Transgression of Human Rights in Clinical Drug Trials

Transgression of Human Rights in Clinical Drug Trials
INTRODUCTION
Overshadowing the law on medical research is the knowledge that under the Nazi regime
medical research was performed by doctors on people without their consent. Such horrors have
led to widespread acceptance that medical research involving human needs careful regulation,
and that great care needs to be taken to ensure that participating are consenting.1
Biomedical research is typically divided into two types: pre-medical research and clinical trials.
The first type focuses on research, development and non-human testing of new treatments. The
second type of biomedical research, clinical trials involve human testing of safety and efficacy of
treatments that have shown potential benefits for human health in pre-clinical research. 2
International Clinical Trials Day, on May 20th, first established in 2005 to raise awareness of the
importance of clinical trials. The first recorded controlled clinical trial back in 1747, when a
Scottish naval surgeon called James Lind carried out a clinical trial on sailor with scurvy.3
Clinical trials are typically broken down into several phases starting with trials on a small
number of volunteers and ending with testing of the treatment on hundreds or thousands of
people over a prolonged period of time. Newly developed treatments and products are approved
for general population only when their safety and efficacy is proven by the last phase of clinical
trials.4As clinical trials and sentinel data expanding number and location, the necessity and
1 Jonathan Herring, medical law and ethics, Oxford University Press, 4th ed. (2012) p. 598.
Catalyst
Biomedica,
About
Biomedical
Research,
available
at
http://www.catalystbiomedica.org.uk/, visited on June 02, 2014.
3 Cancer Research UK- Science Blog, International Clinical Trials Day: The Wales Cancer Trials
Unit
Goes
Global,
(2012),
available
http://scienceblog.cancerresearchuk.org/2012/05/21/international-clinical-trials-day-the-walescancer-trials-unit-goes-global/, visited on June 01, 2014.

1
at

relevance of research's worth to participants represents both an ethical and human rights
concern.5 The approval of 100 % FDI in the pharmaceutical sector 6 under the automatic course
for Greenfield investments as well as under the Government sanction route for investments in
present companies has made India as one of the developing markets for direct investment in
pharmaceutical sector.
Issues arising in clinical trials are not limited to ethical concerns, but at times enter the world of
international human rights law.
What is research?
If a patient is given a new drug, the effectiveness of which is not yet proven, is that research or
simply providing the patient with what is thought to be best practice? The key distinction is
whether the treatment is given in order to derive knowledge, in which case it is research, or
whether it is provided for the benefit of the patient. Where there is not a firm basis of support in
the clinical community for the proposed treatment that is likely to amount to research rather that
treatment.
To perform a human experiment on patient without their consent or other legal
4 Supra.
5 Trouiller P, Olliaro P, Torreele E, Orbinski J, Laing R, and Ford N: Drug development for
neglected diseases: a deficient market anda public-health policy failure. Lancet 2002, 359:21882194.
6 Reserve Bank of India, Foreign Direct Investment in Pharmaceutical sector- Clarification

(RBI/2013-14/567),
Available
at
http://www.rbi.org.in/scripts/NotificationUser.aspx?
Id=8845&Mode=0, visited on June 02, 2014.
7 Jonathan Herring, medical law and ethics, Oxford University Press, 4th ed. (2012), p. 599.
2

authorization could infringe patients rights under the European Convention on Human
Rights, Article 3 or 8.8
Unethical clinical trials conducted without obtaining informed consent of the participants have
struck India again, killing 254 women from the most marginalized sections of society. The
deaths, or rather murders, have taken place in the course of a 15-year long United States funded
clinical trial for a cervical cancer screening method. The women who perished were part of a
control group kept without screening.9 The Drugs & Cosmetics (Amendment) Bill, 2013 (for
short "Bill") has been introduced in the Parliament on August 29, 2013. The Bill has a separate
chapter containing penal provisions for violation and non-compliance of the provisions relating
to the conduct of the clinical trials.10
ISSUES AND DIMENSIONS REGARDING CLINICAL DRUG TRIALS
1. Informed Consent in Course of Clinical Trials

Informed consent is the process in which trial volunteers are informed about the nature, significance,
implications and risks of the trial. Informed consent is crucial to protect people against unwanted
experimentation.11
8 X v. Denamark (1983) 32 DR 282.
9 Asian Human Rights Commission, INDIA: Clinical trials kill 254 women under Supreme Courts watch,
available at http://www.humanrights.asia/news/ahrc-news/AHRC-STM-070-2014, visited on June 01, 2014.
10 Swasthya Adhika Manch, Indore & Anr. v. Union of India & Others, 2013(13) SCALE 148.
3

In 2011, a parliamentary enquiry committee found that the process of informed consent was
inadequate (especially questioning the fact that school head masters signed consent forms on behalf
of the children, calling it wrongful authorization). 12 Obtaining Informed Consent from study
subjects is a core requirement in the conduct of clinical trials and protection of human rights. In case
of minors, the Consent has to be signed by parents/guardians. In the case of uneducated signatories,
an independent person has to explain and witness the consent process. 13 In 2009, the States of Andhra
Pradesh and Gujarat launched a research project for the vaccination against the human papilloma
virus (HPV) which can cause cervical cancer.14 In the case of Andhra Pradesh 9,543 forms were
signed, 1,948 had thumb impressions while hostel warden had signed 2,763 forms. In the case of
Gujarat 6,217 forms were signed, 3,944 had thumb impressions and 545 were either signed or
carried thumb impression of guardians. The data shows that a very large number of
11 European Centre for Constitutional And Human Rights , Human rights violations in clinical trials in India, the
case of the HPV vaccination project, available at http://www.ecchr.de/index.php/clinical-trials.html, visited on June
03 2014.
12 Parliament of India Rajya Sabha: Department Related Parliamentary Standing Committee on

Health and Family Welfare, Alleged Irregularities in the Conduct of Studies using Human
Papilloma Virus (HPV) Vaccine by Path in India (Department of Health Research, Ministry of
Health
and
Family
72nd
Welfare),
Report
(2013),
p.
11-13,
available
at
http://164.100.47.5/newcommittee/reports/EnglishCommittees/Committee%20on%20Health
%20and%20Family%0Welfare/72.pdf, visited on June 03, 2014.
13 Ibid.
14 European Centre for Constitutional And Human Rights, Human rights violations in clinical
trials
in
India,
the
case
of
the
HPV
vaccination
project,
http://www.ecchr.de/index.php/clinical-trials.html, visited on June 03 2014.

4
available
at

parents/guardians were illiterate and could not even sign in their local language i.e. Telugu or
Gujarati.15
In landmark judgment Mary Schloendorff v. Society of New York Hospital16 it was held by the
Highest Court of New York that informed consent refers to the idea that physicians and
surgeons are obligated to disclose certain. A patient has the right to determine what happens to
his or her body, and physicians have corresponding duties to provide a patient with enough
information to make an educated decision regarding his or her condition. Special efforts must be
put into obtaining informed consent when patients come from linguistically and culturally
disparate backgrounds, in children, and in experimental medicine. Consent in children is highly
charged and complex. In the case of children and unemancipated minors, only parents or those
appointed by the court as guardians can provide legally binding consent. Nevertheless, the assent
of the child or minor should be obtained, in a manner and to a degree consistent with intellectual
development and emotional maturity.
2. Regulatory Concerns Pertaining to Clinical Trials in India
The Clinical Trials Registry- India (CTRI), hosted at the ICMRs (Indian Council for Medical
Research) National Institute of Medical Statistics (NIMS), is a free and online public record
system for registration of clinical trials being conducted in India that was launched on 20 th July
2007.17 The CTRI not only registers trials being conducted in India, but also accepts trials from
countries that do not have a primary registry of their own. 18 Further, Drugs & Cosmetics
(Amendment) Bill, 2013 has been introduced in the Parliament on August 29, 2013. The said Bill
15 Ibid.
16 211 N.Y. 125, 105 NE 92 (1914)
17 Clinical Trials Registry- India, National Institute of Medical Statistics (Indian Council of
Medical Research), available at http://ctri.nic.in/Clinicaltrials/cont1.php#mission, visited on June
03, 2014.
5

has a separate chapter containing penal provisions for violation and non-compliance of the
provisions relating to the conduct of the clinical trials.19
Clinical trials in India are regulated by Schedule Y of the Drugs and Cosmetics Rules.20 The
Rules are enforced by the office of the Drug Controller General of India (DCGI) who is also
responsible for monitoring all clinical trials submitted to that office for approval. For new drugs
being developed in India clinical trials have to be conducted in India from phase 1.21
Schedule Y of the Rules deals with the requirements and guidelines to obtain permission:
(a) To import and/or manufacture new drugs for sale;
(b) To undertake clinical trials in India.
18
Pandey A, Aggarwal AR, Seth SD, et al., Clinical Trials Registry-India: raising the veil, Natl Med J India.
2010; 23(3):1878.
19 Swasthya Adhika Manch, Indore & Anr. v. Union of India & Others, 2013(13) SCALE 148.
20 Government of India. Ministry of health and family welfare, The Drugs and Cosmetics Act
and Rules, available at http://cdsco.nic.in/html/Drugs&CosmeticAct.pdf, visited on May 28,
2014.
21 Supra.
6

A. Process of Conducting Clinical Drug Trial
Pharmaceutical Clinical trials in Human beings are commonly classified into Four Phases and the
Drug development process will normally proceed through all four stages over many years. If the drug
successfully passes through the phases I, II, and III, it will usually be approved for use in general
population. Before Pharmaceuticals Companies start clinical trials on drugs-extension pre-clinical
studies are conducted. And Phases are conducted as per the guidelines of the National Institute of
Health.22
Phase I- Clinical trials test a new biomedical intervention in a small group of people (e.g., 20-80) for
the first time to evaluate safety (e.g., to determine a safe dosage range, and to identify side effects). 23
Phase II- Clinical trials study the biomedical or behavioral intervention in a larger group of people
(several hundred) to determine efficacy and to further evaluate its safety.24
Phase III- Studies investigate the effectiveness of the biomedical or behavioral intervention in large
groups of human subjects (from several hundred to several thousand) by comparing the intervention
to other standard or experimental interventions as well as to monitor adverse effects, and to collect
information that will allow the intervention to be used safely.25
Phase IV- Studies are conducted after the intervention has been marketed. These studies are designed
to monitor effectiveness of the approved intervention in the general population. 26
22
Clinical
Trials
Different
Phases
of
the
trial,
available
at
http://www.medindia.net/patients/patientinfo/clinical-trials-phases.htm, visited on June 01,

2014.
23 Ibid.
24 Ibid.
25 Ibid.
7

B. Addition of Rule 122- DAB in the Drugs and Cosmetics Rule, 1945 (First Amendment)
Rules, 201327
As per Rule 122-DAB (1) the requirement of providing free medical management as long as
required, in the case of a harm happening to a clinical trial subject. And if the injury suffered
by the trail subject is related to the clinical trial conducted on such subject, he or she shall
also be entitled for financial compensation as per order of the Licensing Authority. In case
the clinical trial results in the death of the subject, financial compensation, as per the order of
the Licensing authority, has to be compensated to the nominee (s) of the deceased subject.
The preceding subsections of the Rule explain the circumstances which are considered as a
"direct nexus" to an immediate cause to the injury/death, consequences of non-payment of
compensation, etc.
C. Addition of Rule 122 DAC in the Drugs and Cosmetics Rule, 1945 Rules, 201328
As per Rule 122 DAC the prerequisites required for a clinical trial to be considered as
adequate so as to grant permission by the Licensing Authority to be conducted on any human
body. And the rule lays down the power of the Licensing Authority to impose any additional
conditions to be fulfilled in case of grant of permission in respect of any specific clinical trial,
as it is deem fit.
26 Ibid.
27 Ministry of Health and Family Welfare, Drugs and Cosmetic (First Amendment) Rules, 2013,
Available
at
http://www.manupatra.com/manufeed/contents/PDF/634969625902580076.pdf,
visited on June 02, 2014.
28 Ibid.
8

D. Insertion of Rule 122 DD in the Drugs and Cosmetics Rule, 1945 Rules, 201329
As per Rule 122 DD mandatory registration of the Ethics Committee and requires that no
Ethics Committee shall review and accord its approval to a clinical trial practice without priorregistration with the Licensing Authority as defined in clause (b) of Rule 21 and defines the
procedure of such registration to be made by filling an application to be made to the Licensing
Authority in accordance with the requirements as specified in the Appendix VIII of Schedule
Y of the Rule and the procedure thereof.
According to International Medical Guidelines and Legislation from the EU, UK, and US, sponsors
have the obligation to implement a proper monitoring system to verify that the research
protocol is followed, that adverse events are properly reviewed and reported, and that all regulations
are complied with. ECCHR further concludes that sponsors have the obligation to put and keep in
place arrangements for the purpose of ensuring or verifying that informed consent was taken
properly.30The licensing system was ineffective and the DCA did not maintain proper record.
Monitoring at State level was poor. Thus the objective of prevention of the menace of spurious
drugs to eliminate the danger to human life had not been achieved.31
29 Ibid.
30 Supra.
31 Health, Medical And Family Welfare Department, Performance Review: Implementation of

Drug and Cosmetic Act 1940, available at www.agap.cag.gov.in, visited on May 27, 2014.
9
INTERNATIONAL HUMAN RIGHTS LAWS PERTAINING TO CLINICAL

DRUG TRIALS
1. Declaration of Helsinki
In the early 1960s the World Health Organization recognized, in part because of the Thalidomide
tragedy, that greater international cooperation was necessary on standards for the conduct of
research.
The regulation of research involving humans is governed by a patchwork of legislation, common
law, and international regulation. The eagerly awaited seventh version of the Declaration of
Helsinki (DoH) was released by the World Medical Assembly (WMA) on October 19, 2013 at
the 64th General Assembly.32
This Declaration includes a number of important principles:33
a. The need for consent for all competent participants in research.
32 World Medical Association Declaration of Helsinki Ethical principles for medical research involving human
subjects. WMA General Assembly, Fortaleza, Brazil; October 2013. World Med J. 2013 Oct;59(5):199202.
10

b. The rights of subjects to withdraw from the research.
c. Human experimentation is to be used as a last resort where other forms of research not
involving human subjects are not possible.
d. There must be proportionality between the benefits of the research and the risk run by the
subjects.
Paragraph 6 of the Declaration contains an overarching principle:34
In medical research involving human subjects, the well-being of the individual research
subject must take procedure over all other interest.
This means that if there is ever a clash between the rights of the human subjects of research and
the interests of society, the rights of the subject prevail. 35 The reasoning used by House of Lords
in R v. Brown36 that as long as the medical research involved is in the public interest, consent
may provide a defense to even serious injuries. But this still leaves unanswered the question of
where the line would be drawn. Of course euthanasia is unlawful and so a participant could not
agree to be killed as part of a research project. But what about small risk of death or a higher risk
of serious harm? A court considering where the line is to be drawn would, no doubt, take account
of following points.37
Also, the World Medical Association, in its revision of the Declaration of Helsinki, now specifies
that every clinical trial must be registered in a publicly accessible database before recruitment of
the first subject.38 In November 2008, the Drugs Controller General of India (DCGI) started
advising all those applying to the DCGI for permission to conduct clinical trials to register their
34 Ibid.
35 Erikson, S., Hoglund, A.T., & Helgesson, G., Do ethical guidelines give guidance? A critical
examination of eight ethics regulations, Cambridge Quarterly of Healthcare Ethics, (2008), p. 15.
36 [1994] 1 AC 212.
37 Jonathan Herring, medical law and ethics, Oxford University Press, 4th ed. (2012), p. 602
11

trials.39 However, the DCGIs decision to make it mandatory for trials initiated
after 15 June 2009 to be registered has provided the maximum support to
the initiative in India.
i. Paragraph 21 of the Declaration of Helsinki states:40
Medical research involving human subjects may only be conducted if the importance of the
objective outweighs the inherent risks and burden to research subjects.
There are two points worth noting. First, risk of harm to participant is only permissible where the
research has important benefits. Research into finding a cure for AIDS or malaria may justify a
risk of harm to participants, but it is unlikely that such a risk would be acceptable to find a
solution to male hair loss. Second, a distinction is drawn between research that may directly
benefit the participant and that which will not. So where the participant suffers from a condition
and the research project is aimed at finding a treatment for that condition, then a higher level of
risk may be legitimate than otherwise.41
2.
International Covenant on Civil and Political Rights (ICCPR)
38 World Medical Association (WMA), Declaration of Helsinki: Ethical principles for medical
research involving human subjects. 59th WMA General Assembly, Seoul, October 2008.
39 Pandey A, Aggarwal A, Maulik M, Seth SD, Clinical trial registration gains momentum in
India, Indian J Med Res (2009), pp.856.
40 Ibid.
12

The ICCPR was adopted by the United Nations General Assembly on 16 December 1966 and
entered into force on 23 March 1976.42Article 7 of the International Covenant on Civil and
Political Rights (ICCPR) recognizes that a lack of informed consent constitutes a human rights
violation:
No one shall be subjected to torture or to cruel, inhuman or degrading treatment or
punishment. In particular, no one shall be subjected without his free consent to medical
or scientific experimentation.
According to international medical guidelines and legislation from the EU, UK, and US, sponsors
have the obligation to implement a proper monitoring system to verify that the research protocol is
followed, that adverse events are properly reviewed and reported, and that all regulations are
complied with.
42 World Health Organization, Health and Human Rights: International Covenant on Civil and
Political Rights, available at http://www.who.int/hhr/Civil_political_rights.pdf, visited on June
02, 2014.
13

RULINGS AND GUIDELINES
A. In Swasthya Adhika Manch, Indore & Anr. v. Union of India & Others 43, followings are
the findings and rulings:
1. It has been brought to the notice of Honble Court that the Drugs & Cosmetics
(Amendment) Bill, 2013 (for short "Bill") has been introduced in the Parliament on
29.8.2013. The Bill has a separate chapter containing penal provisions for violation and
non-compliance of the provisions relating to the conduct of the clinical trials.
2. The additional affidavit that 577 clinical trial sites have been inspected and notices have
been issued to the investigators/sponsors/ethics committees seeking clarifications in 235
cases.
3. The clinical trials of new chemical entity shall be conducted strictly in accord with the
procedure prescribed in Schedule 'V of Drugs & Cosmetics Act, 1940 under the direct
supervision of the Secretary, Ministry of Health & Family Welfare, Government of India,
it is stated that a system of supervision of clinical trials of new chemical entities by
constituting Apex Committee and Technical Committee has been put in place.
4. The Expert Committee under the chairmanship of Prof. Ranjit Roy Chaudhury to prepare
guidelines for approval of clinical trials and new drugs in the country was appointed
which has submitted its report on 8.8.2013. It is stated that the said report is under
consideration.
B. Guidelines for Conducting Clinical Trials:44
The Union health ministry has accepted the recommendations of the Prof. Ranjit Roy
Chaudhury expert committee which had recently submitted its report to the ministry.
Accepting the recommendations of the expert panel for accreditation of ethics committees,
43 2013(13) SCALE 148.
44 Report of the Prof. Ranjit Roy Chaudhary Expert Committee, Policy And Guidelines For
Approval
of
New
Drugs,
Clinical
Trials
And
Banning
of
Drugs,
available
at
http://www.cdsco.nic.in/writereaddata/Report_of_Dr_Ranjit_Roy.pdf, accessed on May 29,

2014.
14

investigators and the clinical trial sites, the ministry decided that in order to strengthen the
clinical evaluation of new drugs, the clinical trials should be conducted in accredited sites by
accredited investigators with the oversight of accredited ethics committees (ECs). 45
Following are the salient recommendation given the said committee:46
1. The 12 drug advisory committees which are functioning at present will be replaced by
one broad expertise-based Technical Review Committee to ensure speedy clearance

of applications without compromising on quality of data and rules and regulations.
The Committee would be assisted as required by appropriate subject experts selected
from the Roster of Experts.
2. An informed consent from each participant is a mandatory prerequisite for a clinical
trial. In circumstances where informed consent has to be obtained from special groups
of people who have diminished capacity to protect their interests or give consent for
them, the consent given by the guardian should be witnessed by an independent
person who also has to sign the informed consent document. Audiovisual recording of
the informed consent process should be undertaken and the documentation preserved,
adhering to the principles of confidentiality.
3. Compensation need not be paid for injury or death due to totally proven unrelated
causes. In all other cases of death or injury/disability, compensation should be paid to

the participant or his legal heirs. Compensation will be paid to the trial participant if
any drug-related anomaly is discerned at a later stage and accepted to be drug related
by a competent authority whether in India or abroad.
4. A Central Accreditation Council should be set up to oversee the accreditation of
institutes, clinical investigators and institute ethics committees.
45 Ramesh Shankar, Policy And Regulation: Govt. Accept Ranjit Roy panel report on approval
of
new
drugs,
clinical
trials
&
banning
of
drugs,
available
http://www.pharmabiz.com/NewsDetails.aspx?aid=78617&sid=1, visited on May 29, 2014.
46 Supra.
15
at

5. In cases of clinical trials being carried out on patients suffering from terminal
illnesses such as cancer, compensation may be payable if the ethics committee, after
deliberation, is of the considered opinion that:
there is an increase in the number of SAEs occurring in such a patient as
compared to a standard treatment, and which may be irreversible; or

Life expectancy has been severely curtailed.
For such patients, compensation may not be given if the primary end-point is death,
as per the clinical trial protocol.
16

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http://www.catalystbiomedica.org.uk/, visited on June 02, 2014.

http://scienceblog.cancerresearchuk.org/2012/05/21/international-clinical-trials-day-the-walescancer-trials-unit-goes-global/, visited on June 01, 2014.