National Ethical Guidelines for biomedical and health research: Issues to ponder overSB Bavdekar1, S Karande2
1 Department of Pediatrics, Surya Children's Hospital, Mumbai, Maharashtra, India
2 Department of Pediatrics, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpgm.jpgm_474_22
Source of Support: None, Conflict of Interest: None
The Indian Council of Medical Research (ICMR) published the National Ethical Guidelines for biomedical and health research involving human participants in 2017. The document provided detailed guidance on various ethical issues and concerns related to health research in India. Compared to the previous version published in 2006, it dropped topics that concerned medical practice rather than research (e.g. transplantation and reproductive technologies) and attempted to cover newer areas such as responsible conduct of research, public health research, and socio-behavioral research, among others. Changes were also made in the list of general principles through addition (e.g. principle of social responsibility, the principle of environmental protection) and re-grouping and rearrangements (e.g. the principle of maximization of the public interest and distributive justice being covered through the principles of maximization of benefit and social responsibility and the principle of the public domain being incorporated under the principle of transparency and accountability). In addition, the new guidelines provided additional information about various topics such as risk categorization, research misconduct, vulnerability, and ethical issues related to the review of research protocols. The guidelines took an explicit stand on the issue of providing compensation for research-related harm in the investigator-initiated studies and included an enabling provision permitting a common review for multi-centric studies. It has been about five years since the national guidelines were laid down. It would be worthwhile finding out the impact of newer recommendations and initiatives. We could also take this opportunity to identify areas requiring generation of more data or those requiring additional actions and, list newer challenges.
The newer guidelines put forth in 2017 amended the composition and quorum requirements. The earlier guidelines provided by the ICMR described the quorum for approving the drug trials as stated in the then revised Schedule Y of the Drugs and cosmetics act, 1940; which required the presence of lay person from the community for attaining the quorum at the Ethics Committee (EC) meetings. No separate recommendation was provided for other types of research studies. Thus, most ECs adhered to these quorum requirements irrespective of the type of research study. The New Drugs and Clinical Trials rules, 2019 continue to require the presence of a member representing lay persons from the community for completing the quorum. Inexplicably, the current ethical guidelines state that it is “preferable” (and not mandatory) that a lay person should be part of the quorum. Difficulty in getting lay persons representing the community on board cannot be the reason for their exclusion from the quorum, as they are an essential part of the ECs, anyway. This watering down of the requirement is all the more surprising, as the guidelines otherwise have attempted to ensure that several sections get a representation on the ECs by advising that their members be drawn from multiple sectors and disciplines and that there should be adequate representation of age and gender in the EC.
Members representing laypersons play an important role in the functioning of ECs, as they represent the community or the patient population. Their presence is used to demonstrate openness in decision-making and they ensure probity and provide oversight. They safeguard the public interest by bringing in the views of the public or the community. Most importantly they could be the only ones providing a “participant or patient” perspective in professional discussions that occur in various committees including the ECs. They undertake review of research proposals and informed consent documents with translations, undertake risk-benefit assessment from participants' perspectives, serve as participant or community representative and bring in ethical and societal concerns and assess societal aspects. They provide valuable input about the comprehensibility of the consent documents by prospective participants. As they have a unique role in the EC, their presence should be considered mandatory for the quorum requirements at every EC meeting.
Many ECs review and approve both regulatory as well as other research studies. Such ECs are simultaneously registered with the Department of Health Research (DHR) and Central Drugs Standard Control Organization (CDSCO) and have common Standard Operating Procedures (SOPs) that comply with the NDCT Rules as well as the Guidelines published by the ICMR. Thus, having similar requirements (whenever possible) for various procedures will be of great help for such ECs. As an example, one may look at the composition of the ECs. The NDCT rules, 2019 prescribe the minimum number of members for the EC to be 7 (without an upper limit), while the National Guidelines recommend a cap of 15 on the number of members of the EC. Many ECs that cater to a higher load of regulatory studies, appoint more than one member in the categories of legal expert and lay persons representing the community; so that at least one from each of these categories is available for the meetings. They also appoint more number of clinicians, so that the burden of reviewing research studies is shared. A ceiling on the number of members that can be appointed to serve on an EC may pose unnecessary hurdles in the working of these ECs. It may be advisable to leave the choice of the size of an EC to the discretion of the respective institution.
The topic of optimum tenure for the EC members is often discussed. Those in favor of a short-fixed tenure argue that this will help new ideas coming to the fore and also prevent ECs from becoming a closed group of a select few. Others think that the job of assessing protocols for ethical issues requires aptitude and commitment. In addition, the right skills and attitude develop over a period of time by getting trained while doing the job. Also, in many institutions, several staff members, given their busy schedule, are reluctant to serve on the institutional EC. Both these views have some merit and hence a consensus may have to be evolved and some guidance can be provided in the guidelines.
The Guidelines support the universal application of the principle of providing compensation for research-related injuries. Earlier, it was misconstrued that this principle is applicable only to regulatory or sponsored research studies. The guidelines clearly state that the principle is applicable to investigator-initiated research/student research and clarify that the investigator/institution where the research is conducted becomes the sponsor and takes up the responsibility of providing compensation for research-related injury. However, this continues to be a matter of discussion and dispute between the investigators initiating research studies and the institutional ECs. First of all, many institutions have not yet taken any explicit position on this issue. Secondly, some investigators do not provide for compensation pointing out that the participation is associated with negligible or no risk or that there is no possibility of physical injury in an observational study or that they have no resources to pay for insurance premiums. Research participants have the risk of physical injury, and also of psychological, social, and/or legal harm. The risk of loss of confidentiality is inherent in most research studies and these, in turn, can also lead to social, psychological, legal, or even physical harm. The NDCT rules and ethical guidelines seem to lay emphasis on physical harm and compensation for the same. However, a research participant can claim compensation for injury from other types of harm or injuries, too. Considering this, the investigator, in absence of an institutional mechanism or assurance, should strive to make budgetary provision for providing compensation for any and all types of harms.
The recommendation seems to put a greater onus on the institutions. After stating that the investigator/institution where the research is conducted becomes the sponsor, the guidelines suggests that these institutions should provide an insurance cover or undertake to pay the compensation (by an in-built mechanism), if and when it becomes due. Many institutions have arranged for insurance for investigator-initiated studies, or have established a corpus fund to take care of compensation-related issues, as and when they arise. It is suggested that the investigator should request the funding agencies to make budgetary provisions for the payment of compensation or for insurance cover. Where the institutions have not taken any stand in this regard, their institutional ECs direct the investigators to arrange for insurance or give an undertaking that they will pay the compensation, if and when it becomes due. This results in arguments between them, with consequent delays in approval of studies. Some ECs do not ask for insurance for studies that use approved drugs. However, this is fraught with dangers. Injuries can occur as a consequence of a protocol deviation and many a times, it is not clearly stated, as to who will pay for compensation in such an eventuality. The ECs should be alert to this possibility and make sure that these are covered through insurance or investigator undertaking. Post-graduate students and their guides undertake research studies as thesis is an essential part of many post-graduate courses. Many of them take up observational studies requiring analysis of already collected data, to avoid the issue of compensation. Although, several good research questions can be addressed through such studies; this approach restricts the number of interventional studies that can be taken up by students. It limits the opportunities available for learning the skills of conducting prospective and interventional studies. It also leads to a wastage of talent. A directive by the universities and the National Board of Examinations to the medical colleges and post-graduate training institutions to develop an institutional mechanism for providing insurance cover for studies undertaken as a part of thesis work can help improve the scope and quality of research undertaken. In addition, the ICMR or the DHR should collect information about various strategies employed by different institutions and ECs. The guidance may have to be improved based on the information collected and institutions that have not clarified their stand could be coaxed to do so. There is a view that institutions should provide insurance cover for all the investigator-initiated studies undertaken at the institution, as they are conducted only after approval from the institutional ethics committees and administrative approval from the respective institutions. This notion may also be debated upon.
The Guidelines lay a welcome stress on the training of EC members and prescribe that they be trained in human research protection, EC functions and SOPs, ethical guidelines, Good Clinical Practice (GCP) guidelines, and relevant regulations. It emphasizes that EC members should undergo initial and continuing training and that they should be updated whenever guidelines and regulatory requirements are amended. Most ECs conduct workshops periodically to train their own members. However, the duration for and frequency of such workshops and the quality of training offered are variable. In addition, there are organizations that conduct workshops or certificate courses for training members of various ECs. It is desirable that there should be a standardized course at least for the initial training of the EC members with a prescribed standardized syllabus and mandated hours of training. The DHR can devise such a course (online, offline, or hybrid), which can be run by its bioethics unit. It may also allow other institutions (both government and private) to conduct similar courses, provided they adhere to the standards prescribed by the DHR/ICMR and are supervised periodically.
Other initiatives and newer challenges
The National Guidelines 2017 constituted a big step forward. The ICMR should be commended for the good work done. It is obvious that the guidelines will need to be updated in due course of time. Therefore, the DHR or its bioethics unit should start collecting data about the implementation and impact of the new measures and initiatives that were incorporated. This can be done by requesting the ECs to submit information in a prescribed format on an annual basis. In addition, the unit can initiate a dialogue with the registered ECs and its members to understand the challenges that they face.
Financial support and sponsorship
Conflicts of interest
Dr. SB Bavdekar is a member of institutional and independent ethics committees.