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Faculty of Health Sciences Research Ethics Committee University of Pretoria

TERMS OF REFERENCE AND STANDARD OPERATING PROCEDURES

Dated 6 June 2017

*This supersedes all previous documents

Tswelopele Building, Level 4, Rooms 4-59; 4-60 and 4-61 Dr Savage Road, Gezina, Pretoria Postal address: Private Bag X323, Arcadia, 0007 Web address: http://www.up.ac.za/healthethics Chair: Prof C W van Staden Tel: 012 319 9748 E-Mail: [email protected] Vice-Chair: Dr R Sommers Tel: 012 3563084/5 E-Mail: [email protected]

Vice-Chair: Prof T Rossouw Tel: 012 3563084/5 E-Mail: [email protected]

Vice-Chair: Prof A Nienaber Tel: 012 3563084/5 E-Mail: [email protected]

Administrators Telephone E-Mail Deepeka Behari 012 356 3084 [email protected] Manda Smith 012 356 3085 [email protected]

http://www.up.ac.za/healthethics

mailto:[email protected]






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Index

1. Constitutive terms…………...……………………………………………..…………………….3

2. Appointment and membership to the Research Ethics Committee .............................. 8

3. Administrative procedures ............................................................................................ 12

4. The Review Processes ................................................................................................... 20

5. The Participant Informed consent Document and the consent process ................... 29

6. Post Approval Follow-up and continued review ........................................................... 31

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1. Constitutive terms

1.1 The Faculty of Health Sciences Research Ethics Committee (FHSREC) is tasked with the ethics of all health research and operates in terms of the National Health Act (Act 61 of 2003), the Code of Ethics for Research of the University of Pretoria, and the National Health Research Ethics Council.

It is accredited nationally and internationally as follows:

National Health Research Ethics Council of the South African Department of Health. REC-120208-018

Office of Human Research Protection of the USA Department of Health & Human Services'

o Federal-wide Assurance FWA 00002567, Approved dated 22 May 2002 and

expires 20 Oct 2016.

o IRB 0000 2235 IORG0001762 Approved dated 22 April 2014 and expires 22

April 2017.

It is a legally imperative that all health research in the Faculty of Health Sciences be reviewed by the Research Ethics Committee in terms of the National Health Act as well as the policy (Rt 429/99) of the University of Pretoria.

An annual report is to be submitted by the Faculty of Health Research Ethics Committee (FHSREC) to the Senate Ethics Committee of the University of Pretoria and to the National Health Research Ethics Committee (NHREC) committee of the Department of Health.

All health research must be considered by the Research Ethics Committee, where the section of the National Health Act defines health research as: any research which contributes to knowledge of-

(a) the biological, clinical, psychological or social processes in human beings; (b) improved methods for the provision of health services; (c) human pathology; (d) causes of the diseases; (e) the effects of the environment on the human body; (f) the development or new application of pharmaceuticals, medicines and (g) the development of new applications of health technology.

The role of the Research Ethics Committee in reviewing health research projects undertaken by members of staff, registered students and affiliates of the University, is to ensure the safety, dignity, rights and well-being of all research participants, involved in any health related research. The fundamental ethical principles for research are outlined in the Belmont Report. They provide a framework for ethical decision-making in research involving human any health related research. The three principles are:

Respect for persons

Beneficence

Justice

http://web.up.ac.za/sitefiles/file/45/2875/Health%20Act%2061%20of%202003.pdf

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Respect for persons

Respect for persons highlights the individual as an autonomous being, capable of making individual choices and decisions. Respect for persons includes allowing the individual to have the freedom to make his/her decision voluntarily. For those individuals with diminished capabilities – such as children or those with mental disabilities – extra protection must be granted to protect the individuals from any risk of harm.

Beneficence

The principle refer to the concept of maximizing potential benefits to society and/or to research participants and minimizing anticipated risks for the research participants. Beneficence includes protecting the individual form any undue harm (non-maleficence). In this way, the risks involved in the research can only be justified by the expected benefits.

Justice

Justice emphasizes the need for treating participants of research fairly. This means there must be equity in research among various classes of society. For example, prisoners should not be unfairly excluded or included in research without ethical or scientific justification.

1.2 The Research Ethics Committee do, at the discretion of the Chairperson and vice-

chairs, accept review of research protocols submitted to it, by researchers from other institutions who are not UP staff members, students or affiliates.

1.3 Guidelines to which this Ethics Committee adhere

The Research Ethics Committee functions in compliance with, but not limited to the following documents and guidelines:

1.3.1 International Guidelines

The International Guidelines that are applicable are inter alia the following:

The Nuremberg Code (1946); The Helsinki Declaration (1964; 1975; 1983; 1989; 1996; 2000; 2008; 2013);

Updated with notes of clarification dated Washington 2002; and Tokyo 2004. (http://www.wma.net/e/policy/b3.htm)

The Belmont Report (1979) http://ohsr.od.nih.gov/guidelines/belmont.html; The WHO Geneva 2000 Operational Guidelines; The Code of Federal Regulations of the USA (Title 45 Part 46)

http://www.doh.gov.za/docs/factsheets/guidelines/ethnics/sec4.pdf The US Offfice of Human Research Protections 45 CFR 46US;

http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html The International Conference On Harmonisation - Good Clinical Practice

(1997) (ICH-GCP); Council for International Organisations of Medical Science (CIOMS)

Guidelines (1982, updated in 2002); http://www.cioms.ch/frame_guidelines_nov_2002.htm and

Singapore Statement on Research Integrity

http://www.wma.net/e/policy/b3.htm

http://ohsr.od.nih.gov/guidelines/belmont.html

http://www.doh.gov.za/docs/factsheets/guidelines/ethnics/sec4.pdf

http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html

http://www.cioms.ch/frame_guidelines_nov_2002.htm

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1.3.2 National Legislation

The following National Legislations are applicable:

1.3.2.1 National Health Act, Act No. 61 of 2003

Specific sections of Chapter 9 have direct relevance on the responsibility of Ethics Committees and Research Procedures. They are:

Section 71 (a)(b): Research on or experimentation with human subjects

(1) Notwithstanding anything to the contrary in any other law, research or experimentation on a living person may only be conducted-

(a) in the prescribed manner; and (b) with the written consent of the person after he

or she has been informed of the objects of the research or experimentation and any possible positive or negative consequences on his or her health.

Section 72 (1): National Health Research Ethics Council (NHREC) (1) A council to be known as the National Health Research

Ethics Council is hereby established.

Section 73: Health Research Ethics Committees (1) Every institution, health agency and health establishment

at which health research is conducted, must establish or have access to a health research ethics committee, which is registered with the National Health Research Ethics Council.

(2) A health research ethics committee must- (a) review research proposals and protocols in

order to ensure that research conducted by the relevant institution, agency or establishment will promote health, contribute to the prevention of communicable or non-communicable diseases or disability or result in cures for communicable or non-communicable diseases; and

(b) grant approval for research by the relevant institution, agency or establishment in instances where research proposals and protocol meet the ethical standards of that health research ethics committee.

1.3.2.2 The Constitution of SA – Act 108 of 1996 / Chapter 2: Bill of Rights

– Section 12 C

http://www.policy.org.za/pdf/NationalHealthB32D

Everyone has the right to bodily and psychological integrity, which includes the right not to be subjected to medical or scientific experiments without their informed consent.

http://www.policy.org.za/pdf/NationalHealthB32D

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1.3.2.3 Ethics in Health Research- Principles, Processes and Structures. 2nd Edition: Department of Health (2004/2006/2008/2015)

Website address: www.doh.gov.za

1.3.3 Local Regulations:

University of Pretoria Senate Ethics Committee - Code of Ethics for Research

Website: www.up.ac.za/healthethics

Institutional Permission for each study CEO permission.

Private Hospitals: Director to sign an approval letter.

Other Provincial Departments to sign an approval letter. Note: These approvals must be given to the investigator preferably prior to Ethics Committee evaluation.

Departmental Approval

The research proposal must be approved by the Department or a specific Academic Committee, where applicable (see 5.3.1)

Specific permission must be given that the study can be done in a specific Department.

HPCSA – Code of Conduct

All health professionals registered at this Council, must adhere to the specific guidelines (website: www.hpcsa.co.za)

1.3.4 Additional requirements since 29th July 2005

Dispensing licences for non-pharmacists (doctors) who are to dispense clinical trial medicine (Act 101 or 1965);

The storage of such medicines should be consistent with the Pharmacy Act No 88 of 1974;

Good Clinical Practice Courses (GCP) for researchers doing clinical medication trials must be updated every three years. The GCP certificate must be submitted to the Committee.

Note: GCP courses must be applicable to local requirements – therefore must be based on South African conditions.

1.4 The General Attitude of the Research Ethics Committee In line with international ethics standards for health research as well as the commitment of the University of Pretoria to ensuring ethically sound research, the Research Ethics Committee like to highlight the following points that are pertinent to us fulfilling our role diligently and accountably:

http://www.doh.gov.za/


http://www.hpcsa.co.za/

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The Research Ethics Committee upholds the principle that the primary responsibility for ethically sound research practice resides with researchers.

The role of the Research Ethics Committee is to support and guide researchers towards better/best ethical research practice. The Research Ethics Committee is in this way a resource in the Faculty of Health Sciences for researchers.

We approach the ethical review of proposals in a collaborative spirit in order to arrive at decision making that involves the researchers.

The main purpose of questions or queries from members of the Research Ethics Committee is to clarify or better understand researchers’ intentions in order to assist us working together with researchers towards solutions.

The comments made and questions asked by any one member of the Research Ethics Committee are important to the deliberations of the Committee as a whole.

1.5 Research Evaluation Policy

The Ethics Committee reviews all health research that are connected to the Faculty of Health Sciences. No retrospective (post ex facto) ethics approval can or will be granted (as enforced by the Senate Ethics Committee in January 2008). All personnel and pre- or postgraduate students affiliated to the University of Pretoria must apply to the Ethics Committee for the approval of their research proposals, before research may be undertaken.

The Faculty of Health Sciences Research Ethics Committee oversees research conducted at the following sites, among others-:

1.6 Independence of the Research Ethics Committee

• The Ethics Committee of the Faculty of Health Sciences is an independently functioning body. This means:

a) its decisions and resolutions are made independently;

Department of Animal and Wildlife Sciences (Only where human participants are involved)

Department of Veterinary Sciences (Only where human participants are involved)

Oral and Dental Hospital Hammanskraal Hospital

Jubilee Hospital Kalafong Hospital

Mamelodi Hospital / Campus Pretoria West Hospital

School of Health Systems and Public Health, UP Steve Biko Academic Hospital

Tembisa Hospital Tshwane District Hospital

Weskoppies Hospital Witbank Hospital

Health-related research in other UP-faculties

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b) no pressure from outside the REC may be exerted on the REC or its members to effect a particular resolution;

c) resolutions may not be overturned or overruled by an office bearer of the University or other party but complaints/objections should be subjected to the appeals procedure with potential recourse to the National Health Research Ethics Council.

• Both the University of Pretoria and the Steve Biko Academic Hospital are responsible for the financial support of the Committee.

• The Ethics Committee also generates funds by evaluating contract

research or research proposals that are conducted in terms of a grant for a fee.

2. Appointment and membership to the Research Ethics

Committee

2.1 The Research Ethics Committee is tasked with the ethics of all health related research at University of Pretoria. It has been established principally but not exclusively to oversee the safety, rights and welfare of human participants in research.

The composition and functions of the Research Ethics Committee should meet the minimum standards and requirements, as set out in the Department of Health Ethics in health research: Principles, structures and processes and (2015) South African Good Clinical Practice Guidelines, and as specified in the US Federal Wide Assurance.

2.2 Appointments of members

2.2.1 Appointment to the Committee will be by nomination and co-option. Nominations for a Chairperson and committee members are called for, when specific

vacancies arises. Committee members and Faculty members are called on to submit in writing names of possible candidates who would be suitable.

Nominations received by the Ethics Committee are then evaluated with regard to the ability of the nominee to evaluate research protocols ethically and contribute to the operations of the REC. The committee members then vote to elect a new member.

The nominated candidate’s name is then sent with recommendation to the Dean of the Faculty of Health Sciences, University of Pretoria for final approval. Committee members are thus appointed by the Dean.

Committee members serve for a non-specific time period, even though a regular turn-over is promoted.

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2.2.2 Professional liability insurance

The University of Pretoria has obtained professional liability insurance to cover both affiliated and non-affiliated members when carrying out any professional duties under the auspices of ECFHS UP.

2.2.3 Conflicting interests

A member is obliged to declare any potential and/or conflicting interests, pertaining to any study under consideration by the REC.

2.2.4 Confidentiality agreement

A member signs a confidentiality agreement upon appointment and annually regarding the meeting’s deliberations, information and related matters.

2.3 Membership

2.3.1 The composition of the Ethics Committee

The composition of the Ethics Committee currently fulfills the guidelines proposed by the DOH as follows: http://www.doh.gov.za/docs/factsheets/guidelines/ethics

Have at least 14 members—currently there are 20 members. Have at least a chairperson with vice-chairs From the 1st May 2009, the Chairperson is Prof C W van Staden. Dr Rita Sommers, Prof Annelize Nienaber and Prof Theressa Rossouw are

the vice-chairs A quorum is defined as 6 members attached, plus 3 members, not attached to

the University of Pretoria. at least one layperson at least one member with knowledge of, and current experience in, the professional care, counseling or health-related treatment of people. Such a

member might be e.g. a medical practitioner, psychologist, social worker or nurse at least one member with professional training and experience in qualitative

research methodologies members with professional training and experience in quantitative research

methodologies a member with expertise in bio-statistics a member with expertise in research ethics at least one member who is legally qualified

2.3.2 Members need to provide the Research Ethics Committee’s administrative office with an abbreviated CV regarding their ethics training and experiences, at the beginning of their term.

2.3.3 Members need to have continuous personal development in research ethics.

http://www.doh.gov.za/docs/factsheets/guidelines/ethics

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2.3.4 The committee meetings can be attended by bona fide students, researchers

and other interested parties as non-voting observers, subject to the signing of confidentiality undertaking.

2.3.5 The membership and composition of the Research Ethics Committee is

reflected on the committee’s website.

Members attached to the University of Pretoria

Dr I J Ayo-Yusuf (female) PhD (UWC); M.Sc. Dent.Sc. (Stell); PDD (Comm. Dentistry) Stell; Dip. Odont. (Ortho.) (Pretoria); BDS (Univ.of Benin, Nigeria)

Prof MJ Bester (female) BSc (Chemistry and Biochemistry); BSc (Hons)(Biochemistry); MSc(Biochemistry); PhD (Medical Biochemistry)

Prof R Delport (female)BA et Scien, B Curationis (Hons) (Intensive care Nursing), M Sc (Physiology), PhD (Medicine), M Ed Computer Assisted Education

Prof T W de Witt (female) MBChB; MMed(Paed);DTE;

Prof MM Ehlers (female) BSc (Agric) Microbiology (Pret); BSc (Agric) Hons Microbiology (Pret); MSc (Agric) Microbiology (Pret); PhD Microbiology (Pret); Post Doctoral Fellow (Pret)

Dr R Leech (female) B.Art et Scien; BA Cur; BA (Hons); M (ECI); PhD Nursing Science

Prof A Nienaber Deputy Chairperson (female) BA(Hons)(Wits); LLB; LLM;

LLD(UP); Dipl.Datametrics(UNISA)

Dr E Osman MBBS (Khartoum) Mmed Surg (Pret)

Prof F Paruk (female) MBChB, FCOG,Cert Crit Care,MD

Dr GP Stevens LLB, LLM, LLD

Prof T Rossouw Deputy Chairperson (female) MBChB (cum laude); M.Phil (Applied Ethics) (cum

laude), MPH (Biostatistics and Epidemiology (cum laude), D.Phil , PhD

Dr R Sommers Deputy Chairperson

(female) MBChB; MMed(Int); MPharmMed; PhD (Health Ethics)

Prof CW van Staden Chairperson

MBChB; MMed (Psych); MD; FCPsych; FTCL; UPLM

Dr E Webb (female) BSc Agric (Genetics); BSc Agric Hons (Genetics); MPH (cum laude); PhD (Epidemiology)

Members NOT attached to the University of Pretoria

Rev S Bapela (female) Dipl. Theology and Ministry

Dr D Diale (female) B.Pharm; PharmD

Dr NE Khomo (female) BSc (Pharm), MBChB, MMed (Comm.Health), post graduate diplomas in Public Health (DPH), Health Services Management (DHSM) and Tropical Medicine And Hygiene (DTM&H)

Mr SB Masombuka BA (Communication Science) UNISA; Certificate in Health Research Ethics Course (B compliant cc)

Dr MP Mathebula (female) MBCHB, PDM, HM

Mrs MC Nzeku (female) BSc(NUL); MSc(Biochem)(UCL, UK)

Dr C Oliphant (female) MBChB, FCPHM (SA), MMed (Public Health), MPhil (Applied Ethics) (cum laude)

A quorum is defined as 6 members attached plus 3 members not attached to the University of Pretoria

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2.3.6 Serious Adverse Event Committee Members

Dr NE Khomo

All Serious Adverse Events s are listed on the monthly Agenda of the Main Research Ethics Committee. (For definitions see page 32). Members who would like more information, can evaluate the complete documents at the Ethics office.

2.3.7 Protocol Amendment Committee Members Dr NE Khomo (commenced July 2016)

Dr R Sommers

Prof R Delport

Prof F Paruk (commenced January 2016)

Amendments are sent to the above members. Their written comments are placed on the monthly Agenda of the Main Research Ethics Committee and discussed as necessary. Researchers need to respond to the comments, where after approval will be given.

2.3.8 Protocol Progress Report Committee Members

Dr R Sommers

All Progress Reports are attached to the monthly Agenda of the Main Research Ethics Committee for notification to all members.

2.4 Conflict of interest

2.4.1 Members of the Research Ethics Committee should make decisions and conduct

their oversight responsibilities in an independent manner, free from bias and undue

influence.

2.4.2 Research Ethics Committee members who have a conflict of interest related to any

research protocols that is to be considered, should refrain from participating in

discussion of the protocol. This recusal will be minuted in the minutes.

2.4.3 In the event that the conflict of interest involves the chairperson, the vice-

chairperson will be acting chairperson, for the remainder of the discussion, of

the item in question. This will be minuted in the minutes.

2.5 Confidentiality

Research Ethics Committee members and support staff signs a standard

confidentiality and non-disclosure agreement on appointment and on a regular basis.

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2.6 Continuous professional development in research ethics

2.6.1 All newly appointed members undergo an orientation training session pre- appointment to Research Ethics Committee, by attending a meeting as an observer.

2.6.2 Education in Ethics and Capacity Building

2.6.2.1 For all Faculty and Institutional members

Ethics lectures will be advertised on the UP Intranet.

Researchers doing clinical medication trials need to attend GCP- courses. This needs to be reviewed every 3-4 years.

2.6.2.2 For Ethics Committee members

CPD accredited lectures, workshops, conferences and seminars will be identified and members can attend on an alternative basis. Request to attend such courses can be submitted to the Secretariat.

All members will receive the following handbook: “Institutional Review Board Member Handbook”, 2nd Edition. Authors Robert J, Amdur and Elizabeth A Bankert.

2.7 Independent consultants and Reviewers

2.7.1 The Ethics Committee may call upon independent consultants who provide

special expertise to the Ethics Committee on specific research protocols.

2.7.2 These consultants may inter alia be specialists in ethical or legal aspects, specific disease or methodologies, or they may be representatives of communities, patients, or special interest groups.

2.7.3 The Research Ethics Committee can consult with other Research Ethics Committees if appropriate, bearing in mind confidentiality constraints.

3. Administrative procedures

The following are guidelines for submitting the required documents to the Research Ethics Committee for research activities involving human participants.

3.1 What is "health research" that needs to be considered by the Research Ethics Committee? All research that may be health related as such:

All research using human participants;

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Research not using human participants (e.g. research on chemicals or instruments);

Clinical “audits” and surveys;

In vitro, laboratory, non-human and human tissue research;

The Faculty of Health Sciences Research Ethics Committee reconsidered the submission process for “in vitro” studies and resolved that it should be aligned better with the processes at other Faculties and the National Health Act: Act 61 of 2003. Accordingly, as from 26 May 2013 a full protocol must be submitted for consideration by the Committee for all research studies to be conducted through commercial cell lines, blood samples, human tissues, human bodily products and/or “in vitro” work;

Quality control procedures in laboratories, like assay validations and instrument calibrations, that are NOT for publication or student research purposes are not considered as research and need not be submitted for ethics approval, unless human tissue, blood samples, and/or human bodily products need to be collected for these purposes in which case that should be incorporated into the research protocol of the relevant study(s) that depends on these quality control procedures;

Research on data already collected for clinical or educational purposes;

Secondary research on data already collected as part of another research project;

Case series for publication purposes;

Service delivery “statistics” for research, scientific reports, degree or publication purposes;

Reports and publications of health surveillance;

Research on education in the Health Sciences Faculty;

All research involving patients or materials from Steve Biko Academic Hospital, Kalafong Hospital, Tshwane District Hospital, Weskoppies Hospital, or NHLS;

All research involving healthcare workers or other personnel at Steve Biko Academic Hospital, Kalafong Hospital, Tshwane District Hospital, Weskoppies Hospital, and NHLS;

All research involving students of the Faculty of Health Sciences as research participants;

All research involving personnel of the Faculty of Health Sciences as research participants.

3.2 Submission dates

Please consult the website to ensure timeous submission for a specific meeting during the year.

The administrative secretaries may not distribute late submissions.

3.3. Submission details

Protocol documents submitted for evaluation at a specific meeting are received and checked by the secretariat. Submission dates are available on the website www.up.ac.za/healthethics

Researchers and applicants need to apply for ethics review via the electronic process.


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For electronic submissions, the necessary instructions and information can be obtained to the Ethics Committee’s website: www.up.ac.za/healthethics / https://rims.up.ac.za

Researcher need to obtain an username and password from Ms Manda Smith – contact details: [email protected] or [email protected] as the first step. In order to generate such the researchers need to provide the administrator with their personnel or student number, where applicable.

Submissions of Amendments, SAEs and Progress reports follow the same electronic process.

Line Listings should be uploaded electronically in batches (with clear reference to the approved study).

Upon electronic submission of the researcher’s documents, the system will allocate a “Temp Number, e.g. Temp2016-0000”. This “Temp Number” will be converted to a protocol reference number e.g 000/2017, at the Research Ethics Committee’s office, when a hard copy of all the protocol documents is personally submitted by the researcher.

It is the responsibility of the researcher to log onto https://rims.up.ac.za and keep track of the progress of the research study and check for correspondence from the Research Ethics Committee’s office.

The Principal Investigator is the main responsible contact person.

The necessary cover pages for the SAEs, Progress Reports and Amendments (available on the website), must be completed and signed by the Principal Investigator.

Should two research sites submit the same protocol and supporting documents, the Principal Investigator from each site is responsible for his/her own submission process and communication with the secretariat. This is applicable only if the two research sites operates individually.

Note: Researchers must complete all forms by themselves, as by signing these forms, they take responsibility for all the information.


https://rims.up.ac.za/




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3.4 Academic Committee Approvals prior to Ethics Committee Submission Researchers may wonder when they should submit their study protocols to other committees in relation to the submission to the Research Ethics Committee. An appropriate answer would depend on the specific study as applied to the considerations below: Internationally, the standard requirement is that research be conducted according to the research plan, contained in the particular version of a protocol approved by an independent ethics committee. This requirement has practical bearing where:

i) protocols also serve at one of the scientific committees (and consequently may be amended);

ii) research projects are related to or are subsets of other research projects.

Where research is for degree purposes, the protocol serves at one of the

scientific committees. It would ordinarily be best to have that committee consider the protocol first, unless the researcher is required to clarify particular ethical issues first.

Should the researcher submit the protocol to the Ethics Committee first, the researcher will then need to re-submit amendments required and approved by the scientific committee, to the Ethics Committee for final approval.

Where a researcher wants to do a pilot study first, before submitting the protocol

to the scientific committee, he/she should submit a protocol to the Ethics Committee for the pilot study, and later, following the consideration by the scientific committee, submit to the Ethics Committee an amendment that will cover the full study.

Where research projects are related or a subset of another, the above-mentioned

requirement applies. o It applies to all aspects of the research; and not merely to the data

collection part of the protocol. o This means that any change in the protocol, whether a change or addition

of a researcher or in the way that data are obtained or data are used must be considered for its ethical implications by the Ethics Committee.

Practically, since the scientific committees require a unique research protocol for

each post-graduate student, and that the postgraduate student will execute the research following that very protocol, the Ethics Committee needs to consider that protocol even if the study is a subset of another study that has already been approved by the Ethics Committee.

o The latter submission needs to refer to the study already approved and may consequently be less comprehensive (for example, the previously-approved Participant Information Leaflet and Consent documents may suffice).

Written approvals from the following Committees must be attached when submitting a protocol for Ethics Committee approval. It is preferable that the following approval first be obtained, before submission to the Research Ethics Committee. The reason being that should these Committees request changes, the amended documents must once again be submitted to the Research Ethics Committee for final approval.

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3.4.1 MMed Committee (All postgraduate students including Aerospace; Sports Medicine and Family Medicine) – Chairperson Prof P Rheeder (www.up.ac.za, click on Faculties, click on Health Sciences, click on School of Medicine, click on MMed Protocol Committee);

3.4.2 PhD Committee - Chairperson Prof B G Lindeque; 3.4.3 School of Health Systems and Public Health students must submit to

the Academic Programme Committee (APC) - Chairperson Prof B Girdler-Brown (Secretariat Ms Rene de Waal - [email protected]);

3.4.4 Academic Advisory Committee (AAC) - Chairperson Prof B Girdler-

Brown (Secretariat Ms Cathy Pieterse - [email protected]); 3.4.5 MSc. Committee: Chairperson Prof E Pretorius ([email protected]); 3.4.6 Dental Research Committee (RESCOM) Chairperson: Prof L Sykes

([email protected]).

3.5 Submission documents that are required (this is indicated on the website according to the type of submission)

3.5.1 Health Research Ethics Committee Electronic Application form which is available from: https://rims.up.ac.za.

3.5.2 Detailed Research Protocol

A protocol of the proposed study should address the following:

Introduction and relevance of the proposed research study

Background and problem statement (Literature references)

Hypothesis / Aims

Objectives (primary / secondary)

Methodology o Sample size and population o Randomisation process o Exclusion criteria / inclusion criteria o Procedures / frequency of visits o Quality assurance of specific tools to be used o Data collection and analysis

Ethical aspects e.g. anonomysing of data and participants.

Assurance of data anonymity must be given. Details on how this will be done, must be written in the protocol under “Ethics.” Any such study using data only, must be approved by the Ethics Committee.

Statistical analysis to be done

References (Vancouver style)

3.5.3 Research synopsis/summary

A short summary should accompany the research protocol.

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3.5.4 Patient / Participant’s Information Consent Document (PICD)

Different pro-formas of the Patient Information Consent Document are available on the website www.up.ac.za/healthethics.

To be read in conjunction with section 5 of this document.

The pro-forma PICD applicable to the specific research study must be adapted to that research study by the researcher, and needs to be typed (no handwritten changes may be done on the pro-forma example).

The PICD must be in layman language. A grade 6 pupil should be able to understand the PICD. Medical terms should be given in brackets and sufficiently be explained in the PICD.

Pages of the Patient Informed Consent Document must be numbered accordingly, ie, Page 1 of XXX, Page 2 of XXX, etc, to indicate that it is one document.

When Questionnaires are used it must be attached to the Patient / Participant’s Informed Consent Document and these pages must also be numbered as above. o NB: For anonymous Questionnaires, please use the Patient /

Participant’s Informed Consent Document (PICD 4), as available on the website (adapted to the specific research study).

Parental Informed Consent Document: If children (younger than 18 years) are research participants, the parents or legal guardians must give written consent as per approved document.

Assent Form: Additionally children older than 7 years must give written assent, indicating they are willing to take part in the research study.

Waiving of Informed Consent from specific participants for a research study can be motivated and requested in writing from the Research Ethics Committee.

Requirements for the signature of witnesses: There is a distinction between a signature confirming that the consent process was performed on the one hand, and a contractual witness that merely confirms the authenticity of the signatures by the contracting parties but not the consent process. The UP Health Sciences REC requires that the consent process be witnessed (i.e., the former) and duly signed for subjects who are not fully capable of consenting or illiterate – we agree with GCP that for these cases, someone who is not research personnel would suit better as a witness. In other cases, however, where subjects are fully capable of consenting and literate, we recommend witness signatures of the latter kind (i.e., a witness signature that authenticates the signatures of the subject and the researcher but not necessarily the consent process).”


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Translation of the Patient / Participant’s Information Informed Consent Document (PICD):

PICD documents must be submitted in either English or Afrikaans. These documents will be approved by the Research Ethics Committee.

Other language translations than Afrikaans or English, must be submitted to the Research Ethics Committee together with a translation certificate, as this will be processed as a notification by the committee’s secretariat.

3.5.5 Curriculum Vitae (CV)

An updated and signed Curriculum Vitae (with an MP number and a HPCSA number) needs to be submitted electronically by all Investigators. Researchers doing frequent research need only to submit an updated and signed CV annually.

In collaborative research, the Principal Investigator must be South African based.

3.5.6 The Declaration of Helsinki

This document must be read and signed by all Investigators, submit only the signature page.

3.5.7 The Declaration of Storage of Research Data

This form must be completed as all research documents must be kept for 15 years.

3.5.8 Promotion of Access to Information: Act No. 2 of 2000 (Permission to Access files/records) (where appropriate)

Health information is regarded as confidential and is the property of the patient. Therefore consent is needed to access patient information. If it is not possible to obtain such consent from the patient, the “custodian of the information”, usually the CEO or the Director of a Hospital/Clinic can give consent to access information.

Application to such custodian must be in writing, and reasons why the information is sought must be stated on the form (pro forma letter is available on our website www.up.ac.za/healthethics).

3.5.9 Written permission from the CEO of the hospital or institution to do research and access records/files and data (when appropriate)

The CEO or the Director of the clinic or hospital must give written permission for the research to be done at their premises.

Where research is performed in another department, as the department where the researcher is receding from, that specific


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Head of Department need to give permission for the research to be done in the specific department.

3.5.10 Statistical support letter (if applicable)

A statistician need to be consulted before submission of the final protocol to the Research Ethics Committee.

This is not a requirement for an undergraduate degree.

3.5.11 For Medication Trials:

1. MCC Permission (when appropriate)

The MCC must give permission according to The SA Medicines and Related Substance Control Act – Act 101 of 1965.

The following drugs must be approved by the MCC:

Trials done with unregistered drugs;

Trials done with registered drugs, but used for a new indication;

If both the drug and the indication are registered, the MCC must still be informed of the trial and the trial must be approved; and

If a trial is done on natural extracts/complimentary medication etc. for which a specific medicinal claim is sought.

2. Financial Contracts (when appropriate)

Financial contracts between an Investigator and Pharmaceutical firm must be signed and submitted to the Head of the Financial Contract Committee (Mrs Karen du Preez).

3. Registration at the National Health Research Ethics Committee (NHREC)

All clinical medication trials must be registered with the National Health Research Ethics Committee (www.ethicsapp.co.za). This has been implemented from 1st July 2005 (www.sanrr.gov.za).

4. Insurance Certificates Clinical Medication Trials must have informed consent covering participants for research related problems, eg. ABPI-coverage.

5. Summary of Protocol 6. Investigator’s Brochure – 1 complete copy 7. Researcher’s Responsibility Form for Principal Investigator and Sub-Investigator

8. GCP Training Certificate of the Principal Investigator and Sub-

Investigator 9. Copy of eg. Diary cards, advertisements etc. (if applicable) 10. Participant’s Information Consent Document (PICD) 11. Questionnaires/interview schedules (if applicable)

http://www.ethicsapp.co.za/

http://www.sanrr.gov.za/

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3.6 The following fee-structure is applicable for 2017. Note: Researchers must budget for these expenses in their grant application. Researchers must budget accordingly for ethical evaluation fees:

A. For all studies which are merely funded from Departmental budget

and/or NAVKOM or any other University of Pretoria grant the review is free

B. All research for degree purposes the review is free.

C. Studies sponsored by outside grant organisations within South Africa such as the NRF, MRC, NIH, CSIR, ECOG, BCIRG, as well as research by non-UP faculty gant (below R500 000.00) are charged a reduced fee.(Note: Researchers must budget for these expenses in their grant application.) Description Price excluding VAT VAT Price including VAT Protocols R3 000.00 R420.00 R3 420.00 Amendments R900.00 R126.00 R1 026.00 D. Research funded from International grants exceeding R500 000.00, all contract

research and non-UP researchers with funding exceeding R500 000.00, the full fee is payable.

Description Price excluding VAT VAT Price including VAT Protocols R14 000.00 R1960.00 R15 960.00 Amendments R3 500.00 R490.00 R3 990.00

*Note: For minor Amendments (e.g. advertisements, diary cards, posters, gifts, presents), no fee is applicable.

Upon receipt of an invoice from The Research Ethics Committee the researcher needs to pay the account. The reference number for the deposit will be reflected on this invoice. Proof of payment needs to be sent to [email protected]. Note: No Approval Certificate will be released before the proof of payment has been submitted.

4. The Review Processes

4.1 The National Health Act (Act No. 61 of 2003) proposes the following functions for a Research Ethics Committee:

Review of research proposals and protocols to ensure that research will be conducted in the spirit of endeavoring to promote health, and to prevent or cure disability and disease;

Ensuring that humans involved in research are treated with dignity and that their well-being is not compromised;

Ensuring that informed consent is obtained in the case of human participants; and

Granting approval in instances where research proposals and protocols meet ethical standards.


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Note: This section should be read in conjunction with the Department of Health Ethics Guidelines, i.e. Department of Health (2015) Ethics in Health Research: Principles, Structures and Processes, ISBN: 1-920031-04, (www.doh.gov.za)

The Research Ethics Committee reviews research applications according to a predefined review processes:

Full board review;

Case reports and case series review; and

Endorsements for Inter- Faculties: eg. GIBS,EBIT; Education and NAS 4.2 The Faculty of Health Sciences, Research Ethics Committee, University of

Pretoria must satisfy themselves that all research proposals follows the Good Clinical Practice Guidelines.

The elements of the research proposal to be reviewed as prescribed by the South African Good Clinical Practice Document

http://www.doh.gov.za/docs/factsheets/guidelines/ethnics/sec2.pdf.

To enable the Committee, to ensure the protection of the rights, safety and well-being of research participants, as well as that of their communities, the following elements of the research proposal are to be reviewed:

The design of the research proposal must be well designed, ethically sound and scientifically acceptable. The chosen methodology and design must be clear and worthy to be done. There must be evidence of literature review and that the study will contribute to advancement of knowledge. (sample size, hypothesis, aims, objectives and outcomes must be stated and will likely produce valid outcomes);

The prospective study population must be appropriate for the research question. Certain individuals or communities may be considered vulnerable in the research context and will require careful consideration, e.g. minors (<18 years of age), adults with incapacity to provide informed consent, persons highly dependent on medical care, prinsoners and other vulnerable groups. Particular caution should be exercised before undertaking research involving participants in vulnerable communities and the proposal should demonstrate why inclusion of such groups is essential to the research and how vulnerability would be managed.

Where the proposed study population includes participants from vulnerable groups, consult the Department of Health Ethics Guidelines, i.e. Department of Health (2015) Ethics in Health Research: Principles, Structures and Processes, ISBN: 1-920031-04, (www.doh.gov.za), for more information and guidance.

The sample size must be appropriate for the research question. Fair selection and inclusion, as well as exclusion criteria must be stated. The fairness for inclusion of participants has ethical implications (distributive justice). It should be avoided that particular groups of participants bear more than a fair share of burden regarding research participation. However vulnerable groups need not be excluded, the risk-benefit ratio must be evaluated either for the participants or for the possible benefit to society;


http://www.doh.gov.za/docs/factsheets/guidelines/ethnics/sec2.pdf


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The recruitment of subjects must be free of coercion and the level of compensation (if any) must be fair (Time, Inconvenience and Expenses method to be used) and properly discussed in the proposal. Participants should not incur expenses to take part in the research. Where potential participants are in a dependent relationship, such as student/lecturer or patient/doctor relationships the participants’ ability to make a voluntary decision must be discussed in the proposal;

Inducements can encourage participation but should be justified in the proposal;

Any risks associated with the research project are minimized to the greatest extent possible and the potential benefits are maximized to the greatest extent possible;

There must be a favourable risk-benefit ratio. The participants involved should not be exposed to more than minimal risk. These harms should be discussed in the proposal as well as in the informed consent document. The potential benefits of the research to participants and/or the wider community must be identified and maximized.

NOTE: Compensation for time and inconvenience, and reimbursement for expenses such

as travel are not considered research benefits;

The degree and method to which confidentiality will be assured must be appropriate. How data (written, audio or visual) will be kept confidential and for how long it will be stored needs to be discussed in the proposal under “ethics”. Where focus group discussions are planned, the participants need to be informed of possible confidentiality issues;

The method used to obtain informed consent must be ethically and legally acceptable (individual and community consent where applicable). Appropriate documentation of this process needs to be submitted and described in full;

The Informed Consent Document must contains the necessary elements: (An assent document for children older than 7 years up to 18 years is necessary);

The investigator must have the appropriate qualifications, experience and facilities to conduct the specific research in an ethical manner, e.g. paediatric training is necessary for paediatric research procedures;

Post-study commitments must be declared – the local standard of care must be discussed, where applicable; and

That the dissemination of research results must be discussed in the proposal, eg publications, congress seminars or lectures.

4.3 Full Board Review This is how the majority of research protocols, continuing reviews, protocol amendments adverse events are reviewed:

The committee has a meeting once a month, from January to

November each year.

The researcher needs to do an online submission of the protocol and all relevant documents. A hard copy, which forms a properly collated

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document, also needs to be submitted personally at the office of the Research Ethics Committee.

Note that submissions may only be done once the appropriate scientific committee approval has been obtained (see section 3.4: Academic Committee Approvals).

The required dates for submission for each month’s committee meeting are available on the website.

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4.3.1 Schematic Visualisation of the REC review process

Researchers REC

deadline Submission deadline

3 weeks

2 weeks

NO

1 week

YES

Submission of

documents:

1 hard copy and submit

electronically on

https://up.rims.ac.za

Distribution and

review of

documents by REC

members

All issues

resolved

Time

Line

Prelim Committee

meeting

Researcher should

address issues identified

by Prelim Committee

REC meeting Researchers attend

REC- meeting on their

request or by invitation

Issue of approval

certificate

As per decision of

REC

https://up.rims.ac.za/

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4.3.2 The Prelim Committee Meeting

The electronic version of the protocol proposal and supporting documents will be sent to specific members.

A prelim committee meeting will be held 1-2 weeks later.

At this meeting the Chairperson and the 3 Vice-Chairs, as well as a specific committee member, will be present.

Researchers are not requested to attend this meeting.

The five identified committee members will assess the comments received, from all the committee members, together with the specific research protocol documents.

At this prelim committee meeting, research protocols that can be approved at the main meeting will be identified and final approval will be ratified at the full committee meeting (the next week).

All outstanding issues identified must be addressed by the researcher for the full committee meeting a week later.

Attendance by the researchers for the main meeting is by invitation only.

If a researcher wants to attend the main Ethics Committee meeting, a request can be lodged with the Secretariat.

4.3.3 At the Main Meeting

During this meeting, the recommendations of the Prelim meeting, as well as the requested amended documents are discussed, as put on the Agenda. The meeting proceeds as follows:

The chairperson opens the meeting.

A quorum, as described earlier must be present for all decision making.

The secretary records those present and also notes apologies. A register is signed by all members present.

The minutes of the previous main REC meeting are corrected and accepted.

New Agenda Items are generally discussed in the following order, but this may be subject to change depending on volume and type of items received at each meeting:

4.3.3.1 Attendance and Apologies 4.3.3.2 Pre-discussion items 4.3.3.3 Matters arising from the previous meeting; 4.3.3.4 Protocols standing over; 4.3.3.5 New applications; 4.3.3.6 Amendments; 4.3.3.7 Serious adverse events (SAEs); and 4.3.3.8 Progress Reports.

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Where identified by the prelim meeting, the Principal Investigator will be invited to

attend the meeting at a proposed timeslot (obtained from the secretariat). If the Principal Investigator cannot attend, a sub-investigator must be appointed to attend the meeting.

The outstanding issues can then be deliberated with the committee.

Confidentiality is maintained, by discussing the relevant protocol with only the

specific investigator/s present (if indicated).

Should amended documents be submitted at the meeting, be complicated or lengthy, specific identified members will evaluate such after the meeting. Feedback will then be sent to the secretariat.

Further correspondence will be e-mailed to all the relevant investigator/s.

It is the directive of the Ethics Committee that ethical approval can be granted and issued within 5 days after all outstanding documents are received by the secretariat.

4.3.4 Decision making rules

The following pertain:

a) Final decisions may only be made at meetings where a quorum (A quorum is defined as 6 members attached plus 3 members not attached to the University of Pretoria) are present; if a quorum is not reached, then the protocols will be ratified at the next meeting.

b) The Committee usually makes a decision by consensus, but

infrequently it is done by a voting process. In the Minutes, a final decision is indicated by a voting score.

c) An Ethics Committee member must indicate and withdraw from the

final voting process, where a conflict of interest arises.

d) The following decisions can be made at the meeting:

(1) Protocols are approved (with or without stipulations) and an approval letter is issued within 5 days after the meeting.

(2) Protocols are provisionally approved pending modifications: (i) Outstanding documents or changes needed to be made by the investigator will be clearly indicated and conversed to the researcher. (ii) As soon as all these documents are received, it will be

forwarded to a sub-committee indicated at the meeting for final approval.

(iii) If the sub-committee approves the amended documents, an approval letter will be forwarded to the researcher.

(iv) If the sub-committee still has difficulties, the protocol will be further discussed at the next Ethics Committee meeting.

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(3) Protocols which require major revisions will be referred back for

revision. A new full submission will then be required. This will be reviewed as a new research proposal.

(4) Rejected protocols. The file will be closed. (5) Should the protocol stand over from the previous meeting, the

protocol will be discussed at the next month’s Ethics Committee meeting. The researcher will be invited to attend the meeting if it is necessary.

4.3.5 Communicating the review decisions

After the Minutes have been drafted, the committee’s final decision per protocols will be conveyed in writing to all investigators within 5 working days (as per schematic diagram).

The committee approves a research study for a specific time period, as indicated on the electronic Application Form (1 to 2 to 3 years). This period will be stated on the final approval letter, with the provisio that six monthly reports and any amendments be submitted during the above granted period. This therefore omits the need for applying annually for permission to continue the research.

The final approval letter will indicate that a quorum of members have evaluated and approved the research, the date of approval, as well as the period for which the approval is valid.

The certificate of ethics approval does not disclose the names of the Research Ethics Committee (REC) members who were present at the vote for or against a specific study, for doing so may compromise the free participation of members in the voting. Sponsoring companies requested this information in the past to audit that resolutions were taken at a quorate meeting and that researchers with a conflict of interest were recused from the voting. However, this auditing on the compliance of the REC with its own Terms of Reference and Standard Operating Procedures is not within the mandate of a sponsoring company or the researcher. In the REC’s Terms of Reference and Standard Operating Procedures Sections, section 4.3.4 (a) is explicit about quorate resolutions and sections 2.4 and 4.3.4(c) are explicit about recusal in case of a conflict of interest. Furthermore, the REC is registered with the NHREC and adheres to requirements on how it should be constituted and transparency about who the members of the REC are.

4.3.6 Follow-up Review and re-certification procedures

Protocols reviewed before 2011: The Principal Investigator must write a letter to request re-approval for the estimated time duration still necessary to complete the research.

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Protocols reviewed from 2011: A protocol is approved for a pre-determined time period during the initial evaluation. This is indicated on the approval letter. No annual approval necessary.

4.3.7 Appeals Procedure

Researchers have the right to appeal a decision of the Ethics Committee. The request to appeal must be submitted to the chair of the Ethics Committee via the secretary’s office.

The appeal must contain a clear motivation as to the reasons for the appeal. The documents must include an executive summary and motivation from a subject specialist other than the author of the protocol, stating clearly the reasons for appeal and why this protocol should be reconsidered.

The chair will then approach outside consultants to evaluate the protocol and to furnish the Ethics Committee with a report and a recommendation.

The Ethics Committee will then reconsider the entire protocol with new motivations at the meeting following the one at which the appeal was tabled.

The decision of the Ethics Committee after the Appeals Process is final.

4.4 Case reports and case studies The Research Ethics Committee’s office accepts new case report and case series applications. The application for Research Ethics Committee review should include:

• A cover letter outlining the rationale for the case report and steps taken to protect patient privacy and confidentiality;

• Signed consent from the patient(s) or their legally appointed representative, or an explanation stating why consent was not obtained. The Research Ethics Committee will consider clear and adequately motivated justification for the lack of formal informed consent; and

• The case report or draft article.

4.5 Endorsements - Inter-Faculty Research: GIBS, EBIT, Faculty of Education and NAS

A full protocol (1 hard copy plus online submission) needs to be submitted, after the specific Faculties approval of the research study. This will then be circulated to all the members for review and reviewed at the prelim meeting and then at the main meeting.

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5. The Participant Informed Consent Document and the consent process

(Refer to section 3.5.4 Patient / Participant’s Information and Consent Document)

5.1 Language of Informed Consent Documents: 1) We acknowledge the South African context in which

a. There are 11 official languages; b. English is spoken by less than 10% of people at home even though this is the most

commonly spoken language in South Africa in general discourse; c. Most people are able to speak more than one language, and operate and

communicate within a multilingual society in everyday discourse; d. Researchers reflect the multilingual context and not merely patients or research

participants, meaning most researchers are usually also able to speak languages other than English; and

e. Some research participants may prefer English even when it is not their home language, for example when their home language is in their view not adequate to convey the nuances relevant to the research context.

2) We underscore that informed consent to participation in research is a process that is distinct

from its affirmation in an informed consent document. Congruently, the language in which informed consent process is conducted may not always be the language in which the informed consent document is written. The flexibility to use the language that is most effective in communication or even more than one language to obtain consent and its written affirmation is considered congruent to and required in a multilingual society, and should be seen and deployed as providing added value rather than being a compromise (as it may appear when judged from a unilingual context).

3) If research participants are by virtue of research selection all speaking the same language at

home, we strongly advise that the informed consent document be in that language. However, we appreciate that most studies are not restricted to people who all speak the same language, hence we acknowledge that English as the lingua franca in South Africa is usually the most practically appropriate language in which an informed consent document will be written, reflecting the local realities as expressed in point 1 above.

4) We encourage that (but do not insist upon) informed consent documents be made available in several languages from which a specific research participant may choose. Note that translations of informed consent documents from English should be properly certified as accurate.

5) In case an informed consent document is available in more than one language, we underscore that research participants may choose to use an informed consent document in a language that is different from their home language.

5.2 General requirements If the participant is unable to give informed consent, researchers need to obtain informed consent from the participant's legally authorized representatives, before any research related procedure may be done. Where necessary the Research Ethics Committee may waive the need to obtain informed consent, if motivated by the researcher and deliberated by the Research Ethics Committee. The information that is given to the participants needs to be presented in language that promotes their understanding of the proposed research study. Translated PICDs or translators can be used.

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Researchers need to obtain written, valid and voluntary informed consent from prospective participants and/or from their representatives and need to give them sufficient time to consider whether or not to participate in the research. If the participant is unable to read or write an independent witness needs to verify in writing that the informed consent process was valid and in accordance with the requirements of this SOP document. The process of recruitment, the study population and the documentation of how informed consent will be obtained from participants, needs to be described in detail in the study protocol. In addition, the researcher must document the informed consent process in the source notes of the research participant. Once the participant has signed the PICD, a PICD must be kept at the investigator’s site and the participants must get a copy of the signed PICD. For multi-site international clinical trials, the PICD must be adapted to the requirements of the Research Ethics Committee. 5.3 The Elements of Informed Consent 5.3.1 Basic Elements of Informed Consent The following information needs to be provided to each participant when seeking informed consent:

A statement that the study involves research;

An explanation of the purposes of the research;

The expected duration of the participant's participation;

A description of the procedures to be followed, and identification of the specific procedures which are experimental;

A disclosure of appropriate alternative procedures or treatments, that are available as standard care of treatment;

A description of any reasonably foreseeable risks or discomforts to the participant;

A description of any benefits to the participants themselves or to the community;

A statement that participation is voluntary and that refusal to participate will not involve any penalty or loss of benefits or of care to which the participant is otherwise entitled to;

A statement regarding the confidentiality of the participants’ information;

A statement that the participants will be reimbursed for any out of pocket expenses related to the research;

Researchers’ names and 24 hour phone numbers must be provided on the PICD for any questions about the research; and

A statement that the participant may discontinue participation at any time without penalty or loss of benefits to which the participant is otherwise entitled.

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5.3.2 Additional Elements of Informed Consent When appropriate, one or more of the following elements of information can also be provided to each participant:

A statement that the particular treatment or procedure may involve risks to the participant (or to the embryo or foetus, if the participant is or may become pregnant);

Anticipated circumstances under which the participant's participation may be terminated by the investigator, if the investigator is worried about the safety of the participant;

A statement that significant new findings developed during the course of the research which may relate to the participant's willingness to continue participation will be provided to the participant; and

The approximate number of participants involved in the study.

6 Post Approval Follow-up and continued review So as to ensure ongoing communication between the Ethics Committee and researchers, the following should be taken into consideration:

6.1 Protocol Amendments

An “Application for Approval of Amendment” form must be completed (this form needs to be in the required format as available on the Research Ethics Committee’s website).

Amendments should be submitted electronically via the electronic process. https://rims.up.ac.za

1 hard copy of the Amendment plus an updated protocol needs to be submitted to the Ethics Committee.

The Principal Investigator must explain the rationale for the amendment on the specific form and also clearly mark the amended sections, as indicated on the form. This ensures that the Research Ethics committee members can easily identify the changes as well as the rationale of the amendment.

Protocol Amendments cannot be implemented until the Ethics Committee has reviewed and approved it at the monthly meeting.

Should an Amendment need expedited approval, as patient safety is at stake, it can be submitted as such to the secretariat. Provisional approval can be granted, which then needs to be ratified at the next formal Ethics Committee meeting.

In the case of minor administrative modifications (which do not have an impact on the safety of the participant and the protocol methodology)


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can be submitted as a notification to the ethics office and will be approved as such.

6.2 Adverse and Serious Adverse Events (SAE), Line-listings, SUSARs

(i) The Principal Investigator needs to interpret and complete the required “Reporting of Serious Adverse Event” form. This must to be completed electronically. (form available on our website)

(ii) On this form, it is important that the Principal Investigator interprets the SAE and comments as to how the Ethics Committee should construe it.

Note: The Research Ethics Committee is guided solely by the content of this form as completed by the Principal Investigator.

Serious Adverse Events (SAE) from the local approved site must be submitted and will be noted per study, per site.

SAEs should be submitted electronically via the electronic process. https://rims.up.ac.za

One hard copy of the above form and SAE must be submitted.

Dr N E Khomo will review the SAE and it will be put on the Agenda of the Main Ethics Committee’s meeting for discussion.

(iii) Line Listings should be uploaded electronically in batches (with clear reference to the approved study).

• Line listings for Clinical Trials can be submitted bi-annually.

• These listings will be considered a simple notification, which do not require formal approval.

(iv) Suspected Unexpected Serious Adverse Reactions (SUSAR Reports) and

Global Safety letters can be submitted to the Ethics Committee as a notification.

• Monthly to Six Monthly submissions are acceptable – as indicated by the specific sponsoring pharmaceutical company.

DEFINITIONS: (Refer to the MCC Guideline: www.mcc.za.com ) Adverse Event:

Any untoward medical occurrence that may present during treatment, with a medicine or intervention, but which does not necessarily have a causal relationship with this treatment.

Adverse Drug Reaction or Adverse Reaction:

A response to a medicine or intervention which is noxious and unintended.


http://www.mcc.za.com/

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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 investigator’s brochure or other product information for unregistered products).

Serious Adverse Event or Serious Adverse Drug Reaction:

Any untoward medical occurrence that: o results in death, o is life-threatening, o requires patient hospitalisation or prolongation of existing hospitalisation, o results in persistent or significant disability/incapacity, or o 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 Faculty of Health Sciences Research Ethics Committee’s approved sites:

o All deaths o 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.

o 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.

o All Serious Adverse Events

o Non-serious unexpected adverse drug reactions:

• Report as part of the 6-monthly progress reports. OTHER REPORTING REQUIREMENTS:

o Serious, unexpected, adverse drug reactions occurring at other South African and Foreign sites:

• Report as part of the 6-monthly progress reports. o New information which may affect the safety of participants or the conduct of a

trial:

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• Report within 3 calendar days of first knowledge and in the six-monthly progress report.

o 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.

6.3 Progress Reports (form can be downloaded from www.up.ac.za/healthethics )

Bi-Annual Progress Reports must be submitted in a typed format, pertaining to the progress of the envisioned research.

Due dates for submission of same are 31st May and 30th September of every year.

6.4 New Information; Diary cards; Advertisements

• Notification by submitting the required documents with a covering letter.

6.5 Protocol deviations and protocol violations

All protocol violations (instances where the selection criteria of the protocol was not adhered to) must be reported to the Ethics Committee as soon as the researcher becomes aware of the violation; and

Protocol deviations (all other deviations from the protocol) and minor GCP violations must be reported to the Committee as part of the application for re-approval or on the progress report form.

6.6 Premature Suspension/Termination of a research study

The researcher must immediately notify the Ethics Committee.

A summary must be communicated regarding the reasons of the suspension or termination, if before the anticipated date of completion.

6.7 Completion of a research study

The researcher must notify the Ethics Committee when the study has been completed.

This should then be followed up with a final report.


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6.8 Dissemination of Research Results

The researcher must state in the protocol how the results (positive or negative) will be disseminated for example:

Publication (Article/Abstract);

Congress Presentation / Posters; and

How the community will be informed (if applicable).

Note: All research results must be put into the public domain.

6.9 Monitoring of Research

The Declaration of Helsinki, paragraph 23 states that Research Ethics Committees have the right and need to monitor research similarly the “Ethics in Health Research- Principles, Processes and Structures 2nd

Edition: Department of Health” (2015) and the National Health Act (Act 61 of 2003).

The Ethics Committee may from time to time monitor research sites. Should it be necessary an external auditor may be appointed to do an audit.

Active monitoring becomes likely when research misconduct and/or complaints are received by the Ethics Committee.

Passive monitoring is done by evaluating Progress Reports and Annual Review applications.

6.10 Archiving of Documents Ethics Committee: All documentation regarding protocols, Agendas and

Minutes will be kept in the office for 5 years after a protocol has been completed. Thereafter, all files will be stored at Metrofile for another 10 years. This 15 year retention of all documents is a requirement as prescribed in the National Health Act (Act 61 of 2003).

Researcher’s duties: Investigators must also indicate on the Data Storage form where they will store their documentation for 15 years after their research protocol has been completed. Supervisors are responsible to store their student’s documentation.

6.11 Record Keeping

All protocols are allocated a number for the particular year of submission, eg. x/2017. On the electronic RIMS site all the information of evaluated research studies, such as name of investigators, title of protocol, date of submission, approval date etc. are recorded.

A hard copy of the minutes of the Research Ethics Committees’ meetings will be kept in the office, which will show all the relevant deliberations regarding each protocol.