Clinical Trial Regulation In India: Need For Accountability In Ethical Review

India's multi-ethnic population, cost-effective location has led to a growth in its clinical trial industry; multiple regulatory bodies attempt to control and streamline the process of quality requirements, hence clinical research regulation has been revised and clarified several times to accommodate needs of clinical trials.^[4] The Central Drugs Standard Control Organization ('CDSCO') is the central authority responsible to regulate, conduct clinical trials, oversee and approve new drugs in India, and under it, the Drug Controller of India ('DCGI') approves the conduct of clinical trials. Compliance of regulatory requirements in trials for vaccine development in India has been questioned during the Covid-19 pandemic, and there has been increased scrutiny of its research industry following reports of trials conducted with questionable ethical review. Ethical issues in clinical trials arise in case of protection of participants' safety and rights, and ensuring the validity of data collected, which are to be regulated by the state agencies.

New Drugs And Clinical Trials Rules 2019: The Central Government published these rules in 2019, under the Drugs and Cosmetics Act 1940. The ethics committee is to be registered with the CDSCO, for a period of 5 years, and would be disqualified if its members are not trained. Application for conduct of trial is to be made to the DCGI, and permission for 2 years for trial has to be given within 30 days. Marketing approval to drug would be given if there is remarkable efficacy in Phase II trial, in case of a life-threatening disease, or if there is no other alternative drug available. The First Schedule contains the general principles for clinical trials, the Second Schedule contains the requirements for permission to conduct trials, and the Third Schedule governs the conduct of clinical trials, while the Seventh Schedule specifies the formulae to determine the quantum of compensation in cases of death or injury in trial.

Drugs and Cosmetics Rules 1945: The rules provide for composition and registration of ethics committees, granting of approvals for clinical trials, compensation in case of injury/death during trial, prior approval of trial by ethics committee, audit by CDSCO to check compliance of GCPs or Schedule Y, registration of trial with the Clinical Trials Registry of India, submission of reports for adverse events, medical services in case of injury, and compensation in case of death/injury.

ICH-GCP (Good Clinical Practices) 2001: GCPs are international ethical and scientific quality standards to design record and report trials of human subjects, invoked in the Declaration of Helsinki 1964, and compliance provides assurance that the rights and safety of trial subjects are protected, and that the clinical data is credible. Sponsors, clinical investigators, ethics committees, research organizations, research coordinators, data entry personnel, others are responsible for GCP compliance. The ICH GCP guidelines were adopted by CDSCO after they were originally released by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ('ICH'). They express principles such as the ethical conduct of trials, benefits to justify risks, compliance with detailed protocol, prevalence of rights and safety of subjects over protocol and science, approval prior to initiation, medical care by physician, informed and free consent prior to participation, accurate and confidential data recording, and quality assurance system in trials. This helps to facilitate acceptance of international clinical data by authorities in countries which recognize these guidelines.

Developed countries have a better standard of living with access to health care. Since economic and educational circumstances differ vastly, trial subjects can be more vulnerable in clinical research in developing countries. The regulatory requirements in India have been compared to that of developed countries such as the United States ('US'), since they share similarities in the structure of conducting clinical trials, and ensuring compliance of requirements, as per international standards. In the US, the Food & Drug Administration ('FDA') has issued a guidance document for clinical practices. There are both central and local review boards, for approval of trials and a report of trial status is submitted by the sponsor to them.^[6] Research conducted by federal agencies/departments is also subject to a Common Rule, a set of human subject protection (HSP) regulations, which includes requirements such as informed consent and confidentiality of records and specifies the criterion for review boards and informed consent. It provides guidelines for establishment of review boards, and sets out criteria for approval of research and written informed consent, investigator training, data and safety monitoring.

About the research climate in India, The Evolving Regulatory Landscape for Clinical Trials in India^[7] had commended the measures taken by India to address risks for trial participants, by providing compensation in injury, ensuring accreditation of ethics committees, and by developing a robust regulatory framework, but it opined that these regulations lack clarity, and discourage trial funders from initiating trials, which means the government has to find a balance between the safety of population and the need for clinical research. Regarding the implementation of ethical guidelines in India, JS Srivastava's Need for Ethical Oversight of Clinical Trials in India^[8] had emphasized the value of ethics review in a developing country like India, and pointed out that, either the ethics committee may not understand the ethics review, or the investigators themselves may view it as a hindrance in research, which ultimately results in an unwillingness to undergo any ethical review at all.

The process of ethics review in India is relatively new as compared to its implementation in the West.^[9] Risk evaluation and mitigation strategy is an FDA program to ensure that benefits of the medication outweigh the risks, by identifying and assessing the risks involved, mitigating them and reviewing them. India could benefit from such a program as it would give an additional review along with that of the ethics committees. Also, audit procedures of clinical trial data are conducted by the ethics committees in India, while in the US, the FDA itself conducts audits at trial sites.

It is the responsibility of the stakeholders in the research to ensure safety of subjects and quality of data. Since drug development can improve quality and lifespan of patients, governments have to secure the safety as well as the rights of the human subjects in clinical trials, and ensure that the clinical trials conform to international standards. India has already strengthened the CDSCO office of DCGI by organizing it on the lines of the US FDA. US has emphasized on the specification of criterion to provide additional safeguards in research risks by adopting Common Rule, risk evaluation strategy and HSP. There is a need to specify the criteria for approval of research, elements of informed consent, as provided under US regulation, so there can be no compromise on public confidence and public participation. To improve the quality in the clinical trial system, experts have suggested that better ethical review to analyse the risk-benefit ratio as included in the criteria in the US Common Rule, along with dynamic monitoring tools such as risk evaluation and mitigation strategies by the sponsors as required by the FDA in US could assist in the safe availability of drugs in the public domain.

The writer is a postgraduate student of Law. The views are personal.

[1] Clinical trials, World Health Organization website, https://www.who.int/health-topics/clinical-trials/#tab=tab_1 last seen 4/6/21