Where do Indian systems for Ethics Oversight of Human Research stand on the WHO benchmarking tool?
On 25th Sep 2023, the World Health Organization (WHO) released a tool for benchmarking ethics oversight of health-related research in human participants by Research Ethics Committees (REC). The WHO website states the tool is "Jointly developed by WHO’s Regulatory System Strengthening, Regulation, and Safety Unit and the Health Ethics & Governance Unit; it is intended to assist countries in evaluating their capacity to provide appropriate ethical oversight of health-related research."
The objectives are outlined in the Introduction of this manual.
The tool is intended to -
The tool has seven categories of parameters to assess three core areas.
a) Country-level legal provisions and guidelines for ethics oversight. (Category 1)
b) Structure, resources, and functioning of research ethics committees in a country. (Category 2 to 6)
c) Institutional responsibilities to facilitate ethics oversight. (Category 7)
Categories under b) and c) points listed above are oriented toward an individual ethics committee or site, respectively. Each of these categories has multiple indicators. The manual provides a description, evidence to confirm conformance and a rating scale for each indicator.
India has a robust system for ensuring ethical oversight of all human research. The New Drug and Clinical Trial Rules (NDCT), released in 2019, outlines the legal framework for research-related activities in India. This includes clinical trials, Bio-availability and Bio-equivalence studies, and Biomedical health research. The National Ethical Guidelines for Biomedical and Health Research involving Human Participants (ICMR Guidelines) was last updated in 2017 by the Indian Council of Medical Research (ICMR). The Indian Good Clinical Practice guidelines (GCP) mentioned in the NDCT have existed since 2001.
In addition, the National Accreditation Board for Hospital and Healthcare Providers (NABH) has been conducting an accreditation program for Ethics Committees in India since 2017. The Standards for Clinical Trial in India were first released in 2015 with sections for the Ethics Committee (EC), Investigators, and Institution. The accreditation program was implemented for only the Ethics Committees.
It will be interesting to evaluate the level of ethics oversight in India with the WHO tool. This article addresses three primary questions.
Q 1. Do the NDCT, ICMR Guidelines, and NABH standards meet WHO tool indicators?
Q 2. Will adherence to NABH standards assist ethics committees in India in aligning their systems and processes to the WHO performance tool?
Q 3. What are the gaps between the WHO tool and NDCT, ICMR guidelines, and NABH standards?
CATEGORY 1: Legal Provisions and Regulatory Framework
The fourteen indicators in this category help "determine whether the legal and regulatory framework is adequate to support ethical oversight of health-related research involving humans."
The regulatory framework includes the laws and guidelines in effect in a country. Hence, we used the NDCT, ICMR Guidelines, and Indian GCP to ascertain the level of adherence of the Indian systems to the WHO tool.
NDCT fully met Ten out of fourteen criteria. One indicator was met partially.
Indicator: 1.02 -Legal provisions that require RECs to review proposed research to determine whether it is consistent with the ethical standards in WHO guidance. Chapter III of the NDCT, Rule 11 (i) states that the ethics committee shall review proposals "in accordance with these rules, Good Clinical Practices Guidelines, and other applicable regulations." The elements of review, as listed in the WHO tool, are not outlined. However, Ethics committees in India comply with ICH GCP, ICMR Guidelines, and Indian GCP. All three of these guidelines are based on the Declaration of Helsinki and include the specifics required by the WHO tool.
Three indicators under Category 1 were not met, as per our understanding. Indicator number 1.06 requires 'Legal provisions to ensure that a REC’s decision not to approve a study cannot be overruled, except in cases of abuse of authority as determined by a regulatory agency or court.' Such a provision is not there in either NDCT, ICMR, or Indian GCP guidelines.
Indicator 1.08 requires Legal provisions that make institutions with their own RECs responsible for ensuring that those RECs have the resources described in category 3 of the WHO tool. The Third Schedule of NDCT outlines the responsibilities of only the Sponsor, Investigator, and Ethics Committee. The ICMR guidelines have a reference under Principle 1.1.9 Institutional responsibility, but no detailed guidance is provided.
Indicator 1.11 requires national, subnational, multinational, and/or local oversight authorities to support RECs and ensure they adhere to ethical and legal requirements. One of the critical elements under this indicator requires establishing REC oversight bodies and giving them legal powers. As stated earlier, the NABH program for accreditation of Ethics Committees was started in 2017. However, the NDCT released in 2019 remained silent on the legal sanctity of this accreditation. Hence, it has become a voluntary exercise dependent on the research institutions and their ethics committee's willingness and availability of resources. The ICMR guidelines under 4.15 mention accreditation, but the language again implies that it is voluntary.
Categories 2 to 6 are specific to individual REC, so we assessed them against the NABH standards primarily. We also looked at the ICMR guidelines for these categories to help ascertain requirements for Ethics Committees even if they do not participate in the NABH program.
CATEGORY 2: REC structure and composition
The indicators in this category help "determine whether RECs have appropriate mechanisms for appointing and retaining diverse, qualified members and for supplementing members’ contributions with outside expertise when necessary."
If a REC adheres to NABH standards (1.3.1; 1.3.2; 1.3.3; 1.3.4) and ICMR guidelines, they will meet all five indicators in this category.
领英推荐
CATEGORY 3: REC resources
Adherence to indicators in this category will ensure "there are adequate resources, including staffing, facilities, technological support, and financial resources, to ensure that the REC can effectively meet its responsibilities."
Compliance with NABH standards 1.3.5, 1.5.1, 1.5.2, and ICMR guidelines will ensure that the REC meets all five indicators in this category. The level of evidence required and review of technical support is higher in the WHO tool than in NABH requirements. In addition, training topics, as outlined in the WHO tool under Indicator 3.02, are much more elaborate.
CATEGORY 4: REC procedures
Indicators in this category help establish the robustness of Standard Operating Procedures (SOP), systems, and processes of a REC. They "determine whether the REC has documented procedures to conduct its ethics oversight. The procedures should cover the submission and screening of applications, protocol review, monitoring of ongoing research, and the document management system."
NABH standards have elaborate requirements under this category. A REC focusing on Standards 1.6 and 1.7 shall perform well under the WHO tool. ICMR guidelines also have detailed requirements to support RECs to meet the seven indicators in this category.
A mention should be made for Indicator 4.05- The REC has procedures for ensuring fast-track review of research proposals in public health emergencies. There is no concept of 'fast-track' under NABH standards or ICMR guidelines. This terminology will cause confusion with the concept of 'expedited review' as mentioned under ICH GCP, Indian GCP, and ICMR guidelines.
The fast-track procedure requirements outlined in the WHO tool are similar to the expedited review process, where ad hoc meetings or sub-committee REC meetings may be conducted to expeditiously review studies in case of public health emergencies. The WHO tool suggests providing approvals for generic protocols and consent forms, which can be customized when the need arises for fast-track/expedited review.
CATEGORY 5: Mechanisms to promote REC transparency and accountability.
This is one of the two categories where Indian systems do not meet the WHO tool indicators.
This category aims to "determine whether mechanisms are in place to promote REC transparency and accountability. The mechanisms should provide the public with information about the ethics review process, the sources of REC funding, the composition of RECs, and the research proposals that the REC approves. In addition, they should enable current and prospective research participants and researchers to pose questions to RECs and to obtain a response."
Except for Indicator 5.05, none of the other indicators are part of NABH standards or ICMR guidelines. Indicator 5.05 states that the REC enables current and prospective research participants to ask questions, raise concerns, or lodge complaints about their rights as research participants and about the ethics review process, and it responds to questions and complaints in a timely manner.
There are no provisions that mandate -
CATEGORY 6: Mechanisms for REC to monitor their performance.
This is an important quality measure to ensure the proper functioning of a REC.
The three indicators in this category help "determine whether the REC has mechanisms to ensure its adherence to ethical standards and to assess and improve its performance."
NABH standards (19.1; 1.9.2; 1.8.4) have specific requirements for ensuring the Ethics committee has self-assessment and review procedures for its SOP and functions. The standards also outline the need for having root cause analysis and corrective and preventive actions for any identified gaps.
CATEGORY 7: Responsible Research Institution
This is the second WHO tool category where Indian systems are found lacking.
The eight indicators in this category help "assess whether research institutions fulfill their responsibility to ensure that any health-related research under their purview adheres to ethical principles in WHO guidance, as well as any national laws and policies consistent with those principles. These indicators are not designed to provide a comprehensive assessment of research institutions; rather, they focus on clear markers of institutions’ commitment to protecting research participants."
ICMR guidelines have a passing mention of institution responsibilities. The NDCT does not outline any institutional responsibility; hence, this is one area that needs to be looked at by the authorities. When the NABH standards were released in 2015, they included sections 2 for Investigators and 3 for Institutions/research sites. However, only the EC accreditation program was started. All but two of the WHO indicators are missing from NABH standards.
The following indicators will be met if the NABH standards for institutes/research sites are implemented.
CONCLUSION:
a) Provision for ensuring transparency and accountability of REC. These elements must be incorporated into NABH standards and ICMR guidelines.
b) Ensuring Institutional responsibilities are implemented. The NABH standards for research sites/ Institutes should be implemented. It would help if the next revision of the ICMR guidelines elaborated on these responsibilities.
Providing legal sanctity to the NABH accreditation program will go a long way in elevating the performance of RECs in India.