Clinical trials are an essential part of drug development and drug trial injuries are often inevitable. An investigational drug trial may lead to untoward side effects or injuries called adverse events (AEs) and serious adverse events (SAEs) or adverse drug reactions (ADRs). An adverse event may be relatively minor in the form of bruises or vomiting or major such as organ damage and temporary physical disability, or catastrophic injuries leading to permanent disability or death. Injuries may be psychological, emotional, social or economic and may require only acute or emergency care or long-term medical care.
SAEs are untoward medical occurrences during clinical trials, associated with death, prolonged hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defects or otherwise life-threatening conditions. An adverse event may be unexpected or suspected. An unexpected ADR is an AE that is not consistent with the applicable and available product information as per the investigator’s brochure (IB) or prescribing information, e.g. the IB mentions hepatitis as a suspected AE and the subject develops hepatic encephalopathy, or the IB mentions urticaria and the subject develops anaphylaxis.
The regulation of Indian clinical trial injuries is based on a “no-fault approach”, in accordance with schedule Y of the Drugs and Cosmetics Act, 1940, the Drugs and Cosmetics Rules, 1945, Indian Good Clinical Practice Guidelines and the Indian Council of Medical Research (ICMR) Ethical Guidelines for Biomedical Research on Human Participants, 2000. The principles enunciated in the ICMR guidelines are in consonance with guideline 19 of the Council for International Organizations of Medical Sciences and the World Medical Association’s Declaration of Helsinki.
The Drugs and Cosmetic Rules relating to drug trial injury compensation were amended in January. The amendment states that in case of any injury a clinical trial subject must be given free medical management as long as required. The subject is also entitled to compensation over and above the expenses incurred on the medical management of the subject. The sponsor must bear the expenses for medical management and financial compensation in case of clinical trial injury or death. In cases of drug-trial related deaths, the subject’s nominee would be entitled to financial compensation.
As per the amendment, any injury or death of a clinical trial subject due to an adverse effect of the product being investigated; violation of the approved protocol; scientific misconduct or negligence by the sponsor, the sponsor’s representative or the investigator; failure of the product to provide the intended therapeutic effect (this is likely to be amended as there is always a chance that an investigational drug may fail to provide the intended effect and the trial is conducted with the aim of assessing the therapeutic effect of the drug along with safety); or injury to a child in utero, will be considered as a clinical trial-related injury that will entitle the subject to financial compensation.
The SAE currently is to be reported and compensation decided within 21 days but this is likely to be increased to 30 days. An independent expert committee is to establish cause of death during a trial within 30 days but this is likely to increase to 60 days.
The amendment also mandates incorporating the trial subject’s right to claim compensation in the informed consent document in addition to information on the essential elements relating to compensation in the event of clinical trial-related injuries or death.
The regulation of compensation for clinical trial injuries is fraught with challenges. Whether failure of intended result of an investigational drug or death of a terminally ill patient especially in diseases such as cancer and HIV/AIDs justifies compensation is a debatable issue. The amended rule also fails to define drug trial injuries adequately and states that drug trial injury would include in addition any other unrelated injury during the period of a drug trial. This would be confusing when subjects sustain injuries unrelated to the drug per se. However the new norms may require proof of injury or death being related to the drug.
The drug trial compensation amendment has conferred an additional cost for drug development on the sponsor. This could further escalate drug costs in the future. Academic research institutes may not be able to afford research considering high compensation costs. This would jeopardize clinical research. The adequacy or inadequacy of the quantum of financial compensation could lead to trial injury litigation in the future.
Clinical research in biosimilars, biobetters, stem cell and more innovative drugs could lead to changes in drug trial injuries and more complex issues of compensation could arise. The future is likely to witness major amendments in the area of clinical trial injury compensation in India.
Dr Rachna Bharadwaj is an associate at Krishna & Saurastri Associates and an advocate registered with the Bar Council of India.
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