Ethics in Clinical Trials: Its Role and Importance
Dr. Ashok Peepliwal
Associate Professor
IIHMR University, Jaipur

Clinical trial ethics are the set of relevant ethics considered in the conduct of a clinical trial in the field of clinical research. It borrows from the broader fields of research ethics and medical ethics. This article discusses the role and importance of ethics in clinical trials.

Clinical trials are a necessary practice in drug development to certify the safety and efficacy of a new drug and involve the participation of human subjects. Healthy volunteers and patients of specific diseases are considered legitimate trial units provided their free and informed consent is obtained under the law.

Exploitation in the Clinical Testing arena

Low and middle-income countries provide easy test subjects for clinical trials because in many cases, participating in a trial is the only way for the poor or needy to access expensive healthcare. However, this exposes them to the risk of exploitation. Experience has shown that unregulated practices in drug development can lead to unhealthy consequences for the people involved. In the 1960s, a chemical called Thalidomide was administered to pregnant women who had complained of morning sickness. The drug was marketed as a mild sleeping pill that was projected as being safe even for pregnant women. However, babies born to the mothers who took the pills were born with congenital deformities as a result. This spurred authorities and pharmaceutical companies to employ more rigorous testing standards before the introduction of a drug for human consumption.

Guidelines and Frameworks for Clinical Trials in India

Ethical concerns are to be addressed responsibly by all the stakeholders involved including doctors, pharmaceutical companies, ethics committees, regulatory agencies, CROs, patients and drug testing laboratories. Patients can help by honestly describing symptoms and therapeutic progression during testing. ICH-GCP (E6 guidelines) unequivocally declares that the rights of the individual, safety and well-being shall prevail over the interests of both science and society. The safety of the trial subject is an inalienable right to be protected at any cost. To ensure that this happens, stakeholders are required to undergo periodic training in order to comply with requirements of the Indian Council of Medical Research (ICMR) and the World Medical Association's (WMA) Declaration of Helsinki on the ethical guidelines for biomedical research on human participants. These principles themselves stem from the Declaration of Geneva, one of which binds the physician with the words, "A physician shall act in the patient's best interest when providing medical care".

The central concern of medical research is to study and understand the causes, development and effects of diseases and improve preventive, diagnostic and therapeutic interventions (methods, procedures and treatments ). Evaluation should continue beyond preliminary stages to as long as the tested molecule resides within the human subject. Nor does this declaration stop at lofty ephemeral ideals.

Comprehensive guidelines include the compulsory performance of medical research/clinical trial by appropriately trained and qualified personnel with the requisite scientific and ethical bent of mind. Clinical trials should also minimize harm to the environment. Known adverse effects should act as a breach of preliminary conditions before subjecting humans to trials . Suitable compensation and treatment in case of subjects who have been harmed should be available.

The Ethics Committee (EC) in Clinical Trials

ICMR guidelines (2006) require the establishment of and oversight by an ethics committee. An EC is to be registered with the Central Drugs Standard Control Organization (CDSCO). Approval or disapproval of a clinical trial is in the hands of the EC. The EC examines the pros and cons of a clinical trial protocol before approval. The committee members including the Chairman , Member Secretary, Clinician, Pharmacologist, Lawyer, Layperson, etc, must scrutinize protocols, investigate brochures, informed consent forms and other relevant documents thoroughly to ensure that the patient does not undergo any suffering due to negligence of document oversight.

Once the Ethics Committee nod is acquired, the principal investigator and her team members can begin recruiting patients according to inclusion and exclusion criteria. These criteria are to be strictly followed even if the numbers are low so as not to endanger the patient's life. All queries of a patient must be satisfied even after the informed consent form has been signed and received. All the benefits and adverse effects of the Investigational Medicinal Product (IMP) ought to be disclosed beforehand. Only when the patient or his/her relatives agree to all conditions should the participation in the clinical trial begin. The patient should have the freedom to discontinue with the experiment should she so desire.

Role of the Principal Investigator

It is the job of the PI to ensure that deprivation and vulnerability of the subject is not taken undue advantage of. An official report says that India serves 1.4% of the world's clinical trial needs while holding 16% of the world's population and 20% of its burden of disease. In the past, thousands of trials have been conducted here and several cases of death due to negligence or other serious accidents have come to light. Compensation to the victims has been a persistent bone of contention.

Recent Amendments

The CDSCO has been assigned the task of clinical trials regulator by the government of India as per the Drugs and Cosmetics Rules, 1945. GSR 53(E) dated 30-01-2013 inserted a new rule, 122-DAB and Appendix XII in Schedule Y to arrive at the compensation due to aggrieved patients and their relatives. Rule 12-DD of the DCR, 1945 mandating compulsory registration of ECs with it has enabled more transparency in the drug development regime. About 1200 ECs are currently registered. They are empowered to approve and implement ethics in clinical testing in India. Ethical measures have the ability to define and increase the reliability and authenticity of clinical research while at the same time pushing the limits of human understanding of disease.