Protection of Research Participants: The IRB Process—Current Overview

and Future Directions Ethics in Patient-Oriented Research

October 17, 2012

Sharon FriendDirector, OHRPP

IRB Charge and Function

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Human Research Is…

any research or clinical investigation that involves people or identifiable data from people.

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UCLA’s Institutional Review Board (IRB)

An independent internal review committee that reviews and approves human research

Composed of UCLA faculty with relevant expertise, at least one nonscientific member, and at least one nonaffiliated member

Reviews proposed research involving human subjects conducted by UCLA faculty and students regardless of funding source and usually regardless of site

Based on federal criteria, IRB has the authority to approve, require changes or disapprove human research.

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What is the mission and charge of UCLA IRBs?

Support and facilitate the conduct of human research at UCLA by

Ensuring ethical principles are applied to the conduct of human research;

Assuring federal criteria for approval of human subjects research and institutional policies are met; and

Promoting and facilitating the protection of the rights and welfare of human subjects in research.

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What do both IRB and PI need to consider in applying the

ethical principles? Beneficence (Be nice!) – Design studies to

Minimize risk to the extent possible Maximize benefit (both individual and societal)

Respect for Persons (Be respectful!) Obtain informed consent before involving participants (or

using private identifiable information) in research Assure confidentiality provisions are in place.

Justice (Be fair!) Select participants who are likely to benefit from research

participation Do not systematically include or exclude participants for

convenience.

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What Are the Primary Federal Criteria for IRB

Approval? Risks to participants are minimized by

using procedures consistent with sound research design and which do not unnecessarily expose participants to risk.

Risks to participants are reasonable in relation to anticipated benefits, if any, to participants, and the importance of the knowledge that may reasonably be expected to result.

What Training Does IRB Require?

At UCLA, and most academic sites throughout USA: on-line CITI training Collaborative Institutional Training Initiative.

Required every three years at UCLA for IRB approval.

Plenty of additional training available (in addition to, not instead of CITI) and may be required by departments and programs

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Tips for Preparing an Excellent IRB Submission

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Tip #1: Determine if Science is Sound

Sound Scientific Basis and Rationale:  Is the protocol scientifically sound and based

on well-established scientific principles?  Is there convincing clinical and/or preclinical

evidence that the trial will have valuable results? 

Do preclinical studies demonstrate promising results regarding safety and potential efficacy? 

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Science continued…

Is proposed study design appropriate? Are the primary and secondary objectives sound?  Is the study designed to meet objectives?  Does the protocol distinguish between standard and/or routine care

and research? Are patient populations and associated criteria for

inclusion/exclusion well defined?  Is the statistical design appropriate?  Are the endpoints clearly defined?Are study personnel qualified?Are there sufficient resources to conduct the study?

Science continued…

Preferably, scientific review, by a group of peers, occurs before submitting a full committee application to the IRB. If it does not occur beforehand,

the UCLA IRB will conduct the scientific review.

Cancer Center ISPRC provides scientific review.

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Tip #2: Determine if IRB Review is

RequiredIs the project research? DHHS regulations define human research as a

systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.

FDA regulations define a clinical investigation as any experiment that involves a test article and one or more human subjects…the results of which are intended to be…submitted to…the FDA.

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Does the research involve human subjects?

DHHS: a living individual about whom an investigator (faculty or student) conducting research obtains data Through an intervention or interaction with the

individual, or

Access to identifiable, private information.FDA: an individual who becomes a participant in

research, either as a recipient of the test article or as a control

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What is not Human Research?

The following are types of studies that may not be considered human research at UCLA:

Analysis of data or specimens that do not include private health or personally identifying information (PHI or PII)

Studies using public data sets 3 or fewer individual case studies Quality improvement/assurance activities

How Do You Confirm?

Use short questionnaire in webIRB Check UCLA OHRPP Guidance and decision

trees: (http://ohrpp.research.ucla.edu/pages/policies-guidance#4): Determining Which Activities Require UCLA OHRPP/IRB Re

view Determining When Collection or Use of Data and Specimens

for Research Requires IRB Review

Call the OHRPP.

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When Is IRB Review Required?

All human subjects research requires prior IRB review and approval before initiation (New Studies)

All modifications or changes made to an IRB-approved study require IRB approval prior to initiation (Amendments)

All continuation of an IRB-approved study beyond its approval period (usually one year) requires IRB approval (Continuing Review)

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Tip #3: Assess Risk and Determine Level of Review

Identify risks associated with the research: How are risks different than those risks the subject would

encounter if not participating in the research?

Consider the subject population: Are the research participants particularly sensitive or

vulnerable to the risks posed by the research?

Do the risk(s) meet the federal definition of minimal risk?

Does research fit into an expedited category of review or does it require full committee review?

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Regulatory Definition of Minimal Risk

“Minimal risk” means that the probability and magnitude of harm or discomfort

anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life

of the general population or during the performance of routine physical or

psychological examinations or tests.

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Which potential risks need to be considered for all levels of

IRB review? Loss of Confidentiality

Has to do with issues surrounding data Data security needs to established and described—

seek IT help if needed Primary source of complaints to IRBs (beyond “Why

didn’t I get paid on time?”) Loss of Privacy

Has to do with personal privacy Important in recruitment and screening as well as

clinical practice

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What are the levels of IRB Review?

Three levels of IRB Review, depending on level of risk:

Full Committee for more than minimal risk

Expedited review for minimal risk studies

Exempt certification for studies that fall into one of six federal categories

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Expedited Research No more than minimal risk to subjects

“Expedited” protocols are reviewed by an IRB subcommittee

Seven federally-defined categories

Informed consent or waiver of consent or waiver of signed consent with appropriate justification required

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Full Committee Research

Greater than minimal risk to subjects

Full committee protocols are reviewed at a convened IRB meeting

Informed consent required in almost all cases

Includes most clinical trials: studies involving non FDA-approved drugs and devices or medical interventions

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Examples of Expedited or Full Committee Research or Research

Not Requiring IRB Review

Randomized double-blind study for the safety and efficacy of investigational drug XYZ

Review of medical records of patients in hospital from 1990 to present to study correlation of Alzheimer’s and heart disease

Randomized study to compare two approved treatment regimens for cervical cancer

Comparison of psychotherapy vs medication for the treatment of depression

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Examples continued

Study of elder abuse among caregivers Skin samples collected via punch biopsy for

SCNT (somatic cell nuclear transfer) study Skin samples sent from UCSF with or without

PHI (private health information) Collection of saliva samples from people

who developed a cold and cough within the last 48 hours to study the genes related to asthma

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Tip #4: Allow Sufficient Time for IRB Process

From time of complete submission to time of full IRB approval:

Full Committee: ~ 4 to 8 weeksExpedited:

No Subject Contact ~ 2 weeks Subject Contact ~ 4 weeks

Continuations: Expedited < two weeks Full Committee ~4 weeks

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What are the Special Issues for Industry-Sponsored Clinical

Trials? Need to coordinate IRB approval and contract Sponsor pays IRB Review Fees Consent form needs to be revised to

Use UCLA standard requirements for indemnification and ownership of tissue

Be in lay language and not overly legal Data Safety Monitoring Boards usually required IRB does not typically require a major change in

the science and expect the company to revise the protocol—review is either thumbs up or thumbs down

Tip #5: Apply for via webIRB On-Line Application

Web-based system for IRB submission, review and trackingAll levels of review use the same webIRB application with branching based on responses to questionsHelp text and links within applicationUploads of supporting materials requiredTraining available

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#6: Understand the IRB Review Process

Administrative pre-review by staff to check for completeness

IRB review (UCLA does not ask researchers to be present unless study may be disapproved)

Post Review communication of IRB actions via webIRB, including Approval Accepted pending modification Deferral Disapproval

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UCLA IRB Review Process

Triage byReview LevelReview Type

Full Committee Pre-Review

Expedited Pre-Review

Back to the PI for

Changes

To the Committee for Review

Back to the PI for

Changes

Correspondence Approval!

To the Chair or Delegate for Review

Correspondence Approval!

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#7: Use UCLA Consent Templates and Refer to

Standards Minimal Risk Consent Templates More than Minimal Risks Consent

Templates Child and Adolescent Assent Templates Addendum Consent Templates Screening Templates Consent Standards and Sample Language

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#8: Ask for Help; Use On-OHRPP References

Ask for help within department Check with OHRPP--Medical IRBs

Telephone: (310) 825-5344E-mail: MIRB@RESEARCH.UCLA.EDU

Contact webIRB Help Desk310-267-1887 webIRBhelp@research.ucla.edu

Refer to OHRPP Website: www.research.ucla.edu/ohrpp

Sign up for Human Research News

 

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Bonus Tips!

Grouping Studies Do not group related full committee studies

into a complicated application. Submit a separate application for each study or phase of study.

Do group data analysis or retrospective chart reviews into one study when useful for your purposes.

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Writing Musts Consider the audience! Avoid acronyms and jargon in protocol and consent

documents Use lay language for recruitment and consent

documentsBe consistent! Within the application Make sure that study aims, methods, risks, benefits

and alternatives are consistent Between application and consent documents Between application and funding documents Use the same name for the study drugs throughout

the submission

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Winds of Change Use of IRB Agreements to

Rely on Other IRBs Increased Interest in

Developing Informed Consent for• Use of Residual Tissue and• Use of Health Care Information for Future Unspecified Research

                                             

"The Winds of Change are Coming....

What Is an IRB Reliance Agreement?

By mutual or collective written agreement, one or several IRBs agree to rely on the IRB review of one or several other IRBs.

The agreement is typically called an “MOU” (Memorandum of Understanding).

36Particle Accelerator in Switzerland

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IRB MOUs

Outline responsibilities of PIs (Both Lead and Relying) Reviewing IRBs and Relying IRBs

Describe need for Registration for PI from relying institution

Do not provide implementation guidelines or procedures for each campus or institution

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How a Reliance Agreement Works*

Reviewing IRB assumes full

responsibility as IRB of record

reviews entire study assures local issues are

identified and addressed coordinates

communication with all PIs

Relying IRB accepts determinations

made by Reviewing IRB in their entirety

has responsibility for ensuring that ancillary approvals (MRSC, COI, IBC) are in place

*NOTE: This is model commonly used by commercial IRBs

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>Two CTSI’s Involved in IRB Reliance Agreements for UCLA Investigators

UCLA Cedars-Sinai Medical Center Charles Drew University of Medicine and Science LA Biomedical Institute at Harbor UCLA Medical Center UCLA

UC Medical Centers UC Davis UC Irvine UCLA UC San Diego UC San Francisco

How to Use the UC MOUs

General process is the same for both UC MOU and UCLA CTSI MOU but because UC process is web-based procedures are slightly different.

Review information on UCLA CTSI site for “CTSI IRB Reliance Review Process” at http://ctsi-vhome.ctrl.ucla.edu/research/pages/irb

Review information on “UC IRB Reliance Registry for Studies under the UC MOU” on UC Berkeley site at http://cphs.berkeley.edu/irbreliance.html

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Other External IRBs Available to UCLA Researchers

See OHRPP website for details: The National Cancer Institute Central

IRB (NCI CIRB) for some oncology groups studies (submit through webIRB)

Western IRB Rand Rarely, others may approved on a case-

by-case basis41

“Global Informed Consent”

Being developed at UCLA for UC medical centers for• Unspecified use of residual biological samples

and associated health care data• To be incorporated into a UCLA BioBank and• To be able to be transferred to other approved

scientific databases, i.e., NIH dGAP.• Will include study of DNA, cell lines, and

stem cells42