Public Input for Changes to Reportable Events Policy May 23, 2017 - - PowerPoint PPT Presentation

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Public Input for Changes to Reportable Events Policy May 23, 2017 - - PowerPoint PPT Presentation

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Public Input for Changes to Reportable Events Policy May 23, 2017 Richard Guido, MD, IRB Chair Jamie Zelazny, PhD, RN, Regulatory Affairs Specialist Outline Regulatory basis for reporting policies Importance of consistency between IRBs

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Public Input for Changes to Reportable Events Policy

May 23, 2017 Richard Guido, MD, IRB Chair Jamie Zelazny, PhD, RN, Regulatory Affairs Specialist

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Outline

  • Regulatory basis for reporting policies
  • Importance of consistency between IRBs
  • Evaluation of Pitt IRB policies and IRBs across

the country

  • Proposed changes re: deviations
  • Discussion

Human Research Protection Office

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Regulatory Requirements for Reporting

Human Research Protection Office

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HHS regulatory requirements

Institutions engaged in human subjects research conducted or supported by HHS must have written procedures for ensuring prompt reporting to the IRB, appropriate institutional officials, and any supporting department or agency head of any unanticipated problem involving risks to subjects or others (45 CFR 46.103(b)(5)).

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HHS regulatory requirements

For research covered by an assurance approved for federalwide use by OHRP, HHS regulations at 45 CFR 46.103(a) require that institutions promptly report any unanticipated problems to OHRP.

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OHRP Guidance (2007) Unanticipated Problems Involving Risk To Subjects or Others

Any incident, experience or outcome that meets all of the following criteria:

  • Unexpected (in terms of nature, severity, or

frequency)

  • Related or possibly related to participation in the

research

  • Suggests that the research places subjects or others

at a greater risk of harm (including physical, psychological, economic or social harm) than was previously known or recognized

http://www.hhs.gov/ohrp/policy/advevntguid.html

Human Research Protection Office

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OHRP’s Venn Diagram

Human Research Protection Office

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FDA Regulatory Requirements: Investigator to IRB

  • Investigators are required to report promptly

“to the IRB… all unanticipated problems involving risks to human subjects or others,” including adverse events that should be considered unanticipated problems (§§ 56.108(b)(1), 312.53(c)(1)(vii), and 312.66).

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FDA Guidance (January 2009)

AE should be considered an unanticipated problem involving risk to human subjects and reported to the HRPO, only if:

– unexpected and, – serious and, – would have implications for the conduct of the study (significant, and usually safety‐related change in the protocol like revising inclusion/exclusion criteria, new monitoring requirements, ICF or IB)

http://www.fda.gov/cder/guidance/OC2008150fnl.pdf

Human Research Protection Office

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FDA Guidance January 2009

  • An individual AE occurrence ordinarily does not

meet these criteria because, as an isolated event, its implications for the study cannot be understood.

  • FDA provided specific examples of AE’s that

would meet the definition of an unanticipated problem involving risk to subjects.

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FDA Guidance January 2009

  • Most AE’s generally require an evaluation of

their relevance and significance to the study

  • Aggregate analysis of other occurrences of the

same (or similar) event

  • DSMB, DSMB, DSMB!!!!!

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What about protocol deviations?

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Noncompliance/Protocol Deviations

  • Inconsistencies between HHS and FDA

regulations

  • Inconsistencies within FDA regulations for drugs

and devices

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HHS and FDA Regulations

  • Prospective approval is required for changes to

the research protocol except for deviations performed to eliminate apparent immediate hazards to the subject in compliance with 45 CFR 46.103 (b) (4) and 21 CFR 56.108(a)(4)

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FDA Compliance Program Manual – Ch 48

  • Protocol deviations: generally an unplanned excursion

from the protocol that is not implemented or intended as a systematic change…….Like protocol amendments, deviations initiated by the clinical investigator must be reviewed and approved by the IRB and the sponsor prior to implementation, unless the change is necessary to eliminate apparent immediate hazards to the human subjects (21 CFR 312.66), or to protect the life or physical well-being of the subject (21 CFR 812.35 (a)(2)), and generally communicated to FDA.

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Noncompliance/Deviations

  • No real guidance from FDA or OHRP about what
  • r how deviations should be reported to IRBs

after they occur.

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Need for consistency between IRBs

  • Same regulatory basis for policies and

procedures

  • Single IRB review

– Need to follow reporting policies of the IRB of record for your study

Human Research Protection Office

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Need for consistency between IRBs

  • Move to more standardized IRB electronic

submission systems

– Pitt’s electronic IRB submission process currently being rewritten, which will change our Reportable Event Policy in 2018

Human Research Protection Office

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National review of IRB policies

  • Generally consistent regarding unanticipated

problems involving risk to subject or others

  • Wide variation in reporting of deviations

Human Research Protection Office

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How does Pitt IRB’s reporting policy compare to others?

  • UAPs

– Fairly similar overall – Separate reporting pathways for AEs and UAPs not always required – Deviations that are UAPs need to be reported as UAPs

Human Research Protection Office

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How does Pitt IRB’s reporting policy compare?

  • Deviations

– Pitt is more conservative overall – National trend is to require 2 levels of reporting

  • Reportable event – deviations that affect the rights and

welfare of human subjects or compromise the quality

  • f the data
  • Time of continuing review – upload a log of “minor”

deviations which occurred during the review period.

Human Research Protection Office

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Reportable Events

Deviation or Non- Compliance

Adverse Events that are Unanticipated Problems Involving Risk to Subjects

  • r Others

“Other” Unanticipated Problems Involving Risk to Subject or Others

Types of Reportable Events

Human Research Protection Office

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Protocol Deviation or Non‐Compliance ‐Current Pitt IRB Policy

  • Investigators must submit all incidents of

non‐compliance/protocol deviations within 10 working days of the investigator becoming aware of the event

Human Research Protection Office

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Definitions

Human Research Protection Office

Current definition Proposed definitions Non‐compliance: Failure on the part of the investigator or any member of the study team to follow the terms of University of Pittsburgh IRB approved protocol or to abide by applicable laws

  • r regulations, or University of

Pittsburgh IRB policies. This includes protocol deviations. Incidents of noncompliance on the part

  • f research participants which do not

involve risk need not be reported to the IRB. No change in the definition – only in how these will be reported to the IRB

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Definitions

Human Research Protection Office Current definition Proposed definitions All incidents require reporting Noncompliance requiring submission of a reportable event: Incidents of noncompliance

  • r protocol deviations that adversely affect

that rights and welfare of human subjects, or significantly compromises the quality of the research data. The IRB will determine whether reports meet the definition of serious

  • r continuing non‐compliance.

N/A Noncompliance reportable at the time of continuing review: Incidents of non‐ compliance which do not meet the above definition should be logged by the study team in real time and then uploaded into the renewal application in OSIRIS at the time of continuing review. The IRB expects that the investigator and study team will regularly monitor the log for patterns of noncompliance that may represent serious or continuing noncompliance.

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Example of log

Date of Deviation Study ID Description of Deviation (attach extra pages, if needed) Reason for Deviation Corrective Action Plan Sponsor Notification Date (required for IND/IDE studies) Human Research Protection Office

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Human Research Protection Office

Examples Current policy Proposed policy Performing non‐exempt human subject research without obtaining prospective University IRB approval Report within 10 working days Report within 10 working days Conducting research during a lapse in IRB approval; Report within 10 working days Report within 10 working days Implementing protocol modifications without

  • btaining prospective IRB

approval Report within 10 working days Report within 10 working days

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Examples

Human Research Protection Office

Examples Current policy Proposed policy Obtaining consent using an

  • utdated consent form, when the

new consent form contained new information that may have caused the subject to change their mind about participating; Report within 10 working days Report within 10 working days Obtaining consent using an

  • utdated consent form when there

were no substantive differences between the consent form that was used and the consent form that should have been used (i.e., dates in the footer) Report within 10 working days Log and submit at time of continuing review

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Examples

Human Research Protection Office

Examples Current policy Proposed policy Not ‐adhering to inclusion/exclusion criteria Report within 10 working days Report within 10 working days Enrolling more subjects that approved in the protocol in a greater than minimal risk study Report within 10 working days Report within 10 working days Enrolling more subjects than approved in a minimal risk study Report within 10 working days Log and submit at time of continuing review Performing non‐safety related research procedures outside the protocol specified window Report within 10 working days Log and submit at time of continuing review

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Discussion

How difficult will it be to log deviations throughout the year and report at the time of continuing review?

Human Research Protection Office

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Discussion

How comfortable would investigators feel about making the determination about what should be reported as a reportable event and what should be reported at the time of continuing review?

Human Research Protection Office

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Discussion

How much of a burden is our current system for reportable events?

Human Research Protection Office

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Discussion

What are your experiences with other IRBs and

  • ther common networks?

Human Research Protection Office

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Comments?

Human Research Protection Office

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Upcoming HRPO Seminar

Using SMART IRB and Single IRB Review

  • Find out the advantages of SMART IRB.

Learn how Pitt can be the IRB of record

  • r rely on another IRB

– June 6, 2017 – 12:00pm – BST S120