Institutional Review Board (IRB) and Clinical Research Shu B. Chan, MD, MS, FACEP Research Director, Emergency Medicine Residency Program, Member, IRB

Institutional Review Board (IRB) and Clinical Research

Shu B. Chan, MD, MS, FACEPResearch Director, Emergency Medicine Residency

Program,Member, IRB

Resurrection Medical Center

Agenda

History of the development of the IRBComposition of the IRBOperation of the IRBDuties of the IRBIRB and the EM ResidentTypes of IRB ApprovalsHelpful Tips Regarding IRB

Submissions

Nuremberg Code-1949

Along with the trials of war criminals before the Nuremberg Military Tribunals were a series of directives regarding human experimentation Voluntary consent of the human subject

is absolutely essential Experiments should be necessary for the

good of society and likely to yield results

Nuremberg Code

Experiment designed, based, and justified on prior knowledge

Avoid all unnecessary physical and mental suffering and injury

No a priori reason to believe that death or disability will occur

Risk should not exceed the benefits Proper preparation to protect the

subjects from possibilities of harm

Nuremberg Code

Experiments done by qualified persons Right of the subject to terminate the

experiment Duty of the scientist in charge to

terminate an experiment if continuation is likely to result in injury, disability, or death

Declaration of Helsinki-1964

The World Medical Association adopted a set of ethical principles for medical research involving human subjects

These principles included all the directives from Nuremberg and expanded on them Medical research involving human

subjects includes research on identifiable human material or identifiable data

Declaration of Helsinki-1964

When providing care, the physician shall act only in the patient’s interest

Some research populations are vulnerable and require special protection

Clear formation of an experimental protocol An “ethical review” committee, independent

of the researcher should review all protocols Confidentiality and privacy of the subject

must be respected

The Belmont Report-1979

Report of the meeting of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research at the Belmont Conference Center at the Smithsonian

By this time IRB have been established in most institutions and having difficulties implementing all the rules and directives from Nuremberg and Helsinki

The Belmont Report-1979

It was felt that to better guide the researchers and IRB reviewers, especially in more complex situations, boarder general ethical principles were needed

The concept was that these boarder principles would provide the basis for interpretation of the specific rules and guidelines

The Three Basic Ethical Principles from the Belmont Report

Principle One: Respect of Persons (a.k.a. Autonomy) The principle of “respect for persons” is

divided into two moral requirementsFirst is to acknowledge that to respect a

person’s autonomy requires that the person enters into the research on a voluntary basis and has adequate information to make such a decision

Second is to recognize that certain individuals may have decreased capacity for self-determination and so require special protection


Principle Two: Beneficence The principle of “beneficence” can be

summarized by two general rules“Do no harm” - the old Hippocratic maximHowever, many times this dictum does not

lend itself to clear cut interpretations and so the second general rule is more applicable

“Maximize possible benefits and minimize possible harms”


Principle Three: Justice The principle of “justice” can be understood

by considering these important questionsWho should receive the benefits of the research?Who will receive the benefits of the research?Who will bear the burdens of the research?

There needs to be fairness in distribution of persons involved with the answers to those questions

Composition of the IRB

Since much clinical research is funded or under the perusal of the federal government, the Department of Health and Human Services ( Office for Protection from Research Risks) has set specific rules regarding the composition and duties of individual local IRB

Composition of the IRB

Minimum of five membersDiversity of race, gender, and

cultural backgroundDiversity of experience and expertiseProfessional competence necessary

to review researchMembers may not review their own

projects

Operations of the IRB

Have written procedures and follow themMajority of members must be present to

convene a meetingApproval of a research project requires

the approval of a majority of those members present at the meeting

Officials of the institution may not approve research that has not been IRB approved

Duties of the IRB

Review and have authority to approve, require modifications, or disapprove all research activities involving humans

Review and approve informed consent from the research subjects

Continuing review of approved research not less than once per year

Duties of the IRB

Review and approval in accordance with the three Belmont principles of 1: Autonomy (Respect of Person) 2: Beneficence 3: Justice

Prepare and maintain adequate records and documentation of IRB activities

Duties of the IRB

In addition, the IRB must follow more specific rules when reviewing research involving Pregnant women Fetuses Children Prisoners

IRB and the EM Resident

Almost all research done by an EM resident will involve humans in some fashion The humans need not be “experimental

subjects” for the research to fall under IRB perusal

Recall that the Helsinki directives expanded research protection to all identifiable human data

IRB and the EM Resident

The IRB process may be time consuming and residents have specific time tables

Protocol modifications requested by an IRB may make a project not doable

The IRB has the authority to halt a project at any point

Types of IRB Approvals

Expedited review and approval The chairperson may individually review

and approve a proposal or designate an IRB member(s) to review and approve a proposal

There are strict guidelines on when an expedited review is allowed

However a proposal can only be disapproved by the full IRB


Exemption from further review This is not an exemption from review All research involving human must have

some sort of initial review and approval The exemption is so that future review

by the IRB is not needed, thus not having to submit follow up reports


Waiver of written informed consent Key to the first Belmont principle of autonomy

is the requirement that all human subjects give informed consent to the study

The IRB may give a waiver so that this informed consent need not be in written form

If a written consent form is not included in an application, then that application is incomplete unless a waiver has not requested

Tips for IRB Submission

Because IRB operate under very specific rules and guidelines from the federal government, record keeping tend to be very strict Make sure the application is complete Leave no blanks, write not-applicable if so Be sure consent templates and other

attachments are in order and included


All submitted applications should be signed All investigators in the study should be

listed Be sure to submit the necessary number of

copies Don’t forget to include any funding source,

even when the amount is minuscule or the funding is not cash

Have a clear and concise cover letter


Many studies by residents are retrospective and involve no or minimal risk to the subjects and so qualifies for expedited review

If the study involves no or minimal risk, then very often further IRB oversight is unnecessary and the study can be exempt


If the study qualifies for expedited or exempt status, so state that in the application or cover letter and specifically ask for expedited and/or exempt status

Be sure to list the reasons for the request for expedited and/or exempt status Minimal risks Retrospective study design, etc.


If a waiver of written informed consent is requested Be sure that the section of the application

where the written consent is placed has a notation that a waiver is requested

Regardless of whether a waiver is requested or not, the process of obtaining informed consent still must be clearly spelled out


Loss of subject confidentiality is an important aspect embodied in the first Belmont principle of autonomy

This issue has become a hot one since the passage of HIPAA regulations

Be very detailed when describing how subject confidentiality is maintained


The IRB is charged with protecting the economic rights of the subjects also under the Belmont principle of justice

Any possible increased expense to the subjects must be clearly explained and justified

Provisions for meeting these expenses must be stated


If using an established template for IRB application, be sure to review the documents completely so that the application is specific to your project

When in doubt, give more not less information

Have the application reviewed by an experienced mentor

Documents

Institutional Review Board (IRB) and Clinical Research Shu B. Chan, MD, MS, FACEP Research Director, Emergency Medicine Residency Program, Member, IRB