National Ethical Guidelines for biomedical and health research: Issues to ponder over
SB 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
S B Bavdekar
Department of Pediatrics, Surya Children's Hospital, Mumbai, Maharashtra
|How to cite this article:|
Bavdekar S B, Karande S. National Ethical Guidelines for biomedical and health research: Issues to ponder over.J Postgrad Med 2022;68:125-128
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Bavdekar S B, Karande S. National Ethical Guidelines for biomedical and health research: Issues to ponder over. J Postgrad Med [serial online] 2022 [cited 2022 Nov 30 ];68:125-128
Available from: https://www.jpgmonline.com/text.asp?2022/68/3/125/353847
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.
Composition of the IEC and Quorum for EC Meeting
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.
Compensation for Research-Related Harm
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.
Training of Investigators and EC Members
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
Registration with the Clinical Trial Registry-India (CTR-I): Clinical trials registered under the Drugs and Cosmetics Act have to be registered with the CTR-I. The national guidelines encourages all other research studies enrolling human participants to register with the CTR-I. This is a welcome initiative. Many studies that have been unsuccessful in showing a benefit of a new drug do not get published and hence this information is not easily available in public domain. With the CTR-I registration, investigators become aware of these studies and are able to avoid taking up studies to evaluate interventions that have already been proved to be futile or excessively risky. This not only conserves resources but it also helps in avoiding potential risks to the participants. However, data regarding what proportion of non-regulatory studies get registered is not easily available.Facilitation of multi-centric research: When a multi-centric study is proposed, the protocol is reviewed by ECs of all the participating sites. This is a duplication of work and results in a waste of resources. It also delays study initiation. Recognizing these drawbacks, the guidelines have allowed for EC of one of the participating sites to take up the responsibility of reviewing the protocol on behalf of all the consenting sites. However, it is not clear if this enabling provision was gainfully used by various ECs, what has been their experience with its implementation, and if they faced any challenges. It would be also interesting to learn if some of the ECs had any apprehensions and reservations in this regard. This information, if collected and analyzed, can be helpful in modifying the guideline.It is noteworthy that the guidelines have discussed the issue of responsible authorship and publication under the topic of responsible conduct of research and recommended that the researchers follow the guidance issued by the International Committee of Medical Journal Editors (ICMJE). The issues of author misconduct and the mechanisms for monitoring for or dealing with author misconduct have not been discussed in great detail. However, going beyond the ICMJE guidelines, it has been recommended that when research has been carried out as a part of mandatory requirement of a course (e.g. thesis) and for student research, the candidate should be the primary author. It would be helpful if justification for this recommendation is provided in the updated guidelines.Independence of EC: The requirements that the EC should be headed by an individual who is not affiliated to the institution is helpful for independent working of the ECs. The question is whether this is enough to guarantee the independence of the ECs. Fears about institutional heads interfering in EC's functioning by sending “requests” or “directives” to individual EC members or to the EC, are often expressed. The need for additional safeguards to ensure EC's independence should be debated on before drafting the updated guidelines. Data regarding interference by the Heads of institutions in the working of ECs is difficult to find and one may have to use novel ways to gather this information. Obtaining information from anonymous sources has certain drawbacks, as its authenticity cannot be assured. Also, every alleged “interference” cannot be construed as mala fide. Institutional ECs are ultimately a part of the institution and it is the institutional head's responsibility to ensure that they work efficiently and, in accordance with the regulations and guidelines and assist in fulfilling the institutional goals. The head of the institution also has to act as an arbitrator if the investigators have reservations regarding the working of the EC. However, laying down of certain broad guidelines [such as, institutional heads communicating with the EC Chairperson or the member secretary only (and not with individual EC members), that the communications be by email or in writing and desisting from making recommendations for individual research projects or administrative matters on a “case-by-case basis”, etc.] can help. However, their authority to review the overall working of the institutional ECs and to adjudicate in conflicts between the investigators and the EC should be protected and respected.Ethical issues in medical practice: Matters pertaining to ethics in medical practice (e.g. use of an unapproved or off-label drug in a patient) are being increasingly referred to the institutional ECs. The institutional ECs established primarily with the aim of safeguarding the health and well-being of the research participants and for ensuring the integrity of the research data should not be burdened with this work, more so because they may not be having the expertize to deal with medical practice-related issues. In such matters, the subject experts should have a greater role. Such issues should better be handled by separate committees consisting of clinicians of the related specialty, administrators, and legal experts, among others.Roles and Responsibilities of Funding agencies: Various organizations provide funds (research grants) to partially or fully finance research projects. Usually, such organizations (funders) release funds on the basis of attainment of certain study-related milestones agreed upon earlier. In the past, such funding agencies never aspired to own the data generated in the research that they may have funded. Of late, it has been noticed that proposals are being received for investigator-initiated (non-regulatory) studies that are funded by pharmaceutical companies. Being a mere funder, they do not take any responsibilities of the sponsor; but micro-monitor the study (even through a contract research organization). In addition, they wish to own the data and insist that research study findings cannot be published without their permission. Generally, the data is jointly held by the investigator and the sponsor. In an investigator-initiated study, the investigator dons the role of sponsor as well and hence becomes the sole owner of the data. Most EC members see this as an effort of the funder to grab the fruits that a sponsor is entitled to, without bearing the responsibilities expected of the sponsor. They also argue that this sharing of/transferring the ownership of data creates unwarranted hurdles in the way of dissemination of the study results. In contrast, the investigator argues that being the sole owner of the data, he/she is at liberty to share or transfer the ownership to the funder. Some ECs have not approved such research projects, while a few others have made a distinction between government and private sector funding agencies. Considering the differing views, a guidance in this regard will be helpful.
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.
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