THE PHARMA REVIEW
(SEPTEMBER - OCTOBER 2010)
Present Status of Clinical
Trials in India: Unfolding The Truth
Dr. Papiya Bigoniya, Alok Shukla,
Chandra Shekhar Singh
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
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.
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
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
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
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
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
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
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
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
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
5. Quintiles Spectral Limited Ahmadabad 380 015,
6. Specialty Ranbaxy Limited Mumbai - 400 093,
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
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.
Inadequate source documentation.
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
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
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
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
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
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
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
f) Community involvement at all stages of the
g) Sharing results with all persons involved in
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
should be protected from any harm.
k) All the legislations should be implemented strictly.22,
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
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
Compulsory registration of all CROs with DCGI.
Discontinuation or termination of trials with reimbursement to
participants should be implemented for fraud and misconduct.22
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
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