It is Time to Make a Move! Ensure the Safety and Overall Wellbeing of the Human Subjects Involved in Clinical Research

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.

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.

 According to Belmonte there are 3 ethical principles that guides the clinical research

• Respect for person
• Beneficence
• 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.

Role of Investigator, Clinical Research Coordinator and Other staff;

• 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.


• The investigator has to be aware of the tension that could arise as a result of balancing the science and protection to the subject.


• The investigator has to inform subject accordingly.


• Take an opinion from other members, physicians who are involved in the clinical trial to minimize the risk to the subject.

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:-

• Review of important documents like informed consent form, protocol.
• Investigator brochure update, financial document and advertisement.
• Review research to ensure that benefit outweighs the risk.
• Review reports related to death, serious unexpected adverse event sent by the investigator.
• 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.
• 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.
• 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 signatures are not obtained.
• Poorly written consent form.
• Missing required elements.
• Amended form is not signed.

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 June18, 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-behavioral research.

In addition to inaugurating the OHRP, Education and training of clinical investigators and IRB staff.

Improved monitoring to quickly detect problems in 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.

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, CRA and CRC, makes India an attractive location for foreign companies. Nevertheless, the subject enrolled in India is more vulnerable .Why?

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.

2. Inadequate dissemination of information

3.Unemployment:-

The unemployed and people below poverty line choose to be part of clinical trials to get free treatment.

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.

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.

           

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.