Stanley Estime, MSCI

QA/QI Specialist

February 12, 2014

Looking at the Man in the Mirror: What to Do When You Find Non-Compliance?

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Agenda

Why is reporting required? Types of Reportable New Information Top Ten Investigator Common Deficiencies Creating an RNI Submission in ESTR Post Reporting: What’s Next? Reporting Scenarios

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Why is reporting required?

DHHS and FDA regulations require that IRBs have:

Written procedures for ensuring prompt reporting of any unanticipated problems or serious continuing noncompliance.

21 CFR 56.108(b)(1) and 45 CFR 46.103(b)(5)

New information becomes available during study which may require IRB/Investigator to reassess the risk/benefit to participants

Last but not least to avoid continuous non-compliance

To Report or Not to Report?

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Common Findings QA/QI Assistance“The PI is unfamiliar with regulatory requirements and/or institutional policy...”

• Reporting to IRB/Sponsor/FDA• Drafting/Implementing Corrective

Action Plan• Provide Study Management

Tools in order to track and avoid future non-compliance

• Provide federal and institutional guidance/requirements pertaining to finding

• Provide external audit prep

Possible Root Causes

• Misinterpretation; don’t understand

• Don’t know where to find information

• Fears potential consequences• Don’t believe it’s a “big deal”

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Reportable “New” Information

Change in Risks/Benefits Adverse Events (Internal and External) Findings/Allegations of Regulatory Non-Compliance Audits/Inspections by Federal Agency Protocol Deviations/Violations Breach of Confidentiality Incarceration of Enrolled Participants Participant Complaints Protocol Suspension/Termination

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Reporting Adverse Events

Useful to maintain an Adverse Event Tracking log:– Date of Event– Description– Severity– Expectedness*– Relatedness*– Date Reported to the IRB, Sponsor or FDA

*A harm is unexpected when its specificity and severity are not reflected in the IRB-approved protocol/consent form.

*A harm is possibly related when the research procedures more likely than not caused the harm

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Report Findings of “Regulatory” Non-compliance

Examples include: Conducting human research procedures without IRB

approval Failure to obtain/document informed consent from

participants Improper use of a witness during consent process Investigator not maintaining regulatory or participant

files

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Report Audit Inspection

Report any audits by federal agencies:– FDA, OHRP, DOD, VA

Pre-Audit Notification Recommend QIP- Also notify QIP/IRB of any sponsor inquiries which may potentially result in an audit

Post Audit Notification IRB– i.e. suspension/termination of research by sponsor

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Report Protocol Deviations/Violations

WHO is at fault? Failure to follow protocol due to actions or inactions

of investigators, staff, or participants participants

WHAT needs to be reported? Any deviation from the IRB-approved protocol which

places participants at increased risk of harm or requires change to the protocol in order to eliminate an apparent hazard to participants

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Report Breach of Confidentiality

For example: A stolen laptop containing identifiable study information or an email containing the names of participants inadvertently sent to individuals outside the research team.– Breach information may be damaging to

participants’ financial standing, employability, reputation or place participant at criminal or civil liability

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Report Incarcerations

Any participant who is incarcerated during the course of the study for a protocol which has not been previously approved to enroll prisoners

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Report Participant Complaints

“Significant” complaints by participants that the PI cannot resolve:

– Rights;– Welfare;– Safety; OR– Willingness to participate

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Protocol Suspension/Termination

Any premature suspension or termination of the research by the sponsor, investigator, or institution

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OHRA Reporting Time Frame

Within 5 business days from the time the study team became aware of the information

Ensure knowledge of Sponsor’s and/or FDA reporting requirements when applicable

Top Ten Investigator Common Deficiencies Identified through QIP Onsite Reviews & For Cause Audits

1. Inadequate knowledge of regulatory requirements/institutional policies

2. Failure to follow IRB-approved protocol3. Failure to report protocol violations4. Failure to report adverse events & UAPs5. Improper documentation of informed consent6. Failure to document subject eligibility7. Incomplete/inaccurate source documentation 8. Poor/insufficient record keeping9. Lack of IRB approval10. Lack of study monitoring15

Creating an RNI Submission in ESTR

An RNI (Reportable New Information) submission can be created:– From the personal workspace for RNIs NOT associated with a particular study– From the approved study workspace for RNIs related to that specific study

Study Workspace:Personal Workspace:

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RNI Form in ESTR

The RNI Form captures the following information:– Date PI became aware of the information– Category of the new information (New or increased

risk or unexpected and possibly related harm)– Description of the information– If the new information in the PI’s opinion:

Poses a change to the study risk(s) Requires a modification to the approved research

Note: If new information is associated with more than one study a separate report should be created for each

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Tips for Completing RNI Form

Enter Protocol # as part of description of new information as well as indicate the corrective action plan by the study team (Question 3)

Users will only be able to link to studies for which they are already affiliated (Question 5).

Attachments on RNI workspace are only used as reference/supporting documents and will not be “approved” as part of RNI submission. Any documents requiring IRB approval should be attached to appropriate ESTR section via Initial, Continuing, or Modification submission (Question 6)

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IRB Actions - Post Reporting

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Post Reporting: RNI Notification

To: Stanley Estime

Subject: Reportable new information acknowledged

Study Link: New Reportable Information 12/12/2012 9:59 AM

Study Title: New Reportable Information 12/12/2012 9:59 AM

Principal

Investigator:

Stanley Estime

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Notification of AcknowledgementThis report of new information has been acknowledged. No further action is required.

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Reporting Tools

Utilize tools to keep track of reporting/ensure proper reporting:

– Adverse Event Tracking log– Protocol Violation/Deviation Tracking log

http://www.hsph.harvard.edu/ohra/qip/study-management-tools/

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Reporting Scenario?

During a monitoring visit the following observations were discovered:

1. Unsigned copies of participant consent forms2. Dates missing from executed consent documents3. Protocol deviations 4. A note-to-file regarding a missing study laptop which was later recovered by HUPD5. Case report forms on file for a participant enrolled into the incorrect arm of the study. He withdrew after his first study visit as a result of complaints of headaches possibly associated with study medication.

Which of the following observations would you report to the IRB as an RNI?

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When in Doubt?

Quality Improvement Program Staff Stanley Estime, sestime@hsph.harvard.edu, 617-432-2164 Lisa Gabel, lgabel@hsph.harvard.edu, 617-432-5842 Leslie Howes, lhowes@hsph.harvard.edu, 617-432-2153

IRB Operations Staff Department Assigned IRB Review Specialist:

http://www.hsph.harvard.edu/ohra/department-assignments/

IRB Administrative ChairJulie Kaberry, jkaberry@hsph.harvard.edu, 617-432-2149