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150406P - THE INSTITUTIONAL REVIEW BOARD (IRB): STRUCTURE, FUNCTIONS, AND CHALLENGES

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Presentation at a training program ‘Applying the Principles of Ethics to Clinical Practice:’ held at Aramco Dhahran April 6, 2015 by Professor Omar Hasan Kasule Sr. MB ChB (MUK). MPH (Harvard), DrPH (Harvard) Chairman of the Ethics Committee King Fahad Medical City.


Definition: IRB
·         An independent body reporting directly to the CEO through a report  once or twice a year
·         Members from diverse disciplines including non-health professionals
·         Main function is protection of  the rights and welfare of research subjects and assures the public that this role is carried out well
·         Works mainly to review and approve research protocols, investigator qualifications, and methods of informed consent
·         Follow up / monitor on-going research for adverse effects, protocol adherence

Definition: investigator:
·         A qualified person who is responsible for the conduct of research.
·         Sub-investigators assist the investigator in all aspects of the study.
·         The investigator or sub-investigator may be or may not be a staff member at KFMC.
·         The investigator / sub-investigator may be a student, a health professional, or any other profession if the project has a health-related component.

Definition: investigations in humans & investigational product:
·         Investigation is research undertaken for purposes of studying the absorption, distribution, metabolism, efficacy, and safety of an investigational product.
·         Investigational product is a pharmaceutical form of an active ingredient or placebo being tested in a clinical study.

Definition: review and reviewer
·         Review is a rigorous and systematic process of assessing a research project regarding its scientific merit, validity and reliability of the research methodology, qualification of the investigators, research subject rights and safety, and other ethical considerations
·         A Reviewer is a person with specialist knowledge in a field of medicine, healthcare, and research methodology asked to review a research project and recommend to IRB its approval, modification, or rejection.

Roles of IRB 1: overview
·         The primary role of the IRB is protecting the rights, safety, and welfare of the subject/patient.
·         The secondary role is assuring that data from a study will be accurate, reliable, and accurate.

Roles of IRB 2: Procedures of assuring objectives
·         Review and approval of the protocol
·         Assessing the qualifications of the investigator
·         Assuring that methods and materials for informed consent are appropriate
·         Reviewing financial aspects to ensure no conflicts of interest
·         Monitoring the conduct of the study
·         IRB shall operate according to written SOPs.

Roles of IRB 3: assurance of patient protection
·         Independent review and monitoring of the protocol to ensure a favorable risk-benefit ratio
·         Putting patient interests before public interest
·         Assuring informed consent
·         Conducting the study according to the protocol
·         Making sure that the study is carried out by qualified personnel.

Roles of IRB 4: Assurance of data accuracy
·         Monitoring reports
·         Auditing reports
·         Inspection reports

Membership of IRB
·         IRB shall consist of at least 5 members representing various disciplines of science, medicine, and ethics.
·         KFMC IRB has 18 members including the chairman and a non-medical community representative
·         At least one member must be a non-scientist and one must be a lay community representative.
·         Alternate members shall attend and vote if principal members notified the chairman of their absence.
·         Members shall be independent of the sponsor and the investigator to avoid potential conflict of interests.
·         Members are appointed on the basis of their expertise and not as representatives of their departments or units

Quorum
·         The quorum shall be half of the members and decisions shall be carried by a simple majority.
·         Members shall sign an attendance roster indicating time of arrival and if time of departure if they do not sit throughout the meeting.
·         If members do not attend the whole session a notation must be made in the minutes on what protocol discussions they missed.

Meetings of the IRB
·         IRB shall meet once every 4-6 weeks unless an emergency meeting is necessary.
·         The meeting dates and venues are advertised 6 months in advance.
·         Members receive the agenda and documents relating to the meeting 10 days in advance.
·         The chairman designates 1-2 members to make a detailed analysis of each submission and report to the meeting.
·         The agenda includes the following sections: follow up of previously approved studies, safety reports, amendments, and new studies for approval (exempt, expedited, and full review).

Types of submissions for review
·         Exempt, expedited, and full review submissions for projects to be carried out at KFMC that have a KFMC staff member as an investigator or a co-investigator.
·         Exempt, expedited, and full review submissions of projects to be carried out at KFMC by external investigators.
·         At its discretion the IRB shall review (a) exempt projects carried out in other institutions if they have a KFMC staff as an investigator or a co-investigator. (b) Projects carried out at other institutions without a KFMC staff member as investigator or co-investigator. At its discretion IRB may charge for this service.

Documents submitted to IRB:
·         Exempt studies: IRB application form, protocol/research proposal, informed consent material if applicable, data collection instruments if applicable, current curriculum vita (e) of the researcher(s).
·         Clinical research either expedited or full review: protocol and its amendments, written information provided to the research subjects and the informed consent form (ICF), the case report form (CRF), the investigator brochure (IB), study recruitment procedures not in the protocol including recruitment advertisements, insurance / payments for study subjects, financial agreements between the sponsor and the investigator, any other applicable agreements, and the current curriculum vita (e) of investigators, safety reports from this site and other sites.

Criteria of review for initial approval:
·         Risks are minimal and are reasonable in relation to the anticipated benefits.
·         Consent is informed and is properly documented
·         Provisions are adequate to ensure privacy and confidentiality
·         The research plan contains adequate provisions for monitoring the data to ensure safety
·         Subject selection is equitable
·         There are adequate safeguards to protect vulnerable subjects (children, pregnant women, mental patients etc.).

Criteria for reviewing a protocol:
·         Simple and logical eligibility and exclusion
·         Objective and easy to assess outcome measures
·         Proper subject selection and randomization
·         Simple intervention not likely to be mistaken
·         Adequate sample size and power to detect a difference
·         Low risk of missing important data by too short a follow up
·         Overall reliability of the trial results.

Criteria for reviewing the qualifications of the investigator
·         Education
·         Training
·         Experience
·         Familiar with the investigational product
·         Knowledge of GCP guidelines
·         Has time to devote to the study
·         Has sufficient qualified staff.

Criteria of review for continuing approval
·         Reports of adverse effects
·         Protocol amendments / violations / deviations
·         Patient recruitment
·         Any special problems

Criteria for auditing, monitoring, and inspections:
·         Compliance with the protocol
·         Submission of necessary reports
·         Safety reporting
·         Termination or suspension
·         Final report / close out

IRB records
·         All documents submitted by the PI, IRB correspondence, and IRB minutes are part of IRB official records
·         IRB official records must be kept for a minimum of 3 years after the end of the study.

Case Scenario 1
A very experienced professor of surgery wanted to undertake research comparing two surgical approaches that he has been using alternately over the past 15 years. He reviewed the Nuremberg and Helsinki declarations as well as the ICH-GCP guidelines and the Saudi regulations on research. He made sure he fulfilled all stipulations of these documents in his research and saw no reason to seek the approval of the local IRB that in his view consisted of young inexperienced members most of whom had been his students. (PEER Handbook SCHS 2014)

Case Scenario 2
A physician was given a fat grant to study a new drug. The sponsor provided a well written and detailed protocol. Implementation of the protocol was difficult in the local circumstances: the informed consent information was too much and the subjects could not adhere to the visit dates fixed in the protocol. The physician made alterations in the protocol that he thought were simple and did not affect study validity or patient safety and saw no reason to inform IRB/REC. The sponsor sent monitors who discovered the discrepancy. The physician ignored their observations and continued the study without documenting the changes he had made. . (PEER Handbook SCHS 2014)

Case Scenario 3
A physician in a local hospital agreed to be an investigator of a multi-center international trial sponsored by the pharmaceutical company. He regularly completed and sent CRFs to the sponsor overseas. On one occasion the sponsor questioned the data submitted and insisted that the original patient’s chart be shipped to him for inspection and verification. . (PEER Handbook SCHS 2014)