1. Ensuring the safety and well-being of human subjects in clinical trials requires adherence to ethical principles like respect for persons, beneficence, and justice. Informed consent is also crucial, and involves fully informing subjects of risks, benefits, alternatives, and the voluntary nature of participation. 2. Proper oversight from investigators, research coordinators, and institutional review boards (IRBs) is needed to review protocols and documents, ensure risks are minimized, and that the rights and welfare of subjects are adequately protected. 3. Developing countries present additional challenges in protecting subjects due to factors like poverty, lack of education, weak regulatory systems, and cultural issues that can compromise truly informed consent. Strengthening

1. It is Time to Make a Move! Ensure the Safety and Overall Wellbeing of the
Human Subjects Involved in Clinical Research
Dr. Smita Singh (Academic Head ACRI)
Mr. Shaji Paulose (Head of Formulation, SPL
Introduction:-
Subject/Trial Subject is an individual who participates in a clinical trial, either as
a recipient of the investigational product or as a control.
The clinical trial is incomplete without the participation of an eligible human
subject. It is known that Clinical trial is the heart and soul of the modern drug
development process. It has become the necessity to evaluate the safety and efficacy
of the drug in the human participant. Amidst the intangible benefits that we accrue
through these systematic and organized clinical trials, it is crucial and imperative
that we diligently address the issue of protection to all the human subjects
participating in the respective clinical trial. Many events and incidents occurred in
the past clinical trial processes have an impact on both the researcher and the
participant involved in clinical trial. Therefore, the question remains, how can we
ensure the safety and overall well being of the human subjects?
Ethical principles that guides safety in Clinical Research
There are established guidelines and processes that monitor and ensure the safety
of the human volunteers.
1. According to Belmonte there are 3 ethical principles that guides the
clinical research
a) Respect for person
b) Beneficence
c) Justice
Patient autonomy or respect for the person is an important principle in the
medical ethics; in actual practice, especially in the context of developing
countries, this important principle is usually disregarded or misrepresented or
only partially acknowledged..

2. 2 .Role of Investigator, Clinical Research Coordinator and Other staff;
a) The investigator should understand that clinical research, is not only valuable
for the society but it is also ethically challenging. It requires an able and adept
handling of both the science and human values.
b) The investigator has to be aware of the tension that could arise as a result of
balancing the science and protection to the subject
c) The investigator has to inform subject accordingly
d) Take an opinion from other members, physician who are involved in the clinical
trial to minimize the risk to the subject
3. Responsibility of IRB/IEC in assuring the safety of human subjects
An IRB is defined as a committee which is responsible for the review, approval,
disapproval, modification and suspension or termination of trial related to human
subject
IRB is responsible for:-
a) Review of important documents like informed consent form, protocol,
b) Investigator brochure update, Financial document and advertisement
c) Review research to ensure that benefit outweighs the risk
d) Review reports related to death, serious unexpected adverse event sent by the
investigator
e) Conducting periodic review of all the documents, benefits, risks and informed
consents etc.,
Common Problems associated with IRB:-
 Advertisement not reviewed and approved prior to conduct of clinical trial. 

 Investigator qualification like CV not reviewed 

 Various document like protocol, Informed consent form not review prior to the
conduct of clinical trial 
4. Informed Consent
Informed consent is defined as “Subject willingness to participate in the clinical
trial after being informed about all the aspects of the clinical trial’.
It demonstrates that
Person has freely given conformation without any coercion

3. Person knows that this is research but not a treatment
Person has been given all the important and relevant information related to the
trial
Must include important information:-
 Objective and purpose of the research 
 Benefit and risk associated with the research 
 Duration of the research 

 Any alternative treatment available 
 Can withdraw from the treatment 
 Compensation of unexpected injury 
Common Problems associated with Informed Consent
 Consent may not correct 

 Proper signature are not obtained 

 Poorly written consent form 

 Missing required elements 

 Amended form is not signed 
5. Subject protection in U.S:-
There are different methods which are followed in the U.S to protect the rights of
the study subject:-
Office for Human Research Protections which came in existence in the year June
18, 2000, has a considerable power over the conduct of clinical trials.
The Office for Human Research Protections (OHRP) provides leadership in the
protection of the rights, welfare, and wellbeing of subjects involved in research
conducted or supported by the U.S. Department of Health and Human Services
(HHS).
OHRP helps ensure this by
 Providing clarification and guidance, 
 Developing educational programs and materials, 
 Maintaining regulatory oversight, 

 Providing advice on ethical and regulatory issues in biomedical and social-
behavioural research. 
In addition to inaugurating the OHRP, Education and training of clinical
investigators and IRB staff. Improved monitoring to quickly detect problems in

4. patient’s safety, and penalties of up to $250000 per clinical investigator and up to
$1 million per institution for violations of patient protection agreements.
6. Subject protection in developing countries
With a population of more than a billion of people and prevalence of disease like
cancer and HIV, and excellent pool of investigator, CRAand CRC, makes India an
attractive location for foreign companies. Nevertheless, the subject enrolled in
India is more vulnerable .Why?
6.1 Poor public health and educational system in Developing countries:-
Due to which the participant may not fully understand about the rights while
participating in the clinical trial
6.2 Inadequate dissemination of information
6.3 Unemployment:-The unemployed and people below poverty line choose to be
part of clinical trials to get free treatment
6.4 Corruption in the public and private sectors.
In the context of developing countries, informed consent was nonexistent till the
Consumer Protection Act came into existence. Now, both doctors and patients are
becoming more aware about this concept, and patients are better informed of their
rights, safety and well being.
Informed consent is very important before any medical treatment. Such consent
can be implied, as in the case of a general physician’s treatment, when physician is
trying to administer any drug or to perform any surgical procedure. In developing
countries, where informed consent is infancy, most important elements of the trials
are hidden and particularly in hospitals they are expected to sign the Informed
consent form with a rider stating that they are willing for any kind of treatment.
Hence, it is very significant that subject knows about all the important and
relevant information pertaining to the trial.
6.5 Lack of facility and coordination among regulatory agencies
In August 2008, according to a report there are: "Fewer than 40 ethics committees
in India are properly constituted and functioning”
Ironically there is no proper linkage between Director Control General of India
and Ethics Committee which are the governmental and institutional level of
regulatory respectively .The DCGI fully depends upon the EC to implement the
ethical principles. The DCGI neither cares for the proper functioning of ECs nor
take care of how the rules and regulations are implemented. It’s been 30 years of
EC in India but still there is no effective review process in India. This is the time to
break the silence and improve the ethical challenges that India is facing today.

5. Conclusion
The clinical trial is done to produce knowledge about treatment efficacy by well
controlled experiment in groups of patients with the aim of promoting the right
safety and wellbeing of the patients. It is very important for the participant to
understand that every drug and treatment has its side effect. In order to achieve
this, the investigator has to ensure that the respective information is passed on to
the participating human volunteers effectively in its complete form without undue
bias. The benefit-risk ratio of every treatment is paramount in the conduct of any
clinical trial. Modern science cannot guarantee the benefit of clinical research
because the drug is in the process of trial. The expectation of patient in clinical trial
is obvious. Therefore, improving communication skill between the investigator and
the subject has become mandatory for better informed consent.
Enforcement of ethical standards in the profession and Communication forms the
core of the concept on informed consent.
Reference
Journal of the Forum for Medical Ethics Society
http://www.theheart.org/article/129765.do
www.crc.gov.my
http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html
http://www.hhs.gov/ohrp/
Publication: Bulletin of the World Health Organization; Type: News Article DOI: 10.2471/BLT.08.010808
http://www.medindia.net/indian_health_act/consumer_protection_act_and_medical_profession_doct
or_patient_relationship.htm