The WHO Research Ethics Review Committee in the Western Pacific Region Standard Operating Procedures

1 The WHO Research Ethics Review Committee in the Western Pacific Region Standard Operating Procedures (SOP) (Revised from the 2011 version) 2 Table of Contents I. Purpose of the Document ............................................................................................................... 3 II. The Role of the Committee ............................................................................................................. 3 III. The Structure of the Committee ................................................................................................. 3 A. Members ..................................................................................................................................... 4 B. Chair and Vice-Chair .................................................................................................................... 4 C. Secretary and Secretariat ............................................................................................................ 5 IV. Committee Meetings .................................................................................................................. 6 A. Frequency.................................................................................................................................... 6 B. Attendance .................................................................................................................................. 6 C. Confidentiality ............................................................................................................................. 7 D. Quorum ....................................................................................................................................... 7 D. Meeting records .......................................................................................................................... 8 V. Submission and Review of Research Proposals .............................................................................. 8 A. Submission of Research Proposals .............................................................................................. 8 B. Standard of WPRO-ERC review ................................................................................................... 9 C. Exemption from WPRO-ERC review .......................................................................................... 10 D. Expedited review ...................................................................................................................... 11 E. Review by the Committee ......................................................................................................... 12 F. Accelerated Review ................................................................................................................... 13 G. Outcome of the Review and Reporting the Outcome of Review ............................................. 13 H. Review of Special Categories of Proposals ............................................................................... 15 I. Continuing Oversight and Monitoring ...................................................................................... 17 VI. Conflicts of Interest ................................................................................................................... 18 A. Investigators .............................................................................................................................. 19 B. Committee members ................................................................................................................ 19 VII. Adoption and Amendment of the Rules of Procedure ............................................................. 20 Appendix 1: Documents to submit to WPRO-ERC for review ............................................................... 21 Appendix 2. WPRO-ERC Risk Assessment Checklist .............................................................................. 23 3 The WHO Research Ethics Review Committee in the Western Pacific Region Standard Operating Procedures (SOP) I. Purpose of the Document These Standard Operating Procedures (SOPs) are intended to delineate the role, structure, and process of the WHO Research Ethics Review Committee in the Western Pacific Region (“the Committee” or “WPRO-ERC”) which was created in pursuant to WHO Manual Part XV, section 3, paragraph 20. II. The Role of the Committee 1. The role of the Committee is to provide ethics review, in accordance with the provisions set forth in WHO Manual Part XV section 3 and as hereinafter specified in these SOPs, of all research projects involving human participants that are funded or otherwise supported by WHO in the Region. 2. Research is defined as any social science, biomedical, behavioral, or epidemiological activity that entails systematic collection or analysis of data, with the intent to develop or contribute to generalizable knowledge. Generalizable knowledge consists of theories, principles or relationships, or the accumulation of information on which they are based, that can be corroborated by accepted scientific methods of observation and inference. 3. Human participants (sometimes termed “human subjects”) are defined as human beings (i) whose biological material, or medical or other records are collected or used by investigators’ and/or (ii) who are exposed to manipulation, intervention, observation, or other interaction with investigators either directly or through alteration of their environment as part of a research activity. III. The Structure of the Committee The Committee shall consist of 11 members including 1 Chair, 1 Vice-Chair and 1 secretary. 4 A. Members 1. Members shall be appointed by the Regional Director for an initial term of three years, renewable for a maximum of two consecutive terms. 2. Membership shall be gender balanced, and from the full range of disciplines (including, but not limited to, medical, behavioral and social-sciences, public health, epidemiology, and other relevant disciplines) relevant to the work of the Committee. 3. Members shall be appointed based on but not limited to: a. Their willingness to commit the time required for their duties on the Committee; b. Their expert knowledge in medicine, science, or another field, as appropriate; or their knowledge of research ethics; and c. Their willingness to acquire knowledge of research ethics through appropriate training and education within two months of beginning service on the Committee. B. Chair and Vice-Chair 1. The Regional Director shall appoint a Chair and a Vice-Chair of the Committee from among its Members. The persons appointed as Chair and Vice-Chairs should have experience in the design and review of research involving human participants and knowledge of the relevant ethical standards. 2. The Chair or, when the Chair is absent or unable to carry out the responsibilities of the office, the Vice-Chair, shall, in addition to such other functions provided for in these SOPs: a. Preside at Committee meetings. b. Sign, on behalf of the Committee, the review outcomes and recommendations on the proposals reviewed by the Committee. c. Work with and provide general direction to the Secretary regarding the operation of the Committee and the Secretariat. d. Recommend to the Regional Director possible new members, endeavoring to ensure appropriate balance of expertise, gender, geography, and cross- division involvement. 3. The Chair will hand over the responsibility of the office to the Vice-Chair whenever proposals from the Chair’s immediate area of work are being reviewed or discussed. Similarly, the Vice-Chair shall not act as the Chair if proposals from their immediate area of work are being reviewed or discussed. 5 (See section VI for more details regarding conflict of interest). In the event that neither the Chair nor the Vice-Chair is available, the Chair will designate in writing, the Committee member who will be authorized to act on behalf of the Chair. C. Secretary and Secretariat 1. The Secretary shall be a WHO official designated by the Regional Director. The Secretary shall be assisted by such additional technically qualified and administrative staff as is required to fulfil the function of the Secretariat. 2. In addition to such other functions as are provided in these SOPs, the Secretary shall ensure that the Secretariat operates in an efficient, accountable and transparent manner, specifically by: a. Liaising with the Chair and the Committee members on policy issues relating to WPRO-ERC. b. Ensuring access to any administrative assistance that may be needed by the Chair and members in carrying out the Committee’s functions. 3. The Secretariat, under the leadership of the Secretary shall: a. Manage the Health Research Portal b. Undertake a preliminary review of all submitted proposals to assess whether they are complete and, if not, to liaise with the WHO Responsible Technical Officer (RTO) in order to bring them up to the required standards. c. Schedule, coordinate, and organize Committee meetings to ensure prompt reviews of new and pending research proposals. d. Inform the WHO RTO in a timely manner of the Committee’s decision for each research proposal reviewed. e. Draft of meeting minutes, the annual report and other reports as may be required regarding the work of the Secretariat and of the Committee. f. Make readily available information to WHO staff in the Region about WPRO-ERC, including its standards, rules, procedures, activities and disposition of proposals. g. Make readily available to WPRO-ERC Committee members information educational and education materials, and training on ethical issues related with human research, including particularly ethical 4. The Secretariat, under the leadership of the Secretary shall maintaining and archive the following documentation: a. a copy of these SOPs and any amendments; 6 b. an up-to-date list of all Committee members, with their terms of service, titles and curricula vitae or other biographical information sufficient to describe their qualification; c. a full set of minutes of Committee meetings and decisions and such additional detailed records as the Committee may require; d. the Health Research Portal data documenting the status of all research proposals submitted to the Committee (e.g. whether exempt from review, approved, awaiting changes before action, or not approved); e. copies of all research proposals submitted to the Committee, including comments from any scientific or technical bodies and any other research ethics committees that reviewed any such proposal; f. all project-related documentation, for a minimum of three years after the closure of the project; and g. all Secretariat-related documentation (meeting agenda, minutes of meetings, annual reports, reports etc.) shall be retained for five years unless otherwise advised by the Records and Archive Department of WHO. IV. Committee Meetings A. Frequency 1. Committee meetings shall be convened by the Chair every month, or more often, depending upon the number and timing of research proposals received by the Secretariat for review. 2. The Secretariat shall provide the Committee members with at least one week’s notice of all meetings together with a copy of the proposed agenda and required meeting materials. B. Attendance 1. Committee meetings may only be attended by members, the Secretary and the Secretariat staff and such additional people who are permitted under these rules to be present for a particular meeting or a portion thereof. 2. At the invitation of the Chair, the RTO who submitted the proposal (or in his or her absence such other person(s) designated by the RTO) may attend meetings at which the proposal will be reviewed for the purposes of offering additional information and clarifications requested by the Committee. 7 3. The Chair may invite additional staff of WHO, other United Nations agencies or experts to provide advice on special issues when the Chair considers that their expertise is needed for the review of a research proposal or for other matters before the Committee. When consulted on a research proposal, such experts may attend those portions of the meeting at which the proposal is being reviewed and participate in the discussion. 4. In the interest of transparency and improving the wider understanding of the work of the Committee, the Chair may also, at his or her discretion, invite a limited number of individuals as observers to the Committee meetings. Observers may attend the entire meeting to which they have been invited, but may not take part in discussions unless explicitly invited by the Chair to do so. The Chair at his or her discretion may decide to request the invited observers to leave the meeting room during specific portions of the discussions. C. Confidentiality 1. The project documentation and the deliberations of the Committee are confidential and all Committee members are bound to respect such confidentiality. 2. All experts and observers invited to any Committee meeting must commit to maintain confidentiality regarding the Committee’s work for each meeting that they are invited to attend. 3. In order to ensure that the Committee is able to engage in a candid evaluation of research proposals, the minutes of its meetings and all other Committee records shall be kept in such a manner that the points discussed are recorded without ascribing the views or conclusions to particular members of the Committee. 4. In all communications from the Committee and Secretariat, reasonable steps will be taken not to reveal confidential or proprietary information concerning any research proposal or investigator. Such measures, however, shall not interfere with the ability of the Committee to fully perform its function. D. Quorum 1. At least six members, including the Chair, must be present to constitute a quorum. 2. A meeting can only commence once a quorum is obtained. If at any time during the meeting the quorum is lost, the meeting must be concluded. 8 3. Members of the Secretariat and other experts or observers do not count towards the quorum. D. Meeting records 1. Minutes shall be recorded by the Secretariat for all meetings and shall be submitted to the Chair and subsequently to the Committee for approval. 2. Meeting agenda and minutes of meetings shall be retained by the Secretariat for ten years. V. Submission and Review of Research Proposals A. Submission of Research Proposals 1. In order to ensure that appropriate ethics review has occurred for all research involving human participants that meets the requirements of these SOPs and that is funded or otherwise supported by WHO in the Region, the RTO, working in close collaboration with the Principal Investigator, shall submit the proposal for such research to the Secretariat through the Health Research Portal, in accordance with the documentation requirements of Appendix 1 and fill the risk assessment checklist(Appendix 2). 2. Before submitting a research proposal to the Secretariat, the RTO shall ensure that: a. Such research has been previously reviewed and approved by a scientific review committee, panel or group that is external to WHO and whose entire membership is independent from the research project team; b. Such research conforms not only to the ethics requirements established by WPRO-ERC but also to those of any other applicable ethics review body convened by the Organization, if any; c. Such research has been authorized by the relevant health authorities in the country where the research will be conducted when so required by the country concerned; if such authorization has not yet been granted, an explanation is provided concerning the reasons for the delay of such a granting and if and when such authorization approval will be forthcoming; d. Such research has been submitted for review to at least one ethics committee in the country in which the research will be undertaken with the understanding that the country-level committee shall take responsibility for ensuring that all locally-relevant ethics standards and other local 9 requirements are being followed. The WPRO-ERC shall review but not grant final approval of a research proposal until a copy of the approval by the designated local ethics committee has been provided; e. It shall be the responsibility of the Principal Investigator to identify any other relevant committees that also need to approve the proposal in a given setting according to local and institutional requirements. Any such local requirements shall be brought to the attention of the Secretariat when the proposal is submitted to the WPRO-ERC, and a copy of these approvals are provided; f. The Principal Investigator and the institution under whose auspices the research will be conducted have formally committed to safeguard the rights and welfare of the research participants in accordance with international ethics requirements, in addition to all local and national ethics and legal requirements, to conform to the standards for research ethics adopted by the Committee, to adhere to the obligations of Principal Investigators as specified in these SOPs and to adhere to other requirements as may be made by the Committee in granting approval. 3. Once a proposal has been submitted, the Committee Secretariat will review whether the documentation is complete or incomplete within five working days of submission of the proposal. Incomplete submissions will be returned back to the RTO with a comment to provide the missing supplementary files. Any comments or questions on the research proposal will be directed to the RTO B. Standard of WPRO-ERC review 1. The evaluation of research proposals by the WPRO-ERC shall be guided by the World Medical Association Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects (2008), the International Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002), and the International Guidelines for Ethical Review of Epidemiological Studies (CIOMS 2008). The Committee may, from time to time, officially recognize other statements on research ethics or formulate its own standards for particular topics in addition those contained in these documents. 2. The principal considerations for WPRO-ERC review will usually be whether the proposal exhibits a favorable balance of benefits to risks, whether the risks to participants and others have been minimized, whether participants will be 10 fairly selected, whether potential participants are so situated as to be able to make a free and competent decision, and whether the information provided to potential participants about the research project is in its nature and form such as to permit them to make an informed decision about whether to participate. 3. In determining the balance of benefits to risks, the Committee may consider the nature (including the adequacy) of any scientific review of the proposal, but the existence of such prior review does not preclude raising questions about the design and, when appropriate, asking for further information, requesting modifications in the design, or not approving the proposal, since a research project involving human participants that lacks scientific merit is inherently unethical. The Committee shall also review the plans for dissemination of the outcome of the research to ensure that the research results are disseminated to the research participants and other concerned stakeholders in an appropriate manner. 4. Once the proposal is complete and ready to be reviewed, the Secretariat shall ensure that the WHO RTO receives a review outcome within the stipulated time frame as follows: a. Exemption from WPRO-ERC review: within 5 working days; b. Expedited Review: within 15 working days; c. Review by the Committee: within 30 working days; d. Accelerated Review: within 7-15 working days. C. Exemption from WPRO-ERC review 1. A research proposal may be exempted from review by the Committee when: a. it does not involve human participants; b. the data (including health-care records and specimens) being studied already exist and are either publicly available or are recorded by the investigator in such a manner as to be unidentifiable by the investigator or any member of the research team; c. public officials are interviewed in their official capacity on issues that are in the public domain; d. the data for the study are generated by observation of public behavior; or e. the relevant activity is limited to public health surveillance or evaluation of health programmes carried out pursuant to statutory or regulatory requirements. 2. If the Secretariat and the Chair both find that a proposal is exempt from review by the Committee in accordance with the criteria set forth in subparagraph (1) 11 above, the research proposal shall be classified as "Exempt from WPRO-ERC review", an appropriate notation shall be made in the Health Research Portal, and the RTO shall be notified accordingly. Such notification shall include a brief explanation of the grounds for the exemption and a reminder that the Secretariat must be consulted in the event that material changes are made in the design or execution of the activity in question. 3. If the Secretariat and Chair cannot agree whether a research proposal qualifies as exempt from review, the proposal shall be categorized as eligible for expedited review as provided in the section V.D below, and reviewed accordingly, and the RTO shall be informed accordingly. D. Expedited review 1. A research proposal is eligible for an expedited review when; a. it will expose research participants to no more than minimal risk i.e. the level of risk to which it will expose participants is no greater than that encountered by people involved in their normal daily activities, such as working at home, in an office, or on a farm, attending school, or undergoing a routine health examination. b. minor changes are planned in research that has been previously approved by the WPRO-ERC and where proposed changes do not create more than minimal risks; c. an additional research centre is to be added to a project previously approved on a multi-centre basis, such that WPRO-ERC review is limited to ensuring that the necessary local review and approval has taken place. 2. If the Secretariat and the Chair determine that a proposal is eligible for expedited review in accordance with the criteria set forth in articles V.C.3 or D.1a above, the research proposal shall then be reviewed on its merits by two Committee members independently. The reviewers shall be identified by the Secretariat based upon relevant knowledge and availability to evaluate the proposal and such other criteria as may be determined by the Committee. 3. Following the review of a research proposal, the two reviewers shall recommend an outcome. Based on their recommendations, the Chair, on behalf of the Committee shall make appropriate actions; a. The recommendations of two reviewers except in case of (b) and (c) below shall be discussed by the Secretariat with the Chair. Based on their recommendations, the Chair, on behalf of the Committee shall make a determination of the outcome of the review and the Secretariat shall 12 communicate this decision to the RTO accordingly. Such notification shall include a reminder that any material changes in the design or execution of the activity in question must be approved pursuant to these SOPs prior to implementation. b. If either of the two reviewers, based on their review, determine that the proposal poses more than minimal risk to the research participants or that it involves participants who have diminished autonomy and/or who are not capable of giving informed consent, the Secretariat shall submit the proposal for a Committee Review at the next available meeting, and notify the responsible staff member accordingly. c. If either of the two reviewers make a determination that the proposal is ethically unacceptable, and recommend that it be Rejected, the Secretariat shall submit the proposal for a Committee Review at the next available meeting, and notify the responsible staff member accordingly. No proposal shall be Rejected based on an expedited review. 4. A proposal that is eligible for expedited review in accordance with the criteria set forth in article V.D.1b and 1c may be reviewed by the Chair on behalf of the Committee. Following the review of a research proposal, the Chair shall provide an outcome of using either option article V.G.1a or b. E. Review by the Committee 1. All proposals for research involving human participants funded or otherwise supported by WHO in the Region that are neither determined to be exempt from WPRO-ERC review, nor approved by expedited review in accordance with these SOPs shall be subject to a review by the Committee at a convened meeting. 2. Research that involves persons with diminished autonomy and/or who are not capable of giving informed consent must be submitted to the Committee for review and cannot be approved through an expedited review process. 3. The Committee shall perform such review in a conscientious and expeditious manner. a. In reaching decisions about research proposals, Members must exercise their judgment in applying the applicable ethical standards for review to the facts of each case, including what they know about the circumstances and conditions under which the research will be conducted. b. Two members of the Committee scheduled to be present at the meeting where a research proposal will be discussed shall be assigned by the 13 Secretariat as “primary reviewers”. Such primary reviewers shall summarize the proposal at the Committee meeting and provide their opinions on relevant ethical considerations, including recommendations for action by the Committee. In the event a primary reviewer determines that additional material is needed for review, or that the presence of the RTO at the Committee meeting would be desirable, he/she should promptly notify the Secretariat, who shall then attempt to obtain the needed information. c. All Members present at the Committee meeting shall be familiar with each proposal and shall participate in the discussion and in the decision to be taken with respect to each proposal. 4. Following a discussion of a proposal, the Committee shall provide an outcome of the discussion using any one of the options provided under section V.G.1 below. 5. Except as otherwise provided in these SOPs, decisions on review of proposals shall be taken by consensus. When consensus cannot be reached, the Chair may ask the Committee to vote, by a show of hands. In case of voting, decisions on review of proposal shall be taken by two-thirds majority of the Members present and voting. F. Accelerated Review 1. All proposals carry out in the context of public health emergencies such as the investigation of a disease outbreak or a disaster relief operation shall be subject to accelerated review. 2. The standards and procedures for review of these proposals shall be guided by sections V.B. 1-4 and V.C.D.E; however, recognizing the urgency of the situation, the Secretariat shall ensure that the review of such research proposals is conducted in an accelerated manner, including convening a special ERC meeting, if required. The procedure of review in such a case is described under section V.H.3 below (Review of Special Categories of Proposals). G. Outcome of the Review and Reporting the Outcome of Review 1. The outcome of the review of a research proposal, notwithstanding the procedure followed for carrying it out, must be in accordance with one of the following actions: a. Approved as submitted: means that the proposal is approved and no modifications are required. 14 b. Not approved; requires amendments and/or clarifications. This means that final approval is contingent upon an adequate response by the Principal Investigator, to the satisfaction of the reviewers or the Chair on behalf of the WPRO-ERC. c. Not approved; requires additional information and/or rewriting. This means that the revised version of the proposal should be re-submitted by the RTO as a new submission to the Secretariat for re-review by Committee. d. Rejected. This means that the proposal is ethically unacceptable, and may not be approved by the WPRO-ERC. 2. The outcome of a review shall be communicated by the Secretariat to the RTO in writing, together with an explanation of the reasons for the decision. If, following a Committee review, a proposal is rejected, the explanation shall include the ethical principles underlying the decision. 3. If a proposal is "rejected", the Chair shall provide an opportunity to the RTO to appeal the decision in writing. When the Chair considers it is warranted on the basis of the information provided by the RTO, she/he may decide to have the decision of rejection of that proposal reconsidered by the Committee at its next meeting. 4. Notwithstanding the action chosen, among those listed above, for conducting the final review of a proposal that requires amendments and/or clarifications, the Secretariat shall, upon a final approval of the proposal, have the approval signed by the Chair of the Committee. 5. At each meeting of the Committee, the Secretariat shall provide the Committee with a summary report on the outcome of all research proposals since the previous meeting, as well as a summary report on all proposals which were determined to be eligible for expedited review or to be exempt from review. At that time, any Member may request a re-assessment of the proposals that were deemed to be exempt from review or eligible for expedited review. When such a request has been made, the Secretariat shall immediately notify the RTO not to proceed further with the research project until the Committee has reviewed the matter and he/she has been informed of the outcome of the Committee's review. 6. If the Committee decides to override the determination made by the Chair and the Secretariat in either V.C.2 or V.D.4, it shall then determine the type of review the proposal shall undergo. 15 H. Review of Special Categories of Proposals 1. Multi-Centre Studies: Research projects that are to be conducted at more than one centre. Data are pooled for analyses to accomplish the specific aims of the study, and results are disseminated jointly by the investigators. Review of multisite research studies require review in the same manner as any other research funded or supported by the WHO in the Region that involves human participants, but the multi-centre nature of such projects can lead to two variations in the process of approval: a. When WHO is the lead agency funding or organizing the research, an expedited review by the Secretariat in consultation with Chair may be used to add new centres to an approved research project. i) Once the Committee has approved a research proposal for the first centre as a “master protocol”, the review and approval of additional research centres as sites for the same project can be undertaken on an expedited basis by the Secretariat and the Chair. But each proposed new site shall be given a new ID in the Registry, with a notation that it is derivative of a particular master protocol. The Secretariat, however, will report about all these proposals to the Committee at its next meeting, for the information of all the members. ii) In such a situation, an expedited review can be limited to determine whether the research proposal remains unchanged from the master protocol; whether any variations in the local circumstances (in terms of the characteristics of the population, the local manifestation or nature of the disease, etc.) could adversely affect the benefit-risk ratio, the minimization of risk, or the validity of informed consent; and whether any translation of information and documentation has been prepared in an adequate and culturally appropriate fashion. iii) If the Secretariat and the Chair conclude on initial review that the benefit-risk ratio is adversely affected, the proposal will be submitted for full review by the Committee and the RTO shall be so informed. b. When WHO is involved in only one or a few sites of a multi-centre study being led by scientists unaffiliated with the WHO and when another institutional review board or research ethics committee has been designated as the “lead ethical review board” for the study with the aim of promoting consistent and uniform conditions for the research at all sites, the 16 Committee may choose to postpone review of the research proposal until such board has completed its review. i) The decision to postpone review should be made in a manner that will not unduly delay the final decision on WHO involvement in the study. ii) A decision to postpone review is dependent upon a determination by the Committee that the lead ethics review board for the study is capable of providing a review of comparable scope and quality to that which the Committee would otherwise provide. iii) The RTO for the research proposal shall submit to the Secretariat the results of the review by the lead ethics review board. When this documentation is received, the Committee will commence its review of the proposal. 2. Nested Studies: Any study which is part of another, i.e. “nested” within another study, shall be subject to the procedures and criteria for review as set forth in these rules. However, the RTO shall also submit the protocol for the main study. While the main protocol need not be formally reviewed by the Committee, it should be satisfied with the ethical aspects of the main study before approving the nested study. 3. Research conducted in the context of public health emergencies: Research studies that are to be conducted in the context of public health emergencies, such as the investigation of a disease outbreak, or during a disaster relief operation, may require review on an urgent basis. The proposal shall be subject to the standards and procedures for review as set forth in these SOPs, however, the procedure for Committee Review may be modified depending upon the nature of the emergency. In cases where the proposal warrants a Committee Review, as set out in these SOPs, the Secretariat shall endeavor to conduct an accelerated review, by calling a special meeting of the WPRO-ERC. If however, the quorum for the conduct of business provided in IV.D.1 is not reached, the Chair may decide, depending upon the nature of the circumstances that the proposal be reviewed by a minimum of 3 members attending the special meeting of the WPRO-ERC. a. The outcome of such a review, to be provided using one of the options provided under section V.F.1 above, shall be communicated to the RTO as quickly as possible; b. The proposal and the outcome of the review shall however be presented by the Secretariat at the next Committee Meeting for information. At this time 17 any Member may make additional recommendations. When such recommendations have been made, the Secretariat shall immediately notify the RTO to incorporate these additional recommendations in to the approved protocol; c. Notwithstanding the availability of this review procedure, the Secretariat shall work in collaboration with the concerned WHO teams, and encourage the development of protocol templates that may be pre-reviewed by the Committee as per these SOPs, such that any new protocol based on a pre- reviewed protocol may be reviewed by an expedited review. I. Continuing Oversight and Monitoring 1. WHO’s obligation to ensure continuing oversight of approved research projects with human participants which it funds or otherwise supports, creates responsibilities for the RTO and for the Committee beyond the obligation to perform continuing reviews. 2. The RTO for each approved research shall promptly report to the Committee any developments in the project that might have ethical implications. 3. Principal Investigators shall inform the RTO of any changes in an approved research proposal or consent documentation proposed to be made before implementation, and these shall be reported immediately to the Committee by the RTO. a. When the Secretariat receives a report of changes that are proposed to be made in the protocol or consent documentation of a research project that the Committee has previously approved, a determination shall be made by the Chair and the Secretariat whether the proposed changes should be subject to review by the Committee in accordance with these SOPs. b. Pending the Committee’s decision, which it shall endeavor to produce in a timely manner, the changes proposed for the research project shall not be instituted, with the exception of any modifications urgently needed to protect the well-being or important interests of participants already enrolled in the study. 4. Any deaths as well as any serious adverse events or unexpected events that occur to participants during their participation in any approved research project shall be reported immediately by the Principal Investigator to the RTO and to any other people, ethics review bodies, funding agencies or other bodies with whom such information must be filed pursuant to national regulations and the terms and conditions agreed by WHO. The RTO must in turn promptly 18 convey such reports to the Secretariat including the feedback from other review bodies. a. The Secretariat shall review all such reports and determine whether the information reported warrants another review of the research project, with particular attention to the benefit-risk ratio, the adequacy of the steps taken to minimize risk and the information provided to prospective participants. Such determinations will be reported to the Committee at its next meeting. b. If the Secretariat determines that another review should occur, it shall take place as soon as possible (including through an extraordinary Committee meeting, if necessary under the circumstances). c. The results of the second review will be promptly conveyed to the Responsible Technical Officer. d. It shall remain the obligation of the RTO, rather than of the Committee, to ensure that adverse event reports, and the determinations reached by the Committee in a second review, are filed with all appropriate people and agencies, pursuant to terms and conditions agreed by WHO. 5. Procedures on completion of research project: a. The Principal Investigator is requested to submit a final report and a financial report (if financially supported by the WHO in the Region) upon completion of the research project, if it had been reviewed by the Committee earlier, to the RTO. The final report also should include information about how the results have been used and disseminated to relevant stakeholders. b. The RTO shall report the final research project outcome (completion or discontinuation) and submit a final report on the study to the Secretariat. A notation shall be made in the Registry accordingly. c. The RTO also will submit a copy of any reports that were published in the public domain or any publications in any peer-reviewed journals, which will be linked with the project ID in the electronic registry. VI. Conflicts of Interest 1. The avoidance of conflicts of interest or the appearance thereof is important to ensure both the quality and credibility of research ethics review. The Committee will therefore take necessary steps to avoid conflicts of interest and the appearance of conflicts of interest for investigators, RTO, the Committee members and the Secretariat. 19 2. It is important that all people participating in the submission and review of proposals involving human research avoid situations that could affect their ability to provide objective guidance for, or review of, research proposals regarding particular drugs, devices, vaccines, or other interventions. 3. The Committee shall ensure that its resolution of any situation involving a potential conflict of interest avoids not only the occurrence of unacceptable interests but also the appearance of such conflicts of interest. 4. In all cases in which a conflict of interest is revealed, but is not so material as to warrant not approving the project, the Committee shall determine the type of description of such interest that needs to be included in the information provided to prospective participants in the research and shall ensure that the consent documentation also includes an appropriate disclosure. A. Investigators 1. The Principal Investigator who will conduct the research should not have any material conflict of interest or any other interests that may damage the scientific objectivity of the research. 2. All Principal Investigators involved in the proposed research proposal have to clearly mention in the proposal cover page that they do not have any conflict of interest with the proposed research. 3. The Committee shall approve a research proposal only if it concludes that the Principal Investigator does not have any material conflict of interest or that such interests are not sufficient to damage the scientific objectivity of the research (in light of other means such as the independence of other investigators or the oversight of a monitoring board to counterbalance the interest). B. Committee members 1. Financial conflict: The Committee members and the Committee Secretariat are bound by Staff Rule 110.7.1 to inform the Regional Director of any interest they, as well as their spouses and dependent children, may have in any entity that has a commercial interest or a common area of activity in the work of WHO. In the case of an interest in an entity having a commercial interest or common area of activity involving a research proposal submitted to the Committee, all such staff members shall inform the Secretariat. 2. Role conflict: A Committee member who is also a RTO for a proposal under review or is connected closely to a proposal (such as being on the same team as 20 the RTO submitting the proposal or being in a supervisory position with the submitting RTO) would have a conflict of interest if he or she participated in the ethics review of the proposal. 3. When asked to perform an expedited review or to be a primary reviewer, a Committee member that has a financial or role conflict shall disclose such a conflict and decline to undertake the review. 4. Committee members having reported a financial or role conflict may, unless the Chairperson determines otherwise, comment on the matter before the Committee but may not participate in the Committee’s decision on the matter. 5. The Chair may impose additional restrictions (such as requesting the member to leave the meeting while the matter is discussed) as he or she believes are warranted under the circumstances. The conflict of interest shall be announced during the meeting and the minutes of the meeting shall record the declared conflict of interest and the steps taken to deal with the situation with regard to the Committee’s deliberations and decisions. 6. Similarly, the Chair will hand over his or her responsibility to the Vice-Chair whenever he or she has a role conflict and the minutes of the meeting shall record the declared conflict of interest and the steps taken to deal with the situation with regard to the Committee’s deliberations and decisions. VII. Adoption and Amendment of the Rules of Procedure The Committee may adopt detailed Rules of procedure as it deems necessary in implementing these SOPs. 21 Appendix 1: Documents to submit to WPRO-ERC for review 1. A research proposal that includes the following information: a. Brief background and justification b. Objective/purpose of study and a brief statement as to why the research question(s) is relevant; c. Methodology (including sampling methodology and sample size), procedures and analysis plan; d. Limitations, if any e. Significance of study with a careful assessment of predictable risks and burdens to the individuals and communities involved in the research in comparison with foreseeable benefits to them and to other individuals or communities affected by the condition under investigation f. Self-assessment of level of risk g. Plans for dissemination of research results to the relevant stakeholders h. Detailed budget and timelines; and i. References 2. A structured abstract (fewer than 300 words) providing a succinct summary of the research question, the population and interventions involved, main outcomes, methods, potential risks for subjects and names of participating institutions and countries. The abstract briefly should mention the potential value of this research for public health. 3. Curriculum vitae (abbreviated, two pages) of the Principal Investigator and any co-investigators. There is no mandatory format for CVs. Summary CVs are preferred provided that they contain key recent information. 4. Results of the independent technical / scientific review: Independent reviews can be conducted by a Scientific Review Board, or alternatively, two technical reviewers demonstrably independent from the research. a. Reviewer comments in a separate document (i.e. separate from the protocol). b. Protocol and other document(s) with changes made in response to the review highlighted or tracked, ensuring there are no boxes visible in the margins (formatting or comment boxes) c. The research team’s point-by-point responses to the reviews, clearly indicating any changes made to study documents in response to the reviews, and including the page numbers where the changes have been made 22 d. Confirmation of final approval by the Board or each of the reviewers (email is acceptable) e. Names and affiliations of individual reviewers (not necessary for Boards) 5. Documentation that the proposal has been reviewed and approved by the appropriate institutional review board or any other research ethics committee for the site(s) where the research will be conducted, or in the absence thereof, an explanation of when such review will occur. Proof of local submission (e.g. acknowledgement of receipt) is required prior to WPRO-ERC review, and proof of local approval is required prior to WPRO-ERC approval. 6. Informed consent documentation: Consent/assent documents comprise participant information pages and signature page(s)that will be used in the study and a description of how the subjects will be protected, including how data safety and monitoring will work and how deaths and unexpected events will be prevented or analyzed and dealt with. There is no mandatory format. 7. Study instruments/data collection tools (Surveys, questionnaires, interview schedules, case report forms, patient diaries, data dictionaries, etc.) 8. Documentation confirming that (1) all investigators have completed standard WHO Declaration/Conflict of Interest forms, (2) these have been reviewed by the WPRO RTO, and (3) no conflicts of interest exist (or describing any potential conflicts of interest that were identified and how these conflicts will be managed) 9. The following documents may need to be submitted depending on the research being proposed: a. Recruitment materials: advertisements, flyers, posters b. Investigator brochure and/or package inserts c. Clinical Trials registration details (WHO primary register ID, name of register, date of registration, and URL). Required for all interventional/clinical trials (details to be provided prior to approval) d. ToRs/Roles and responsibilities for Data Safety Monitoring Board/Committee (DSMB/C) or other statistical analysis groups, steering groups, etc. e. Description of study insurance arrangements or insurance procured for interventional/clinical trials. 23 Appendix 2. WPRO-ERC Risk Assessment Checklist Please complete the filter questions - these determine the level of risk and the review procedure your application will undergo by WPRO-ERC. Risk level assessment checklist Yes No Does your research involve the following criteria? a. it does not involve human participants; b. the data (including health-care records and specimens) being studied already exist and are either publicly available or are recorded by the investigator in such a manner as to be unidentifiable by the investigator or any member of the research team; c. public officials are interviewed in their official capacity on issues that are in the public domain; d. the data for the study are generated by observation of public behaviour; e. the relevant activity is limited to public health surveillance or evaluation of health programmes carried out pursuant to statutory or regulatory requirements. ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ If you answered YES to ANY of the above criteria, your application will be EXEMPTED from review. You will receive the notification within 5 working days. Otherwise, please proceed with answering the following questions. Does your research involve: a. it will expose research participants to no more than minimal risk i.e. the level of risk to which it will expose participants is no greater than that encountered by people involved in their normal daily activities, such as working at home, in an office, or on a farm, attending school, or undergoing a routine health examination. b. minor changes are planned in research that has been previously approved by the WPRO-ERC and where proposed changes do not create more than minimal risks; c. an additional research centre is to be added to a project previously approved on a multi-centre basis, such that WPRO-ERC review is limited to ensuring that the necessary local review and approval has taken place. ☐ ☐ ☐ ☐ ☐ ☐ If you answered YES to ANY of the above, your application will undergo expedited review within 15 working days. Does your research: a. neither determined to be exempt from WPRO-ERC review, nor ☐ ☐ 24 approved by expedited review. b. involves persons with diminished autonomy and/or who are not capable of giving informed consent must be submitted to the Committee for review and cannot be approved through an expedited review process. ☐ ☐ If you answered YES to ANY of the above, your application will be reviewed by the committee within 30 working days.