Around the globe, some of the above-named drugs and treatments have been administered on patients infected with Coronavirus, even though their clinical efficacy against this particular virus is yet to be established.
By Arjun Dewan
As of May 15th 2020, the World Health Organization [WHO] has reported 4.39 million cases and 300,441 deaths from COVID-19. As the world is gripped with the unprecedented death and suffering caused by the microscopic virus, namely SARS-CoV-2, scientists, pharmaceutical companies and governments across the globe are all engaged in an unannounced race to develop a cure or vaccine for the virus. Various drugs such as Remdesivir, Favipiravir, Ribavirin, Lopinavir-Ritonavir [used in various combinations], as well as chloroquine or hydroxychloroquine and treatments such as Convalescent Plasma Therapy have been identified as possible cure(s).
Around the globe, some of the above-named drugs and treatments have been administered on patients infected with Coronavirus, even though their clinical efficacy against this particular virus is yet to be established. For example, Hydroxychloroquine, a drug primarily known to treat or prevent Malaria has been widely used on patients infected with Coronavirus. In fact, its use was recommended by Chinese Authorities and the Food and Drug Administration, USA[Emergency Authorization] for the management of such patients. Even in India, the Indian Council of Medical Research [ICMR] by way of advisory dated 22nd March 2020 and others, has permitted the use of Hydroxychloroquine for its frontline doctors and workers. Its use is further recommended for persons in direct contact with COVID-19 cases including family members /caregivers of self-isolating patients residing in the same house.
Whilst such directions have been issued in various countries, there is no credible or conclusive evidence [at least in the public domain] establishing the efficacy of the drug on Coronavirus/ SARS-CoV-2. Subsequently, in two of the latest studies published in the British Medical Journal by Chinese and French researchers, found Hydroxychloroquine to be of no benefit for patients with mild to moderate COVID- 19 symptoms. In fact, one of the two studies noted adverse effects ranging from mild to severe on patients who were administered Hydroxychloroquine. Last month, a small study on Chloroquine being conducted in the city of Manaus, Brazil had to be halted after Coronavirus patients administered a higher dose of the drug developed irregular heart rates.
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In such a situation, questions have understandably been raised regarding the advisories, issued by the ICMR and other authorities regarding the administration of Hydroxychloroquine without first ascertaining its efficacy and safety. Though we as citizens, repose complete faith in our Scientists and Healthcare professionals who continue to risk their own lives for the benefit of society at large, we do ponder on the legal and ethical aspects of administering such investigative treatments/medicines.
Clinical trials in India are regulated by the Central Drugs Standard Control Organization [CDSCO] which is headed by the Drugs Controller General of India [DCGI]. Clinical Trials simply put means a controlled systematic study conducted to establish the efficacy, tolerance, safety and adverse events of a ‘new drug’ or ‘investigational new drug’. CDSCO is the regulatory authority responsible for granting permission for conducting clinical trials and for regulating the sale and importation of drugs for use in such clinical trials.
On 19th March 2019, Ministry of Health and Family Welfare had notified the ‘New Drugs and Clinical Trials Rules, 2019’ which laid down detailed regulations governing clinical trials. The need for experimental treatment during a pandemic like the present one cannot be underestimated, but its use even during such times cannot be panic-driven, unregulated or without some credible and conclusive data regarding its efficacy and safety. The WHO had previously published guidelines called the ‘Monitored Emergency Use of Unregistered and Investigational Interventions’ [MEURI], which was an ethical protocol for use of experimental drugs during public health emergencies. Pursuant to this, the ICMR in 2017published its own ‘National Ethical Guidelines For Biomedical and Human Participants’, which were made applicable on all biomedical, social and behavioural science research for health conducted in India involving human participants, their biological material as well as data. Rule 16  of 2019 Rules, mandated that any biomedical and health research must be conducted in accordance with the 2017 guidelines.
These guidelines issued by ICMR were a much-needed revision of the 2006 guidelines and a step in the right direction to address the ethical challenges in such research. These guidelines have a total of 12 sections. Pertinently, Section 12 titled ‘Research during humanitarian emergencies and disasters’ which was introduced in 2017, recognizes that a humanitarian emergency, like we are witnessing today, raises complex issues in relation to ‘health care system, communications research infrastructure and research governance framework’. It also notes that though in such circumstances, there may be a need to undertake research quickly, however, the same should not impact scientific validity and need to uphold ethical requirements. Section 12.7.3 specifically permits Monitored Emergency Use of Unregistered and Experimental Interventions [MEURI] with a list of precautions mentioned therein.
The question that arises does the use of Hydroxychloroquine require to be in accordance with these guidelines? In an article published on 8th May 2020 on a website, namely ‘The Wire’, it has been stated that the head of ICMR’s bioethics unit has suggested that the 2017 guidelines are not applicable in the case of prophylactic use of Hydroxychloroquine. While others have argued that India has violated its own guidelines in relation to the usage of Hydroxychloroquine to fight Coronavirus.
In April 2020, the ICMR has issued ‘National Guidelines For Ethics Committees Reviewing Biomedical and Health Research During COVID – 19 Pandemic. These guidelines reiterate the 2017 guidelines and lay down procedures to be followed during research and treatment during the pandemic. It specifically lays down how the consent of the Patient is to be obtained during the pandemic. It also specifically provides that in certain situations consent can be waived during a pandemic. It also provides for the role of various authorities such as the ethics committee.
Clinical trials have always raised legal – ethical issues globally. The Nuremberg Code was the first international code laying ethical principles for clinical research on humans. In 1964, WHO formulated guidelines known as the Helsinki Declaration and subsequently various nations have adopted their own ‘code’ or ‘guidelines’. Principles of voluntariness and informed consent, essentiality, no – exploitation, transparency and accountability, privacy and confidentially, and non-exploitation amongst others during clinical research are the core principles required and accepted worldwide.
In my opinion, the need for informed consent of the patient and Rule of Law cannot be undermined even during pandemics, no matter how grave the situation might be. Ethical aspects in advising and administering new and investigational drugs must be strictly adhered to. The Regulatory oversight and compliance in such situations are also of paramount importance. The rights of the patient/subjects such as voluntariness, compensation in case of a serious adverse event, free medical aid must also be protected even during pandemics. Whether patients rights have been infringed around the world remain to be examined and must be examined so that history does not repeat itself. The debate regarding Hydroxychloroquine will continue to grow globally due to its widespread use during the Coronavirus pandemic. While we hope humanity is not faced such pandemics again, but if we do, I sincerely hope that there is no room for any such debate on that occasion.
(The author is Advocate, Delhi High Court. Views are personal.)