Welcome to the IRBWelcome to the IRB

IRB ORIENTATION IRB ORIENTATION

New Member New Member

Helen Panageas, CIPAssociate Director

NYU School of MedicineNYU School of Medicine

INSTITUTIONAL REVIEW BOARDINSTITUTIONAL REVIEW BOARD

www.med.nyu.edu/irb

What we will Cover Today What we will Cover Today What is the IRB What is the IRB ……and how does the IRB work?and how does the IRB work? Mechanics: the process…Mechanics: the process…

10 minute BREAK10 minute BREAK Mechanics: how to review a protocol, review Mechanics: how to review a protocol, review

strategies and meeting timestrategies and meeting time10 minute BREAK10 minute BREAK

History and RegulationsHistory and Regulations Research ethics & essence/spirit –a bit distilledResearch ethics & essence/spirit –a bit distilled Commonly Vexing DetailsCommonly Vexing Details Wrap – Up: Questions, issues, considerations, Wrap – Up: Questions, issues, considerations,

and last words….and last words….

What is an IRB?What is an IRB?

An Institutional Review Board (IRB) is a An Institutional Review Board (IRB) is a group of people formallygroup of people formally designated (by designated (by feds and Institution) to review and monitor feds and Institution) to review and monitor research involving human subjects. research involving human subjects.

Direct arm of the federal government Direct arm of the federal government when it comes to protection of human when it comes to protection of human subjectssubjects

New York University School of Medicine New York University School of Medicine has three IRBshas three IRBs

What is the IRB?What is the IRB?

The purpose of the IRB is to The purpose of the IRB is to protect protect the rights and welfarethe rights and welfare of individuals of individuals who are participating as subjects in who are participating as subjects in research. research.

The IRB has the authority to The IRB has the authority to approve, approve, disapprove, and require disapprove, and require modificationsmodifications to research projects to research projects involving human subjects.involving human subjects.

What is an IRB?What is an IRB?

Federal Government says: Federal Government says: An Institutional Review Board is a An Institutional Review Board is a federally mandated group required to federally mandated group required to review and approve human research review and approve human research projects in accordance with projects in accordance with Title 45 Title 45 Public Welfare DHHS, PART 46 PROTECTION Public Welfare DHHS, PART 46 PROTECTION OF HUMAN SUBJECTS and FDA regulated OF HUMAN SUBJECTS and FDA regulated studies in accordance with TITLE 21 FOOD studies in accordance with TITLE 21 FOOD AND DRUGS, PART 50 PROTECTION OF AND DRUGS, PART 50 PROTECTION OF HUMAN SUBJECTS, PART 56 INSTITUTIONAL HUMAN SUBJECTS, PART 56 INSTITUTIONAL REVIEW BOARDSREVIEW BOARDS

Federal Wide AssuranceFederal Wide Assurance

NYU SoM holds a NYU SoM holds a Federal wide Federal wide Assurance (FWA)Assurance (FWA) 0000495200004952

The FWA assures that the Institution The FWA assures that the Institution will be compliant with the federal will be compliant with the federal regulations for the protection of regulations for the protection of human subjects for all research human subjects for all research regardless of funding sourceregardless of funding source

The FWA is also approved by OHRPThe FWA is also approved by OHRP

IRB MembershipIRB Membership

At least 5 membersAt least 5 members

IRB shall include at least IRB shall include at least one memberone member whose primary concerns are in whose primary concerns are in scientific scientific areasareas and at least and at least one memberone member whose whose primary concerns are in primary concerns are in nonscientific nonscientific areasareas..

Federal Regulations at 45 CFR 46.107Federal Regulations at 45 CFR 46.107

IRB MembershipIRB Membership(Continued)(Continued)

IRB shall include at least IRB shall include at least one one membermember who is who is not otherwise not otherwise affiliatedaffiliated with the institution and who with the institution and who is not part of the immediate family of is not part of the immediate family of a person who is affiliated with the a person who is affiliated with the institution.institution.

Federal Regulations at 45 CFR 46.107(d) Federal Regulations at 45 CFR 46.107(d)

IRB MembershipIRB Membership(Continued)(Continued)

Consultant as ReviewersConsultant as ReviewersAn IRB may, in its discretion, invite An IRB may, in its discretion, invite individuals with competence in special individuals with competence in special areas to assist in the review of issues which areas to assist in the review of issues which require expertise beyond or in addition to require expertise beyond or in addition to that available on the IRB. These individuals that available on the IRB. These individuals may not vote with the IRB.may not vote with the IRB.

Federal regulations at 45 CFR 46.107(f)Federal regulations at 45 CFR 46.107(f)

The Individual IRB MemberThe Individual IRB Member

It’s tough job but you add to the processIt’s tough job but you add to the process

Your unique professional and personal Your unique professional and personal perspective.perspective.

This includes your This includes your scientific, social, ethical, scientific, social, ethical, community, minority, legal, administrative or community, minority, legal, administrative or operationaloperational perspectives, maybe all of these. perspectives, maybe all of these.

The Individual IRB MemberThe Individual IRB Member

Members must attend a minimum of Members must attend a minimum of ten meetings annually, ten meetings annually,

should attend all meetings for which should attend all meetings for which they are scheduled. they are scheduled.

If a member is unable to attend a If a member is unable to attend a scheduled meeting, that member scheduled meeting, that member should inform the IRB Chair, Vice should inform the IRB Chair, Vice Chair, or an IRB Office staff member. Chair, or an IRB Office staff member.

The IRB as a Privacy BoardThe IRB as a Privacy Board

At NYU SoM At NYU SoM

The IRB is the Privacy BoardThe IRB is the Privacy Board

What does that mean? What does that mean? The IRB makes all HIPAA findingsThe IRB makes all HIPAA findings

How does it Work?How does it Work?

Human Subjects Protection is a Shared

Responsibility

IRB Investigator/Researcher

Institution

Team ApproachTeam Approach

InstitutionalOfficial

PrincipalInvestigator

Co-Investigator Co-Investigator

ResearchCoordinator

Human ProtectionsAdministrator

Other Associates

Institutional Review Board Infrastructure

IRB Chair

IRB Members

Research Team

Institutional Official Institutional Official obligations:obligations:

Sets tone for culture for respect of human Sets tone for culture for respect of human subjectssubjects

Serves as Signatory official on Federa-lwide Serves as Signatory official on Federa-lwide AssuranceAssurance

Is Knowledgeable contact for OHRP/FDAIs Knowledgeable contact for OHRP/FDA Ensures effective communication and Ensures effective communication and

access to human subject informationaccess to human subject information Ensures investigators fulfill responsibilitiesEnsures investigators fulfill responsibilities Facilitates educational activitiesFacilitates educational activities Holds administrative responsibilities which Holds administrative responsibilities which

includeinclude appoint IRB members and chairappoint IRB members and chair provide IRB with resources and staffprovide IRB with resources and staff support IRB authority and decisionssupport IRB authority and decisions

Institutional Obligations:Institutional Obligations: Assure that the IRB has necessary resources to support the Assure that the IRB has necessary resources to support the

review of human subject research at the institutionreview of human subject research at the institution

Assure autonomy of IRB decision making processAssure autonomy of IRB decision making process

Provide education and training in the responsible conduct of Provide education and training in the responsible conduct of research for all researchers and key personnelresearch for all researchers and key personnel

Develop policies and procedures to administer human subject Develop policies and procedures to administer human subject programprogram

Ensure assurances are in place and certification of IRB review Ensure assurances are in place and certification of IRB review submitted (include collaborating performance sites)submitted (include collaborating performance sites)

Implement oversight to ensure compliance with regulationsImplement oversight to ensure compliance with regulations

Promptly correct any situations of non-compliance with rules Promptly correct any situations of non-compliance with rules and regulations which could jeopardize research, funding, or and regulations which could jeopardize research, funding, or reputationreputation

IRB Chair role:IRB Chair role: Full knowledge of regulations and their applicationFull knowledge of regulations and their application Maintain current knowledge of trends and changes in Maintain current knowledge of trends and changes in

protection requirementsprotection requirements Convene IRB meetingsConvene IRB meetings Perform review functions as needed for new, and Perform review functions as needed for new, and

continuing researchcontinuing research Assist institution in review of non-complianceAssist institution in review of non-compliance Perform “expedited review” and/ or designate Perform “expedited review” and/ or designate

experienced reviewersexperienced reviewers Assist in the education and development of IRB membersAssist in the education and development of IRB members Assure that documentation (minutes etc.) adhere to Assure that documentation (minutes etc.) adhere to

regulatory requirementsregulatory requirements Assure that Assure that all members have equal voiceall members have equal voice in meeting in meeting

deliberations and votingdeliberations and voting Keep deliberations of IRB confidentialKeep deliberations of IRB confidential

IRB panel IRB panel obligations:obligations:

Apply the rules and regulations to specific Apply the rules and regulations to specific projects/protocolsprojects/protocols

Provide constructive review of research proposals Provide constructive review of research proposals (in a timely manner)(in a timely manner)

Assist with education of research communityAssist with education of research community Respond to staff requests for attendance and Respond to staff requests for attendance and

informationinformation Communicate new developments to research Communicate new developments to research

communitycommunity Seek outside consultation when lacking expertiseSeek outside consultation when lacking expertise Model exemplary research behaviorModel exemplary research behavior

IRB member roles:IRB member roles: Full knowledge of regulations and their Full knowledge of regulations and their

applicationapplication Maintain current knowledge of trends and Maintain current knowledge of trends and

changes in protection requirementschanges in protection requirements Attend IRB meetingsAttend IRB meetings Perform review functions as needed for Perform review functions as needed for

new, and continuing researchnew, and continuing research Perform “expedited review” if designatedPerform “expedited review” if designated Keep deliberations of IRB confidentialKeep deliberations of IRB confidential

Principal Investigator Principal Investigator ObligationsObligations

Protect Human Subjects Protect Human Subjects Know and apply rules and regulationsKnow and apply rules and regulations Apply for prospective IRB approvalApply for prospective IRB approval Follow dictates of IRBFollow dictates of IRB Report unanticipated problems to IRBReport unanticipated problems to IRB Report changes in research activities Report changes in research activities

and ensure changes not initiated and ensure changes not initiated without IRB approval (except to without IRB approval (except to eliminate immediate hazard to eliminate immediate hazard to subject)subject)

Provide continuing reports of researchProvide continuing reports of research Obtain informed consent/assent Obtain informed consent/assent Retain records as required by Retain records as required by

regulation regulation Train and supervise research team Train and supervise research team

and associatesand associates

IRB Autonomy and SupportIRB Autonomy and Support

Autonomy of IRB decision Autonomy of IRB decision making is mandated by making is mandated by regulation and assured by regulation and assured by the institution through the the institution through the Federalwide assurance. Federalwide assurance. (FWA)(FWA)

In essence, the IRB is a In essence, the IRB is a franchise of the federal franchise of the federal agencies, OHRP and FDA agencies, OHRP and FDA when operating as a duly when operating as a duly constituted IRB.constituted IRB.

Review by InstitutionReview by Institution45 CFR 46.112 and 21 CFR 56.11245 CFR 46.112 and 21 CFR 56.112

Research may be subject to “further Research may be subject to “further appropriate review and approval or appropriate review and approval or disapproval by officials of the disapproval by officials of the institution. institution. However, these officials However, these officials may not approve the research if it may not approve the research if it has not been approved by an IRB. has not been approved by an IRB.

System IntegritySystem Integrity Team system is based on trust and open Team system is based on trust and open

communicationcommunication Issues and problems should be openly Issues and problems should be openly

reviewed and addressedreviewed and addressed Complaints or problems should be Complaints or problems should be

handled fairly and efficientlyhandled fairly and efficiently The Primacy of the Rights and Welfare of The Primacy of the Rights and Welfare of

subjects should guide us all decisionssubjects should guide us all decisions

How does it work? How does it work? Basically:Basically:

Protocols submitted for review Protocols submitted for review IRB Admin Office processes reviewIRB Admin Office processes review

Reviews to ensure conformity to regulations and Reviews to ensure conformity to regulations and NYU policyNYU policy

Forwards all ‘full’ board reviews up to board Forwards all ‘full’ board reviews up to board IRB meets once a month (sometimes more by IRB meets once a month (sometimes more by

teleconference) to review and make decisions teleconference) to review and make decisions on new research and the continuation of on new research and the continuation of researchresearch

IRB also may, at times, have to make tough IRB also may, at times, have to make tough decision – disapprove, suspend, terminate decision – disapprove, suspend, terminate etc..etc..

How does it work? How does it work? In detail:In detail:

That is what we will discuss todayThat is what we will discuss todayHow this IRB worksHow this IRB worksYour responsibilities as a memberYour responsibilities as a memberHistory of research and the History of research and the development of regulations and development of regulations and ethical principlesethical principles

MechanicsMechanics Background Background

Types of review Types of review How Review is determinedHow Review is determined

Some IRB speak Some IRB speak The ProcessThe Process

Meeting materialsMeeting materials What happens at the meetingWhat happens at the meeting

Meeting TimeMeeting Time QuorumQuorum Voting and COIsVoting and COIs Review Process at the meeting and the Review Process at the meeting and the

Belmont Belmont

Types of IRB ReviewTypes of IRB Review

ExpeditedExpedited

FullFull

ExemptExempt

How is Review Type How is Review Type Determined?Determined?

Four Basic Questions:Four Basic Questions:

1.1. Is the Proposed project Is the Proposed project Research?Research?

2.2. Does the proposed project involve Does the proposed project involve Human Subjects?Human Subjects?

3.3. What type of What type of RiskRisk is involved in the is involved in the proposed project?proposed project?

4.4. Does the proposed project meet the Does the proposed project meet the criteria for the criteria for the Review CategoryReview Category??

ResearchResearch is defined as a is defined as a systematic systematic investigationinvestigation, including research , including research

development, testing and evaluation, development, testing and evaluation, designed to develop or contributedesigned to develop or contribute to to

generalizable knowledge.generalizable knowledge.

Is the Proposed Project Is the Proposed Project ResearchResearch??

Are Are Human SubjectsHuman Subjects involved ?involved ?

Human subjectHuman subject means a means a living individualliving individual about whom an investigator (whether about whom an investigator (whether professional or student) professional or student) conducting conducting researchresearch obtains obtains

(1)(1) Data through Data through intervention or intervention or interactioninteraction with the individual, or with the individual, or

(2)(2) Identifiable private informationIdentifiable private information. .

What is the Type of What is the Type of RiskRisk??

Minimal RiskMinimal Risk is defined as is defined asthe probability and the probability and magnitude of harm or magnitude of harm or discomfortdiscomfort anticipated in the proposed anticipated in the proposed research are not greater, in and of research are not greater, in and of themselves than those themselves than those ordinarily ordinarily encountered in daily lifeencountered in daily life or or during the performance of routine physical during the performance of routine physical or psychological examinations or tests.or psychological examinations or tests.

Review CategoriesReview Categories

Three Review Types:Three Review Types:

Full, Expedited, ExemptFull, Expedited, Exempt

Only Only

Expedited Expedited

& Exempt & Exempt

have Review Categorieshave Review Categories

The level of review depends on The level of review depends on the risk to the human the risk to the human

participants.participants.

Review Continuum

Risk: Low Minimal Higher

Review: Exempt Expedited Full

Informed Consent: None May be Waived Required

Review DeterminationsReview Determinations

Who makes it?Who makes it? PIPI Designees of the ChairDesignees of the Chair

What does it mean?What does it mean? Exempt- review by designeeExempt- review by designee Expedited- review by designee Expedited- review by designee Full Board- IRB meeting reviewFull Board- IRB meeting review

And then there’s ………And then there’s ………

HIPAA

PHIPHI18 Identifiers18 Identifiers

Names/InitialsNames/Initials Postal Address Postal Address Dates (DOB, DOA, DOD)Dates (DOB, DOA, DOD) Telephone numbersTelephone numbers Fax numbersFax numbers E-mail addressE-mail address Social Security NumberSocial Security Number Medical Record NumberMedical Record Number Health Plan NumbersHealth Plan Numbers Account NumbersAccount Numbers

Certificate/License Certificate/License numbersnumbers

VIN including license plate VIN including license plate numbersnumbers

Device identifiers Device identifiers Web URLsWeb URLs Internet Protocol addressInternet Protocol address Biometric identifiersBiometric identifiers Photographs and Photographs and

comparable imagescomparable images Any other unique Any other unique

identifying number, identifying number, characteristic, or characteristic, or codecode

Some IRB Speak Some IRB Speak AE- Adverse Event AE- Adverse Event CFR - Code of Federal Regulations CFR - Code of Federal Regulations CIP- Certified IRB Professional CIP- Certified IRB Professional COG- Children’s Oncology GroupCOG- Children’s Oncology Group COI- Conflict of Interest COI- Conflict of Interest DSMB - Data Safety Monitoring Board DSMB - Data Safety Monitoring Board GOG- Gynecologic Oncology Group GOG- Gynecologic Oncology Group HDE- Humanitarian Device ExemptionHDE- Humanitarian Device Exemption HIPAA- Health Insurance Portability and Accountability HIPAA- Health Insurance Portability and Accountability

Act Act UAP- Unanticipated ProblemUAP- Unanticipated Problem PHI – Private/Protected/Public Health PHI – Private/Protected/Public Health

Information Information

The Process

Mechanics of the processMechanics of the process

About 2 weeks prior to the meeting, About 2 weeks prior to the meeting, an RSVP is sent via email.an RSVP is sent via email. If you don’t use your email, give us an If you don’t use your email, give us an

alternative method by which to alternative method by which to communicate with you.communicate with you.

If you are an alternate you are If you are an alternate you are expected to attend if the member expected to attend if the member you are assigned, can not attend.you are assigned, can not attend.

Your Review MaterialsYour Review Materials Applications, attestations, signaturesApplications, attestations, signatures Protocol summary – lay summaryProtocol summary – lay summary Detailed protocol – typically authored by Detailed protocol – typically authored by

sponsor or the PIsponsor or the PI Recruitment materials: ads, letters, flyersRecruitment materials: ads, letters, flyers Diaries, information sheetsDiaries, information sheets Consent and assent documentsConsent and assent documents NIH grant document NIH grant document Drug/device brochuresDrug/device brochures Additional review requirements: Nursing, Additional review requirements: Nursing,

Biomedical Engineering, Radiation SafetyBiomedical Engineering, Radiation Safety

Your Review MaterialsYour Review Materials Initially daunting but you’ll soon be Initially daunting but you’ll soon be

able to move through them quickly.able to move through them quickly. Check your assignments.Check your assignments. If you are primary or secondary – read If you are primary or secondary – read

in depth.in depth. Otherwise, review the protocol Otherwise, review the protocol

summary, the consent forms and any summary, the consent forms and any advertisements.advertisements.

Feel free to add to any discussion Feel free to add to any discussion regardless of your assignment.regardless of your assignment.

Your Review MaterialsYour Review Materials The Reviewer’s ChecklistThe Reviewer’s Checklist

Why was it created?Why was it created? FunctionFunction Do you need to fill it out?Do you need to fill it out? Do you need to hand it in?Do you need to hand it in?

BREAK BREAK

How to PrepareHow to Prepare

Who Is the IRB Again?Who Is the IRB Again?

Human subjects protection committee Human subjects protection committee Scientific reviewScientific review Ethical reviewEthical review

NOT A DSMBNOT A DSMB NOT the OCT or SPANOT the OCT or SPA NOT Research ComplianceNOT Research Compliance

Do a little Quality Control

The IRB, reviewing from the principal perspective of human protection, begins with a scientifically sound

clinical trial

Bad science = bad clinical trial

Good science ≠ good clinical trial

Who is Vulnerable?

Populations: Pregnant women,

Prisoners, Children, Mentally Disabled

persons, Economically or educationally disadvantaged persons

What about: limited English proficiency, employees, students, end-of life cases, etc. ???

What Must be Done? Always consider

vulnerability of individuals/groups (PI protocol/application and IRB review)

Document considerations where practical/notable (PI protocol/application and IRB review)

Document required findings (IRB level only): Pregnant women Prisoners Children

The research involves VULNERABLE research participants

any time some or all of the subjects are likely to bevulnerable to coercion or undue influence.

IRB Review RequirementsIRB Review Requirements

In order for a project to receive IRB In order for a project to receive IRB approval the IRB Board and reviewers approval the IRB Board and reviewers must review and document certain must review and document certain findings according to the Federal findings according to the Federal Regulations. Regulations.

Research CANNOT be approved unless Research CANNOT be approved unless these findings can be made.these findings can be made.

Regulatory RequirementsFor IRB Approval45 CFR 46.111

Minimized risksReasonable risk/benefit ratioEquitable subject selectionInformed consent processInformed consent documentationData monitored for safetyConfidentiality/privacy maintainedVulnerable populations protected

Regulations and GuidelinesRegulations and Guidelines

HHS Regulations 45 CFR Part 46 HHS Regulations 45 CFR Part 46 FDA: CFR 21 Parts 50, 56, 312, 812FDA: CFR 21 Parts 50, 56, 312, 812 ICH Good Clinical PracticeICH Good Clinical Practice

The regulations are open to interpretationThe regulations are open to interpretation 45 CFR 46, OHRP is the interpreter45 CFR 46, OHRP is the interpreter 21 CFR and it subparts are interpreted by 21 CFR and it subparts are interpreted by

the FDA the FDA

SubpartsSubparts

Three subparts under HHS Three subparts under HHS regulations regulations Subpart B – Fetus, Pregnant Women, In Subpart B – Fetus, Pregnant Women, In

Vitro and neonates of uncertain viabilityVitro and neonates of uncertain viability Subpart C - PrisonersSubpart C - Prisoners Subpart D – ChildrenSubpart D – Children

Subparts under FDA regulationsSubparts under FDA regulations Subpart D - Children Subpart D - Children

ConsentConsentInformed Consent DocumentsInformed Consent Documents NYU SoM IRB standard templateNYU SoM IRB standard template

TitleTitle PurposePurpose # of Subjects to participate – at NYU and in total # of Subjects to participate – at NYU and in total

(multicenter)(multicenter) Description of ProceduresDescription of Procedures CostsCosts RisksRisks BenefitsBenefits AlternativesAlternatives Confidentiality –including Authorization to use PHIConfidentiality –including Authorization to use PHI Treatment for injuryTreatment for injury Voluntary Participation and WithdrawalVoluntary Participation and Withdrawal Permission to contact for future researchPermission to contact for future research Contact information – for more information or question on Contact information – for more information or question on

rightsrights HIV Reporting Disclosure HIV Reporting Disclosure

ConsentConsent

Research that Requires ConsentResearch that Requires Consent Greater than minimal riskGreater than minimal risk Practicable to obtain consentPracticable to obtain consent Identifiers being collected- AuthorizationIdentifiers being collected- Authorization

Research that MayResearch that May Not Not Require Require ConsentConsent

Minimal RiskMinimal Risk Impracticable to obtain consentImpracticable to obtain consent Anonymous information collectedAnonymous information collected No identifiers collectedNo identifiers collected

HIPAA

The Authorization is combined with the The Authorization is combined with the consent formconsent form

What does that mean? What does that mean? Subject sign only one document not twoSubject sign only one document not two

Elements of a ProtocolElements of a Protocol Background Background Project Description including Specific Project Description including Specific

AimsAims Literature Review Literature Review Rationale Rationale Inclusion/Exclusion CriteriaInclusion/Exclusion Criteria MethodsMethods Risks and BenefitsRisks and Benefits Primary and Secondary OutcomesPrimary and Secondary Outcomes Statistical AnalysisStatistical Analysis Informed Consent Process or Waiver infoInformed Consent Process or Waiver info

Background and Specific Background and Specific AimsAims

Should contain a summary of previous Should contain a summary of previous work and rationale for the studywork and rationale for the study

May be a cut and paste from the NIH grantMay be a cut and paste from the NIH grant

References should be includedReferences should be included Feel free to make use of the referencesFeel free to make use of the references

There should be clear aims and endpointsThere should be clear aims and endpoints

Subject Selection and Subject Selection and EnrollmentEnrollment

How are subjects identified?How are subjects identified? charts, referrals, PI’s own clinic, support charts, referrals, PI’s own clinic, support

groups, public records.groups, public records. How, when and by whom are subjects for How, when and by whom are subjects for

contacted about study?contacted about study? In person? Should be by someone who In person? Should be by someone who

has reason to know confidential medical has reason to know confidential medical information.information.

Letters? Letters should be co-signed by Letters? Letters should be co-signed by the MD know to the patient-subject.the MD know to the patient-subject.

No cold calls.No cold calls.

Subject Selection and Subject Selection and EnrollmentEnrollment

Advertising for subjects?Advertising for subjects? Radio scripts, web page content, Radio scripts, web page content,

advertisements, etc.. All need IRB advertisements, etc.. All need IRB approvalapproval Content for ads must meet IRB Content for ads must meet IRB

requirements requirements Cannot be coercive Cannot be coercive No $ amounts listedNo $ amounts listed

Subject Selection and Subject Selection and EnrollmentEnrollment

Inclusion/Exclusion CriteriaInclusion/Exclusion Criteria Should be a detailed listShould be a detailed list Should include appropriate laboratory Should include appropriate laboratory

parametersparameters Should include appropriate medical exclusionsShould include appropriate medical exclusions Should not/rarely exclude non English speakersShould not/rarely exclude non English speakers

Who obtains consent? Who gives consent?Who obtains consent? Who gives consent?

Study ProceduresStudy Procedures

Should include sufficient detail to Should include sufficient detail to ascertain what subjects will actually ascertain what subjects will actually experience while in study.experience while in study. Time commitment.Time commitment. Setting or site where study procedures Setting or site where study procedures

occur.occur. Any “routine” agents to be used – such Any “routine” agents to be used – such

as sedation.as sedation. ALL this should also be in the Consent ALL this should also be in the Consent

form with detail in lay terms.form with detail in lay terms.

BiostatisticsBiostatistics A formal sample size is generally necessary.A formal sample size is generally necessary.

Why does the PI need this many subjects?Why does the PI need this many subjects?

Are there enough subjects to answer the Are there enough subjects to answer the study question?study question?

How are the data to be analyzed?How are the data to be analyzed?

Just because the PI says it is a pilot study Just because the PI says it is a pilot study doesn’t mean they don’t need statistics.doesn’t mean they don’t need statistics.

Risks and DiscomfortsRisks and Discomforts Should be listed clearly, quantitatively and Should be listed clearly, quantitatively and

in order of seriousness.in order of seriousness. Should include risks of withdrawal from current Should include risks of withdrawal from current

medications.medications. Non medical risks? Social, legal, financial or Non medical risks? Social, legal, financial or

psychological risks? psychological risks? Is loss of confidentiality a legitimate risk or Is loss of confidentiality a legitimate risk or

concern?concern? What about loss of privacy?What about loss of privacy? Is there a complete list of adverse events in the Is there a complete list of adverse events in the

drug or device brochure?drug or device brochure? Any foreseeable but maybe still theoretical Any foreseeable but maybe still theoretical

risks – for example tumorigenesis?risks – for example tumorigenesis?

BenefitsBenefits Compensation is not a benefit.Compensation is not a benefit. If there are benefits to the individual If there are benefits to the individual

subjects these should be discussed first, subjects these should be discussed first, then any potential benefits to future society.then any potential benefits to future society.

A common error we see is the A common error we see is the “overstatement” of benefits.“overstatement” of benefits.

Example of good benefit statement: Example of good benefit statement: There is no direct health benefits to you as a There is no direct health benefits to you as a

result of your participation in this study. result of your participation in this study. However we hope to find information that However we hope to find information that will help improve treatment of your condition will help improve treatment of your condition in the future. in the future.

Safety MonitoringSafety Monitoring How are the data to be monitored and by How are the data to be monitored and by

whom?whom? All studies involving more than minimal risk All studies involving more than minimal risk

require a data and safety monitoring plan. require a data and safety monitoring plan. Not all studies require a DSMB but if one is Not all studies require a DSMB but if one is

necessary who does it involve? Is it necessary who does it involve? Is it independent? Should it be?independent? Should it be?

Are there objective criteria for withdrawal of Are there objective criteria for withdrawal of subjects when safety is in question?subjects when safety is in question?

Are there stopping rules?Are there stopping rules? Is there a plan for reporting to the IRB?Is there a plan for reporting to the IRB? Does the PI state that NYU SoM’s IRB Does the PI state that NYU SoM’s IRB

Reportable Events guidelines will be followed?Reportable Events guidelines will be followed?

Review Strategies

Suggested Review StrategySuggested Review Strategy Review application Review application

Look for special issues such as kids, radiation, Look for special issues such as kids, radiation, emergency use issues, new drugs/devices, emergency use issues, new drugs/devices, genetics, storing samples for future usegenetics, storing samples for future use

Read protocol summaryRead protocol summary Look for site specific issues; can we logistically Look for site specific issues; can we logistically

perform the study here?perform the study here? Read detailed protocolRead detailed protocol

Look also at any study specific tools, letters, ads, Look also at any study specific tools, letters, ads, extrasextras

Suggested Review StrategySuggested Review Strategy Prepare your commentsPrepare your comments

Written and submitted are wonderfulWritten and submitted are wonderful Emailed is even betterEmailed is even better

Editing the consent formEditing the consent form Edit right on the documentEdit right on the document Use legible handwritingUse legible handwriting Submit marked up documentSubmit marked up document

NIH grantNIH grant Review for consistencyReview for consistency

Is the study captured in the grantIs the study captured in the grant If PI says study pays, are there funds to payIf PI says study pays, are there funds to pay

Suggested Review StrategySuggested Review Strategy Scientific ReviewersScientific Reviewers

1. Read protocol – jot down comments, 1. Read protocol – jot down comments, thoughts suggestions etc.. thoughts suggestions etc..

2. Read Consent – Mark it up! 2. Read Consent – Mark it up! 3. Look at any additional info (ads, scripts, 3. Look at any additional info (ads, scripts,

etc..)etc..)4. Think about 45 CFR 46.111 – can you make 4. Think about 45 CFR 46.111 – can you make

the findings?the findings? If yes, be prepared to explain howIf yes, be prepared to explain how If no, be prepared to explain how If no, be prepared to explain how

Come to the meeting ready Come to the meeting ready to state your opinion and be able to justify itto state your opinion and be able to justify it

Suggested Review StrategySuggested Review Strategy Non- Scientific ReviewersNon- Scientific Reviewers

1. Read protocol summary 1. Read protocol summary 2. Read Consent – Mark it up! 2. Read Consent – Mark it up! 3. Think about one important question 3. Think about one important question

before you come to the meeting – before you come to the meeting – Do I Do I know what this study is ALL about? know what this study is ALL about?

3. Look at any additional info (ads, scripts, 3. Look at any additional info (ads, scripts, etc..)etc..)

4. Think about 45 CFR 46.111 – do you 4. Think about 45 CFR 46.111 – do you think the findings can be made? think the findings can be made?

5. jot down comments, thoughts 5. jot down comments, thoughts suggestions etc.. suggestions etc..

It’s Meeting TimeIt’s Meeting Time

How Our IRB System WorksHow Our IRB System Works Primary and Secondary ReviewersPrimary and Secondary Reviewers

Assignments made 1 week ahead of meetingAssignments made 1 week ahead of meeting Discussion by Full CommitteeDiscussion by Full Committee

Reviewers lead discussion Reviewers lead discussion Everyone contributesEveryone contributes

Committee VoteCommittee Vote ApproveApprove Conditional ApprovalConditional Approval DeferralDeferral DisapproveDisapprove One year maximum approvalOne year maximum approval

At the MeetingAt the Meeting

Primary reviewer, present a 2-3 minute Primary reviewer, present a 2-3 minute summary of the studysummary of the study

Present clear, concise, well defined reviewPresent clear, concise, well defined review Focus on Focus on majormajor consent form issues, leave consent form issues, leave

grammar and typos to the consent teamgrammar and typos to the consent team Assume everyone else has read their Assume everyone else has read their

assignmentsassignments Present your recommended dispositionPresent your recommended disposition Secondary reviewer, add anything that the Secondary reviewer, add anything that the

Primary didn’t touch onPrimary didn’t touch on

QuorumQuorum

45 CFR 46.108 IRB functions and operations.45 CFR 46.108 IRB functions and operations.

In order to fulfill the requirements of this policy In order to fulfill the requirements of this policy each IRB shall:each IRB shall:

…… (b) Except when an expedited review procedure (b) Except when an expedited review procedure is used, is used, …… review proposed research at review proposed research at convened convened meetingsmeetings at which a at which a majority of the membersmajority of the members of of the IRB are present, including at least the IRB are present, including at least one one member whose primary concerns are in member whose primary concerns are in nonscientific areasnonscientific areas……. .

QuorumQuorum

Regulations require we meet quorum.Regulations require we meet quorum. We define quorum as more than half the We define quorum as more than half the

members present. members present. Since we can’t cut anyone in two, this means Since we can’t cut anyone in two, this means

if there are 22 people on the board, we can’t if there are 22 people on the board, we can’t start the meeting until 12 people are present.start the meeting until 12 people are present.

We need your expertise.We need your expertise. Meetings begin 9:00 AM Please be on Meetings begin 9:00 AM Please be on

time.time.

At Convened Meetings At Convened Meetings

A majority of members must be presentA majority of members must be present Nonscientist must be presentNonscientist must be present

No nonscientist ---> no meetingNo nonscientist ---> no meeting Community member: not always = Community member: not always =

nonscientistnonscientist Meeting must stop whenever number Meeting must stop whenever number

present drops below quorum or present drops below quorum or nonscientist leavesnonscientist leaves

45 CFR 46.10845 CFR 46.108

At Convened MeetingsAt Convened Meetings

IRB Meeting Convened without QuorumIRB Meeting Convened without Quorum (Scientist or Nonscientist Absent or a majority (Scientist or Nonscientist Absent or a majority

of member not present)of member not present)

When no scientist or nonscientist member is When no scientist or nonscientist member is present during the course of the meeting or present during the course of the meeting or the quorum fails during a meeting (e.g., the quorum fails during a meeting (e.g., those with conflicts being excused, early those with conflicts being excused, early departures), the IRB may not take further departures), the IRB may not take further actions or votes until a nonscientist member actions or votes until a nonscientist member returns.returns.

OHRP guidanceOHRP guidance

At Convened MeetingsAt Convened Meetings Review of ProtocolsReview of Protocols

Members must receive protocols Members must receive protocols PRIOR to the meeting, with sufficient PRIOR to the meeting, with sufficient time to review. time to review.

Protocols may not be distributed at Protocols may not be distributed at the meeting for review at the the meeting for review at the meeting. meeting.

Convened MeetingsConvened Meetings VoteVote

We do a show of hands to record We do a show of hands to record vote:vote: for, against, abstainfor, against, abstain

Record in minutes (Example):Record in minutes (Example): Total = 8 ;Total = 8 ; For = 6; Against = 1;Abstain = 1 For = 6; Against = 1;Abstain = 1

Convened MeetingsConvened Meetings VoteVote (Continued)(Continued)

Total number present is Total number present is important especially if anyone important especially if anyone has left the roomhas left the room

Must vote separately on each Must vote separately on each protocolprotocol

IRB Members and IRB Members and CONFLICT OF INTERESTCONFLICT OF INTEREST

Regulations...Regulations...

DHHS and FDA regulations [45CFR DHHS and FDA regulations [45CFR 46.107(e) & 21CFR 56.107(e)] prohibit 46.107(e) & 21CFR 56.107(e)] prohibit members from participating in IRB reviews members from participating in IRB reviews if they have a conflict of interest.if they have a conflict of interest.

No IRB may have a member participate in the No IRB may have a member participate in the IRB's initial or continuing review of any project IRB's initial or continuing review of any project in which the member has a conflicting interest, in which the member has a conflicting interest, except to provide information requested by the except to provide information requested by the IRB.IRB.

NYU SoM Policy for Conflict of NYU SoM Policy for Conflict of Interest DisclosureInterest Disclosure

It is the expectation of the University that It is the expectation of the University that IRB members will voluntarily IRB members will voluntarily recuse recuse themselves from review and discussionthemselves from review and discussion of research protocols if they have a conflict of research protocols if they have a conflict of interest. of interest.

Members of the IRB must disclose to the Members of the IRB must disclose to the IRB Chair or Administrator any conflict of IRB Chair or Administrator any conflict of interest that may arise in the review of interest that may arise in the review of research or compliance matters for the IRB. research or compliance matters for the IRB.

Members should not divulge the details of Members should not divulge the details of their conflict - just that one existstheir conflict - just that one exists

Risk of “Non-Recusal”Risk of “Non-Recusal”

Compromised ObjectivityCompromised Objectivity Biased opinion of the merit of the studyBiased opinion of the merit of the study Biased opinion of whether IRB criteria Biased opinion of whether IRB criteria

for approval have been metfor approval have been met Undue influence on other IRB membersUndue influence on other IRB members Appearance of impropriety; loss of Appearance of impropriety; loss of

public trustpublic trust

Conflicts of Interest that Conflicts of Interest that Require Member RecusalRequire Member Recusal

Members who are an Members who are an investigator or faculty investigator or faculty sponsorsponsor on the project under review, or whose on the project under review, or whose spouse or childspouse or child is an investigator or faculty sponsor is an investigator or faculty sponsor

Members who have any Members who have any financial interestsfinancial interests (i) that (i) that would reasonably appear to be affected by the would reasonably appear to be affected by the research; or (ii) in entities whose financial interests research; or (ii) in entities whose financial interests would reasonably appear to be affected by the would reasonably appear to be affected by the researchresearch

Members who believe Members who believe existing circumstancesexisting circumstances may directly affect their objectivitymay directly affect their objectivity should should recuse themselves from the reviewrecuse themselves from the review

At Convened MeetingsAt Convened Meetings

You have a conflicting interest in You have a conflicting interest in a proposal under review.a proposal under review.

How should the IRB handle this?How should the IRB handle this?

At Convened MeetingsAt Convened Meetings

Recusal Recusal If an IRB member has a conflicting If an IRB member has a conflicting

interest in a project under review, interest in a project under review, the member the member MUSTMUST leave the room leave the room during the discussion and vote of during the discussion and vote of the project.the project.

RecusalRecusal

The member may be present if the The member may be present if the IRB requests clarifications from the IRB requests clarifications from the member.member.

Vote is not valid if member does not Vote is not valid if member does not leave the room. leave the room.

There can be no exceptions.There can be no exceptions.

RecusalRecusal

What if quorum is lost if the What if quorum is lost if the member with the conflict leaves member with the conflict leaves the room for the discussion and the room for the discussion and vote on the proposal?vote on the proposal?

RecusalRecusal

The proposal must wait for the The proposal must wait for the next convened meeting for which next convened meeting for which there will be a quorum without there will be a quorum without the conflicted member.the conflicted member.

Other Responsibilities of the IRB

Annual review and re-approval Annual review and re-approval (Continuing Review)(Continuing Review)

Observe, Monitor and Audit Observe, Monitor and Audit

Suspend or Terminate ApprovalSuspend or Terminate Approval

IRB Approved Research what IRB Approved Research what happens next…happens next…

Continuations Continuations -- usually require full board usually require full board reviewreview

Modifications Modifications – major modifications require – major modifications require full board review full board review

Reportable eventsReportable events – – Unanticipated problems causing risk of harm to Unanticipated problems causing risk of harm to

subject or othersubject or other Unanticipated adverse events (not in original Unanticipated adverse events (not in original

proposal) proposal) Deviations/violationsDeviations/violations Patient ComplaintsPatient Complaints Imprisonment of subjectsImprisonment of subjects

Continuing ReviewContinuing Review

Reporting on study to dateReporting on study to date Reality check on how it is really goingReality check on how it is really going Any new developments in alternatives?Any new developments in alternatives? Risks and discomforts haven’t changed?Risks and discomforts haven’t changed? Benefits haven’t changed?Benefits haven’t changed? Any new risks identified?Any new risks identified? Are the initial statistical assumptions Are the initial statistical assumptions

still validstill valid

Continuing ReviewContinuing Review

Have any/all amendments been Have any/all amendments been incorporated into the protocol document?incorporated into the protocol document?

Have any/all amendments been Have any/all amendments been incorporated into the consent document?incorporated into the consent document?

If NIH funded, is the progress report If NIH funded, is the progress report consistent with the continuing review consistent with the continuing review report?report?

BREAK BREAK

History of Protection of Human History of Protection of Human SubjectsSubjects

Nuremberg Code (1947)Nuremberg Code (1947) Unethical Research in the U.S.Unethical Research in the U.S. RegulationsRegulations Modern Day ProblemsModern Day Problems Declaration of Helsinki Declaration of Helsinki

(1964,’75,’83,’89,2000,2008)(1964,’75,’83,’89,2000,2008)

Nuremberg

During the Nuremberg War Crimes Trials:

23 German doctors were charged with crimes against humanity for “performing medical experiments upon concentration camp inmates and other living human subjects, without their consent, in the course of which experiments the defendants committed the murders, brutalities, cruelties, tortures, atrocities, and other inhuman acts.”

Nuremberg

As part of the verdict, the Court enumerated some rules for "Permissible Medical Experiments", now known as the

“Nuremberg Code”. These rules include:

-voluntary consent

- experiment yielded results for good of society

- benefits outweigh risks

-ability of the subject to terminate participation

NurembergNuremberg

Creation of the Nuremberg Code (1947)

Although it did not carry the force of law, the Nuremberg Code was the first international document which advocated voluntary participation and informed consent.

10 principles includes: 10 principles includes: informed consent and absence of coercion; properly formulated scientific experimentation; and beneficence towards experiment participants.

SUCH CONDUCT COULD NOT SUCH CONDUCT COULD NOT OCCUR IN THE U.S. OCCUR IN THE U.S.

RIGHT?RIGHT?

Well Known Major Cases Well Known Major Cases Involving Unethical Involving Unethical Research in the U.S.Research in the U.S.

Willowbrook (1956 -1965)Willowbrook (1956 -1965) Jewish Chronic Disease (1963)Jewish Chronic Disease (1963) USPHS Syphilis Study USPHS Syphilis Study (aka Tuskegee Study)(aka Tuskegee Study)

(1932-72)(1932-72) And More modern day problems….And More modern day problems….

The Willowbrook Hepatitis StudyThe Willowbrook Hepatitis Study

New York (1963-1966)New York (1963-1966) Conducted on mentally retarded, Conducted on mentally retarded,

institutionalized childreninstitutionalized children Involved systematically infecting the Involved systematically infecting the

children with hepatitischildren with hepatitis Parents were coerced into Parents were coerced into

consentingconsenting

Jewish Chronic Disease Hospital

New York (1963)New York (1963) Cancer Experiments Injection of live cancer cells Hospitalized elderly patients Indigent subjects were injected with Indigent subjects were injected with

live cancer cells without their live cancer cells without their knowledge or consent knowledge or consent

US Public Health Services “Study of Untreated Syphilis in the Negro Male”

American medical research project conducted by the

U.S. Public Health Service from 1932 to 1972 Tuskegee syphilis study examined the natural course of untreated syphilis in black American men when there was no effective treatment

subjects all poor sharecroppers - unknowing participants subjects not told that they had syphilis - nor offered effective treatment once it came available

US Government Regulation

After problems in US Medical Research After problems in US Medical Research were highlighted, the US government were highlighted, the US government decided to look into government decided to look into government regulation regulation of human experimentation and develop of human experimentation and develop ethical guidelinesethical guidelines for such research. for such research.

US Government Response1973 Kennedy Hearings “Quality of Health Care – Human Experimentation”

1974 National Research Act

Established the “National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research”

Required IRBs at institutions receiving federal support for human subjects research

National Research Act 1974National Research Act 1974 Established the Established the National Commission for National Commission for

the Protection of Human Subjects of the Protection of Human Subjects of Biomedical and Behavioral Research (i.e., Biomedical and Behavioral Research (i.e., “The National Commission”)“The National Commission”) Initially met over a four-day period in 1976Initially met over a four-day period in 1976 Met at the Smithsonian Institute's Belmont Met at the Smithsonian Institute's Belmont

Conference Center (thus “The Belmont Conference Center (thus “The Belmont Report”)Report”)

Monthly deliberations over the next four yearsMonthly deliberations over the next four years Resulted in The Belmont Report Resulted in The Belmont Report

Respect for Personsinformed consent , respect for privacy

Beneficence(nonmalficence)first do no harm,good research design, competent investigators, favorable risk/benefit analysis: maximize benefits, minimize risks.Justiceequitable selection of subjects appropriate inclusion and exclusion criteria.

The Federal Government and the IRB

DHHS

FDA NIH Office of Human Research Protection

21 CFR 50,56 45 CFR 46

Institutional Review Board

Regulations and GuidelinesRegulations and Guidelines

HHS Regulations 45 CFR Part 46 HHS Regulations 45 CFR Part 46 FDA: CFR 21 Parts 50, 56, 312, 812FDA: CFR 21 Parts 50, 56, 312, 812 ICH Good Clinical PracticeICH Good Clinical Practice

The regulations are open to interpretationThe regulations are open to interpretation 45 CFR 46, OHRP is the interpreter45 CFR 46, OHRP is the interpreter 21 CFR and it subparts are interpreted by 21 CFR and it subparts are interpreted by

the FDA the FDA

SubpartsSubparts

Three subparts under HHS Three subparts under HHS regulations regulations Subpart B – Fetus, Pregnant Women, In Subpart B – Fetus, Pregnant Women, In

Vitro and neonates of uncertain viabilityVitro and neonates of uncertain viability Subpart C - PrisonersSubpart C - Prisoners Subpart D – ChildrenSubpart D – Children

Subparts under FDA regulationsSubparts under FDA regulations Subpart D - Children Subpart D - Children

Modern Day Problems Modern Day Problems The public, congress, and universities react to:

Ethical and scientific mistakes

September 1999, University of Pennsylvania, 18-yearold volunteer named Jesse Gelsinger died from drugs administered as part of a gene therapy study

June 2001, Johns Hopkins, Ellen Roche, a 24-year-old volunteer, died one month after inhaling an unapproved drug as part of a study into the causes of asthma.

Declaration of HelsinkiDeclaration of Helsinki

At the conclusion of the Nuremberg Trials it At the conclusion of the Nuremberg Trials it was decided that as biomedical research was decided that as biomedical research efforts expanded, there was an international efforts expanded, there was an international need for a more specific code of ethics to need for a more specific code of ethics to review research. review research.

This specific code was formulated in 1964 and This specific code was formulated in 1964 and called called the Declaration of Helsinkithe Declaration of Helsinki. .

Declaration of HelsinkiDeclaration of Helsinki

Recommendations Guiding Medical Doctors in Biomedical Research Involving Human

Subjects

Adopted by the 18th World Medical Assembly, Helsinki, Finland, 1964 and as revised by the World Medical Assembly in Tokyo, Japan in 1975, in Venice, Italy in 1983, and in Hong Kong in 1989 and the 48th General Assembly, Somerset West, Republic of South Africa, October 1996, 52nd General Assembly, Edinburgh, Scotland in 2000, Note clarification on paragraph 29 added by WMA, Washington 2002, Note clarification on paragraph 30 added by WMA, Tokyo 2004, 2008 Cairo/Sao Paulo.

“Concern for the interests of the subject must always prevail over the interests of science

and society.”

Declaration of HelsinkiDeclaration of Helsinki

In cases of incompetence informed consent should be obtained from legal guardian or responsible relative

Some risks justified by potential therapeutic or diagnostic value to the patient

The Belmont Report The Belmont Report as a Review Toolas a Review Tool

Belmont Principles:Belmont Principles: Are general prescriptive judgments; Are general prescriptive judgments;

(Other principles may also be relevant)(Other principles may also be relevant) Cannot always be applied so as to Cannot always be applied so as to

resolve beyond dispute particular resolve beyond dispute particular ethical problems;ethical problems;

But the objective is to provide an But the objective is to provide an analytical framework that will guide the analytical framework that will guide the resolution of ethical problems arising resolution of ethical problems arising from research involving human from research involving human subjects. subjects.

The Belmont ReportThe Belmont Report

Boundaries Between Practice and Boundaries Between Practice and ResearchResearch IRB must determine that the researcher IRB must determine that the researcher

(and through informed consent, the (and through informed consent, the subject) distinguishes subject) distinguishes practice practice from from experimentexperiment in in bothboth social science and social science and medical science research medical science research

Respect for PersonsRespect for Persons

Treat individuals as autonomous Treat individuals as autonomous agentsagents

Do not use people as means to an endDo not use people as means to an end Allow people to choose for themselvesAllow people to choose for themselves Give extra protection to those with Give extra protection to those with

limited autonomylimited autonomy

BeneficenceBeneficence

Acts of kindness or charity that go Acts of kindness or charity that go beyond dutybeyond duty

Obligations derived from beneficenceObligations derived from beneficence Do no harmDo no harm Prevent harmPrevent harm Prevent evilPrevent evil Promote goodPromote good

JusticeJustice

Treat people fairlyTreat people fairly Fair sharing of burdens and benefits Fair sharing of burdens and benefits

of researchof research Distinguish procedural justice from Distinguish procedural justice from

distributive justicedistributive justice

Protocol Design: Protocol Design: Respect for PersonsRespect for Persons

Consider: Consider: How can the consent process maximize How can the consent process maximize

autonomy?autonomy? How can the protocol maximize autonomy?How can the protocol maximize autonomy? What additional protections can be in place What additional protections can be in place

for protected populations?for protected populations? How can this study maximally protect subject How can this study maximally protect subject

privacy?privacy?

Protocol Design: Protocol Design: BeneficenceBeneficence

Consider: Consider: Can the research design be improved Can the research design be improved to to

enhance safety and benefit ? enhance safety and benefit ? What are the risks? How can they be What are the risks? How can they be

minimized?minimized? What are the benefits? How can they be What are the benefits? How can they be

maximized?maximized?

Protocol Design: Protocol Design: JusticeJustice

Consider:Consider: How can you ensure that recruitment How can you ensure that recruitment

targets the population that will benefit targets the population that will benefit from the research?from the research?

How can you ensure that recruitment How can you ensure that recruitment will not unfairly target a population? will not unfairly target a population? (avoid exploitation of population of (avoid exploitation of population of convenience)convenience)

How can the inclusion/exclusion criteria How can the inclusion/exclusion criteria be made fair?be made fair?

Other Commonly Vexing Other Commonly Vexing DetailsDetails

Or things that will make you Or things that will make you tear your hair out…tear your hair out…

Investigator Conflicts of Investigator Conflicts of InterestInterest

All PIs must be in compliance with the All PIs must be in compliance with the NYU SoM rules.NYU SoM rules.

IRB can and must flag any conflicts we IRB can and must flag any conflicts we become aware of during our reviews.become aware of during our reviews.

IRB can refer PIs to COIC and or IRB can refer PIs to COIC and or Research Compliance Office.Research Compliance Office.

Short FormsShort Forms Use when non English speaking subjects Use when non English speaking subjects

are unexpectedly eligible for the study. are unexpectedly eligible for the study. Short form must be written in the subject’s Short form must be written in the subject’s

native language.native language. Needs an attestation of accuracy of Needs an attestation of accuracy of

translation, where no funding is available translation, where no funding is available for certified translations.for certified translations.

Impartial witness signatureImpartial witness signature Family member of the subjectFamily member of the subject Member of staff not related to the projectMember of staff not related to the project TranslatorTranslator

Does not require prior IRB reviewDoes not require prior IRB review

Consent Process and FormsConsent Process and Forms

Consent is a process and not just a form.Consent is a process and not just a form. The form is the document that captures The form is the document that captures

the signature and records the process of the signature and records the process of agreement to participate.agreement to participate.

Timing is important – Protocol should Timing is important – Protocol should give us details regarding the consent give us details regarding the consent processprocess

Once consent is signed, person is Once consent is signed, person is considered enrolled in study – those who considered enrolled in study – those who do not meet inclusion are screen failuresdo not meet inclusion are screen failures

Consent and AssentConsent and Assent

In NY Adults = age 18 and up.In NY Adults = age 18 and up. Anyone under 18 must have a parent or Anyone under 18 must have a parent or

guardian’s permission (at least one) in guardian’s permission (at least one) in order to participate.order to participate.

Sophisticated teens (15-17) can use the Sophisticated teens (15-17) can use the “adult” consent form for assent purposes“adult” consent form for assent purposes

NYU SoM has research assent form NYU SoM has research assent form templates for kids 7-11 and 12-14.templates for kids 7-11 and 12-14.

Assent may be obtained verbally.Assent may be obtained verbally. Emancipated Minors = A pregnant teen or Emancipated Minors = A pregnant teen or

child.child.

Emancipated Minor Emancipated Minor

Nikki is 15 years old, and she has a 2-Nikki is 15 years old, and she has a 2-month-month- old daughter. She visits the doctor old daughter. She visits the doctor with her with her daughter and her mother. During daughter and her mother. During the visit, the the visit, the doctor keeps talking to Nikki’s doctor keeps talking to Nikki’s mother about mother about the baby. The doctor wants the baby. The doctor wants the baby to be putthe baby to be put on an investigational on an investigational drug. Who can consent? drug. Who can consent?

As the parent, Nikki has the right to As the parent, Nikki has the right to make all make all treatment decisions for her child treatment decisions for her child including including research as treatment option. Nikki research as treatment option. Nikki can seek can seek the advice of her own mother in the advice of her own mother in making those making those decisions but Nikki can decisions but Nikki can consent to her consent to her daughter’s health care and daughter’s health care and any research options any research options with or without her with or without her mother’s input. mother’s input.

AssentAssent Assent means a child’s affirmative Assent means a child’s affirmative

agreement to participate in research, (45 agreement to participate in research, (45 CFR 46.402(b). The child must actively CFR 46.402(b). The child must actively show his or her willingness to participate in show his or her willingness to participate in the research, rather than just complying the research, rather than just complying with directions to participate and not with directions to participate and not resisting in any way.resisting in any way.

When judging whether children are capable When judging whether children are capable of assent, the ages, maturity, and of assent, the ages, maturity, and psychological state of the children involved psychological state of the children involved must be taken into account. must be taken into account.

AssentAssent(cont.)(cont.)

At the IRB meeting if the board determines that At the IRB meeting if the board determines that assent is not required, one of these findings must be assent is not required, one of these findings must be met : met :

(1) capability of some or all of the children is so (1) capability of some or all of the children is so limited that they cannot reasonably be consulted;limited that they cannot reasonably be consulted; or or (2) the intervention or procedure involved in the (2) the intervention or procedure involved in the research holds out a prospect of direct benefit that is research holds out a prospect of direct benefit that is important to the health or well-being of the children important to the health or well-being of the children and is available only in the context of the research. and is available only in the context of the research.

Who May Obtain Consent?Who May Obtain Consent? People can obtain consent for People can obtain consent for

activities commensurate with their activities commensurate with their usual clinical practice in medicine:usual clinical practice in medicine: Mammogram technologistMammogram technologist BA study coordinatorBA study coordinator RN – DPP – GTT, lab workRN – DPP – GTT, lab work RNP – DM, study initiation and RNP – DM, study initiation and

education for FDA approved drugseducation for FDA approved drugs Licensed MD – investigational drugs and Licensed MD – investigational drugs and

device studiesdevice studies

Surrogate ConsentSurrogate Consent Why can’t the subject give consent?Why can’t the subject give consent? NEW YORK law doesn’t cover NEW YORK law doesn’t cover

research but we have research but we have guidance – see guidance – see our web page policies.our web page policies.

How do we consider when surrogate How do we consider when surrogate consent is appropriate?consent is appropriate? Potential/likely benefit is required and/or Potential/likely benefit is required and/or

risk must be very small indeed. risk must be very small indeed. Who can be a surrogate? Spouse? Who can be a surrogate? Spouse?

Children? Siblings?Children? Siblings?

Study StaffStudy Staff

Their qualifications should match Their qualifications should match their responsibilities.their responsibilities.

PIs can delegate but must be PIs can delegate but must be specific.specific.

When someone is assigned as “back When someone is assigned as “back up”, what does this mean to us?up”, what does this mean to us?

WHO MAY BE PRINCIPAL WHO MAY BE PRINCIPAL INVESTIGATOR ?INVESTIGATOR ?

FACULTYFACULTY

OTHER APPROVALSOTHER APPROVALS

Conflict of Interest Committee (COI)Conflict of Interest Committee (COI)** Radiation Safety CommitteeRadiation Safety Committee** Institutional Bio-safety CommitteeInstitutional Bio-safety Committee** Protocol Reviewing and Monitoring Protocol Reviewing and Monitoring

CommitteeCommittee** (PMRC) (PMRC) Bellevue Hospital CommitteeBellevue Hospital Committee BHC Drug and FormularyBHC Drug and Formulary General Clinical Research Center (GCRC)General Clinical Research Center (GCRC)

* Approvals are pre-requisite for IRB approval* Approvals are pre-requisite for IRB approval

International ResearchInternational Research OHRP says if the study is federally OHRP says if the study is federally

funded, then our rules prevail.funded, then our rules prevail. Do we know enough about the local Do we know enough about the local

situation to review the study?situation to review the study? Can we get the information if needed?Can we get the information if needed? Is there an IRB or ethics committee over Is there an IRB or ethics committee over

there?there? Can we get things translated?Can we get things translated? Do we have an expert on this Do we have an expert on this

area/population?area/population? Can be an IRB member or the PI or a consultant.Can be an IRB member or the PI or a consultant.

PrisonersPrisoners To review prisoner research IRB must To review prisoner research IRB must

have a prisoner advocate on the have a prisoner advocate on the board – we doboard – we do Must review research with Subpart C Must review research with Subpart C

regulations – see reviewer’s checklist for regulations – see reviewer’s checklist for detailsdetails

If a subject is imprisoned during If a subject is imprisoned during participation in research that was not participation in research that was not reviewed and approved to include reviewed and approved to include research the IRB must revisit the study research the IRB must revisit the study

Treatment IND/IDE and Treatment IND/IDE and Other Expanded Access To Other Expanded Access To Investigational Drugs and Investigational Drugs and

DevicesDevices

Treatment IND/IDETreatment IND/IDE

A Treatment Use is implemented A Treatment Use is implemented when a patient does not meet the when a patient does not meet the eligibility requirements of any other eligibility requirements of any other clinical trial, and the drug or device is clinical trial, and the drug or device is not approved for marketing but is not approved for marketing but is under a clinical investigation. under a clinical investigation. Treatment Uses are approved to treat Treatment Uses are approved to treat a serious or immediately life a serious or immediately life threatening condition.threatening condition.

Treatment INDTreatment INDTreatment IND [21 CFR 312.34 and 312.35] is a mechanism for Treatment IND [21 CFR 312.34 and 312.35] is a mechanism for providing eligible subjects with investigational drugs for the providing eligible subjects with investigational drugs for the treatment of serious and life-threatening illnesses for which there treatment of serious and life-threatening illnesses for which there are no satisfactory alternative treatments. are no satisfactory alternative treatments.

FDA requires the following to issue:FDA requires the following to issue: The drug is intended to treat a serious or immediately life-The drug is intended to treat a serious or immediately life-

threatening disease; threatening disease; There is no comparable or satisfactory alternative drug or There is no comparable or satisfactory alternative drug or

other therapy available to treat that stage of the disease in the other therapy available to treat that stage of the disease in the intended patient population; intended patient population;

The drug is under investigation in a controlled clinical trial The drug is under investigation in a controlled clinical trial under an IND in effect for the trial, or all clinical trials have under an IND in effect for the trial, or all clinical trials have been completed; and been completed; and

The sponsor of the controlled clinical trial is actively pursuing The sponsor of the controlled clinical trial is actively pursuing marketing approval of the investigational drug with due marketing approval of the investigational drug with due diligence. diligence.

Treatment INDTreatment IND

Treatment IND studies require prospective IRB review and Treatment IND studies require prospective IRB review and informed consent. informed consent.

A sponsor may apply for a waiver of local IRB review under A sponsor may apply for a waiver of local IRB review under a treatment IND if it can be shown to be in the best interest a treatment IND if it can be shown to be in the best interest of the subjects, and if a satisfactory alternate mechanism of the subjects, and if a satisfactory alternate mechanism for assuring the protection of human subjects is available, for assuring the protection of human subjects is available, e.g., review by a central IRB. Such a waiver does not apply e.g., review by a central IRB. Such a waiver does not apply to the informed consent requirement. to the informed consent requirement.

NYU requires IRB review before a treatment IND is NYU requires IRB review before a treatment IND is used, even in cases where FDA has granted a waiver.used, even in cases where FDA has granted a waiver.

OthersOthers

Compassionate Use = Treatment INDCompassionate Use = Treatment IND Humanitarian Device ExemptionHumanitarian Device Exemption Other FDA approved expanded Other FDA approved expanded

access use for a drug/biologic/device access use for a drug/biologic/device 

Wrap Up

General General Pointers/considerationsPointers/considerations

The committee system exists to keep you The committee system exists to keep you out of the hot seat out of the hot seat We do not post IRB member rosters but it is We do not post IRB member rosters but it is

public information and researchers, sponsors public information and researchers, sponsors and anyone else can get this informationand anyone else can get this information

We do not post nor do we release reviewer We do not post nor do we release reviewer assignmentsassignments

Individual’s vote by name is not recorded Individual’s vote by name is not recorded You may contact the PI prior to the meeting You may contact the PI prior to the meeting

if you wish OR you can let the IRB office be if you wish OR you can let the IRB office be the middle man – at your discretion entirely.the middle man – at your discretion entirely.

IRB Review As Peer ReviewIRB Review As Peer Review Strives for consistency but different Strives for consistency but different

reviewers can and do have different reviewers can and do have different opinions.opinions.

Staff meets with the IRB chair in Staff meets with the IRB chair in order to create and communicate order to create and communicate consistent approaches, consistent approaches, requirements, regulations.requirements, regulations.

The system is not perfect but it is The system is not perfect but it is effective.effective.

Determining an ActionDetermining an Action Approval – the criteria for approval are met.Approval – the criteria for approval are met. Conditional approval – IRB Conditional approval – IRB stipulates specific stipulates specific

revisions requiring simple concurrence by the revisions requiring simple concurrence by the investigator, then the IRB Chair or another investigator, then the IRB Chair or another IRB member designated by the Chair IRB member designated by the Chair subsequently approve the revised research subsequently approve the revised research protocol on behalf of the IRB.protocol on behalf of the IRB.

Deferral - substantive clarifications or Deferral - substantive clarifications or modifications required that are directly modifications required that are directly relevant to the criteria for approval.relevant to the criteria for approval.

Disapproval – major ethical or scientific issues Disapproval – major ethical or scientific issues – PI can respond to the IRB or start over.– PI can respond to the IRB or start over.

Common Review IssuesCommon Review Issues PI has failed to provide information about PI has failed to provide information about

reasonable clinical context or apparent reasonable clinical context or apparent withholding of standard of care.withholding of standard of care.

Failure to minimize risk.Failure to minimize risk. Inadequate information about Inadequate information about

collaborating sites, especially when collaborating sites, especially when international sites are involved.international sites are involved.

Poor preparation of materials – cutting Poor preparation of materials – cutting and pasting errors.and pasting errors.

Poor writing skills, no proof reading.Poor writing skills, no proof reading.

Do’sDo’s Do feel free to answer questions and Do feel free to answer questions and

provide information about the study if provide information about the study if you are a co-investigatoryou are a co-investigator

Do remove yourself from the room if Do remove yourself from the room if you are a co-investigator or have any you are a co-investigator or have any other conflict with a study under other conflict with a study under reviewreview

Do vote your conscience Do vote your conscience Do keep reviews confidential – it Do keep reviews confidential – it

protects you and the Board protects you and the Board

Don’tsDon’ts

Don’t discuss IRB meetings outside Don’t discuss IRB meetings outside the meeting or with any one other the meeting or with any one other than the PIthan the PI IRB meetings are confidentialIRB meetings are confidential They include confidential sponsor They include confidential sponsor

informationinformation Discussions could lead to scientific Discussions could lead to scientific

disputes, competition issuesdisputes, competition issues

Bottom LineBottom Line

It is not ethical to subject people to It is not ethical to subject people to risks, discomforts or inconveniences risks, discomforts or inconveniences for research that cannot contribute for research that cannot contribute meaningfully to science!meaningfully to science!

If the IRB can’t understand the If the IRB can’t understand the submission, then the PI hasn’t done a submission, then the PI hasn’t done a good job.good job.

Last WordsLast Words Don’t hesitate to communicate with our Don’t hesitate to communicate with our

office or the IRB Chair/Vice Chairs directly.office or the IRB Chair/Vice Chairs directly. Don’t hesitate to ask for advice at the Don’t hesitate to ask for advice at the

meetings.meetings. If you find things missing from your If you find things missing from your

materials, contact the IRB office prior to the materials, contact the IRB office prior to the meeting so we can get the material to you.meeting so we can get the material to you.

Again we welcome you Again we welcome you

thank you for joining the IRBthank you for joining the IRB

and thank you for giving us your time todayand thank you for giving us your time today

Key ReadingKey Reading

The Belmont ReportThe Belmont Report Our IRB policies and proceduresOur IRB policies and procedures The regulatory criteria for IRB The regulatory criteria for IRB

approvalapproval The regulatory criteria for the The regulatory criteria for the

elements of consentelements of consent The FDA’s information sheetsThe FDA’s information sheets

2008/2009 MEETING 2008/2009 MEETING DATESDATESGo To:

http://www.med.nyu.edu/irb/schedule/index.html

IRB Web siteIRB Web site

Go To:http://www.med.nyu.edu/irb.html

IRB Staff Contact InfoIRB Policies, Forms , Guidelines etc..Information for Research VolunteersIRB Course CalendarIRB Consent Tool KitIRB Newsletter

THANK YOUTHANK YOU