This blog is inscribed by Nishtha Pandey.
Corona Virus is causing havoc for a very long time. Even before it was declared a deadly pandemic, many pharmaceutical companies and other institutes were engaged in making the vaccine for COVID 19. Some of these institutions have even reached the advanced stage and are going in for clinical trials. Recently a COVID 19 vaccine was fast-tracked by skipping an important element of animal testing. This made many medical ethicists to question this shortcut. Therefore, the need to be aware of the intricacies of law and ethics revolving around the clinical trials of human subjects is more than ever in these times.
Clinical trials refer to research investigations in which people volunteer to test new treatments or tests to prevent, detect, treat or manage various diseases or medical conditions. However, to conduct research involving human subjects, there have to be some laws which prevent any form of exploitation. In fact, in many countries laws are made to prevent the exploitation of animals that are the subjects of a clinical trial.
Involvement of A Human Subject
Involvement of a human subject for the clinical trials of a vaccine involves great ethical and legal issues. Different organizations and committees worldwide have adopted several guidelines and documents in this regard. Thus, a need for consolidating all these guidelines into one global document appeared. In 1996, the guideline was issued by the International Conference for Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). Representatives of regulatory bodies and pharmaceutical companies from Japan, United States, European Union, Australia, Canada, and Nordic Countries as well World Health Organization (WHO) participated in the development of these guidelines. In January 1997, the guideline became effective and implemented for clinical trials involving human subjects.
The general rule which has been invoked is that the Investigator may only involve a human being as a research subject if a legally effective informed consent is obtained. Moreover, consent must be obtained beforehand and not obtained through coercion or undue influence. Research subject must understand the terms of the consent. Informed consents may not waive the research subject’s legal rights or release investigators, sponsors, institutions, or agents from liability for negligence.
International Law In Clinical Trials
The basic idea of ethics during clinical trials emerged after World War II where the Nazis used prisoners for conducting experiments. Thereafter the Nuremberg Code 1947 came which necessitated the need for informed consent from the subject of the clinical trials, hence no experiment could be conducted on the mental patients or the vulnerable group.
However, the Nuremberg Code 1947 was very rigid. It lays down that the consent is mandatory in every circumstance, therefore a person who is unconscious due to an accident and is unable to consent to the treatment, could not be given any new treatment leading to the meagre chance of survival.
In 1964, the Declaration of Helsinki was proposed by the World Medical Association. It has mellowed some of the absoluteness present in the Nuremberg Code and has provided the option of “surrogate consent” in a case where the subject, himself couldn’t give informed consent. Moreover, it has categorically stated that medical research should be combined with medical care. It has also stated that the responsibility of the human subject must rest with the medical competent person and not on the human subject himself even if he has given his consent.
All the stakeholders involved in conducting the trial have different liabilities. Generally, the common targets for litigation are the investigators and the institution involved. The company that sponsors the trial has the liability on account of improper disclosure, conflict of interest, violation of good clinical practices, injuries occurring due to the test drug. Although many cases have not reached courts in India, awareness amongst patients is certainly increasing.
Liabilities, in the clinical trials, are likely to arise due to breach in “informed consent” rules or adverse reactions due to drugs, negligence of institution or investigator. Typically, the clinical trial agreement allocates the liability among sponsor, investigator or institution.
As far as sponsor’s responsibility for compensation of an injury related to the study drug is concerned, it would depend on the description of the ‘study’ specified in the Study Protocol and the Informed Consent Form. As per the regulations, the primary responsibility lies on the sponsor to provide compensation for any physical or mental injury arising out of a clinical trial or to provide insurance coverage for any unforeseen injury.
Unfortunately, clinical trial-related insurance is not well developed in India. However, this insurance cover does not protect medical professionals for compensation of claims arising out of their participation in clinical trials. Government of India has tabled legislation called Central Drug Authority (CDA) Bill – that envisages imprisonment of five years, and fine of Rs. 20,00,000 for those violating these norms of a clinical trial.
A major concern for a foreign sponsor in India is that unlike Food and Drug Administration (FDA) and European Medicines Evaluation Agency (EMEA), Drugs Controller General of India (DCGI) does not release any guidance documents providing the current interpretation of the regulations. Since the regulations are highly generalised, their interpretation is extremely subjective and based upon the experience of the regulatory consultants. It is common to have several experts come to different conclusions about the same regulation.
Hence laws in this field are necessary to ensure that the people who undergo clinical trials are not exploited and should be well informed. Indian Chapter of the Association of Clinical Research Professionals (ACRP) has been launched. The likely enactment of law and launching of the Chapter will bring in professionalism in this field. There is a need to regulate clinical trials in India to match the global standards, to clarify the regulations and speed up the licensing procedures.
In 2003-2004 Santa Biotech was testing streptokinase which is an emergency life-saving treatment to stroke patients. In 2002, Dharmesh Vasava was among the daily wage workers who were given a psychiatric drug as part of the study. He developed pneumonia and died. The People’s Union of Civil Liberties, Vadodara, conducted an investigation into the death. PUCL suggested that the participants were unlikely to have given their voluntary informed consent to participate. Incidentally, these studies are conducted by drug exporters, to prove that their product is as effective as the approved branded version. Unfortunately, it is not required not by the Indian regulatory authorities and because of this a number of multinationals are taking advantage of these situations for their business purposes. However, now it is the duty of the Indian Council of Medical Research (ICMR) to control unauthorized clinical trials in India.
The need for a definitive code of conduct is a must for clinical trials. It is necessary that the doctors who carry such trials should consider all the ethical and legal issues in undertaking such trials. One of the major findings was the importance of informed consent in the entire process. Here the subjects must be aware of all the elements present in the study so that they could give informed consent. This requisite is to be satisfied even after the legal requirement is fulfilled. Human lives are very intricate and a single ethical framework, including ours, cannot claim to capture the complexity of research and understand the ethical dilemmas that arise in these diverse settings, but even then paramount care should be taken so that every stakeholder considers research participants as central players, who should be protected from any harm for which appropriate legislation should be in place to ensure the above. Clinical trials for a highly contagious Covid19 demands more precaution and the need for asserting legal rights in this regards has occupied a top niche.
- How ethical are clinical treatment in India by P. Sree Sudha ML
- The Law and Regulation Governing Clinical Research by UK Health Care
- Researchers rush to test coronavirus vaccine in people without knowing how well it works in animals by Eric Boodman
- Issues and Concern in conducting clinical trials in India by Gawree Gokhale and Milind Antani