SOP MHREC 1 Sep 2019

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition Supersedes: Previous MHREC SOPs Prepared by: MHREC SOP Team Reviewed by: MHREC Faculty of Medicine, Public Health and Nursing, Approved by: Universitas Gadjah Mada – Dr. Sardjito General Hospital Dean of Faculty of Medicine, Public Health and Nursing, Effective date: Universitas Gadjah Mada and Director of Dr. Sardjito General Hospital 1 September 2019 1. Medical and Health Research Ethics Committee (MHREC) Structure and Composition 1.1. Appointment of MHREC Members and Officers 1.2. Appointment of Independent Consultants 1.3. Training of MHREC Members and Secretariat Staffs Appendix A Form 1.1 Statement of Responsibilities of MHREC Member Form 1.2 Curriculum Vitae Form Form 1.3 Confidentiality and Conflict of Interest Agreement Form 1.4 Training Record of an MHREC Member Form 1.5 Invitation of Independent Consultants 1

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition 1.1. Appointment of MHREC Members and Officers 1.1.1. Purpose To describe the appointment procedures of the members and officers of the Medical and Health Research Ethic Committee (MHREC) of Faculty of Medicine, Public Health and Nursing, UGM - Dr. Sardjito General Hospital and to identify the roles and responsibilities of the EC members and officers. 1.1.2. Scope While the EC remains under the authority of the Dean Faculty of Medicine, Public Health and Nursing UGM - Dr. Sardjito General Hospital Director, it has to maintain its independence and develop its competence related to decision making as defined in international and national guidelines. The membership SOPs cover the nomination and appointment procedures of EC members and officers 1.1.3. Responsibility It is the responsibility of the Dean of Faculty of Medicine, Public Health and Nursing UGM - Dr. Sardjito General Hospital Director to formally appoint the members and officers of the EC after due consultation with the current members of the EC 1.1.4. Process Flow/Steps PERSON(S) TIMELINE No ACTIVITY RESPONSIBLE Chair, members To be done at 1 Define the composition of the least 60 days membership of the EC EC chairs, before the members, expiry of the 2 Select the nomination of new EC Chair appointment members from all possible candidates The Dean of the 3 Recommend and submit the list of Faculty and the potential members and officers to the Director of the dean and the hospital director Hospital New member, 4 Obtain approval of appointment of EC secretariat members and officers 5 Ensure completion of membership documents 1.1.5. Detailed instructions 1.1.5.1. Define the composition of the membership of the EC  The Chair discusses the qualifications of additional/new members with the existing members of the EC.  The EC members should have diverse background and experience to foster a comprehensive and efficient review of research activities commonly conducted by its own affiliated and non-affiliated researchers. 2

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition  The membership shall include persons whose primary concerns are in medical science and/or public health, with at least one member who is in a non-medical/non-scientific area, and at least one member who is not affiliated with the Faculty of Medicine, Public Health and Nursing, UGM - Dr. Sardjito General Hospital.  Relevant expertise may include medicine and research, social or behavioral science, law, philosophy, environmental science and public health. It is recommended that the EC include a person who will represent the interest and concerns of the community.  The EC shall aim for adequate representation of men and women members in order to promote gender sensitivity in its review procedures.  The EC shall have representatives from both the older and younger generations. During review meetings, the EC shall adhere to quorum requirements as defined in international and national guidelines for ECs that review medical and health research. When reviewing clinical trials involving children or pediatric patients, a pediatrician or child development specialist shall be present during its board meeting (Refer to Chapter 4 Section 4.2 on Conduct of a Full-Board Meeting) 1.1.5.2. Select the nomination of new EC members from all possible candidates  Members are selected based on their good moral character and personal capacities, their scientific expertise and knowledge of ethical principles, as well as their willingness to volunteer their time and effort to perform their functions in the EC.  Members shall have prior training in research ethics, research methodology, and Good Clinical Practice or should be willing to undergo training during their membership  During the EC meeting the Chair presents the credentials of the person being nominated. EC Members discuss and decide by consensus on the final list of nominees to be submitted to the Dean of Faculty of Medicine, Public Health and Nursing UGM - Dr. Sardjito General Hospital Director. Conflict of interest issues of nominees shall also be discussed. 1.1.5.3. Recommend and submit the list of potential members and officers to the Dean of Faculty of Medicine Public Health and Nursing - Dr Sardjito Hospital Director  Dean Faculty of Medicine Public Health and Nursing and Dr Sardjito Hospital Director reviews the list of nominees and decides on the appointment to be made.  The appointment letter should include conditions of appointment, term of office, and honorarium (if any), as follows:  Members and officers are appointed for a period of three (3) years and renewable depending on their performance.  Willingness to make public his/her full name, profession, and affiliation as an EC member or officer 3

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition  Members shall sign the Statement of Responsibilities of MHREC Member/ Officer as well as the Confidentiality and Conflict of Interest Agreements. The agreement should cover all applications, meeting deliberations, information on research participants and related matters.  The EC shall adopt some mechanism to enable participation of new members with fresh outlook and approaches, but it shall also strive to ensure continuity, as well as the development and maintenance of expertise.  The EC chair and secretary, as well as the panel’s chair/secretary are nominated by the members of the EC. They should be highly-respected individuals within or outside the institution, fully capable of managing the EC and ensuring fairness and impartiality in dealing with matters brought the EC. They should have the following qualifications:  Good personal characteristics and reputation  Have training on Basic Research Ethics and GCP in the past 3 years  Willing to bear the responsibility as an officer (Box 1.1) 1.1.5.4. Obtain approval of appointment of EC members and officers  The Dean of Faculty of Medicine Public Health and Nursing and Dr. Sardjito General Hospital Director are responsible for appointing the EC members and officers with due consideration to the EC recommendations.  The Dean of Faculty of Medicine Public Health and Nursing and Dr. Sardjito General Hospital Director issue an appointment letter that identifies the EC members and officers  The appointment letter should include an attachment of the responsibilities of the EC members and/ or officers (Box 1.1) 1.1.5.5. Ensure completion of membership documents  After the approval of the appointment, newly appointed members/officers should complete all documents in their Membership File.  Upon the acceptance of their appointment, and before assuming their responsibilities as members/officers, they shall sign and date the Statements of Responsibilities of MHREC Members/ Officers, Indicating Their Willingness To Assume Their Responsibilities (Form 1.1).  The Secretariat provides duplicate copies of the Confidentiality and Conflict of Interest Agreement form (Form 1.3) to newly appointed members of the MHREC Faculty of Medicine Public Health and Nursing / dr Sardjito General Hospital, one copy for the member and the other for the Membership File. For each protocol that they review, they must disclose their COI (any interest or involvement such as financial, professional or otherwise in a research proposal under review).  The appointee is also required to submit an updated, signed and dated curriculum vitae, and the completed Training Record including photocopies of relevant training certificates. 4

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition Organize and complete the documents in the Membership Files The Membership Files shall contain the following:  Appointment letter  The Statement of Responsibilities of MHREC Member/ Officer signed and dated by the appointee  Updated curriculum vitae that is signed and dated by the member. The CV is updated every time the appointment is renewed.  Training Record and photocopy of Training Certificates of relevant trainings  Confidentiality and Disclosure of Conflict of Interest Agreement signed and dated by the member. Special Conditions: Resignation, Disqualification, and Replacement of Members  Members may resign their positions by submitting a letter of resignation to the Chair and endorsed to the Dean Faculty of Medicine Public Health and Nursing -- Dr Sardjito General Hospital Director  Members may be separated from the committee by disqualification for valid reasons as determined by majority vote of the committee members.  Members who have resigned or have been disqualified may be replaced by following the nomination and appointment procedures previously stated.  The terms of replacement shall be limited to the remaining term of the member that he/she has replaced 1.1.5.6. Executive committee Executive Committee composed of Overall Chair, Vice Chair, Overall Secretaries, together with the Panel Chairs and Panel Secretaries to coordinate and harmonize the operation of the different panels. Coordinating mechanism regularly once in three months and if necessary. 5

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition Box 1.1 Responsibilities of MHREC members and officers Responsibilities of MHREC members:  Serve as Primary Reviewers for research protocol documents within their area of expertise, and as general reviewers for all researches discussed at full-board meetings of the MHREC  Submit on time (within10 working days) to the Secretariat the completed Protocol and ICF Assessment forms when they are designated as the Primary Reviewers  Conduct expedited review of protocols assigned by the Panel’s Secretary and submit the assessment forms on time (within10 working days)  Perform post-approval review procedures of protocol-related documents within 10 working days  Update CV and training record every time appointment is renewed  Conform at all times with the legal and ethical principles accepted by the EC  Attend basic and continuing education on Research Ethics at least once a year  Perform other tasks requested by the Chair. Responsibilities of MHREC Chair and Vice Chair:  He/she receives mandates from the Dean of Faculty of Medicine Public Health and Nursing and Director of Dr. Sardjito General Hospital to chair the MHREC  Responsible for all MHREC related duties and reports to the Dean of Faculty of Medicine Public Health and Nursing and Director of Dr. Sardjito General Hospital  Chair MHREC business meetings  Ensures that all MHREC members receive orientation and undergo Basic Research Ethics Training after their appointment, and continuing education thereafter.  Obtains administrative and logistics support for the sustained operations of the EC  Manages complaints from study participants, authorities or the general public  Designates a member or group of members to investigate in cases of complaints or report of major non-compliance.  Ensures that the MHREC is perceived as fair and impartial, and complies with institutional, national and international standards.  Represents the MHREC in various local, national and international meetings and conferences.  Prepares the Annual Work Financial Plan (WFP) and the Project Procurement Management Plan (PPMP) and obtain approval of the plan to the Dean.  Ensure adherence to quality standards to maintain the accreditation status.  Invites independent consultants Responsibilities of Panel’s Chair and Vice Chair  Responsible for all review processes in the panel  Approves the agenda and presides over full-board review meetings. If Chair has COI relative to the protocol for deliberation s/he designates the Vice Chair of the Panel, the Panel’s Secretary or any Member to preside over the meeting. 6

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition  Signs ethical approvals and other decisions made by the panel. Responsibilities of MHREC Secretary:  Supervises the MHREC Staff related to good MHREC office management  Supervises the MHREC Staff in the preparation of the annual report of the MHREC to be submitted to the Dean Faculty of Medicine Public Health and Nursing / Dr Sardjito General Hospital Director, FERCAP and other bodies.  Ensures good MHREC documentation and archiving.  Ensures overall MHREC compliance with good clinical practice.  Ensures good financial management of MHREC resources Responsibilities of the Panel’s Secretary:  Selects suitable (somebody with related expertise) member/independent consultant to be the primary reviewer of a protocol whether by full board or expedited review, and ensures that aforementioned member does not have conflict of interest.  Prepares and finalizes the meeting agenda of full-board meeting after consultation with the Chair  Collects and reviews the assessment forms submitted by the Primary Reviewers before the meeting  Ensures that the members completely fill out necessary forms used for the review of protocol or protocol related submissions,  Supervises the MHREC Secretariat in the preparation of the meeting agenda and minutes Responsibilities of the MHREC Secretariat: The EC secretariat is composed of the Secretary, the Panel’s Secretary and the administrative staff who are employees of Faculty of Medicine Public Health and Nursing UGM.  Organizing an effective and efficient tracking procedure for each proposal received  Preparation, maintenance and distribution of study files  Organizing MHREC meetings regularly  Preparation and maintenance of meeting agenda and minutes  Maintaining good MHREC documentation and archiving procedures  Communicating with the MHREC members and Investigators  Arrangement of training for personnel and EC members  Organizing the preparation, review, revision and distribution of SOPs and guidelines;  Providing the necessary administrative support for MHREC-related activities to the Chair of the MHREC  Providing updates on relevant and contemporary issues related to ethics in health research, as well as relevant literature to the EC members  Maintaining a library of relevant resource materials and references 7

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition * Vice chair helps the task of the chair. The two secretary divides the task between themselves. 1.2. Appointment of Independent Consultants 1.2.1. Purpose To describe the procedures for the appointment of MHREC independent consultants 1.2.2. Scope This SOP describes the procedures for engaging the services of a professional/expert as a consultant to MHREC of the Faculty of Medicine Public Health and Nursing/ Dr Sardjito General Hospital Director. If the panel’s secretary determines that a study involves procedure(s) that are not within the area of competence or expertise of any of the EC members, the panel’s secretary may invite individuals with expertise in special areas to assist in the review of protocols that require such expertise in addition to those available within the EC 1.2.3. Responsibility Upon the advice or recommendation of the panel’s secretary or any EC member, the panel’s secretary may appoint the name of the independent consultants 1.2.4. Process Flow/Steps PERSON(S) TIMELINE No ACTIVITY RESPONSIBLE To be done as 1 Assess the need for independent Panel’s-secretary, needed consultants and seek approval for contracting their services members 2 Recruit and appoint an independent Secretariat To be completed consultant Secretariat within 5 working days 3 Organize and complete the documents in the independent consultant files 1.2.5. Detailed instructions 1.2.5.1. Assess the need for independent consultants and seek approval for contracting their services  Considering the nature of the protocol for review, the panel’s secretary identifies the expertise needed that the EC membership may not have.  The Chair submits the names of independent consultants to the Dean Faculty of Medicine Public Health and Nursing / Dr Sardjito General Hospital Director to request for corresponding honorarium. 8

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition 1.2.5.2. Recruit and appoint an independent consultant  Once the panel’s secretary decides to invite an Independent Consultant, the Chair request letter of appointment to the Dean that includes the following:  Terms of Reference (TOR) - duration of consultancy, general overview of deliverables  Request for a copy of the consultant’s curriculum vitae (CV)  The secretariat contacts the independent consultant  The secretariat asks the independent consultant to sign and date Confidentiality and Conflict of Interest Agreement 1.2.5.3. Organize and complete the documents in the Independent Consultant Files  The secretariat creates file for independent consultant.  The Independent Consultant Files shall contain the following:  Copy of the letter to the dean requesting appointment of independent consultant  Letter of appointment of independent consultant  Updated curriculum vitae that is signed and dated by the Independent Consultant.  Confidentiality and Disclosure of Conflict of Interest Agreement signed and dated by the Independent Consultant. 1.3. Training of EC Members and Secretariat Staffs 1.3.1. Purpose To describe The MHREC of Faculty of Medicine Public Health and Nursing - Dr Sardjito General Hospital procedures to ensure initial and continuing training of EC members and secretariat staffs 1.3.2. Scope The EC recognizes the importance of training and continuing professional development. This SOP describes the training requirements of the EC members and secretariat staffs from initial training to continuing education to maintain and update EC competence in the review of different types of protocols. Training is conducted at least once a year for topics: research ethics and Standard Operating Procedures 1.3.3. Responsibility It is the responsibility of the EC officers, members and secretariat staffs to have themselves educated and trained regularly. EC members should maintain competence by ensuring that they have updated knowledge of the following:  Good Clinical Practice (GCP)  Declaration of Helsinki 9

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition  CIOMS  Ethical Guidelines  Relevant Indonesian laws and regulations  Relevant developments in science, health and safety, etc.  International meetings and conferences It is the responsibility of the EC Chair along with the Secretariat to assess the training needs and prepare a training plan for all members, and secretariat staffs. The Secretariat keeps track of the training records of all members and secretariat staffs in accordance with the training plan. 1.3.4. Process Flow/Steps PERSON(S) TIMELINE No ACTIVITY RESPONSIBLE 1 Chair, secretariat Needs 2 Require basic research ethics assessment to training for all members and Chair, secretariat be done at the 3 secretariat staffs beginning of Provide opportunities for continuing Members, the year education for members and secretariat secretariat staffs through participation in meetings, conferences and training courses Track member and secretariat staffs participation initial and continuing ethics training and file the documents in the membership file 1.3.5. Detailed instructions 1.3.5.1. Require Basic Research Ethics Training for all members and staff  All EC members are required to have basic research ethics training that shall consist of research ethics principles, GCP, SOPs, etc. Upon appointment, a new member or staff undergoes orientation, individually or as a group, to cover the following:  Member’s/ secretariat staff’s responsibilities;  Confidentiality and Conflict of Interest Agreement;  EC review process and use of Protocol and ICF Assessment forms; and  EC SOPs.  The chair shall ensure that initial research ethics training is provided to all new members 10

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition 1.3.5.2. Provide opportunities for continuing education for members and secretariat staffs through participation in meetings, conferences and training courses  The chair provides training opportunities to members and secretariat staffs through participation in local and national research ethics seminars, conferences and workshops, and allocating funds for this purpose.  The chair and the secretariat plan the training activities for individual EC members and secretariat staffs based on their training needs.  The chair and the secretariat track and facilitate attendance of EC members and staffs of specific training activities needed to ensure that each one gets training at least once a year.  The EC Members who participate in research ethics training course or seminar- workshops either through personal or through EC efforts/funding are encouraged to:  Share information with other members during EC meetings; and  Distribute photocopies/e-copies of relevant materials to the other members 1.3.5.3. Track members and secretariat staffs participation in initial and continuing ethics training and file the documents in the Membership File  For in-house training, the secretariat prepares attendance sheets with relevant information about the topic, duration, date and venue. They ask member-attendees to sign the attendance sheet and keep a photocopy of the attendance in the membership files, if Training Certificate is not given.  All EC Members and secretariat staffs should regularly update their Training Record. They should submit proof of attendance in relevant training or continuing professional education sessions conducted outside of the institution – e.g. certificates of training to the secretariat for filing.  The secretariat should update the Training Record of individual member and staff to reflect their attendance in training activities every time a photocopy of Training Certificate is submitted for filing. 11

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition Appendix A MHREC Structure and Composition Forms Form 1.1 Statements of Responsibilities of MHREC Members/ Officers Form 1.2 Curriculum Vitae of MHREC Member Form 1.3 Confidentiality and Conflict of Interest Agreements Form 1.4 Training Record of an MHREC Member Form 1.5 Invitation of Independent Consultant 12

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition FORM 1.1 Statements of Responsibilities of MHREC Members/ Officers Date Dear (Name of MHREC Member) As an appointed member/ officer* of the MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito General Hospital you will have the following roles and responsibilities: As member of MHREC MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito General Hospital: (See Box 1.1 on list of responsibilities of MHREC members) As chair or vice chair/ secretary or vice secretary/ panel’s chair/ panel’s secretary* of MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito General Hospital: (See Box 1.1 on list of responsibilities of MHREC officers) If you agree with the terms of this appointment, please sign on the space below, and return one copy to the Secretariat. Submit duly-signed updated Curriculum Vitae and the Confidentiality and Conflict of Interest Agreement. Very truly yours, MHREC Chair Conforme: Date: (dd/mm/yyyy) (Print name and sign) * Choose whichever is applicable 13

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition FORM 1.2 Curriculum Vitae of MHREC Member Name : Address : Contact no. : Email : Position in MHREC : Date of Appointment : Education : Research and Ethics Training/s : Work Experience : Occupation : Previous work experience : Present work experience : Research-related Experience (Name) Date Date MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito General Hospital Chair 14

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition FORM 1.3 Confidentiality and Conflict of Interest Agreement In recognition of the fact that I, member/ consultant/ guest name, and his/ her affiliation, has been appointed as a member/ consultant* or is a guest* of the MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito Hospital, and hereinafter is referred to as the Undersigned, and * Choose whichever is applicable Whereas:  the Undersigned has been asked to assess research studies and protocols involving human subjects in order to ensure that the same are conducted in a humane and ethical manner, with the highest standards of care according to the applied national and local laws and regulations, institutional policies and guidelines;  the appointment of the Undersigned as a member of the MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito General Hospital is based on individual merits and not as an advocate or representative of a home province/ territory/ community nor as the delegate of any organization or private interest;  the fundamental duty of an EC member is to independently review both scientific and ethical aspects of research protocols involving human subjects and make a determination and the best possible objective recommendations, based on the merits thereof under review; and  the MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito General Hospital must meet the highest ethical standards in order to merit the trust and confidence of the communities in the protection of the rights and well-being of human subjects; The following terms and conditions covering Confidentiality and Conflict of Interest arising in the discharge of said appointed EC member’s functions, are hereby stipulated in this Agreement for purposes of ensuring the same high standards of ethical behavior necessary for the EC to carry out its mandate. Confidentiality This Agreement thus encompasses any information deemed Confidential, Privileged, or Proprietary provided to and/or otherwise received by the Undersigned in conjunction with and/or in the course of the performance of his/her duties as a member/Independent Consultant of the MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito Hospital. Any written information provided to the Undersigned that is of a Confidential, Privileged, or Proprietary in nature shall be identified accordingly. Written Confidential information provided for review shall not be copied or retained. All Confidential information (and any copies and notes thereof) shall remain the sole property of the EC. As such, the Undersigned agrees to hold in trust and in confidence all Confidential, Privileged or Proprietary information, including trade secrets and other intellectual property rights (hereinafter collectively referred to as the “information”). Moreover, the 15

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition Undersigned agrees that the information shall be used only for contemplated purposes and none other. Neither shall the said information be disclosed to any third party. The Undersigned further agrees not to disclose or utilize, directly or indirectly, any information belonging to a third party, in fulfilling this agreement. Furthermore, the Undersigned confirms that her performance of this agreement is consistent with policies of Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito Hospital and any contractual obligations owed to third parties. Conflict of Interest It is recognized that the potential for conflict of interest will always exist; however, there is concomitant faith in the ability of the EC to manage these conflict issues, if any, in such a way that the ultimate outcome of the protection of human subjects remains. It is the policy of the EC that no member/consultant may participate in the review, comment or approval of any activity in which he/she has a conflict of interest except to provide information as requested by the EC. The Undersigned will immediately disclose to the Chair of the MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito General Hospital any actual or potential conflict of interest that he/she may have in relation to any particular proposal submitted for review by the EC, and to abstain from any participation in discussions or recommendations in respect of such proposals. If an applicant submitting a protocol believes that an EC member has a potential conflict, the investigator may request that the member be excluded from the review of the protocol. The request must be in writing and addressed to the Chair. The request must contain evidence that substantiates the claim that a conflict exists with the EC member(s) in question. The EC may elect to investigate the applicant’s claim of the potential conflict. When a member/consultant has a conflict of interest, the member should notify the Chairperson and may not participate in the EC review or approval except to provide information requested by the Board. Examples of conflict of interest cases may include but is not limited to any of the following:  A member/consultant is involved in a potentially competing research program.  Access to funding or intellectual information may provide an unfair competitive advantage.  A member’s/consultant’s personal biases may interfere with his or her impartial judgment. 16

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition Agreement on Confidentiality and Conflict of Interest [To the Undersigned: Please sign and date this Agreement, if you agree with the terms and conditions set forth above. The original (signed and dated Agreement) will be kept on file in the custody of the MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito Hospital. A copy will be given to you for your records.] In the course of my activities as a member of the MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito Hospital, I will be provided with confidential information and documentation (which we will refer to as the \"Confidential Information\"). I agree to take reasonable measures to protect the Confidential Information, subject to applicable legislation, not to disclose the Confidential Information to any person; not to use the Confidential Information for any purpose outside the Board's mandate, and in particular, in a manner which would result in a benefit to myself or any third party; and to return all Confidential Information (including any minutes or notes I have made as part of my Board duties) to the Chair upon termination of my functions as an EC member Whenever I have a conflict of interest, I shall immediately inform the Chair not to count me toward a quorum for voting. I have read and accept the aforementioned terms and conditions as explained in this Agreement. Title/Name Date MHREC Faculty of Medicine, Public Health and Nursing, Date Universitas Gadjah Mada – Dr. Sardjito General Hospital Chair 17

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition FORM 1.4 Training Record of an MHREC Member Name : Topics Organizer Venue Date Funding Source Basic Course GCP training Research Ethics MHREC Standard Operating Procedures (SOP) Continuing Ethics Education: Research Ethics Workshop, Conferences, Meetings, Lectures, etc. (Name) Date MHREC Faculty of Medicine, Public Health and Nursing, Date Universitas Gadjah Mada – Dr. Sardjito General Hospital Chair 18

Chapter 1 Medical and Health Research Ethics Committee (MHREC) Structure and Composition FORM 1.5 Invitation of Independent Consultant (Name of Independent Consultant) (Institution) Date Dear … We hereby invite you to serve as Independent Consultant for the following protocol: (Title of Protocol), (Protocol Number), (Name of PI), (Sponsor) Please review the technical and ethical issues in the protocol based on the assessment forms that we hereby attach. Please forward your assessment/ comments to the Secretariat within 10 working days. Please attend the full board meeting on ________ at _______. Thank you for your support and cooperation. If you agree with the terms of this appointment, please sign on the space provided below, date your signature, and return one copy of this letter to the MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito General Hospital Secretariat. Please sign, date and submit your latest curriculum vitae and the Confidentiality and Conflict of Interest Agreement. Very truly yours, MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito Hospital Chair Conforme: Date (Print name and sign) 19

Chapter 2 Initial Review Procedures Supersedes: Previous MHREC SOPs Prepared by: MHREC SOP Team Reviewed by: MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito General Hospital Approved by: Dean of Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada and Director of Dr. Sardjito General Effective date: Hospital 1 September 2019 2. Initial Review Procedures 2.1. Management of Protocol Submissions 2.2. Use of Study Assessment Forms 2.3. Exempt for Review 2.4. Expedited Review 2.5. Full-Board Review 2.6. Review of Resubmission Appendix B Form 2.1 Initial Review Submission Form Form 2.2 Summary of The Study Protocol Form 2.3 Document Receipt Form Form 2.4 Reviewers Assignment Form Form 2.5 Protocol Assessment Form Form 2.6 Informed Consent Assessment Form Form 2.7 Protocol Resubmission Form Form 2.8 Review of Resubmitted Protocol 20

Chapter 2 Initial Review Procedures 2.1. Management of Protocol Submissions 2.1.1. Purpose To describe the Medical and Health Research Ethic Committee (MHREC) of Faculty of Medicine, Public Health and Nursing - Dr. Sardjito General Hospital procedure for managing the submission of the initial protocol package for review – from the time of receipt to filing of the initial protocol package in the Active File storage cabinet 2.1.2. Scope This procedure applies to all protocols submitted to the MHREC for ethical review. The MHREC of the Faculty of Medicine, Public Health and Nursing - Dr. Sardjito General Hospital accepts the following research protocols involving human and animal subjects submitted for review: 1) Universitas Gadjah Mada funded researches; 2) Dr. Sardjito General Hospital funded researches; 3) Researches done in Universitas Gadjah Mada; 4) Researches done in Dr. Sardjito General Hospital; 5) Researches done by Universitas Gadjah Mada affiliated researchers; 6) Researches referred from other institutions on the condition that the host hospital/institution where the proposal will be done accepts the review of the EC and agrees to abide by the rules and regulations that the EC follows. All activities are performed through online submission system of the EC 2.1.3. Responsibility The secretariat manages all protocol submissions to the EC. It covers the actions to be done from the time of submission to the filing of the initial protocol package in the digital database and the Active Study File cabinet. 2.1.4. Process Flow/Steps No ACTIVITY PERSON(S) TIMELINE RESPONSIBLE To be done within 5 1 Receive the initial protocol package for Secretariat staff working days review and check the completeness of the protocol package submitted through MHREC online submission system 2 Assign a permanent code to the protocol Secretariat staff package 3 Send notification on the completeness of the Secretariat staff submission through email and online submission system 4 Forward the documents to the panel’s Secretariat staff secretary 5 Determine type of review and assign primary Panel’s secretary reviewers Panel’s secretary 6 Forward the documents to the reviewers 7 File the protocol and all protocol related Secretariat staff documents 21

Chapter 2 Initial Review Procedures 2.1.5. Detailed instructions 2.1.5.1. Receive the initial protocol package for review and check the completeness of the document submitted  Ensure that the Initial Review Submission Form (Form 2.1) and the enclosed Summary of the Study Protocol (Form 2.2) are completely filled up by the researcher.  All research protocols should be completed with a letter of endorsement from the institution where the research is attached (institution letter).  Research protocols of students should be endorsed by the study program and approved by their advisers.  Upon submission of the initial protocol for MHREC review, the principal investigator or his/her representative should ensure that the protocol follows the standard research protocol format and all items in the Summary of the Study Protocol are completely filled up. 2.1.5.2. Assign a permanent code to the protocol package  Assign MHREC protocol number to the protocol package. Guideline for protocol number assignment: KE/four digits consecutive number beginning from the first protocol of the year/month/year 2.1.5.3. Send notification on the completeness of the protocol submission package  Send Document Receipt Form (Form 2.3) as a notification on the completeness of the protocol submission through online submission system and email  Instruct the investigator to use the Protocol Number for further communication to the EC regarding the protocol 2.1.5.4. Forward the protocol package to the panel’s secretary  The scretariat staff forwards the protocol package to the panel’s secretary 2.1.5.5. Determine the type of review and assign primary reviewers  The panel’s secretary determine the type of review for the protocol and assign primary reviewers by completing the Reviewers Assignment Forms (Form 2.4). The three (3) types of review according to The Office for Human Research Protections (OHRP) under the requirements of the U.S. Department of Health and Human Services (HHS) regulations at 45 CFR part 46 are as follow: a) Exempt – for negligible risk protocols b) Expedited – for low-risk protocols c) Full board – for medium to high-risk protocols See enclosed box for detailed instruction (Box 2.1).  The panel’s secretary assigns at least 2 (two) EC members to be the primary reviewers of the protocol.  Primary reviewers consist of medical/scientific reviewer(s) with or without non- medical/ lay person regardless of whether the type of review is expedited or full- board. 22

Chapter 2 Initial Review Procedures  Medical/scientific reviewers are selected on the basis of expertise related to the protocol. The panel’s secretary should choose preverably reviewers of the same panel except there is no suitable expert in the panel.  The medical/scientific reviewer assesses the scientific and ethical aspects of the protocol using the Protocol Assessment Form and the Informed Consent Assessment Form while the non-medical member focuses on the ICF and informed consent procedure using the Informed Consent Assessment Form.  If the EC does not have the required expertise for a specific protocol, refer to Chapter 1 Section 1.2 on Appointment of Independent Consultants 2.1.5.6. Prepare the protocol review package and forward the documents to the primary reviewers  The timeline from receipt of the complete package to the distribution to primary reviewers is within 5 working days.  The initial protocol review package consists of all documents in the initial protocol package and the Protocol Assessment Form (Form 2.5) or the Informed Consent Assessment Forms (Form 2.6) or both. The whole process is done through MHREC online submission system.  The panel’s secretary forwards the submission document to the primary reviewers’ account in MHREC online submission system.  When independent consultant is needed, the secretariat staff will contact him/ her by phone or emails. Special/limited access to MHREC online submission system will be granted to make him/ her able to online review the protocol assigned.  The primary reviewers and the independent consultant should review the documents within the 10 working days. If not, other primary reviewers/ independent consultants are identified  In the full-board meeting of the panel, all protocols assigned to the panel should have been completely reviewed. Expedited protocols that has not been completely reviewed will be reviewed in the full-board. 2.1.5.7. File the protocol and all protocol related documents Protocol related documents consist of Institution Letter, Protocol, Patient information form, Informed consent form, Advertisement, Investigator brochure, Case report forms (CRF), Tools to be used for data collection, Research team list, CVs, GCP certificates, Study budget Refer to Chapter 4 Section 4.5 on Management of Active Study File and Form 2.1 2.2. Use of Study Assessment Forms 2.2.1. Purpose To describe the Medical and Health Research Ethic Committee (MHREC) of Faculty of Medicine, Public Health and Nursing - Dr. Sardjito General Hospital procedures related to the use of study assessment forms in ethics review 2.2.2. Scope 23

Chapter 2 Initial Review Procedures This SOP applies to the use of the study assessment forms in the review and assessment of protocols and related documents submitted to the EC for its initial review and approval. The MHREC uses two study assessment forms to be completed by primary reviewers. All comments, evaluation, recommendations and the initial decision of each reviewer regarding a protocol are all noted in these two forms. The two study assessment forms are designed to standardize the review process and to facilitate reporting of recommendation and comments given to each individual protocol and related documents. These are: a. Protocol Assessment Form (Form 2.5) b. Informed Consent Assessment Form (Form 2.6) 2.2.3. Responsibility It is the responsibility of MHREC reviewers to complete the assessment forms after reviewing each study protocol and submit to the Secretariat within 10 working days. The secretariat is responsible for reminding the primary reviewers to submit the completed assessment forms and update the protocol folders. 2.2.4. Process Flow/Steps PERSON (S) No ACTIVITY RESPONSIBLE Primary reviewers 1 Complete the study assessment forms when reviewing the study protocol and related documents Primary reviewers 2 Submit completed study assessment form to the secretariat Secretariat staff within 10 working days after receipt of the documents Secretariat staff 3 Compile completed assessment forms for decision 4 File copies of completed assessment forms in the protocol folder 2.2.5. Detailed Instructions 2.2.5.1. Complete the Study Assessment Forms when reviewing the study protocol and related documents.  The primary reviewers read the protocol and related documents, and complete the assessment forms.  The primary reviewers should also do literature review to ensure updated knowledge about the protocol.  The primary medical/ scientific reviewers complete the Protocol Assessment and the Informed Consent Assessment Form while the primary non-medical reviewer focuses on the Informed Consent Assessment Form only.  The Protocol Assessment Form allows review of the technical and ethical issues, e.g:  Rationale and significance of the study  Objectives of the study  Sample size  Methodology and data management  Inclusion/exclusion criteria  Control arms (placebo, if any) 24

Chapter 2 Initial Review Procedures  Withdrawal or discontinuation criteria  Vulnerability determination  Risk/ benefit assessment  Review the qualifications of the PI and the research team to include the following:  Education and specialty  GCP training (if necessary)  Review the sites where the study will be conducted  The Informed Consent Assessment Form enables review of the following:  Full disclosure of information, including risks  Benefits that may be derived from the study  Use of understandable language, with appropriate translation  Voluntary participation  Confidentiality  Appropriate person to sign the consent form  If an Assent Form is required, it should be reviewed to ensure that the proper form is available, and the appropriate signature is required.  The primary reviewers decide whether the protocol can be approved, minor modified, major modified or disapproved. 2.2.5.2. Submit completed Study Assessment Forms to the secretariat within 10 working days after receipt of the documents  The Primary Reviewers completed the assessment forms and submit to the Secretariat within 10 working days from date of receipt of the protocol review package.  The secretariat staff print the study assessment forms and filled them in the Active File storage cabinet  2.2.5.3. Compile the completed assessment forms for decision  The Secretariat checks whether the forms are complete, then he/ she compiles the completed assessment forms for decision. 2.2.5.4. File copies of the completed assessment forms  Refer to Chapter 4 Section 4.5 on Management of Active Study files 2.3. Exempt from Review 2.3.1. Purpose To describe the Medical and Health Research Ethic Committee (MHREC) of Faculty of Medicine, Public Health and Nursing - Dr. Sardjito General Hospital procedures for review of protocols that qualify for exemption from review 2.3.2. Scope This SOP applies to the review of a study protocol submitted to MHREC that qualifies for exemption from review. 2.3.3. Responsibility 25

Chapter 2 Initial Review Procedures The panel’s secretary is responsible for the assessment whether the submitted protocol qualifies for exemption from review (See types of review in Section 2.1.5.5) 2.3.4. Process flow/steps (to be done within 10 working days) No ACTIVITY PERSON(S) TIME LINE RESPONSIBLE To be done 1 Review eligibility of a study protocol Panel’s secretary within 10 working days for exemption from review 2 Issue Exemption Letter or recommend Chair expedited or full-board review 3 Prepare a report of protocols that are Secretariat staff exempt from review to full-board 4 Communicate the MHREC decision to Secretariat staff the investigators 5 File the documents Secretariat staff 2.3.5. Detailed instructions 2.3.5.1. Review a study protocol’s eligibility for exemption from review  The panel’s secretary who do not have any conflict of interest should review the study protocol meeting the criteria for review exemption.  The panel’s secretary shall then evaluate the study protocol using the Exemption Criteria (Box 2.1). 2.3.5.2. Issue Exemption Letter or recommend expedited or full-board review 2.3.5.3. Prepare a report of protocols that are exempt from review to full-board  The secretariat staff prepares a report to the next full-board meeting to include details of all protocols exempted from review 2.3.5.4. Communicate the MHREC decision to the investigators  The secretariat staff prepares Exemption letter and forwards to the chair for signature.  The secretariat staff issues the Exemption letter to the Principal investigator 2.3.5.5. File the documents  Refer to Chapter 4 Section 4.5 on Management of Active Study File 2.4. Expedited Review 2.4.1. Purpose To describe the Medical and Health Research Ethic Committee (MHREC) of Faculty of Medicine, Public Health and Nursing - Dr. Sardjito General Hospital procedures for the review of protocols that qualify for expedited review. 2.4.2. Scope This SOP applies to initial review and approval of study protocols with minimal risks to study participants 26

Chapter 2 Initial Review Procedures 2.4.3. Responsibility Expedited review is the responsibility of assigned reviewer appointed to assess a protocol that qualifies for the expedited procedure. The same assessment forms used for full-board review should be used to evaluate the scientific and ethical merits of the protocol 2.4.4. Process Flow/Steps PERSON(S) TIMELINE NO ACTIVITY RESPONSIBLE 5 working Panel’s secretary days 1 Determine whether the submission Panel’s secretary qualifies for expedited review 10 working Panel’s secretary days 2 Assign primary reviewers Primary reviewers (medical/scientific and a non 5 working medical/non scientific members) Primary reviewers days Panel’s secretary/ 3 Send the protocol package to primary secretariat staff reviewers Secretariat staff Secretariat staff 4 The primary reviewers review the documents using the study protocol Secretariat staff assessment forms 5 Return the completed assessment forms to the Secretariat 6 Collate and reviews the review results from the primary reviewers to take appropriate action 7 Communicate MHREC decision to the investigators 8 Prepare a list of all expedited review results and report to the next full board meeting 9 File the documents 2.4.5. Detailed Instructions Detailed instructions for step 1 to 5 of the flow process, refer to section 2.1.5.5, 2.1.5.6, 2.2.5.1 and 2.2.5.2 2.4.5.1. Return the completed assessment forms to the Secretariat  The primary reviewers fill up the assessment form/s within 10 working days from receipt of the protocol review package.  The secretariat checks completeness of the assessment forms and forwards them to the panel’s secretary to recommend appropriate EC follow up action. 2.4.5.2. Collate and review the assessment forms to take appropriate action.  The panel’s-secretary reviews the completed assessment forms to determine if there is agreement in the review/ decision. The comments and decision are consolidated and communicated to the PI by the secretariat staff. 27

Chapter 2 Initial Review Procedures  When the modification is required, the protocol documents are returned for the researchers to revise and resubmit to the EC for approval.  If there are conflicting recommendations and/ or disagreement in the review decision or when the protocol is disapproved, the panel’s secretary includes the protocol in the next full-board meeting for discussion and decision in full-board 2.4.5.3. Communicate the EC decision to the PI.  The secretariat staff communicates approval to the PI uses the Approval Letter (Form 2.6).  In case revision is required, the comments are sent to the PI to comply with the required modifications and resubmit the documents to the EC using the notification form (Form 4.6) . 2.4.5.4. Prepare a report on results of expedited review to full-board  The secretariat staff prepares a list of protocols approved through expedited review and the panel’s secretary reports them during the full board meeting  The report is included in the minutes of the meeting 2.4.5.5. File the documents  Refer to Chapter 4 Section 4.5 on Management of Active Study file 2.5. Full-Board Review 2.5.1. Purpose To describe MHREC procedures when the protocol submissions are classified for full- board review 2.5.2. Scope This SOP applies to MHREC full-board review and approval of study protocols during initial review. 2.5.3. Responsibility Full board review is the joint responsibility of all MHREC members who review and make decisions on the protocol related documents during a convened full-board meeting. In general, full-board review is done for protocols that involve medium to high risk interventions to human like experimental treatments in clinical trials that may involve vulnerable human subjects. 2.5.4. Process Flow/Steps PERSON(S) TIME LINE NO Activity RESPONSIBLE Panel’s secretary 5 working 1 Determine if the submission should days undergo full-board Panel’s secretary Panel’s secretary 2 Assign primary reviewers 3 Send the protocol package through online system to the primary reviewers 28

Chapter 2 Initial Review Procedures 4 Review the documents with protocol Primary reviewers 10 working assessment forms days 5 Return the completed assessment forms to Primary reviewers the secretariat Panel’s chair The next 6 Discuss and decide on the protocol and related documents during a convened full full-board board meeting meeting of the panel 7 Communicate MHREC decision to the PI Secretariat staff 5 working 8 File the protocol and all protocol related Secretariat staff days documents 2.5.5. Detailed Instructions Detailed instructions for step 1 to 5 of the flow process, refer to section 2.1.5.5, 2.1.5.6, 2.2.5.1 and 2.2.5.2 2.5.5.1. Discuss and decide on the protocol and related documents during a convened full board meeting.  Conduct a full board meeting to discuss and make a decision about the protocol and related documents. Refer to Chapter 4 Section 4.2 on Conduct of a Full-Board Meeting.  The members of the EC attending the full board meeting have to approve the following issues:  Principal and Co Investigators and members of the research team  Protocol  Informed Consent  Advertisements or recruitment materials  Study sites covered by the application  The EC members vote on specific items to arrive at a decision as follows:  Approval (when no further modification is required)  Administrative modification (requires minor changes in the documents such as typographical errors, administrative issues, etc.)  Minor modification (requires substantial changes of the protocols or all protocol related documents that do not affect patient safety or credibility of data)  Major modification when the protocol need to be discussed in full-board (requires revision of study design, major sections of the protocol or ICF that affect patient safety or credibility of data)  Disapproval (due to ethical or legal concerns) Reasons for vote of disapproval should be noted in the minutes and communicated to the PI.  If the study is approved, the EC determines the frequency of continuing review.  All meeting deliberations and decision regarding a protocol are noted in the meeting minutes. Refer to Chapter 4 Section 4.3 on Preparation of Meeting Minutes. 29

Chapter 2 Initial Review Procedures 2.5.5.2. Communicate the EC decision to the PI  All MHREC decisions are communicated to the PI.  Approval: The secretariat staff prepares the Approval Letter to be signed by the Chair.  Minor modification: The secretariat staff prepares a notification to inform the PI of the required revisions in the protocol, ICF or in the related documents. The secretariat staff checks compliance to the recommendations of the resubmitted documents, before granting approval.  Major Modification: The secretariat staff prepares a notification to inform the PI of the required revisions in the protocol, the ICF or in the related documents. The resubmitted documents are referred to the primary reviewers and discussed at full- board meeting, unless it was recommended for expedited review in the previous full-board meeting).  Disapproval: The secretariat staff prepares a notification to inform the PI of the EC decision. The reasons should be clearly stated in the notice. Refer to Chapter 4 Section 4.4 on Communicating MHREC Decision to PI 2.5.5.3. File the documents  Refer to Chapter 4 Section 4.5 on Management of Active Study File 2.6. Review of Resubmission 2.6.1. Purpose To describe the procedures of Medical and Health Research Ethic Committee of Faculty of Medicine, Public Health and Nursing - Dr. Sardjito General Hospital when the protocol resubmissions are received. 2.6.2. Scope This SOP applies to the MHREC review and approval of study protocols recommended for minor or major modifications during initial and continuing review. 2.6.3. Responsibility It is the responsibility of the secretariat staff to classify resubmitted protocols for expedited or for full-board review, according to the history of the initial review of the protocol. It is the responsibility of the primary reviewers to review the resubmitted documents with major modifications to determine if they have complied with the required modifications before granting approval during expedited review or to recommend approval of the protocols in full-board. The secretariat staff may review resubmission for minor modifications. It is the responsibility of the panel’s members to approve resubmitted protocols with major modifications after discussion in a full-board meeting. 30

Chapter 2 Initial Review Procedures 2.6.4. Process flow/steps PERSON(S) TIME NO ACTIVITY RESPONSIBLE LINE Secretariat staff 10 working 1 Receive the resubmitted protocol days package from the PI Secretariat staff 2 Forward the protocol package to Primary reviewers primary reviewers Primary reviewers 3 Review if the resubmission complied with the requires Primary reviewers Secretariat staff 4 Return the documents with a decision after expedited review or Secretariat staff recommended a decision to full-board 5 Discus and decide on major modifications received in a full board 6 Complete Approval Letter and communicate the MHREC decision to the PI 7 File the protocol and all protocol related documents 2.6.5. Detailed Instructions 2.6.5.1. Receive the resubmitted protocol package  The secretariat staff receives the resubmitted protocol documents from the PI (Form 2.7) 2.6.5.2. Send the protocol package to the primary reviewers  The secretariat staff sends the package to the primary reviewers of the initial review 2.6.5.3. Review if the resubmission complied with the required modification (Form 2.8)  The secretariat staff may review minor protocol modification.  The primary reviewers review major protocol modifications.  The primary reviewers review the resubmitted documents and compares it with the requirements for modification. 2.6.5.4. Return the documents with a decision after expedited review or recommend a decision to full-board  The primary reviewers return the resubmission package indicating their decision, through on line system.  In expedited review, the primary reviewers approve the resubmitted documents if the PI has substantially complied with the required modifications.  Major modification should go to full-board meeting. 31

Chapter 2 Initial Review Procedures 2.6.5.5. Discuss and decide on major modifications received during a full board meeting  Primary reviewers present their assessment of major modifications during full board discussion  MHREC members vote to endorse or not to endorse the recommendation. 2.6.5.6. Communicate the MHREC decision to the PI  For approved resubmitted protocols, the secretariat staff prepares the approval letter that the panel’s chair and secretary should sign.  The EC decision is communicated to the PI. 2.6.5.7. File the protocol and all protocol related documents Refer to Chapter 4 Section 4.5 on Management of Active Study file Note: the whole resubmission process should be done within 10 working days BOX 2. Types of Review Exempt Research  Research conducted in established or commonly accepted educational settings, involving normal educational practices  Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior, UNLESS:  Information obtained is recorded in such a manner that human subjects can be identified, directly or through identifier linked to the subjects  any disclosure of the human subjects’ response outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects financial standing, employability or reputation  Research involving the collection or study of existing data, documents, records, pathologic specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects can not be identified, directly or through identifiers linked to the subjects.  Research using microbes, cell lines or other materials that do not have direct/ indirect link to human subjects  Research using animal which is not included in to mamalian Expedited review - Minimal/low risk health research that requires personal information:  Research involving animal (mamalia)  About a topic that should not result in causing social stigma  Does not involve vulnerable populations  Retrospective studies using anonymized data from medical records  Studies using simple questionnaires without identifiers  Laboratory research that uses anonymized human tissue/specimen 32

Chapter 2 Initial Review Procedures  Proposals involve interviewing of a non-confidential nature (not of a private e.g. relate to sexual preference etc.), not likely to harm the status or interests of the individual and not likely to offend the sensibilities of the people involved.  Those that involve collection of small amounts of blood samples (and not too frequent)  Those that involve collection of biological specimens for research purposes by non- invasive means (e.g. collection of body fluids or excreta non-invasively, collection of hair or nail clippings in a non-disfiguring or non-threatening manner).  Collection of data for research purposes through non-invasive procedures (not involving general anesthesia or sedation), routinely employed in clinical practice and using medical devices which have been already approved for use. Examples of such procedures include collection of data through application of EEG or ECG electrodes, acoustic testing, tests using the Doppler principle, non-invasive blood pressures and other routine clinical measurements, exercise tolerance etc. However procedures involving the use of x-rays or microwaves are NOT recommended for expedited review. Where medical devices are employed, they must be cleared/ approved for marketing.  Research involving data, documents or specimens that have been already collected or will be collected for ongoing medical treatment or diagnosis, such as data from medical records Full-Board review is for the following research:  Human health research involving medium to high risks to human participants  Intervention studies involving experimental treatments like clinical trials  May involve vulnerable populations who should be protected  Involves private information that may cause stigma  Genetics studies  A study involving sensitive/ confidential information, i.e. sexuality/ reproductive health, sexually transmitted diseases, genetic studies and other information that may cause embarrassment and damage to the subjects’ reputation, such as psychiatric/ psychologic condition, leprosy, etc 33

APPENDIX B INITIAL REVIEW PROCEDURES FORM Form 2.1 Initial Review Submission Form Form 2.2 Summary of The Study Protocol Form 2.3 Document Receipt Form Form 2.4 Reviewers Assignment Form Form 2.5 Protocol Assessment Form Form 2.6 Informed Consent Assessment Form Form 2.7 Protocol Resubmission Form Form 2.8 Review of Resubmitted Protocol 34

FORM 2.1 INITIAL REVIEW SUBMISSION FORM To be filled by investigator MHREC Automatically assigned Submission Automatically assigned after Protocol after the secretariat verify Date the secretariat verify the Number the completeness of the completeness of the documents documents submitted submitted PROTOCOL TITLE: SPONSOR: PRINCIPAL INVESTIGATOR: Full Name Institution Mobile phone (HP) Email PARTICIPATING INVESTIGATORS Full Name Institution Email Mobile phone (HP) 1. 2. 3. 4. 5. (can be added up to …) Study Duration:  0 -12 years Expected start date:  12 - 17 years No. of Study Site: > 18 years Total No. of Participants: Age Range: 35

SUBJECTS OF THE STUDY:  Human (studies involving human subjects or human specimens when the owner of the specimens is known/ identified; informed consent is needed)  Experimental  Observational study  Secondary data (studies using existing data, e.g. medical records, registry, existing national/ regional survey)  Animal (studies on laboratory animals)(automatically linked to Research Involving Animal Form)  In Vitro: studies on commercial cell-lines, microbes, pathological/ human specimens unlinked (blinded) to human identifiers (the owner of the specimen is unknown/ unidentified), etc. Are you an employee of the sponsor?  Yes  No Did you do consultancy or part time work for the  Yes  No sponsor? Other ties with the sponsor: Ethical Responsibility and COI Statement I hereby pledge to address all forms of COI that I may have and perform my tasks objectively, protect the scientific integrity of the study, protect all human participants and comply with my ethical responsibilities as Investigator. PI Signature :(linked to authorization by the PI) DOCUMENTS UPLOADED: Institution Letter Protocol Patient information form Informed consent form Advertisement Investigator brochure Case report forms (CRF) Tools to be used for data collection Research team list CVs GCP certificates Study budget 36

FORM 2.2 SUMMARY OF THE STUDY PROTOCOL To be filled by investigator Background information/ Rationale Objectives Study Design/Methods Inclusion Criteria Exclusion Criteria Data Analysis Plan Anticipated outcomes Ethical Considerations 37

FORM 2.3 DOCUMENT RECEIPT FORM To be filled by secretariat staff MHREC Protocol No Automatically assigned after the secretariat verify the completeness of the documents submitted Title of the Protocol* Automatically assigned Principal Investigator Automatically assigned Sponsor Automatically assigned DOCUMENT(S) SUBMITTED: □ Version no. Institution Letter □ Version no. Protocol □ Version no. Subject information form □ Informed consent form □ Advertisement □ Investigator brochure □ Case report forms (CRF) □ Research team list □ CVs □ GCP certificates □ Tools to be used for data collection □ Study budget □ Revised protocol □ Revised investigational brochure □ Revised consent form □ Protocol amendment submission form □ Progress report (continuing Review) submission form □ Closure/Final Report submission form □ Onsite SAE report Off-site SAE report □ Protocol deviation/ violation report Others, specify Payment of fees BNI a.n UGM FKU KAF PenerimaanLayanan Ethical Clearance No. 98888 070141 60369 (setortunai) sebesarRp. ………… Received by MHREC Secretariat Date 38

FORM 2.4 REVIEWERS ASSIGNMENT FORM To be completed by the Panel’s Secretary SUBJECTS OF THE STUDY:(linked to the assessment forms used)  Human (studies involving human subjects or human specimens when the owner of the specimens is known/ identified; informed consent is needed)  Secondary data (studies using existing data, e.g. medical records, registry, existing national/ regional survey)  Animal (research involving animal)  In Vitro: studies on commercial cell-lines, microbes, pathological/ human specimens unlinked (blinded) to human identifiers (the owner of the specimen is unknown/ unidentified), etc. REVIEW CHANNEL:  Exempted (directly returned to the secretariat)  Expedited  Full Board ASSIGNED REVIEWERS: Protocol Reviewers 1. 2. 3. Reviewer for informed consent documents (if applicable): COMPLETION: Date:………………… Secretary of MHREC-FM UGM: 39

FORM. 2.5 PROTOCOL ASSESSMENT FORM To be filled up by reviewer Protocol Number: automatically Due Date (D/M/Y): automatically assigned as assigned 14 calendar days after reviewer assignment Description of the Study in brief: mark whatever applied to the study: Sponsor-initiated Investigator initiated Intervention Drug Phase 1 Clinical Trial Clinical Trial Medical Device Phase 2 Clinical Trial Vaccine Phase 3 Clinical Trial Diagnostics Phase 4 Clinical Trial Multicenter studies Randomized Global protocol Double-blind Single-blind Open label Community Intervention Observational Epidemiology/ public health Questionnaire Sociobehavioural/ social Qualitative study survey Secondary data Medical records/ registry Human specimens Use of genetic materials Others, specify: Protocol Title: automatically assigned Principal Investigators: automatically assigned automatically assigned Institute: automatically assigned Co – investigator(s): automatically assigned Total No. of automatically assigned Participants: automatically assigned automatically assigned No.of Study site: automatically assigned Sponsor: Duration of the Study: Reviewer’s name: 1 Objectives of the Study o Clear Comments 2 Background information: o Unclear 40 o Sufficient

o Not sufficient 3 Methods o Clear o Not Clear 4 Sufficient number of participants o Yes o No 5 Control Arms (placebo, if any) o Yes o No o Not applicable 6 Data Analysis plan o Appropriate o Inappropriate 7 Study Outcomes o Defined o Incomplete o Not defined 8 Level of risk o Negligible o Low-medium o High 9 Risks Assessment o Appropriate o Inappropriate 10 Benefit Assessment o Appropriate o Inappropriate 11 Inclusion Criteria o Appropriate o Inappropriate 12 Exclusion Criteria o Appropriate o Inappropriate 13 Withdrawal Criteria o Appropriate o Inappropriate o Not applicable 14 Involvement of Vulnerable o Yes Participants o No 15 Protection of Vulnerable o Appropriate Participants o Inappropriate o Not applicable 16 Voluntary, Non-Coercive o Yes Recruitment of Participants o No o Not applicable 17 Are the qualification and o Yes experience of the Participating o No Investigators, research team appropriate? 18 Disclosure of Potential Conflicts o Yes of Interest o No o Not applicable 19 Facilities and infrastructure of o Yes 41

Participating Sites o No 20 Community Consultation o Yes o No o Not applicable 21 Involvement of Local o Yes Researchers and communities in o No the protocols preparation and o Not applicable implementation 22 Contribution to Local Capacity o Yes building o No 23 Benefit to Local Communities o Yes o No 24 Sharing of study results o Yes o No o Not applicable 25 Are blood/tissue samples sent o Yes abroad? o No o Not applicable 26 Is the information provided in o Consistent the protocol consistent with o Inconsistent those in the consent form o Not applicable DECISION:  Approved  Administrative modification  Minor Revision  Major Revision / Full-board  Disapproved Comments (Identify items to be revised): Reviewer’s Name andSignature Date: (automatically assigned (automatically assigned) after verified by reviewer) 42

FORM. 2.6 INFORMED CONSENT ASSESSMENT FORM Comments/ what should be improved 1. Do1es the Informed Consent o Yes document state that the procedure o No are primarily intended for research 2. Are2 procedures for obtaining o Yes Informed Consent appropriate? o No o Not applicable 3. Do3es the Informed consent o Complete document contain comprehensive o Incomplete and relevant information 4. Are4 study related risks mentioned in o Complete the consent form o Incomplete 5. Is 5the language in the informed o Clear consent document understandable o Unclear 6. Is 6the Informed consent translated o Yes into the local language/dialect? o No o Not applicable 7. Are7 there vulnerable participants o Yes o No 8. Are8 the different types of consent o Complete forms (assent, patient representative) o Incomplete appropriate for the types of study participants 9. Are9 names and contact number from o Yes the research team and the MHREC o No in the informed consent 10. Do1es the ICF provide privacy & o Yes 0confidentiality protection o No 11. Is 1there any undue inducement for o Yes 1participation o No 43

12. Is 1there provision for Medical / o Appropriate 2Psychosocial Support o Inappropriate 13. Is 1there provision for Treatment of o Appropriate 3Study-Related Injuries o Inappropriate 14. Pro1vision for compensation: o Appropriate 4 o Inappropriate 15. is 1the amount paid to participants o Appropriate 5stated o Inappropriate o Not applicable DECISION:  Approved  Minor Revision  Major Revision  Disapproved Comments (Identify items to be revised): Reviewer’s Name andSignature Date: (automatically assigned (automatically assigned) after verified by reviewer) 44

FORM 2.7 PROTOCOL RESUBMISSION FORM MHREC Protocol no. : automatically assigned Sponsor Protocol no. (if applicable) : automatically assigned Submission Date : automatically assigned when the secretariat send Document Received Form Date of Initial Approval : automatically assigned Protocol Title : automatically assigned Principle Investigator : automatically assigned Document to be revised Protocol Informed Consent Others, specify: MHREC Recommendation Revisions made by the PI Upload Revised Documents: Protocol Informed Consent Others, specify: PI Signature: Date (automatically assigned) Received by MHREC Secretariat Date (automatically assigned) 45

FORM 2.8 REVIEW OF RESUBMITTED PROTOCOL MHREC Protocol no. : automatically assigned Sponsor Protocol no. (if applicable) : automatically assigned Submission Date : automatically assigned when the secretariat send Document Received Form Date of Initial Approval : automatically assigned Protocol Title : automatically assigned Principle Investigator : automatically assigned DECISION:  Approved  Minor Revision  Major Revision  Disapproved Comments (Identify items to be revised): Reviewer’s Name andSignature Date: (automatically assigned after (automatically assigned) verified by reviewer) 46

Chapter 3 MHREC Monitoring Procedures Supersedes: Previous MHREC SOPs Prepared by: MHREC SOP Team Reviewed by: MHREC Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito General Hospital Approved by: Dean of Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada and Director of Dr. Sardjito Effective date: General Hospital 1 September 2019 3. MHREC Monitoring Procedures 3.1. Review of Protocol Amendment 3.2. Review of Progress Report 3.3. Review of Final Report 3.4. Review of Serious Adverse Event 3.5. Review of Protocol Violation/Deviation 3.6. Responding to Participant’s Request/Query 3.7. Study Site Visit 3.8. Review of Early Protocol Termination See Appendix C Form 3.1 Protocol Amendment Submission Form Form 3.2 Progress Report (Continuing Review) Submission Form Form 3.3 Closure/Final Report Submission Form Form 3.4 Onsite Serious Adverse Event Report Form 3.5 Protocol Violation/Deviation Report Form 3.6 Query/Complaint Record Form 3.7 Study Visit Site Report Form 3.8 Early Study Termination Application 47

Chapter 3 MHREC Monitoring Procedures 3.1. Review of Protocol Amendment 3.1.1. Purpose To describe the Medical and Health Research Ethics Committee (MHREC) Faculty of Medicine, Public Health and Nursing, UGM – Dr. Sardjito General Hospital review procedure for amendments of protocols and related documents 3.1.2. Scope This SOP applies to previously approved study protocols and related documents that are being amended later and submitted for approval to the ethics committee (EC). Any amendment of the study related documents should not be implemented until reviewed and approved by the EC 3.1.3. Responsibility It is the responsibility of the secretariat to manage protocol amendment package submitted by the PI. Protocol amendments are submitted online. It is the responsibility of the original primary reviewers to review the amendments and recommend appropriate action. It is also the responsibility of the primary reviewers to determine whether the amendment goes to expedited or full-board review, It is the responsibility of the panel’s chair and secretary to approve the final decision for amendments submitted by the PI (Form 4.6 ). 3.1.4. Process Flow/Steps NO ACTIVITY PERSON/S TIMELINE RESPOSIBLE 1 Receive the online submitted protocol Secretariat staff Review of amendment package and check its protocol completeness amendments 2 Identify the original primary reviewers Secretariat staff should be and forward amendment package to the completed original primary reviewers within 10 3 Review the amendments, determine Primary working days whether major or minor amendments reviewers when done and recommend appropriate action through 4 Discuss major amendments or report Panel’s chair expedited the expedited review results for minor and review of minor protocol amendments in full-board meeting members amendments 5 Communicate MHREC decision to PI Panel’s secretary/ chair, Secretariat staff, 6 Update and file the protocol and all Secretariat staff protocol related documents 48

Chapter 3 MHREC Monitoring Procedures 3.1.5. Detailed instructions 3.1.5.1. Receive the online submitted protocol amendment package and check its completeness  The EC should properly inform the principal investigator to submit an application for amendment whenever there is any change in the protocol and/ or in any other related documents, e.g. the composition of the study team, the study site, the inclusion or exclusion criteria etc., from those previously approved using the Protocol Amendment Application Form.  The secretariat staff checks the completeness of the protocol amendment package submitted online by the PI. The secretariat staff also verifies whether the protocol number and the form used are correct. 3.1.5.2. Identify the original primary reviewers and forward amendment package to the original primary reviewers  The secretariat staff verifies MHREC approval of the initial protocol submission and identifies the primary reviewers who did the initial review  If the primary reviewers are not available to do the review, the panel’s chair and/or member-secretary may do the review provided they do not have COI. Otherwise the panel’s member secretary designates qualified members to do the review.  The secretariat staff prepares protocol amendment package including access to the original submission to facilitate the assessment of the proposed amendment/s.  The secretariat staff forwards the protocol amendment package and relevant documents of previous review/s to the primary reviewer/s or his/ her alternate.  The secretariat staff tracks the time of review to be within the timeline.  Whenever the review is not returned on day 7th of the timeline, notification will be send to the reviewer’s email. The secretariat staff also sends short message reminder to the reviewer(s). 3.1.5.3. Review the amendments, determine whether major or minor amendments and recommend appropriate action  The primary reviewer or his/her alternate (see section 3.1.5.2) reviews the amended documents and compares them with the previously approved documents in the protocol file folder to assess if the proposed amendment/s would alter the risk/benefit ratio and to make appropriate recommendations using the reviewer-part of the Protocol Amendment Application Form  The primary reviewers also reviews amendment documents to determine whether the amendments are major or minor (see Box 3.1).  Major protocol amendments are reviewed by full-board while minor protocol amendments are reviewed by expedited review by the original primary reviewers or his/her alternate (see section 3.1.5.2) 3.1.5.4. Discuss major amendments or report the expedited review results for minor amendments to the panel’s full-board meeting 49

Chapter 3 MHREC Monitoring Procedures For Major Protocol Amendment  The primary reviewer or his/her alternate presents the results of the review to the panel’s full-board meeting.  The MHREC decides whether or not there is a need for the PI to clarify, elaborate or explain further the amendment/s. The following are possible review decisions of the board:  Approved (when no further modification is required)  Minor Revision (requires minor changes in the documents such as typographical errors, administrative issues, etc.)  Major Revision (requires revision of study design, major sections of the protocol or ICF that affect patient safety or credibility of data)  Disapproved, i.e. use the approved protocol  Request additional information, i.e.: … For Minor Protocol Amendment  The primary reviewer or his/her alternate submits the results of the review using the for- MHREC portion of the Protocol Amendment Submission Form.  The review decision is reported to the MHREC during the full-board meeting 3.1.5.5. Communicate MHREC decision to PI  Refer to Chapter 4 Section 4.4 on Communicating MHREC Decision to PI 3.1.5.6. Update and File Protocols and All Protocol Related Documents  Refer to Chapter 4 Section 4.5 on Management of Active Study Files 50