Protection of Research Subjects: The IRB Process

Ethics in Patient-Oriented Research October 13, 2010

Sharon FriendDirector, OHRPP

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Overview

Charge and Function of the IRB

Conducting Risk and Benefit Assessments

Research Involving Collaborations with Other Institutions

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What is an Institutional Review Board (IRB)?

An independent internal review committee

Composed of institutional members (UCLA faculty) with relevant expertise and at least one nonaffiliated member and at least one nonscientific member

Reviews proposed human subjects in research 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?

Ensure ethical principles are applied to the conduct of research

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

Promote and facilitate the protection of the rights and welfare of human subjects in research

Support and facilitate the conduct of human research at UCLA

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What do both the IRB and the PI 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 researchAssure 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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Human Research Is…

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

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What is research?

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

Systematic Investigation: a proposed research plan that incorporates data collection & analysis

Generalizable Knowledge: designed with intent to draw general conclusions (beyond population(s) studied), inform policy, and/or disseminate findings.

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What is a Human Subject?

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.45 CFR 46.102(f)

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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 or

personally identifying information Studies using public data sets 3 or fewer individual case studies Quality improvement activities

Guidelines and decision tree on OHRPP website and short questionnaire in webIRB to assist investigators

IRB review may not be required

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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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What are the levels of IRB Review?

There are 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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What is the Best News Ever about the UCLA IRB Review

Process?

There is now a web-based on-line submission system: webIRB.

It’s much easier to submit an application. The program uses a “smart form” that walks

you through the process and provides help text on the side or within links.

Approval times are much faster! WebIRB submissions are even faster!

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What is webIRB?

Web-Based IRB Submission, Review and Tracking System

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How does it support PIs and Research Staff?

Homepage with access to information on all studies

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How does it support PIs and Research Staff?

Track status of submissions

Receive feedback and approvals online

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What Were the IRB Turnaround Times in July 2010?

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

Full Committee: 34 daysExpedited:

6 – no subject contact 12 – subject contact

Continuations: 9 – expedited 21 – full committee

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What is the focus of the IRB Review?

Assessing Risks and Benefits: Risks associated with the research, as distinguished

from the risks of procedures the subjects would receive even if not participating in research

Determining that the risks are minimized to the extent possible

Identifying the probable benefits to be derived from the research

Determining that the risks are reasonable in relation to the benefits to subjects, if any, and the importance of the knowledge to be gained

Assuring that potential subjects are provided with an accurate and fair description of the risks or discomforts and the anticipated benefits

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How do you conduct a risks assessment?

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 definition of minimal risk?

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

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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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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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Which potential risks need to be considered for all levels of

IRB review? Loss of Confidentiality

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

seek IT help if neededPrimary source of complaints to IRBs (beyond why

didn’t I get paid on time)

Loss of PrivacyHas to do with personal privacy Important in recruitment and screening as well as

practice

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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 cannot require a major change in the

science and expect the company to revise the protocol—it’s either thumbs up or thumbs down

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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 double-blind study to compare two approved surgical procedures (lumpectomy vs mastectomy)

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More Examples

Analysis and comparison of UCLA medical student socio-economic and educational background and admission records to evaluate predictors of ability to graduate

Questionnaires for parents of parents whose children have recently died from cancer to assess grief coping mechanisms

Phase IV (post marketing) Drug Study

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Examples continued

Comparison of psychotherapy vs medication for the treatment of depression

Collection of saliva samples from people who developed a cold and cough within the last 48 hours to study the genes related to asthma

Survey of physicians at UCLA to ask their opinions about physician-assisted suicidewhether they have participated in physician-assisted

suicides

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Examples continued

Analysis of facial expressions of people who are lying

Analysis of facial expressions of children who are afraid of spiders

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)

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Waves of the Future

Continued push to rely on other IRBs OHRP FDA AAHRPP CTSAs Study Sponsors Local Institutions

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What’s Currently in Place at UCLA?

UC-Wide Memorandum of Understanding (MOU) to rely on each others IRBs 2011) Being used for Expedited and Exempt Studies Used over 700 times since 2006 Plans for expanded use for Full Committee Studies in

spring 2011

CTSA MOU for Cedars, LABioMed, Charles Drew and UCLA – limited implementation but plan for expanded use in spring of 2011

Use of Federal-wide IRBs –NCI, NIDA, NICHD, others

Western IRB – commercial, pay for review

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More Waves

Revised medical consent form templates (to be used also for multi-site UC and CTSA studies)

UCLA-wide guidance on the use of remnant tissue and specimens for research

Expanded education including video-training on advanced topics in human research

Expanded use of ability to rely on other IRBs (beyond UCs and CTSAs--longer term but in planning)

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Last Minute Tips

#1 Refer to the OHRPP website for webIRB online application

Links to applicationInformation about training (monthly Noontime

Series and Learn at Lunch)

UCLA consent form templates

UCLA OHRP guidelines on various topics

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#2 Writing Musts

Consider the audience Not all IRB members are scientists Avoid acronyms Use lay language for recruitment and consent

documents Be consistent

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

and alternatives are consistent Between application and consent documents Between application and sponsor protocols or grants Use the same name for the study drugs throughout

the submission

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Final Tips

#3 Contact the OHRPP with any questions before or during the application process

#4 Bonus Tips: 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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We’re Here to Help

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

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

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