On January 10, 2021, Rashida Bee (representing Bhopal Gas Peedit Mahila Stationary Karmchari Sangh), Nawab Khan (representing Bhopal Gas Peedit Mahila Purush Sangharsh Morcha), Rachna Dhingra (representing Bhopal Group for Information and Action) and Nausheen Khan (representing). Children Against Dow Carbide) wrote a letter to Prime Minister Narendra Modi and Minister of Health and Family Welfare, Dr. Harsh Vardhan. In the letter, he alleged irregularities and ethical violations during the clinical trial for Bharat Biotech’s Covaxin (a vaccine for COVID-19) by the People’s Hospital in Bhopal, Madhya Pradesh and the consequent exploitation of trial participants belonging to a vulnerable group demanding it be stopped. , penalties and damages.
The letter further stated violations of ethical guidelines, including violations of informed consent procedures, enrollment of vulnerable populations among study participants, failure to report adverse events and lack of monitoring and follow-up of study participants.
The authors call for urgent intervention to stop the study at the trial site and for an investigation by an independent body. What the letter was and what it did was unknown. India’s drug regulator, the Central Drug Standards Control Organization has approved the vaccine candidate before completing recruitment for the Phase III study of the vaccine candidate for “Restricted Use of Covaxin in Clinical Trial Mode” – a term and process not found in India’s Drug Regulatory Framework, Drug Act and Cosmetics and the Drugs and Cosmetics Rules, 2019.
Ethics and whistleblower committees
One of the problems seen in this case is the functioning of the trial site and the ethics committee. Dr. Jacob Puliyel, a member of the National Technical Advisory Group on Immunization (NTAGI) filed a writ petition in the Supreme Court of India in which the Court said “subject to the protection of the privacy of individual subjects and until allowed in 2019. Rules, the relevant data that must be published under the statutory regime and the WHO (World Health Organization) Statement on Clinical Trials will be made publicly available without delay.
The development of potential therapeutic agents is often complicated by subjective and sometimes objective violations of ethical guidelines. The role of cautious insiders, and sometimes outsiders, who have unique knowledge of these violations is the subject of a new book, The Occasional Human Sacrifice – Medical Experimentation and the Price of Saying No, by a bioethicist, philosopher and whistleblower at the University of Minnesota , Carl Elliott. The book details some of these incidents in the western world, starting from the Tuskegee Syphilis Study to the Willowbrook Hepatitis Study.
Also see what is happening with Protocol 126 to study cancer on bone marrow transplants at the Fred Hutchinson Cancer Center and at the Eugene Sanger Radioisotope Laboratory, Cincinnati Medical Center, to study the effects of radiation on humans among others. Driven by his own experience to understand Dan Markingson’s suicide at university, Elliot goes through some very difficult and human questions such as what makes people talk, the ethics of disagreement, respect, dignity, guilt and shame, and the concept of dignity. and integrity through the whistle-blower journey. As Nancy Olivieri, the whistle-blower, tells in her review, the threat of legal action and, worse, often leading to the destruction of the whistle-blower’s life is far too common in such cases.
Although one often wonders why such moral courage is few and far between in our society, Satyendra Dubey, Shanmugam Manjunath, Sanjiv Chaturvedi and a few named exceptions, although the lack of a strong whistleblower protection statute is only part of the problem. . Unlike the United States, India has no laws protecting those who take great personal risks to bring wrongdoing to public notice. The existing law, the scope of which was only for civil servants since its inception, was watered down again in 2015, becoming a dead letter law.
The deeper issues we need to deal with, but not fight against are: groupthink and organizational malpractice, loyalty to ivory towers, fear of retribution, social conformity, status hierarchies and the use of power that is ingrained in us as a society. If we don’t study these traits among us as a society, we will never understand why someone chose to be Anand Rai, the blaster who exposed the Vyapam scam.
Innovative therapy and ethics
Back to the topic, namely, the development of life-saving drugs is a quagmire in our country. While we have a vibrant industry producing generic drugs (copycats), developing innovative therapies is not our cup of tea. The development of life-saving drugs often requires balancing the risks to the patient with the projected benefits of using the therapeutic candidate. In most cases, there is not enough data to make the right decision, which is not straightforward and requires specialized knowledge and experience. Using approved drugs that are on the market does not qualify doctors to make these decisions. Drug development is a separate area of expertise. When we see the last green shoots, we don’t have deep expertise in managing clinical development. Therefore, we do it by appointing medical doctors to oversee the development of therapeutics. This requires better guardrails than ours to ensure that basic ethical principles are not violated in the process. For example, when medical doctors who specialize in treating individual patients with certain diseases such as cardiology and pediatrics are appointed to carry out a pandemic response, we will see unreasonable actions such as the projection of cases to zero during the COVID-19 pandemic. Subject matter expert committee members create things like “emergency use authorization in clinical trial mode” and work hard to correct it directly. This is a clear example of past violations of medical ethics.
Indian patients and clinical studies
A bigger problem in our country is the historical and repeated violations of informed consent when patients are enrolled in clinical studies. More than anecdotal evidence exists that poor and uneducated people are enrolled in these studies without fully informing them of the potential harm of therapeutic candidates being evaluated in clinical studies. The task of ensuring that such atrocities do not occur, is called the institutional ethics committee. When these committees are on paper and in our regulations, they function and are most effective.
A publication (2022) by Gayatri Saberwal et al. in the journal PLOS Global Public Health that evaluated 1,359 Phase II or III intervention studies registered in the Clinical Trials Registry–India (CTRI) identified 30 problems with the way our ethics committee worked. These include clinical trials without 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 check the abuse of medical ethics are not functioning in our country. This analysis does not say anything about the competence of the members of the ethics committee, which was evident in the development of Coronil during the pandemic. The biggest misuse of these regulations is the section of the industry which is actively promoted by the Ministry of AYUSH. Poorly designed and poorly conducted “clinical studies” with zero oversight are often used to lend scientific validity to herbs and nothing else.
If there’s one message that comes out clearly in Elliott’s book, it’s how well-designed and well-designed systems of checks and balances are often enforced by people with means and power. We are nowhere near the way the system works in the West. If we really want to bear our mistakes, we have a long way to go before we get the right foundation. That is, if we really want to.
Dinesh S. Thakur is a public health activist and a whistleblower in the case against Ranbaxy Laboratories.