.

  22. Kumar, V., Biomedical research and Ethics review in India. Available online: http://www.google.co.in/#q=Ethical+Guidelines+on+Biomedical+Research+(1980%2F2000%2F2006)+%2Bdr.+vijay&hl=en&sa=2&fp=baefddeb84f546d0. Accessed on 5 Sep. 2010.

  23. Ethical Guidelines for Biomedical Research on Human Participant. Available online http://www.icmr.nic.in/ethical_guidelines.pdf. Accessed on 21th Aug 2010.

  24. Clinical Trials Registry. National Institute of Statistics (ICMR), India. Available online http://www.ctri.in/Clinicaltrials/do/login1. Accessed on 7th Sep 2010.

 

For full text of this article contact the publisher on info@kppub.com

 

Go to Content Index Page

PHARMA REVIEW - ARTICLES ARCHIVE ( COMPLETE LIST)

The above content is an abstract only. For the full Article please contact:
KONGPOSH Publications Pvt. Ltd.
ICS House, C-19, Commercial Complex, SDA, Opp. IIT Gate, New Delhi, India -110016
Tel.: 26855839, 20057149, Fax: 91-11-26855876
Email: info@kppub.com / fpc@vsnl.com, Website: http://www.kppub.com

 
 
 

 Copyright 2008. KONGPOSH PUBLICATIONS Pvt. Ltd.