UNIVERSITY OF PETROLEUM & ENERGY STUDIES

COLLEGE OF LEGAL STUDIES

JURISPRUDENCE
PROJECT: CLINICAL TRIALS IN INDIA

SUBMITTED TO: SUBMITTED BY:

Prof. Ashish Verma Shreya Goel
(Assistant Professor) R450212098

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 ACKNOWLEDGMENT
I am very thankful to everyone who all supported me, for I have completed my project
effectively, moreover on time. Any attempt at any level cant be satisfactorily completed
without the support and guidance of my teacher. I would like to express my immense
gratitude towards Prof. Ashish Verma for his constant support and motivation that has
encouraged me to come up with this project. He gave me moral support and guided me in
different matters regarding the topic. He had been very kind and patient while suggesting me
the outlines of this project and correcting my doubts. I thank him for his overall supports. I
am very thankful to my teacher who has rendered their whole hearted support at all times for
the completion of this project.

Thanking you
Shreya Goel
B.A LL.B
IVth semester sec-B

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 CONTENTS

I. INTRODUCTION 4
II. REGULATORY GUIDANCE FOR CONDUCTION CLINICAL
TRIALS IN INDIA 5
Essential Information for Informed Consent
Understandability
Voluntariness
Record of consent
Compensation
Malpractice

III. WHY IN INDIA? 11

IV. CONDUCT OF ILLEGAL/UNETHICAL TRIALS IN INDIA 12
V. CONCLUSION 14
VI. BIBLIOGRAPHY 15

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 CLINICAL TRIALS IN INDIA

INTRODUCTION
Clinical trials are the scientific term used for testing of newly evaluated drug and to know the
safety and efficacy of that new drug. That modern clinical trial was invented in the middle of
the twentieth century but its pre history dates back exactly 250 years -1753. When English
physician James Lind showed that citrus fruit cured a disease, Scurvy. 1 In 1830 French
physician Piers Levis challenged those seeking new therapies to support their conclusions
with statistics. The clinical trials or medical discovery accelerated rapidly after World War 2
as America and few developing countries and some pharmaceutical companies. In todays
global scientic 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. But Clinical trials also have another side to it, a rather evil one. Some industries and
companies aim poor and illiterate people and perform clinical trials on them without
informed consent and without proper protocol, with that some people face serious health
problems. Unethically administered clinical trials have been taking place in India on a very
large scale and are administered to people coming from disadvantaged and backward sections
of society who are unfortunately being used as guinea pigs by large international
pharmaceutical companies. Experimental drugs and vaccines have been tested on them in the
absence of enforcement of stringent statutory rules. This lapse in enforcement of stringent
rules on account of the corrupt nature of Indian doctors and authorities has become well
known and has resulted in India being represented as a place where poor women and children
are administered drugs without the fear of persecution. This paper will focus on these
unethical trials in India supported by a case study.

1 Chabukswar A.R. Clinical trials: present and future in India. www.pharmainfo.net.

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REGULATORY GUIDANCE FOR CONDUCTING CLINICAL
TRIALS IN INDIA

An important element of conducting clinical trials at any stage is securing informed consent
from trial participants. This helps to respect the autonomy dignity of patients by allowing
them to make informed choices regarding their health. Rules governing informed consent are
contained in domestic laws such as the Drugs and Cosmetics Act 1940, and particularly
Schedule Y of the same act, Indian Council Medical Research (ICMR) Guidelines, and Code
of Medical Ethics Regulations 2002. International guidelines set by the World Health
Organization (WHO) also provide a benchmark for clinical trial regulation [these guidelines
are not from the WHO but a consortium of regulatory agencies from EU, US, Japan, etc
will get correct title. The WHO has recommended these guidelines be followed, however].
This section describes the basic informed consent process that patients should undergo when
participating in a clinical trial.

Essential Information for Informed Consent

According to Appendix V of Drugs and Cosmetics Act 1940, Schedule Y, essential

information that must be communicated to patients include:

Statement that the study involves research and explanation of the purpose of the
research
Expected duration of the Subject's participation
Description of the procedures to be followed, including all invasive procedures and
Description of any reasonably foreseeable risks or discomforts to the Subject
Description of any benefits to the Subject or others reasonably expected from
research. If no benefit is expected Subject should be made aware of this.
Disclosure of specific appropriate alternative procedures or therapies available to the
Subject.
Statement describing the extent to which confidentiality of records identifying the
Subject will be maintained and who will have access to Subjects medical records

Trial treatment schedule(s) and the probability for random assignment to each
treatment (for randomized trials)

Compensation and/or treatment(s) available to the Subject in the event of a trial-

related injury

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 An explanation about whom to contact for trial related queries, rights of Subjects and
in the event of any injury

The anticipated prorated payment, if any, to the Subject for participating in the trial

Subject's responsibilities on participation in the trial

Statement that participation is voluntary, that the subject can withdraw from the study
at any time and that refusal to participate will not involve any penalty or loss of
benefits to which the Subject is otherwise entitled

The ICMR and WHO Guidelines state the same essential elements.

The HPV vaccine investigated in this report was administered to minors. In this case, this
essential information should be communicated to both children and parents, who must both
give informed consent before the vaccine can be administered.

Understandability

This information should be communicated in a format that is easy for patients to understand,
as stated in the WHO Guidelines:

The language used in the oral and written information about the trial, including the written
informed consent form, should be as non-technical as practical and should be understandable
to the subject or the subject's legally acceptable representative and the impartial witness,
where applicable.

ICMR Guidelines similarly state: Adequate information about the research is given in a
simple and easily understandable unambiguous language in a document known as the
Informed Consent Form with Participant/ Patient Information Sheet.

For trials that involve patients who require the consent of the patients legally acceptable
representative, as is the case with minors who received the HPV vaccination in question,
paragraph 4.8.12 of the WHO Guidelines state the subject should be informed about the trial
to the extent compatible with the subjects understanding and, if capable, the subject should
sign and personally date the written informed consent. Schedule Y similarly states in
paragraph vii:

(vii) Pediatric Subjects are legally unable to provide written informed consent, and are
dependent on their parent(s)/ legal guardian to assume responsibility for their participation in

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clinical studies. Written informed consent should be obtained from the parent/ legal guardian.
However, all pediatric participants should be informed to the fullest extent possible about the
study in a language and in terms that they are able to understand where appropriate pediatric
participants should additionally assent to enroll in the study. Mature minors and adolescents
should personally sign and date a separately designed written assent form.

And the ICMR guidelines state the same in paragraph 4d: d. the assent of the child should be
obtained to the extent of the childs capabilities such as in the case of mature minors from the
age of seven years up to the age of 18 years.;

Patients should also be allowed to ask questions, as stated in ICMR Guidelines paragraph:
i. Communicate to prospective participants all the information necessary for informed
consent. Any restriction on participants right to ask any questions related to the study will
undermine the validity of informed consent

Patients should furthermore have sufficient time to weigh their decision to participate, as
stated in WHO guideline paragraph 4.8.7: Before informed consent may be obtained, the
investigator, or a person designated by the investigator, should provide the subject or the
subject's legally acceptable representative ample time and opportunity to inquire about details
of the trial and to decide whether or not to participate in the trial. All questions about the trial
should be answered to the satisfaction of the subject or the subject's legally acceptable
representative.

Voluntariness

Consent should be given freely, without undue pressure. This is stated in WHO guidelines:

2.9 Freely given informed consent should be obtained from every subject prior to clinical
trial participation.

4.8.3 Neither the investigator, nor the trial staff, should coerce or unduly influence a subject
to participate or to continue to participate in a trial.

Voluntariness is also emphasized in ICMR Guidelines paragraph II, whereby all trials should:

ii. Exclude the possibility of unjustified deception, undue influence and intimidation

iii. Seek consent only after the prospective participant is adequately informed. The
investigator should not give any unjustifiable assurances to prospective participant, which
may influence her/his decision to participate;
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Record of Consent

Consent can be recorded can be given in a written or verbal format. Particularly in the case of
written consent, patients should receive a copy of the consent form, as stated in paragraph 1.7
of ICMR Guidelines:

A copy of the participant/patient information sheet should be given to the participant for her/
his record...

Paragraph 4.8.11 of the WHO Guidelines similarly state:

4.8.11 Prior to participation in the trial, the subject or the subject's legally acceptable
representative should receive a copy of the signed and dated written informed consent form
and any other written information provided to the subjects.

In addition, consent forms should be preferably witnessed by a person not related to the trial,
and in case the participant is not competent to do so, a legal guardian or other duly authorized
representative (ICMR Guidelines, paragraph iv).

Compensation

Participants in medical trials should be compensated, as stated in paragraph 3 of the ICMR

guidelines:

Participants may be paid for the inconvenience and time spent, and should be reimbursed for
expenses incurred, in connection with their participation in research. They may also receive
free medical services. During the period of research if the participant requires treatment for
complaints other than the one being studied necessary free ancillary care or appropriate
referrals may be provided.

Drugs and Cosmetics Act 1940, Part XA, Rule 122DAB states that:

(1) In the case of an injury occurring to the trial subject, he or she shall be given free
medical management as long as required.

(2) in case the injury occurring to the trial subject is related to the clinical trial, such subject
shall also be entitled for financial compensation as per order of the Licensing Authority
defined under clause (b) of Rule 21, and the financial compensation will be over and above
any expenses incurred on the medical management of the subject.

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(3) In the case of clinical trial related death of the subject, his/her nominee(s) would be
entitled for financial compensation, as per the order of the Licensing Authority defined under
clause (b) of Rule 21, and the financial compensation will be over and above any expenses
incurred on the medical management of such subject.

(4) The expenses on medical management and financial compensation in case of clinical
injury or death of the trial subject shall be borne by the sponsor of the clinical trial

(6) the Sponsor, whether a pharmaceutical company or an institution shall give an

undertaking along with the application for clinical trial permission to the Licensing Authority
defined in clause (b) of Rule 21, to provide compensation in case of clinical trial related
injury or death for which subjects are entitled to compensation.

The impact of compensation on voluntariness must also be considered, as described in ICMR

guidelines part 3:

However, payments should not be so large or the medical services so extensive as to make
prospective participants consent readily to enroll in research against their better judgment,
which would then be treated as undue inducement

Malpractice

The Code of Medical Ethics Regulations 2002 states further general principles to guide good
practice in the medical profession, and can be applied to clinical trials as well:

1.2.1 The Principal objective of the medical profession is to render service to humanity with
full respect for the dignity of profession and man. Physicians should merit the confidence of
patients entrusted to their care, rendering to each a full measure of service and devotion.

In addition, the Regulations state that physicians should adhere to:

1.9 Evasion of Legal Restrictions: The physician shall observe the laws of the country in
regulating the practice of medicine and shall also not assist others to evade such laws. He
should be cooperative in observance and enforcement of sanitary laws and regulations in the
interest of public health.

Furthermore, the Regulations state grounds for misconduct that can render a doctor liable for
disciplinary action:

7.19 A Physician shall not use touts or agents for procuring patients.

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7.7 Signing Professional Certificates, Reports and other Documents: Registered medical
practitioners are in certain cases bound by law to give, or may from time to time be called
upon or requested to give certificates, notification, reports and other documents of similar
character signed by them in their professional capacity for subsequent use in the courts or for
administrative purposes etc. Such documents, among others, include the ones given at
Appendix 4. Any registered practitioner who is shown to have signed or given under his
name and authority any such certificate, notification, report or document of a similar
character which is untrue, misleading or improper, is liable to have his name deleted from the
Register.

7.22 Research: Clinical drug trials or other research involving patients or volunteers as per
the guidelines of ICMR can be undertaken, provided ethical considerations are borne in mind.
Violation of existing ICMR guidelines in this regard shall constitute misconduct. Consent
taken from the patient for trial of drug or therapy which is not as per the guidelines shall also
be construed as misconduct.

WHY IN INDIA?
India is an attractive destination for conducting clinical trials. A young, highly educated
work-force, a very large population concentrated in a few urban centres, prevalence of all

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major diseases, and importantly, use of English as the primary language make it easy to set up
clinical sites in India.2 Over the last couple of years, Indian regulatory and business processes
have gone through several enhancements to harmonize with the rest of the world with the
goal of making it easier for India to participate in global trials. 3 Outsourcing a clinical trial to
India offers the promise of rapid completion and reduced cost to a sponsor from the US,
Canada and Europe. It is widely projected that India might become a major destination for
outsourced clinical trials in the next few years. India is still relatively new to the scene; only
about 1% of all clinical trials under a US Investigational New Drug application (IND) are
currently being conducted in India.4 Approximately 350 investigators have worked on clinical
studies under US IND regulations. The total may be higher if all clinical trials conducted in
India by indigenous and non-US companies were combined. However, the majority of
clinical studies conducted in India are still in support of generic products. The core
experience of both clinical research and regulatory professionals thus is in generic products.
As a signatory to the WTO agreements, India is looked upon as a favourable destination for
conducting global clinical trials. India clearly provides an opportunity in terms of availability
of large patient populations, highly educated talent, a wide spectrum of disease, lower costs
of operations, and a favourable economic and intellectual property environment. The overall
time and cost advantage in bringing a drug to market by leveraging Indias resources could be
as high as US $200 million, hence the steadily increasing number of global studies in India
over the past two years. Major pharmaceutical companies estimate the total market for
conducting clinical trials either directly or through contract research organizations (CROs) in
India through 2010 at US $2 billion. CROs themselves are fast gaining importance because of
their global presence, specialized local expertise, and competitive pricing strategies. And a
significant number of new CROs have set up operations in India over the past two years.
However, some key barriers stand in the way of opportunities, including patients rights and
safety, regulatory framework, infrastructure, organization of ethics committees, data quality,
lack of training curricula focusing on clinical research, and other factors. Most of these
barriers are common to all developing countries and need to be addressed in a similar way. 5
Because the clinical investigator plays a major role in the ethical conduct of any clinical trial,
2 Kumar M and Kher S. Regulatory Considerations for Conducting Clinical Trials in India. Regulatory Affairs
Focus, 12(3):26-31, 2007
3 Kumar M and Mehra M. Regulatory Harmonization Efforts in India: Keeping In Step with the Globe.
Regulatory Affairs Focus, 13(6):28-33, 2008 www.clinicaltrials.gov
4 Kumar M and Tate K. Designing a Global Product Development Strategy.Regulatory Affairs Focus,
13(6):16-21, 2008
5 Fenn CG,Wong E, and Zambrano D. 2001. The contemporary situation for the conduct of clinical trials in Asia.
International Journal of Pharmaceutical Medicine 15: 169-73.

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its successful outcome depends on how the investigator(s) has assumed overall responsibility.
Most of the barriers mentioned above can be easily addressed if a clinical investigator is
committed to the ethical conduct of trials.

CONDUCT OF ILLEGAL/UNETHICAL TRIALS

Scientific misconduct is a global phenomenon linked to human behaviour rather than to an
individual country. For instance, the U.S. Food and Drug Administration (FDA) website lists
the details of clinical investigators who have been disqualified or restricted from doing
research on grounds of scientific misconduct.6 Details of warning letters issued to various
stakeholders (clinical investigator, ERB/IRB, sponsor, CRO, etc.) can also be obtained from
the same website. However, FDA has not banned clinical trials based on these grounds, these
individuals, or individual organizations. Rather, FDA has increased its surveillance over
clinical research programs. In like manner, the Indian regulatory authority is also in the
process of setting up surveillance teams for ensuring ethical conduct of clinical trials.
Companies acting ethically set globally consistent standards and conduct trials only in the
countries where GCP compliance is assured. Indian investigators have demonstrated their
compliance by virtue of participation in more than 60 global trials so far. Moreover, a
majority of those trials were FDA or European registration trials, requiring strict compliance
with GCP and regulatory guidelines. The data have been accepted by foreign regulatory
authorities and published in international scientific journals of repute.

Studies have proved that malpractices are rampant in clinical trials in India. Recent cases
include unethical testing of contraceptives, fertility drugs, cardiac treatments and cancer
medicines. Analysts say as many as two million Indians may be enrolled in research trials by
2010. Just three years ago, that number was about 2,000. A major problem is that a large
proportion of participants are illiterate and lured into trials by offers of free health care and
financial inducements. They are often unaware of the benefits and risks of taking part in a
trial, and may not even distinguish between treatment and research. The concept of informed
consent is not always understood. The lack of a national ethics body with regulatory control
has further hampered the establishment of a legal framework with policing powers. Other
ethical debates question whether new drugs tested in India will actually benefit patients

6 U.S. Food and Drug Administration. Disqualified/Restricted/Assurance List for Clinical Investigators. Available
from www.fda.gov/ora/compliance_ref/bimo/dis_res_assur.htm.

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locally, and then be made available to them at reasonable prices. A case in point is the recent
clinical trial of trastuzumab (Herceptin) an expensive treatment for early breast cancer.
With 25% of India's population living below the poverty line, it is unlikely that this drug will
be affordable to them.

The Supreme Court has castigated the Union government for being negligent in curbing
illegal clinical trials despite the deaths of at least 2,374 persons who had undergone the
dubious testing for unregistered drugs between 2007 and 2012. During the resumed hearing
of a PIL filed by an NGO Swasthya Adhikar Manch, the court sought an end to illegal clinical
trials of untested drugs by multinational companies. The NGO has alleged that massive
clinical drug trials, estimated at Rs 8,000 crore annually by various pharmaceutical firms, use
Indian citizens as guinea pigs.

The drug trials are creating havoc in the country, the court said, adding that all clinical
trials will be done under the supervision of the Union health secretary. You have to protect
the health of the citizens of the country. It is your obligation. Deaths must be arrested and
illegal trials must be stopped, the bench said and directed the Centre to handle the menace
in an effective manner. The judges slammed the government for slipping into deep slumber
on the issue and for being indifferent in evolving an effective mechanism to stop rackets of
some multinational drug companies which conduct illegal clinical trials.

In 2004, doctors at the Bhopal Memorial Hospital and Research Centre, an exclusive institute
for the victims of the 1984 gas leak disaster, recruited unsuspecting survivors for clinical
trials, without their knowledge or consent.

It is said that 14 participants died during the course of the trials. In an Indore-based hospital,
32 people died in clinical trials between 2005 and 2010. A parliamentary panel says that the
Central Drug Standard Control Organisation (CDSCO) is in collusion with drug companies
and doctors, and approving at least one drug every month, without conducting clinical trials
or seeking expert medical opinion. A report quoting CDSCO says an estimated 150,000
people are enrolled for clinical trials in India. It has been reported that the number of
subjects in clinical trials between 2009 and 2012 were 352,475. The government says
serious adverse events resulting in deaths may occur during clinical trials due to various
reasons. These deaths could be due to life-threatening diseases like cancer, cardio-vascular
conditions like congestive heart failure/stroke and other serious diseases.

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CONCLUSION
From various case studies it has been found that the well off, better educated families are told
that they could refuse taking the vaccine, while the poorer, less literate families are given no
such option. In most cases informed consent is not properly taken from the families and the
participants. In some cases, particularly the poorer families, the participants do not even
know the vaccine was to prevent cervical cancer but were told the vaccine was to prevent
general illness like typhoid and diphtheria. Anywhere in the world, clinical trials are a
carefully regulated area because of the obvious risks involved. In India, with its high levels of
illiteracy, the risks become even greater since it is much more difficult for many of the
potential 'volunteers' in trials to make an informed choice. Further, a public healthcare system
that is woefully inadequate leaves most people who are not well-off desperately seeking any
sort of treatment they can get. This again is a situation that heightens the possibility of
unscrupulous exploitation of those in desperate needs. If anything, therefore, India needs to
be even more cautious than most in regulating clinical trials. Our governments should be

aware of this and act accordingly . Fortunately, in a majority of cases, clinical trials if
administered properly can provide answers regarding the use or not of a therapeutic agent that
can benefit millions of patients worldwide. Being the second most populated country in the
world, India can contribute significantly to global drug development programs.

BIBLIOGRAPHY
CLINICAL TRIALS IN INDIA: SHOULD YOU OR SHOULD YOU NOT PARTICIPATE?,
DR AAKASH GANJU

CLINICAL TRIALS IN INDIA: DILEMMAS FOR DEVELOPING COUNTRIES, P.K. JULKA

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PRACTICAL ASPECTS OF CONDUCTING CLINICAL TRIALS IN INDIA , MUKESH KUMAR, PHD,
RAC

PRESENT SCENARIO OF CLINICAL TRIALS IN INDIA

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