Session 1 - IRB Basics - Christine Epps

7/24/2019 Session 1 - IRB Basics - Christine Epps

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Institutional Review Board

University of South FloridaResearch Integrity and Compliance

August 2014


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What is an IRB?

IRB is an acronym for Institutional Review Board

The IRB is responsible for the review and approval of allresearch involving human subjects

Scientific validity

Ethical review

Function of the IRB: Protecting the rights, welfare and

safety of human subjects through Initial review

Continuing oversight


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Why Were IRBs Formed?

The birth of the Institutional Review Board resulted from an

unfortunate history of crimes against humanity in the name

of science and research.


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Nuremburg Trials: 1946

-

1947

Trials at Nuremburg series of military tribunals in response to WWII

atrocities in the concentration camps (1939 1945)

Researchers conducted cruel experiments on children & adults held in the

camps with no informed consent

Many defendants argued that the experiments were morally justified

Participants were going to die anyway

Sacrifice would provide scientific

knowledge benefiting many

15 of the 25 defendants (20 MDs)

were found guilty and 7 were

sentenced to death
http://upload.wikimedia.org/wikipedia/commons/6/64/Nuremberg_Trials_retouched.jpghttp://upload.wikimedia.org/wikipedia/commons/6/64/Nuremberg_Trials_retouched.jpg


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Nuremburg Code: 1947

As a direct result of the Nazi medical experiment atrocities committed

during World War II that were revealed at the Nuremberg Trials, the

Nuremburg Code was developed as part of the judgment.

Makes clear that

The welfare and rights of human subjects must be protected

The research conducted must be sound and beneficial

The freedom of human subjects to participate or not is unchallengeable


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Outcomes US Public Health Service Tuskegee Syphilis Study led to the National Research Act

of 1974, requiring regulatory protection for human subjects

The National Research Act also created the National Commission for theProtection of Human Subjects of Biomedical and Behavioral Research This commission wrote the Belmont Report in 1979, which is the cornerstone statement of ethical

principles for treatment of research subjects

In 1981 the DHHS & FDA published convergent regulations that were based on theBelmont Principles

In 1991, after 10 years of negotiation, 17 federal departments and agencies agreed

to adopt the basic human subjects protections. This is referred to as the CommonRule

The federal regulations and guidelines govern research in the United States ofAmerica and other countries may have alternate or additional guidelines.


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The Belmont Report

Issued April 1979 by the National Commission for the

Protection of Human Subjects of Biomedical and Behavioral

Research

Summarizes the basic ethical principles identified by the

Commission to address the following: The boundaries between research and the routine practice of medicine Assessment of risk-benefit criteria in determining appropriateness of research

involving human subjects

Appropriate guidelines for the selection of human subjects for participation in

research

The nature and definition of informed consent in various research settings

Established the responsibility of the investigator to submit research activity


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The Three Pillars of the

Belmont Report

Respect

for Persons Beneficence Justice


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Respect for Persons

Two moral requirements:1. Acknowledge autonomy

Individuals should be treated as

autonomous agents

2. Protect those with diminished

autonomy Vulnerable Populations

Demands subjects enter into research

voluntarily and with adequate

information

Informed consent is central to protecting

the autonomy of human subjects


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Beneficence

Assessment of risks and benefits

Researchers have the obligation to secure the well-

being of subjects

Two general rules:

1. Do not harm2. Maximize possible benefits and minimize possible harms


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Justice

Selection of Subjects Researchers question who receives the benefits of

research and who bears its burdens

There must be fairness in the distribution of the risksand benefits of the research

When is differential treatment for certain purposes

justified?

Easy availability vs. directly related to problem


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IRB Jurisdiction

Jurisdiction of the IRB: All research activities involving human subjects

Per Federal Regulations:

Research is defined as a systematic investigation, including researchdevelopment, testing and evaluation, designed to develop orcontribute to generalizable knowledge.

A Human Subject is defined as a living individual about whom aninvestigator conducting research obtains data through interventionor interaction with the individual or identifiable private information.

For a project to include human subjects research under the purview ofthe USF IRB, both of the definitions outlined above must be met.


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Structure of the Board Membership

45 CFR 46.107 IRB membership

Nonscientistmust be inattendance

ScientistUnaffiliated

Each IRB must have at least 5

members including:

one nonscientist,

one scientist and

one unaffiliated with the

institution.


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Children

Pregnant Women

Prisoners

Vulnerable Population Representative

Provides expertise beyond that of board members

May not vote

Consultant

An alternate from a pre-defined membership roster may substitute for aregular member who is unable to attend. The alternate must have equivalent

knowledge and skills as the member they are replacing.

Alternates

A member may not participate if they have a conflict of interest

Conflict of Interest


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Varied Backgrounds

Expertise Gender Race Culture


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Functions of an IRB

Review Human Subjects Research

An IRB shall review and have authority to

approve, require modifications in (to secure

approval), or disapprove all research.

45 CFR 46.109 IRB review of research


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Functions of an IRB

Informed Consent

An IRB shall require that information given to

subjects as part of informed consent is in

accordance with 46.116. The IRB may require

that information, in addition to that specifically

mentioned in 46.116, be given to the subjects

when in the IRB's judgment the information

would meaningfully add to the protection of therights and welfare of subjects.



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Functions of an IRB

Basic Elements of Informed Consent Use of the word Research

Purpose

Duration of participation

Procedures

List any procedures which are experimental

Risks or discomforts

Benefits

Alternatives to participation

Description of confidentiality

Compensation

Contacts info

Voluntary HIPAA Authorization language for all studies conducted by covered entities

45 CFR46.116(a)


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Functions of an IRB

Waiver of Informed Consent

A waiver of the consent process may be granted if all 4apply:

1. The research in its entirety involves no greater thanminimal risk.

2. The waiver of informed consent will not adversely affectthe rights and welfare of the subjects.

3. It is not practicable to conduct the research without thewaiver/alteration.

4. When appropriate, subjects will be provided with

additional pertinent information after their participation.45 CFR46.116(d)


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Functions of an IRB

Documentation of Informed Consent

An IRB shall require documentation of informed

consent or may waive documentation in

accordance with 46.117.



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Functions of an IRB

Documentation of Informed Consent

Informed consent shall be documented by the

use of a written consent form approved by the

IRB and signed by the subject or the subject's

legally authorized representative.

A copy shall be given to the person signing the

form.

45 CFR 46.117 Documentation of Informed Consent


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Functions of an IRB

Documentation of Informed ConsentMay be documented as either:1. A written consent document that embodies the elements of informed consent

required by 46.116. This form may be read to the subject or the subject's legallyauthorized representative, but in any event, the investigator shall give either thesubject or the representative adequate opportunity to read it before it is signed;or

2. A short form written consent document stating that the elements of informedconsent required by 46.116 have been presented orally to the subject or thesubject's legally authorized representative. When this method is used, there shallbe a witness to the oral presentation. Also, the IRB shall approve a writtensummary of what is to be said to the subject or the representative. Only theshort form itself is to be signed by the subject or the representative. However,the witness shall sign both the short form and a copy of the summary, and theperson actually obtaining consent shall sign a copy of the summary. A copy of the

summary shall be given to the subject or the representative, in addition to acopy of the short form.

45 CFR 46.117 Documentation of Informed Consent

Functions of an IRB


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Functions of an IRB

Waiver of Documentation

of Informed ConsentA waiver of documentation of consent may be granted if eitherapply:

1. That the only record linking the subject and the research would be the

consent document and the principal risk would be potential harmresulting from a breach of confidentiality. Each subject will be askedwhether the subject wants documentation linking the subject with theresearch, and the subject's wishes will govern;

2. That the research presents no more than minimal risk of harm tosubjects and involves no procedures for which written consent isnormally required outside of the research context.

Common uses: Online surveys, Screening prior to consent

OR


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Functions of an IRB

Written Notification

An IRB shall notify investigators and the institutionin writing of its decision to approve or disapprovethe proposed research activity, or of modifications

required to secure IRB approval of the researchactivity. If the IRB decides to disapprove a researchactivity, it shall include in its written notification astatement of the reasons for its decision and give

the investigator an opportunity to respond inperson or in writing.



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Functions of an IRB

Continuing Reviews

An IRB shall conduct continuing review of

research covered at intervals appropriate to the

degree of risk, but not less than once per year.



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Full Board Approval

Primarily for research that is greater than minimal risk

or does not qualify for review by expedited procedures.

Reviewed at a convened meeting at which a majority ofthe members of the IRB are present, including at least

one member whose primary concerns are in

nonscientific areas.

Receive the approval of a majority of those members

present at the meeting.

45 CFR 46.108

IRB functions and operations


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Full Board

Institutional Review boards may specialize by review type,such as biomedical and social/behavioral.

Board will meet at a regular interval, as needed tocomplete the number of reviews in a timely manner, For

example: every month to review 10-15 items.

Chairperson conducts the meeting providing for opendiscussion of pertinent issues with each agenda item.

Coordinator will prepare agenda, manage quorum, takeminutes, provide follow-up communication with principalinvestigator.


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Expedited Review of Research

45 CFR 46.110

Expedited review procedures are for certain kinds ofresearch involving no more than minimal risk, and involveonly procedures listed in one or more of the expeditedcategories.

May be used for minor changes to already approvedresearch.

May be carried out by the IRB chairperson or one or moreexperienced IRB members.

A study may not be disapproved by expedited procedures.

There must be a process in place to keep all IRB membersadvised of research approved by expedited procedures.


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Expedited Review Categories

45 CFR 46.110

Category 1: This research is a clinical study of drugs which do not require an investigational new

drug application and does not significantly increase risks to the study population.

Category 2: This research involves the collection of blood samples by finger stick, heel stick, ear

stick, or venipuncture from healthy, non-pregnant adults or children where the amount of blood

and frequency does not exceed federal regulations for normal clinical care.

Category 3: This research involves prospective collection of biological specimens for research

purposes by noninvasive means.

Category 4: This research involves the collection of data through noninvasive procedures (notinvolving general anesthesia or sedation) routinely employed in clinical practice, excluding

procedures involving x-rays or microwaves.

Category 5: This research involves materials (data, documents, records, or specimens) that have

been collected or will be collected solely for non-research purposes.

Category 6: This research involves the collection of data from voice, video, digital, or image

recordings made for research purposes.

Category 7: This research will be performed on individual or group characteristics or behavior

(including, but not limited to, research on perception, cognition, motivation, identity, language,

communication, cultural beliefs or practices, and social behavior) or will employ a survey,

interview, oral history, focus group, program evaluation, human factors evaluation, or quality

assurance methodologies.


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45 CFR 46.110

Category 8: Continuing review of research previously approved by theconvened IRB as follows: where (i) the research is permanently closed to the enrollment of new

subjects; (ii) all subjects have completed all research-related interventions;and (iii) the research remains active only for long-term follow-up of subjects;or

where no subjects have been enrolled and no additional risks have beenidentified; or

where the remaining research activities are limited to data analysis.

Category 9: Continuing review of research, not conducted under aninvestigational new drug application or investigational device exemption

where categories two (2) through eight (8) do not apply but the IRB hasdetermined and documented at a convened meeting that the researchinvolves no greater than minimal risk and no additional risks have beenidentified.


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45 CFR 46.110

The expedited review procedure may not be usedwhere identification of the subjects and/or theirresponses would reasonably place them at risk ofcriminal or civil liability or be damaging to thesubjects financial standing, employability,insurability, reputation, or be stigmatizing, unlessreasonable and appropriate protections will be

implemented so that risks related to invasion ofprivacy and breach of confidentiality are no greaterthan minimal.


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Criteria for IRB Approval of Research

7 criteria must be met for IRB to approveresearch involving human subjects.

When some or all of the subjects are likely to be

vulnerable to coercion or undue influence, suchas children, prisoners, pregnant women, mentallydisabled persons, or economically oreducationally disadvantaged persons, additional

safeguards should be included in the study toprotect the rights and welfare of these subjects.

45 CFR 46.111


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1. Risks to Subjects are Minimized

Risks to subjects are minimized: (i) By using

procedures which are consistent with sound

research design and which do not unnecessarily

expose subjects to risk, and (ii) wheneverappropriate, by using procedures already being

performed on the subjects for diagnostic or

treatment purposes.

45 CFR 46.111


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2. Risks are Reasonable in Relation to

Benefits

Risks to subjects are reasonable in relation toanticipated benefits, if any, to subjects, and theimportance of the knowledge that may reasonablybe expected to result. In evaluating risks andbenefits, the IRB should consider only those risksand benefits that may result from the research (asdistinguished from risks and benefits of therapies

subjects would receive even if not participating inthe research).

45 CFR 46.111


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3. Equitable Selection of Subjects

In making this assessment the IRB should take into

account the purposes of the research and the

setting in which the research will be conducted and

should be particularly cognizant of the specialproblems of research involving vulnerable

populations, such as children, prisoners, pregnant

women, mentally disabled persons, or economically

or educationally disadvantaged persons.

45 CFR 46.111


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4.Informed Consent Properly Obtained

Informed consent will be sought from each

prospective subject or the subject's legally

authorized representative, in accordance with,

and to the extent required by 45 CFR 46.116.

45 CFR 46.111


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5. Documentation of Informed Consent

Informed consent will be appropriately

documented, in accordance with, and to the

extent required by 45 CFR 46.117.

45 CFR 46.111


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6. Data Monitoring

When appropriate, the research plan makes

adequate provision for monitoring the data

collected to ensure the safety of subjects.

45 CFR 46.111


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7. Privacy and Confidentiality

Protected

When appropriate, there are adequate

provisions to protect the privacy of subjects and

to maintain the confidentiality of data.

45 CFR 46.111


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Principal Investigator Responsibilities

All staff engaged in research must complete

human protections education certification and

provide documentation of appropriate

expertise for the job performed.

Supervise research staff

Monitor study for safety of subjects


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Required Documentation

45 CFR 46.115 IRB records

Requireddocumentation

kept by the IRB

Copies of allresearch

proposalsreviewed

Approvedsample

consent forms

Progressreports

submitted byinvestigators Reports of

injuries to

subjects

Scientificevaluation, if

submittedwith proposal


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Required Documentation

to be kept by the IRB, cont.A list of IRB members

Minutes of IRB meetings

Written procedures for the IRB

Records of Continuing Review activities

Copies of correspondence between the IRB and the Investigator

Statements of significant new findings provided to subjects

45 CFR 46.115 IRB records

Federal regulations require documentation be kept

for 3 years after the completion of the research.


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Useful Links and ResourcesU.S. Department of Health & Human Services Code of Federal Regulations:

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

Belmont Report: http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html

Informed Consent Checklist: http://www.hhs.gov/ohrp/policy/consentckls.html

Publication: Institutional Review Board: Management and Function, Bankert E.A., Amdur, R.J.

Human Subject Decision Charts:

http://www.hhs.gov/ohrp/policy/checklists/decisioncharts.html

USF HRPP Policies & Procedures: http://www.research.usf.edu/dric/hrpp/policy-procedure.asp
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htmlhttp://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htmlhttp://www.hhs.gov/ohrp/humansubjects/guidance/belmont.htmlhttp://www.hhs.gov/ohrp/humansubjects/guidance/belmont.htmlhttp://www.hhs.gov/ohrp/policy/consentckls.htmlhttp://www.hhs.gov/ohrp/policy/consentckls.htmlhttp://www.hhs.gov/ohrp/policy/checklists/decisioncharts.htmlhttp://www.hhs.gov/ohrp/policy/checklists/decisioncharts.htmlhttp://www.research.usf.edu/dric/hrpp/policy-procedure.asphttp://www.research.usf.edu/dric/hrpp/policy-procedure.asphttp://www.research.usf.edu/dric/hrpp/policy-procedure.asphttp://www.hhs.gov/ohrp/policy/checklists/decisioncharts.htmlhttp://www.hhs.gov/ohrp/policy/consentckls.htmlhttp://www.hhs.gov/ohrp/humansubjects/guidance/belmont.htmlhttp://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html


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Session 1 - IRB Basics - Christine Epps