Trials, medical ethics and the orbit of power

In India, the primary guardrails that are supposed to be a check on the abuse of medical ethics do not function

Updated - July 04, 2024 12:17 pm IST

Published - July 04, 2024 12:16 am IST

‘Unlike the United States, India does not have a law that protects those who take great personal risks to bring wrongdoing to public notice’

‘Unlike the United States, India does not have a law that protects those who take great personal risks to bring wrongdoing to public notice’ | Photo Credit: Getty Images/iStockphoto

On January 10, 2021, Rashida Bee (representing the Bhopal Gas Peedit Mahila Stationary Karmchari Sangh), Nawab Khan (representing Bhopal Gas Peedit Mahila Purush Sangharsh Morcha), Rachna Dhingra (representing the Bhopal Group for Information and Action) and Nausheen Khan (representing Children Against Dow Carbide) wrote a letter to Prime Minister Narendra Modi and the then Minister of Health and Family Welfare, Dr. Harsh Vardhan. In the letter, they alleged irregularities and ethical violations in the conduct of the clinical trial for Bharat Biotech’s Covaxin (a COVID-19 vaccine) by the People’s Hospital in Bhopal, Madhya Pradesh and the resultant exploitation of trial participants belonging to vulnerable groups demanding stoppage, punishment and compensation.

The letter further alleged gross violations of ethics guidelines including violations of informed consent procedures, enrolment of vulnerable population among study participants, non-reporting of adverse events and a lack of monitoring and follow-up of study participants among others.

The writers sought urgent intervention to stop the study at the trial site and for investigation by an independent body. What became of the letter and any consequential actions are unknown. The Indian drug regulator, Central Drugs Standard Control Organisation had approved the vaccine candidate prior to the completion of the recruitment for the vaccine candidate’s Phase III study for “Restricted Use of Covaxin under Clinical Trial Mode” — a term and process that finds no mention in India’s Drug Regulatory Framework, the Drugs and Cosmetics Act and its accompanying Drugs and Cosmetics Rules, 2019.

Ethics committees and whistle-blowers

One of the issues that stands out in this case is the functioning of the trial sites and their respective ethics committees. Dr. Jacob Puliyel, a member of the National Technical Advisory Group on Immunization (NTAGI) filed a writ petition in the Supreme Court of India where the Court said “subject to the protection of privacy of individual subjects and to the extent permissible by the 2019 Rules, the relevant data which is required to be published under the statutory regime and the WHO [World Health Organization] Statement on Clinical Trials shall be made available to the public without undue delay”.

The development of potential therapeutic agents is often complicated by subjective and sometimes objective violations of ethical guidelines. The role of conscientious insiders, and sometimes outsiders, who have unique knowledge of such violations is the subject of a recent book, The Occasional Human Sacrifice – Medical Experimentation and the Price of Saying No, by bioethicist, philosopher and whistle-blower at the University of Minnesota, Carl Elliott. The book details several such incidents in the western world, starting with the Tuskegee Syphilis Study to the Willowbrook Hepatitis Study.

It also looks at what happened with Protocol 126 for cancer study of bone marrow transplantation at the Fred Hutchinson Cancer Center and at the Eugene Sanger Radioisotope Laboratory, Cincinnati Medical Center, to study the effect of radiation on humans among others. Driven by his own experience to understand the suicide of Dan Markingson at the university, Elliot traverses some very difficult and human questions such as what makes someone speak out, the ethics of dissent, honour, respect, guilt and shame, and the concepts of dignity and integrity told through the journey of whistle-blowers. As Nancy Olivieri, a whistle-blower, recounts in her review, threats of legal action and, worse, often resulting in destroying the whistle-blower’s life are far too common in such cases.

While one often wonders why such instances of moral courage are few and far between in our society, Satyendra Dubey, Shanmugam Manjunath, Sanjiv Chaturvedi and a few other named exceptions notwithstanding, lack of strong whistle-blower protection statutes is only a part of the problem. Unlike the United States, India does not have a law that protects those who take great personal risks to bring wrongdoing to public notice. The existing law, whose scope is limited to public servants to begin with, was further diluted in 2015, making it a dead letter law.

The deeper issues which we should, but do not wrestle with are: understanding group think and organisational wrongdoing, loyalty to the ivory tower, fear of retribution, social conformity, status hierarchies and exercise of power that are so ingrained in us as a society. Unless we study these traits among us as a society, we will never understand why someone chooses to be an Anand Rai, the whistle-blower who exposed the Vyapam scam.

Innovative therapies and ethics

Back to the topic at hand, i.e., the development of life-saving medicines is a morass in our country. While we have a vibrant industry that manufactures generic (copy-cat) drugs, developing innovative therapies has not been our cup of tea. Development of life-saving medicines often entails balancing the risk to the patient with the projected benefit from using the therapeutic candidate. In most cases, there is not enough data to make an informed decision, which is not straightforward and requires specialised knowledge and experience. Using an approved drug that is on the market does not qualify a medical doctor to make such decisions. Drug development is a separate area of expertise. While we see green shoots of late, we do not have deep expertise in managing clinical development. Therefore, we make do with appointing medical doctors to oversee the development of therapeutics. This requires better guardrails than we have in order to ensure that the basic tenets of ethics are not violated in the process. For example, when medical doctors who specialise in treating individual patients with specific diseases such as cardiology and paediatrics are appointed to run our pandemic response, we see absurd actions such as projecting cases to become zero during the COVID-19 pandemic. Members of subject expert committees make up things such as “emergency use authorization in clinical trial mode” and work hard to justify it with a straight face. These are glaring examples of gross violations of medical ethics in our recent past.

Indian patients and clinical studies

The bigger issue in our country is the historic and repeated violation of informed consent when patients are enrolled in clinical studies. More than anecdotal evidence exists that poor and uneducated people are enrolled in such studies without fully informing them of potential harm from the therapeutic candidate being evaluated in a clinical study. The job of ensuring such atrocities do not occur falls to what is called an institutional ethics committee. While such committees exist on paper and in our regulations, their function and effectiveness are at best patchy.

A publication (2022) by Gayatri Saberwal et al. in the journal PLOS Global Public Health that evaluated 1,359 Phase II or III interventional studies registered in the Clinical Trials Registry–India (CTRI) identified as many as 30 problems with the way in which our ethics committees function. These include clinical trials without any ethics committees, and trials with more sites than functional ethics committees — for example, three ethics committees approving one study site. The simple takeaway from this analysis is that the primary guardrails that are supposed to be a check on abuse of medical ethics do not function in our country. This analysis says nothing about the competence of the members of the ethics committees, which was plainly obvious during the development of Coronil during the pandemic. The biggest abuser of these regulations is a section of the industry that is actively promoted by the Ministry of AYUSH. These poorly designed, ill-executed “clinical studies” with zero oversight are often used to provide a veneer of scientific validity to their concoctions and nothing more.

If there is one message that comes out clearly in Elliott’s book, it is how even well-designed and well-run systems of checks and balances on accountability are often run roughshod over by those who have the means and power. We are nowhere even close to how such systems function in the West. If we truly wish to hold wrongdoing to account, we have a very long way to go before we even get the basics right. That is, if we truly want to.

Dinesh S. Thakur is a public health activist and was the whistle-blower in the case against Ranbaxy Laboratories.

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