ࡱ> XZSTUVWc *Bbjbj Tff9&LL$P|ЄE:I!]"T",OQQQQQQ$\bul% ! !@l%l%u,,,l%vO,l%O,,.-sH yp|%uu@;0ЄuXp& y y&3y "#,$l$"""uud*"""Єl%l%l%l%"""""""""L W: SUBJECTPolicy regarding WITS IEC: Approval of Clinical Trials for research on Human Participants The implementation of Amendments to Protocols of Clinical Trials Approved by the WITS IEC Reporting of Adverse Drug Reactions and other Safety Information Implementation of Policies and Procedures and Storage of IEC Clinical Trial Documentation DIVISION / SCOPE:Independent Ethics Committee Secretariat (IEC) REVISION:Independent Ethics Committee Secretariat (IEC) PURPOSE:This policy aims to provide an overall description of the policies followed by the WITS IEC relating to their responsibilities regarding Clinical Trials that are conducted in the WITS medical institutions. PREVIOUS VERSIONS / (REASON FOR REVISION)POL-IEC-001v1; 2; 3; 4; 5; 6; 7, 8, 9, 10 and 11 Added Ethics in Health Research: Principles, Processes and Structures, Department of Health 2015, Second Edition Guidelines CONTENTS: TOC \o \t "Heading 2,2,Heading 3,3" 1. Definitions and Abbreviations  PAGEREF _Toc474737217 \h 2 2. References  PAGEREF _Toc474737218 \h 2 3. Overall policy statement  PAGEREF _Toc474737219 \h 2 3.1. The Approval and ongoing Review of Clinical Trials by the WITS IEC  PAGEREF _Toc474737220 \h 3 3.2. The implementation of Amendments or changes to an approved Protocol or Patient Information/Consent Form for Clinical Research  PAGEREF _Toc474737221 \h 3 3.3. Expedited Review Procedures for Amendments and Additional Investigators and/or 3-4 3.4. Reporting of Adverse Drug Reactions and other Safety Information to the Wits IEC 4 3.5. Development and implementation of Policies and Procedures by the WITS IEC 5 3.6. Storage of WITS IEC documentation 5 4. Refer to RELEVANT SOP-IEC-002v5 FOR ATTACHMENTS: Recertification Application Form CV Format Wits Commitments and Responsibility of Principal; Co and Sub Investigators Declaration Classification of Amendments APPROVALS:Signature of Chairperson / Deputy Chairperson of IEC: Date: Prof C Penny  Definitions and Abbreviations ADRAdverse Drug ReactionCFRCode of Federal Regulations (USA)Clinical InvestigationMeans any experiment that involves a test article and one or more human participants. The terms research, clinical research, clinical study, clinical trial and clinical investigation are considered synonymous for WITS IEC policies and procedures.FDAFood and Drug Administration (USA)GCPGood Clinical PracticesICHInternational Conference on HarmonisationIRBInstitutional Review Boards (USA term for IEC)IECIndependent Ethics Committee (ICH GCP term)SAGCPGuidelines for Good Practice in the Conduct of Clinical Trials in Human Participants in South Africa (2006)SAHPRASouth African Health Products Regulatory AuthoritySAEsSerious Adverse EventsSOPsStandard Operating ProceduresWHCWits Health ConsortiumWITSWitwatersrand 2. References ICH Harmonised Guideline Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice ICH E6(R2) Current Step 4 version dated 9 November 2016 International Conference on Harmonisation (ICH) Topic E2A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting Declaration of Helsinki 2013 21 Code of Federal Regulations Part 56 Institutional Review Boards 21 Code of Federal Regulations Part 50 Protection of Human Participants Code of Federal Regulations - Department of Health and Human Services Part 46 Protection of Human Subjects MRC Guidelines on Ethics for Medical Research, Revised Edition, 1993 Guidelines for Good Practice in the Conduct of Clinical Trials in Human Participants in South Africa (2006) Ethics in Health Research: Principles, Processes and Structures, Department of Health 2015, Second Edition National Health Act 2003, Government Gazette No. 36702 Act No. 12 of 2013: National Health Amendment Act, 2013 Constitution of the Republic of South Africa, 1996 SAHPRA Reporting Adverse Drug Reactions in South Africa 3. Overall policy statement The HUMAN RESEARCH ETHICS COMMITTEE to approve and provide the necessary ongoing review of all Clinical Research conducted under its responsibility in accordance with the following requirements ICH Harmonised Guideline Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice ICH E6(R2) Current Step 4 version dated 9 November 2016 Guidelines for Good Practice in the Conduct of Clinical Trials in Human Participants in South Africa (2006) Ethics in Health Research: Principles, Processes and Structures, Department of Health 2015, Second Edition Declaration of Helsinki 2013 MRC Guidelines on Ethics for Medical Research, Revised Edition, 1993 Council For International Organizations Of Medical Sciences (CIOMS), International Ethical Guidelines for Biomedical Research Involving Human Participants, 1993 The applicable FDA requirements for Institutional Review Boards (21 CFR Part 56) Requirements for Protection of Human Participants (21 CFR Part 50) OHRP Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events This document will be submitted to investigators and sponsors who require more information about the operation of the WITS IEC. The WITS Health Consortium (WHC) will handle all administrative functions of the WITS IEC. 3.1 THE APPROVAL AND ONGOING REVIEW OF CLINICAL TRIALS BY THE WITS IEC All Phase I (one) to Phase IV (four) clinical trials that are conducted in the WITS institutions, as well as those submitted to be conducted in private practice, must be approved by the WITS IEC prior to the enrolment of any participants. Principal, Co and Sub Investigators will be required to sign the Wits/SAHPRA Commitments and Responsibilities Declaration, and submit this document with the trial application for approval. The requirements of the applicable ICH GCP and SAGCP Guidelines and FDA Code of Federal regulations will be applied in considering approval of Protocols and Informed Consent/Participant Information Leaflets. The WITS IEC will review all payments to be made to participants to assess possible problems with coercion or undue influence on participants. Payments to participants should be prorated and should not be wholly contingent on completion of the trial by the participants. So as to facilitate the ongoing review of the clinical investigations that were approved, reports containing the following information are required on a regular basis from the Investigator: Number of Participants recruited Summary description of participants experiences (benefits, adverse reactions) Number of withdrawals and reasons for withdrawal Complaints Results obtained to that point Risk-benefit ratio base on results Any new information obtained since the IECs most recent review The WITS IEC will decide on the required frequency of these reports on a per-clinical investigation basis. This decision will be based on the degree of risk to human participants. The minimum requirement for these reports will be on a six monthly basis. All Serious Adverse Events and Adverse Drug Reactions must be reported as per the requirements of the WITS IEC (see paragraph 3.4.), to ensure ongoing approval of the trial. 3.2. THE IMPLEMENTATION OF AMENDMENTS OR CHANGES TO AN APPROVED PROTOCOL OR PARTICIPANT INFORMATION/CONSENT FORM FOR CLINICAL RESEARCH No deviations from the approved protocol, amendments/changes to the protocol, and changes to the informed consent form or any other written information that is provided to the participants may be implemented prior to obtaining documented approval from the WITS IEC. The only exception is where a change is necessary to eliminate an immediate hazard(s) to trial participants. As soon as possible, the implemented deviation or change, the reasons for it, and, if appropriate, the proposed protocol amendment must be submitted to the WITS IEC for review and approval. Changes that involve only logistical or administrative aspects of the trial (e.g., change in monitor(s), change of telephone number(s)) will obtain chairmans approval only and may be implemented prior to formal documented approval from the WITS IEC. A copy of the notification to the SAHPRA must accompany the submission. The investigator, or person designated by the investigator, should document and explain any deviation from the approved protocol. 3.3 EXPEDITED REVIEW PROCEDURES FOR AMENDMENTS AND ADDITIONAL INVESTIGATORS AND/OR SITES The WITS IEC may employ an expedited review process in the following instances: If only minor changes have been proposed to a previously approved research project If additional study personnel and/or new sites are to be involved in a research project that was previously approved. A copy of the notification to the SAHPRA to accompany these submissions. Such a review process would involve approval by the Chairperson of the IEC or by one or more reviewers designated by the Chairperson from among the members. In reviewing the research, the reviewers may exercise all the authorities of the IEC except that the reviewers may not disapprove the research. A research activity may be disapproved only after review in accordance with the non-expedited review procedure. All members will be informed of the approval by inclusion of this information in the agenda of the next meeting. Major amendments will be referred to the Chairman for approval, co-review or referral to a full committee meeting. Approval will be given subject to the Chairman / Co-review / Committee decision and upon receipt of the approval from the SAHPRA. 3.4. REPORTING OF ADVERSE DRUG REACTIONS AND OTHER SAFETY INFORMATION TO THE WITS IEC (Ref to Secretariat Internal SOP-IEC-005) Definitions: Adverse Event: Any untoward medical occurrence that may present during treatment with a medicine/intervention but which does not necessarily have a causal relationship with this treatment Adverse Drug Reaction or Adverse Reaction: A response to a medicine/intervention, which is noxious and unintended The phrase response means that the causal relationship between the medicinal product/intervention and the adverse event is at least a reasonable possibility. Unexpected Adverse Reaction: One in which the nature, specificity, severity and outcome is not consistent with the applicable product information (i.e. with the approved package inserts for registered products, or the investigators brochure or other product information for unregistered products). Serious Adverse Event or Serious Adverse Drug Reaction: Any untoward medical occurrence that: Results in death, Is life-threatening, Requires patient hospitalisation or prolongation of existing hospitalisation, Results in persistent or significant disability/incapacity, or Is a congenital anomaly/birth defect. Medical and scientific judgement should be exercised when deciding if other situations are serious. Such instances could include medical events that may not be immediately life-threatening or result in death or hospitalisation, but which may jeopardise the patient or may require intervention to prevent one of the outcomes listed in the definition above. Examples include blood dyscrasias or convulsions not resulting in hospitalisation, or development of drug dependency or drug abuse Reporting Requirements For Events Occurring At Wits HREC Approved Sites: All deaths Serious, unexpected, adverse drug reactions which are fatal or life threatening Report within 7 calendar days after first knowledge. The initial notification should be followed by as complete a report as possible within an additional 8 calendar days Format of report: SAE form * Serious, unexpected, adverse drug reactions which are not fatal or life threatening Report as soon as possible and not later than 15 calendar days after first knowledge Format of report: SAE form * All Serious Adverse Events Non-serious unexpected adverse drug reactions Report as part of the 6-monthly progress reports Format of report: Line listing * Other Reporting Requirements: Serious, unexpected, adverse drug reactions occurring at other South African and Foreign sites Report as part of the 6-monthly progress reports Format of report: Line listing * New information which may affect the safety of participants or the conduct of a trial Report within 3 calendar days of first knowledge and in the six-monthly progress report Format of report: Detailed report Change in the nature, severity or frequency of expected Adverse Drug Reactions Report within 15 days after first knowledge and in the 6-monthly progress report Format of report: Detailed report *  HYPERLINK "http://www.mccza.com" www.mccza.com Click on: Documents Guidelines Human Medicine Reporting Adverse Drug Reactions in South Africa Forms Human & Veterinary Medicine Form ARF 1 Adverse Drug Reactions Reporting Form 3.5 DEVELOPMENT AND IMPLEMENTATION OF POLICIES AND PROCEDURES BY THE WITS IEC Policies and Procedures for the WITS IEC will be developed in accordance with the WHC Standard Operating Procedure SOP-WHC-001. For purposes of implementation of this procedure by the WITS IEC the following points should be noted: The Chairperson of the IEC will be considered the Head of the Division that will be authorised to sign off all Policies and Standard Operating Procedures (SOPs) for the WITS IEC, and The Chairperson of the WITS IEC will be responsible for ensuring that all the IEC members are familiar with the requirements of the relevant policies and procedures, and All WITS IEC policies and procedures will be accessible as read-only files on the WHC web page. Only the Chairperson and Wits Ethics Secretariat will have write-access to these documents. 3.6 STORAGE OF WITS IEC DOCUMENTATION The WITS IEC will retain all relevant records, (e.g., written procedures, membership lists, list of occupations/affiliations of members, submitted documents, minutes of meetings, and correspondence) for a period of at least fifteen years after completion of the trial and will make them available on request to the regulatory authority/(ies). Records will be archived according to the relevant WHC procedures for archiving by the Clinical Trials Division. 4. 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