The IRB:The IRB:Friend or Foe?Friend or Foe?

Margaret J. Neff, MD MScMargaret J. Neff, MD MSc

Assistant Professor of MedicineAssistant Professor of Medicine

Pulmonary & Critical Care MedicinePulmonary & Critical Care Medicine

Getting things through the IRBGetting things through the IRB

• Why does it matter?Why does it matter?

• Basic requirementsBasic requirements

• Lay-out of the UW IRBLay-out of the UW IRB

• Specific scenariosSpecific scenarios• Screening, consent, database reviewsScreening, consent, database reviews

• Helpful tipsHelpful tips

Past ResearchPast Research

•1930s-40s: Nazi war1930s-40s: Nazi warcrimes & experimentscrimes & experiments

•1932-1972 Tuskegee 1932-1972 Tuskegee Syphilis ExperimentSyphilis Experiment

•1971 Stanford Prison1971 Stanford PrisonExperimentExperiment

Recent Research Recent Research

•1999 U Penn gene transfer study 1999 U Penn gene transfer study (Jesse Gelsinger); followed incl/excl (Jesse Gelsinger); followed incl/excl criteria?, safety monitoring?, criteria?, safety monitoring?, informed consent?, conflict of informed consent?, conflict of interest?interest?

•2001 Johns Hopkins asthma study 2001 Johns Hopkins asthma study (Ellen Roche); hexamethonium; who is (Ellen Roche); hexamethonium; who is responsible for researching safety? responsible for researching safety?

Common ThemesCommon Themes

• Lack of informed consentLack of informed consent

• Risk >>>>> benefitRisk >>>>> benefit

• Risk assessment not completeRisk assessment not complete

• Vulnerable populationsVulnerable populations• Students; employeesStudents; employees

• Poor safety oversightPoor safety oversight

• Conflict of interestConflict of interest

Troubled WatersTroubled Waters• PennPenn• DukeDuke• Johns HopkinsJohns Hopkins• U of Illinois-ChicagoU of Illinois-Chicago• U ColoradoU Colorado• West LA VAWest LA VA• Rush PresbyterianRush Presbyterian• VirginiaVirginia

• Not a list we want to join……Not a list we want to join……

Ethical Codes Guiding Clinical Ethical Codes Guiding Clinical Research (Human Research)Research (Human Research)

• Nuremberg Code: 1947Nuremberg Code: 1947

• Declaration of Helsinki: 1964Declaration of Helsinki: 1964

• The Belmont Report: 1979The Belmont Report: 1979

Regulations Pertaining to Regulations Pertaining to Clinical ResearchClinical Research

• U.S. Code of Federal RegulationsU.S. Code of Federal Regulations• Health and Human Services Health and Human Services

• 45 CFR 46 (protection of human subjects)45 CFR 46 (protection of human subjects)

• Food and Drug AdministrationFood and Drug Administration• 21 CFR 50 (protection of human subjects)21 CFR 50 (protection of human subjects)• 21 CFR 56 (institutional review boards)21 CFR 56 (institutional review boards)

• State Law State Law • Washington Administrative Code (WAC)Washington Administrative Code (WAC)

• Institutional policies, sponsorInstitutional policies, sponsor

Criteria for approval Criteria for approval of researchof research

• Risks minimized and reasonable in Risks minimized and reasonable in relation to anticipated benefitsrelation to anticipated benefits

• Subject selection is equitableSubject selection is equitable• Informed consent soughtInformed consent sought• Informed consent documentedInformed consent documented• Plan data safety monitoringPlan data safety monitoring• Provisions for privacy/ confidentialityProvisions for privacy/ confidentiality• Additional safeguards for vulnerable Additional safeguards for vulnerable

populationspopulations

www.access.gpo.gov/nara/cfr

Design of IRBDesign of IRB

• At least 5 membersAt least 5 members• Varying backgrounds, genderVarying backgrounds, gender• At least 1 scientist & 1 non-scientistAt least 1 scientist & 1 non-scientist• At least 1 not affiliated with At least 1 not affiliated with

institutioninstitution• No conflict of interest with study No conflict of interest with study

reviewingreviewing• May invite consultants to reviewMay invite consultants to review

www.access.gpo.gov/nara/cfr

Univ. of Washington IRBUniv. of Washington IRB

• Multidisciplinary membershipMultidisciplinary membership• MDs, RNs, pharmacists, lawyers, students, MDs, RNs, pharmacists, lawyers, students,

community memberscommunity members

• 6500 protocols reviewed/year6500 protocols reviewed/year• 10 committees10 committees• 3 biomedical, 3 behavioral, 3 minimal risk, 1 VA3 biomedical, 3 behavioral, 3 minimal risk, 1 VA• Full-time staff but other members are primarily Full-time staff but other members are primarily

volunteering their timevolunteering their time

• Western IRB: now used for all industry-Western IRB: now used for all industry-sponsored trialssponsored trials

When do you need IRB When do you need IRB approval?approval?

• When you’re conducting “human subjects When you’re conducting “human subjects research”research”• Any study where results are intended for Any study where results are intended for

dissemination as research (vs QI)dissemination as research (vs QI)• Patient info or patient samplesPatient info or patient samples

• Waiver of consent possible in some Waiver of consent possible in some instances:instances:• De-identified dataDe-identified data

• 18 specific data points removed 18 specific data points removed • Limited data setLimited data set• Meet specific criteria (emerg research; records Meet specific criteria (emerg research; records

review, etc)review, etc)

Types of ReviewTypes of Review

• Full committee reviewFull committee review• Most studiesMost studies

• Expedited reviewExpedited review• Generally only for database/registry Generally only for database/registry

workwork• No patient contact, no interventionsNo patient contact, no interventions• Using data already availableUsing data already available• May qualify for certificate of exemptionMay qualify for certificate of exemption

General Issues Prior to General Issues Prior to ReviewReview

• Do you have the resources to do it?Do you have the resources to do it?• Coordinator? Funds? Enough time?Coordinator? Funds? Enough time?

• Any financial conflict of interest?Any financial conflict of interest?• Taken ethics/IRB training?Taken ethics/IRB training?• Required for NIH and VA studies; soon Required for NIH and VA studies; soon

for all UW studiesfor all UW studies

• Clinical Research Budget & BillingClinical Research Budget & Billing• Made contactMade contact

The IRB Submission The IRB Submission ProcessProcess

• Complete application, get dept signaturesComplete application, get dept signatures• Submit application (include a cover letter with Submit application (include a cover letter with

a “howdy, here’s what we’re doing” and a “howdy, here’s what we’re doing” and address any anticipated problem points; brief)address any anticipated problem points; brief)

• Once at the IRB:Once at the IRB:• Pre-screeningPre-screening• Full review with deferral or approvalFull review with deferral or approval• Committee letterCommittee letter• Your responseYour response• Re-evaluated in sub-committeeRe-evaluated in sub-committee• Back to full committee, hopefully to approveBack to full committee, hopefully to approve

Who is it you’re hearing Who is it you’re hearing from?from?

• Each committee:Each committee:• Chair, members, administrator, and coordinatorsChair, members, administrator, and coordinators

• The administrator pre-screens the study and The administrator pre-screens the study and often contacts you for clarifications prior to often contacts you for clarifications prior to first reviewfirst review• Get to know this personGet to know this person• If complex study, go and meet If complex study, go and meet • Offer to come to the committee meeting (or be Offer to come to the committee meeting (or be

available by phone) if anticipated available by phone) if anticipated questions/problemsquestions/problems

• Be nice and not defensiveBe nice and not defensive

Some common pitfallsSome common pitfalls• Application should be understandable to Application should be understandable to

an educated, lay audience (the IRB an educated, lay audience (the IRB members)members)

• Avoid lots of cutting and pasting of textAvoid lots of cutting and pasting of text• Be organized! Be consistent.Be organized! Be consistent.• Make it easy to read (not tiny font)Make it easy to read (not tiny font)• Think of it like a grant you’re submittingThink of it like a grant you’re submitting

• Be thorough and follow the instructionsBe thorough and follow the instructions• Appropriate # copies, answer all questionsAppropriate # copies, answer all questions

• If you don’t know what they mean, ask!If you don’t know what they mean, ask!

Screening/RecruitmentScreening/Recruitment

• Screening for potential subjectsScreening for potential subjects• Waiver of consent for screeningWaiver of consent for screening• Confidentiality agreementConfidentiality agreement• Need to report each time access chartNeed to report each time access chart

• RecruitmentRecruitment• Include any flyers or website noticesInclude any flyers or website notices• Generally try to allow potential subjects Generally try to allow potential subjects

to call you rather than “cold calls.”to call you rather than “cold calls.”

Subject approachSubject approach

• Avoid any appearance of coercionAvoid any appearance of coercion• Initial introduction by non-research Initial introduction by non-research

personnelpersonnel• Ideally have clinical personnel separate Ideally have clinical personnel separate

from research personnelfrom research personnel

Privacy/ConfidentialityPrivacy/Confidentiality

• Minimize identifiable information on data Minimize identifiable information on data collection forms; no namescollection forms; no names• No identifiable elements on screened, non-No identifiable elements on screened, non-

enrolled (non-consented) subjectsenrolled (non-consented) subjects

• Describe mechanism for safeguarding Describe mechanism for safeguarding datadata

• Plan for destruction of any links and the Plan for destruction of any links and the data as soon as possible (but feasible)data as soon as possible (but feasible)

Risks and BenefitsRisks and Benefits• Don’t exaggerate the benefitsDon’t exaggerate the benefits• Be honest about the risksBe honest about the risks• Usually “death” is always a risk in any Usually “death” is always a risk in any

intervention studyintervention study• Often useful to group by common and rare Often useful to group by common and rare

risksrisks• How you’ll deal with any adverse eventsHow you’ll deal with any adverse events• Who pays?Who pays?

• Who pays for research studies?Who pays for research studies?• In most cases, it’s the sponsorIn most cases, it’s the sponsor• For NIH or investigator initiated: UW For NIH or investigator initiated: UW

Compensation planCompensation plan

ConsentConsent

• Utilize the consent template (some Utilize the consent template (some standard wording and sections)standard wording and sections)• Assent form for children as wellAssent form for children as well

• Language:Language:• 88thth grade reading level grade reading level• ““Subject” not “patient”Subject” not “patient”

• Go through consent checklistGo through consent checklist

Obtaining ConsentObtaining Consent

• Subject needs adequate time and Subject needs adequate time and information to make a decisioninformation to make a decision

• Competency must be assessedCompetency must be assessed• If limited, at minimum need assentIf limited, at minimum need assent

• Consent is invalid if subject is Consent is invalid if subject is pressured or coercedpressured or coerced

• Ideally assess comprehensionIdeally assess comprehension

Who Can Consent?Who Can Consent?• Subject him or herselfSubject him or herself• Legally authorized representativeLegally authorized representative• This varies state-to-state whether allowed and This varies state-to-state whether allowed and

what order is followedwhat order is followed• In Washington, it’s based on WAC guiding clinical In Washington, it’s based on WAC guiding clinical

decision making, extrapolated to researchdecision making, extrapolated to research• Guardian, Subject, DPOA-HC, spouse, adult Guardian, Subject, DPOA-HC, spouse, adult

children, parents, adult siblingschildren, parents, adult siblings• Who consents for clinical procedures may vary but for Who consents for clinical procedures may vary but for

research, this order is strictly adhered toresearch, this order is strictly adhered to• Recent changes clinically for domestic partnersRecent changes clinically for domestic partners

Waived Consent for Waived Consent for Emergency ResearchEmergency Research

• ““Should the needs of the many ever Should the needs of the many ever outweigh the needs of the one?”outweigh the needs of the one?”

• Waived consent (e.g. pre-hospital, MI, stroke)Waived consent (e.g. pre-hospital, MI, stroke)• Specific criteria must be met and documentedSpecific criteria must be met and documented• If criteria for waived consent are metIf criteria for waived consent are met

• No more than minimal riskNo more than minimal risk• Will not adversely affect rights of subjectsWill not adversely affect rights of subjects• Research not practical without waiverResearch not practical without waiver• Provide info to subjects at later dateProvide info to subjects at later date

• May require survey and notification of communityMay require survey and notification of community

Other IssuesOther Issues

• Federal Certificate of ConfidentialityFederal Certificate of Confidentiality• If “sensitive” questions about drug and If “sensitive” questions about drug and

alcohol abusealcohol abuse

• Vulnerable subjectsVulnerable subjects• Prisoners, pregnant women, childrenPrisoners, pregnant women, children

• Registration of clinical trialsRegistration of clinical trials

Tips for Interacting Tips for Interacting with the IRBwith the IRB

• They are there to help you and to protect They are there to help you and to protect the subjects and the ability to do research the subjects and the ability to do research here at all!here at all!• Research is a privilege, not a rightResearch is a privilege, not a right

• Be prompt in responsesBe prompt in responses• Be cordialBe cordial

• May not be consistent committee to May not be consistent committee to committeecommittee• Each is independent but this is Each is independent but this is

improving; moving towards sending all improving; moving towards sending all of 1 type of specialized study to 1 of 1 type of specialized study to 1 committeecommittee

• There may be delays and lots of questions There may be delays and lots of questions that seem not relevantthat seem not relevant• They’re trying to best understand the studyThey’re trying to best understand the study• If you don’t understand what they’re getting at, If you don’t understand what they’re getting at,

call them. Maybe they didn’t understand call them. Maybe they didn’t understand something you’re trying to do.something you’re trying to do.

• Offer to meet the administrator or go to the Offer to meet the administrator or go to the meeting. Resolve the problems up front.meeting. Resolve the problems up front.

• Try to explain your intentTry to explain your intent

ResourcesResources

• IRB website:IRB website:• http://www.washington.edu/research/hsd/http://www.washington.edu/research/hsd/

• Clinical Research Budget & Billing:Clinical Research Budget & Billing:• http://http://www.uwmedicine.orgwww.uwmedicine.org/Research/ /Research/

ResearchBudgetBillingResearchBudgetBilling//

• HIPPA resources:HIPPA resources:• http://privacyruleandresearch.nih.gov/http://privacyruleandresearch.nih.gov/• http://http://www.hhs.gov/ocr/hipaawww.hhs.gov/ocr/hipaa//

• Me: Me: mneff@u.washington.edumneff@u.washington.edu