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HCCA National ConferenceJune 4, 2012Sarah Putney, JDEmory University

• Challenges for Human Research Protection Programs (HRPPs) dealing with noncompliance• Lexicon

• Solutions: CoRe (Compliance Review) Team model

• Pluses and minuses

• Is this model right for you?

• Cases for discussion

• Conclusions, Questions

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• Is this the image of Compliance you are struggling to change?

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Research compliance officer

Unwittingly noncompliant investigator

• Directing flow of:• Reports of noncompliance

• Complaints from participants and others

• Reports of problems

• Fact-finding

• Issue-framing

• Confidentiality

• Record-keeping

• Answering questions from researchers

• Setting expectations

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• Being the change: helping with the root cause analysis and CAPA plan

• Fulfilling reporting obligations

• Being efficient, consistent and fair• When you have more than one IRB panel

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• Protocol reviews require trained IRB members (and staff)• Certain skills are needed• Practice develops expertiseBUT:• Handling reports of NC demands different skills• Doing NC reviews infrequently means lack of practice, lack of

expertiseSO:• If you have more than one committee, one chair, one set of

members, how to you ensure …• CONSISTENCY?

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• Concern for human participant protections

• Interest in facilitating ethical research

• Communication skills: clear, concise• Respect for others’ time

• Flexibility re group consensus• Can disagree without being disagreeable

• Creativity and practicality in problem-solving

• Organizational/deadline-friendly

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Protocol Reviews Noncompliance Reviews

Regulatory approval criteria Fairness & judiciousness

Communicate clearly Understand definitions & process

FDA requirements (IND, IDE, etc.) Focus on relevant v. irrelevant facts

Informed Consent Elements, reading level Address anxious PIs in person

Subject population Root cause analysis

Scientific or community knowledge Weigh mitigating & aggravating factors

Simplify consent language Creativity re CAPA plans

Practicality

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• You can organize staff, members, SOPs, meetings, and review loops to meet these challenges

• You can specialize training and processes

• You can avoid silo-ing with good communication

• You can provide positive learning experiences through Quality Assurance paired with Education

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• AAHRPP-accredited to 2016

• IRB: 25 staff, 120+ IRB members

• App. 3200 active studies

• 6 biomedical mtgs/mo

• 1 sociobehavioral mtg/mo

• 1 noncompliance review mtg/mo

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• Receives reports & triages

• Suspends judgment

• Listens, responds, sets expectations

• Conducts fact-finding

• Identifies issues

• Writes report for CoRe Team (if needed) or acknowledges simple NC or Not-NC

• Educates

• To support the Emory Research Community via Education/Outreach and effective quality assurance practice on behalf of the Emory IRB

• One Team Lead, one senior consultant, one or more analysts

• Each NC/UP case is assigned to a team member as Case Manager

• Case Manager “owns” the case from fact-finding to record-keeping

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Case Manager reviews: do we have all the info we need?

Email PI questions. 

Is response received in 48 hours?

No

Call PI to discuss.  

All clear?

Meet with  PI.  Do we have all the info we 

need?

Escalate to IRBChair or Director

Send to CoRe Team for review

YES

• 3 senior staff, 2-3 Chairs/Vice Chairs

• “Meets” by email

• Determines if potentially SNC, CNC, and/or UP• Refers those to Committee Q if so

• Assesses root cause analysis

• Develops CAPA plan

• Educates

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IRB receives  event report

Team Q Lead triages: UP?  

NC? 

Not UP, not NC,  expedited review

Maybe UP or NC, Team Q 

does fact‐finding

Team Q develops report CoRe reviews

Committee Q determines SNC, CNC, UP or not

Not possibly SNC, CNC or UP

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• Full Board (Committee Q)

• Reviews cases referred by CoRe Team

• PI attends meeting

• Determines if SNC, CNC, and/or UP

• Assess CAPA plan v. Root Cause Analysis

• Sets compliance deadline

• Reports to sponsor, Institutional Officials & federal agencies

• Educates

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• Meets monthly

• Subject to same quorum requirements

• Members are specially trained for NC/UP reviews

• PI’s are invited to attend or call in

• After meeting, letters to PI, institutional officials, and FDA/OHRPas applicable

• May the data be used for research purposes, after CAPAimplementation?

• Is the corrective and preventive action plan appropriate?

• Does the protocol, informed consent, or data and safety monitoring plan need to be modified?

• Do current or past subjects need to be notified and/or reconsented?

• Should the risk level be reassessed in light of this event?

• Is the risk:benefit ratio still acceptable?

• Does this case need to be referred to other organizational entities?

• Required CAPA completion/fulfillment date:

• Other:

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• Must be preceded by a good root cause analysis (RCA)

• Should be fashioned to address the RCA

• Education is usually not enough!

• Should accomplish both• Resolution of current problem

• Prevention of recurrence

• Familiarity with Guidance (definitions, presumptions, etc.)

• Familiarity with review workflow

• Access to information about precedents

• Observing a Committee Q meeting

• Reviewing Committee Q minutes

• Learning by doing

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• What do you call it? Is “compliance” a dirty word?

• Suggestions:

• “QA” for Quality Assurance: education with enforcement

• “QI” for Quality Improvement: education without enforcement

“post-approval monitoring”

“quality monitoring”

• Instead of “audit,” try “record review”

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• What do you call it? Is “compliance” a dirty word?

• Suggestions:

• “QA” for Quality Assurance: education with enforcement

• “QI” for Quality Improvement: education without enforcement

“post-approval monitoring”

“quality monitoring”

• Instead of “audit,” try “record review”

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• Customer service ethic should drive interactions of staff with investigators

• What you say and how you say it matter!

• “We would like to help you…”

• “Let’s figure this out together.”

• “We’re here to help you stay on the right side of the regs.”

• “It’s all a learning experience. We’re learning too.”

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• Education and compliance are 2 sides of the same coin

• Emphasize the positive, human side of your compliance professionals, how it can benefit researchers

• See for example:

http://www.ctac.emory.edu/

• Incorporate telephone calls and in-person meetings into fact-finding

• Offer assistance and guidance, not just enforcement

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• UP = Any unanticipated problem related to the research, whether serious or not, that adversely affects the safety, rights, or welfare of subjects or others.

• Examples:

• Stolen laptop containing identifiable data

• IND safety report describing external unexpected adverse event using the same study drug, but in a different disease state

• Pattern of data suggesting previously unknown side effect from a drug

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• NC = Failure to comply with regulations or Emory IRB Policies and Procedures or failure to follow the requirements or determinations of the IRB.

• Full board must make the determination of SNC or CNC or UP at a convened meeting.

• Study-specific basis

• Study as a whole is “in” SNC or not

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• Serious Noncompliance (non-VA) – Noncompliance which, in the judgment of the convened IRB, significantly increases risk to participants, and/or significantly decreases potential benefits, and/or compromises the integrity of the Human Research Protection Program (HRPP).

• Individual instances of noncompliance that are deemed not serious may constitute serious noncompliance when considered collectively.

• IRB does not have to find that harm has occurred or was likely to occur to make a determination of serious noncompliance.

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• The U.S. Office of Human Research Protections (OHRP) has advised that it considers the following always to be serious noncompliance

• Human subjects research conducted without IRB approval

• Substantive change to the research implemented without IRBapproval

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• The following are presumed by the Emory IRB to be SNC. Burden is on PI to rebut presumption by presenting compelling evidence of error or mitigating circumstances.

• Human subjects research conducted without IRB approval

• Subjects enrolled without consent (when not eligible for a waiver of consent)

• Subjects enrolled without meeting inclusion/exclusion criteria

• Substantive change to the research implemented without IRBapproval (unless implemented to avoid imminent harm to subjects)

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• CNC = A pattern of noncompliance that suggests a likelihood that NC will continue unless intervention occurs.

• OHRP has advised that it considers that noncompliance is continuing if it persists after the investigator knew or should have known about it.

• NC is presumed by the Emory IRB to constitute CNC if it persists after the PI knew or reasonably should have known about it.

• To rebut the presumption, the burden is on the investigator to present compelling evidence of error or mitigating circumstances.

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• Sets the starting point

• Eliminates a lot of confusion

• Makes it clear what needs to happen

• Note: Consideration of mitigating and aggravating factors enables judicious decision-making• Each case is unique but

• Your process and approach should be consistent

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• Safety and urgency of review should dictate whether a UP case waits for Committee Q to meet

• Our other biomedical committees also review UPs• First available meeting is a good general rule

• Team Q Case Manager presents case to the IRB and does all the usual administrative follow-up

• Copies of the UP worksheet are distributed to IRB members at the meeting for review and collected afterward.

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• NC reported: Investigators used a superseded version of the informed consent document (ICD) to enroll participants. Older form didn’t include extra blood sample.

• RCA shows that during a staff turnover period, the new coordinator was not taught to obtain the latest IRB-approved ICD from the electronic IRB system; she made a photocopy of one she found in a paper file.

• What should the CAPA include?

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• Education?

• Reconsenting?

• Process improvements?

• Compliance deadline?

• Monitoring review by IRB or other monitor?

• Other?

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• NC reported: • Safety-related screening labs were not done • Ineligible participants were enrolled• Adverse events were not graded or attributed• Reportable events were not submitted to the IRB in a timely

manner

• RCA showed: PI had oversight of 20 different studies at one time, coordinator staff were not properly trained on processes, and regulatory staff did not communicate with Pis on timeframe for timely reporting.

• CAPA?

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• NC reported: Sponsor-Investigator (PI holding the Investigational New Drug application from FDA)• Did not file Annual Report to FDA • Did not conduct required study monitoring• Did not obtain consent from verifiable Legally Authorized

Representatives for cognitively impaired participants.

• RCA reveals: Sponsor-Investigator did not understand commitments ensuing from signing Form 1572.

• CAPA?

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• NC reported:

• Study team changed study drug regimen without waiting for final IRBapproval (“I looked in the system and thought it said ‘Approved’”)

• Gave new regimen to participants after obtaining consent using manually annotated ICD (showing proposed changes)

• RCA revealed: a junior co-investigator had joined study team without IRB approval or required online training. She did not know to wait for final IRB approval and approved, revised ICD, etc. PI assumed coordinator took care of “these administrative details.”

• CAPA?

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• You may not have the volume of reports, funding, or enough staff to dedicate a team to support only NC and UPs

• Can the CoRe model be adapted to a small-scale, one-IRBscenario?

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• Problem: Committee Q is a subcommittee of our biomedical IRB

• Our SHB IRB would like its members to review SNC, CNC, UPs

• Since more SHB studies are expeditable, the SHB Committee meets only about 3x/year

• Solution:

• We trained the members in NC review at a meeting

• Ran through practice cases

• Then reviewed the real case

• Team Q did all the usual administrative support

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• Requires resources

• There is a danger of silo-ing if communication loop is not sustained

• Down side of specialization: staff may not learn “normal” IRBskills

• “Committee Q” may get the reputation as some sort of InQuisition

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• Staff and IRB members should be …

• No-drama

• Open-minded

• Reasonable

• Fair

• Good-humored

• Focused on problem-solving,

not punishment

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• “I wanted to be sure I had a chance to thank you for letting me present at the meeting. I really do appreciate your willingness to hear me out. It is greatly appreciated, and I will certainly tell others here about the process. There are often subtleties to each discussion that are very tough to portray through written communications, and the opportunity to present this information in person is a real plus.“

• “Many thanks for educating me about this sort of protocol and permitting the use of the data.”

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From tidal wave to trickle

• Specialization

• Key guidance

• Education

• CAPAs

• QA monitoring

• Communication

• Record-keeping

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• You do not have to operate in a state of overwhelm, inconsistency, and confusion where NC and UP review are concerned

• A CoRe Model can provide consistent, efficient, fair, responsive service to your HRPP

• It can be adapted to scale, frequency, and resources

• Specialization, communication, customer service ethic are key

• Stay humble – no one, including the HRPP can get it right all the time!

• Mistakes are OK as long as we learn from them.

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• For more information:

• Sarah Putney sputney@emory.edu (404) 712-9750

• Maria Davila maria.davila@emory.edu

• Shara Karlebach swilli3@emory.edu

• Emory IRB website Guidance and QA tools:http://www.irb.emory.edu/researchers/formstools/formstools.cfm

• Policies & Procedures: http://www.irb.emory.edu/documents/PoliciesAndProcedures.pdf

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