IRB-Investigator/IRB-Investigator/Research Coordinator Mtg.Research Coordinator Mtg.

““CUMC’s New Progressive Policy For CUMC’s New Progressive Policy For Adverse Event Reporting”Adverse Event Reporting”

April 13, 2004April 13, 2004

George GasparisGeorge Gasparis

Andrew Wit, Ph.D.Andrew Wit, Ph.D.Professor of PharmacologyProfessor of Pharmacology

Columbia University Medical Center IRBColumbia University Medical Center IRB

ObjectivesObjectives

1)1) Present Columbia’s new adverse Present Columbia’s new adverse event reporting policyevent reporting policy

2)2) Provide an understanding of how to Provide an understanding of how to comply with the policy.comply with the policy.

3)3) Improve human subjects protection Improve human subjects protection through monitoring.through monitoring.

45 CFR 4645 CFR 46Reporting Reporting

RequirementsRequirements

To the IRB, institutional officials, To the IRB, institutional officials,

the relevant Department or the relevant Department or

Agency Head, and applicable Agency Head, and applicable

regulatory body, and OHRPregulatory body, and OHRP

45 CFR 4645 CFR 46Reporting Reporting

RequirementsRequirements

1) Unanticipated 1) Unanticipated

problems involving risks problems involving risks

to subjects or others in to subjects or others in

any covered research;any covered research;

45 CFR 4645 CFR 46Reporting Reporting

RequirementsRequirements

2) Serious or continuing 2) Serious or continuing

noncompliance with noncompliance with

Federal, institutional or Federal, institutional or

IRB requirements;IRB requirements;

45 CFR 4645 CFR 46Reporting Reporting

RequirementsRequirements

3) Suspension or 3) Suspension or

termination of IRB termination of IRB

approval for Federally-approval for Federally-

supported research.supported research.

45 CFR 4645 CFR 46Reporting Requirements Reporting Requirements

for Investigatorsfor Investigators

In summary, AE reporting to In summary, AE reporting to

the IRB: Unanticipated the IRB: Unanticipated

problems involving risks to problems involving risks to

subjects or others in any subjects or others in any

covered research.covered research.

FDA – 21 CFR 312.66FDA – 21 CFR 312.66AE Reporting AE Reporting

Requirements for Requirements for InvestigatorsInvestigators

-promptly report to the IRB all -promptly report to the IRB all

changes in the research changes in the research

activity and activity and all all

unanticipated problems unanticipated problems

involving risk to human involving risk to human

subjects or others.subjects or others.

FDA – 21 CFR 312.64 (b)FDA – 21 CFR 312.64 (b)AE Reporting AE Reporting

Requirements for Requirements for InvestigatorsInvestigators

-promptly report to the -promptly report to the

sponsor any adverse event sponsor any adverse event

that may reasonably be that may reasonably be

regarded as caused by, or regarded as caused by, or

probably caused by, the drug.probably caused by, the drug.

FDA – 21 CFR 812FDA – 21 CFR 812AE Reporting AE Reporting

Requirements for Requirements for DevicesDevices

-provides different reporting -provides different reporting

requirements for requirements for

investigational devices,investigational devices,

called adverse device called adverse device

effectseffects

Developing an Developing an Institutional Policy for AE Institutional Policy for AE

reportingreporting

-must be all-inclusive;-must be all-inclusive;

-consistent with all federal -consistent with all federal

regulationsregulations

Columbia’s Old Policy for Columbia’s Old Policy for AE reporting (May 5, AE reporting (May 5,

2003)2003)

-Serious and/or unexpected -Serious and/or unexpected

adverse events must be adverse events must be

reported to the IRB.reported to the IRB.

Columbia’s New Policy Columbia’s New Policy for AE reporting (April for AE reporting (April

13, 2004)13, 2004)

-Decreases the number of AEs that -Decreases the number of AEs that

need to be reported promptly to the need to be reported promptly to the

IRB.IRB.

-All other AEs will be reported in -All other AEs will be reported in

summary to the IRB at the time of summary to the IRB at the time of

continuing reviewcontinuing review

Columbia’s New Policy Columbia’s New Policy for AE reporting (April for AE reporting (April

13, 2004)13, 2004)

Internal AEs:Internal AEs:

-Report AEs that are:-Report AEs that are:

-serious AND unanticipated -serious AND unanticipated

to the IRB within 48 hours.to the IRB within 48 hours.

Columbia’s New Policy Columbia’s New Policy for AE reporting (April for AE reporting (April

13, 2004)13, 2004)

External AEs:External AEs:

-Report AEs that are: -Report AEs that are:

-serious AND unanticipated -serious AND unanticipated

-And possibly related to study -And possibly related to study

proceduresprocedures

to the IRB within 5 business days.to the IRB within 5 business days.

Columbia’s New Policy Columbia’s New Policy for AE reporting (April for AE reporting (April

13, 2004)13, 2004)

Unanticipated Problems (at any Unanticipated Problems (at any

site):site):

-Report to the IRB within 5 -Report to the IRB within 5

business days.business days.

Unanticipated ProblemsUnanticipated Problems

Any unexpected event that affects the rights, safety, or welfare of subjects or others that results from the study. The event could be physical, such as an adverse experience. The event could also involve social harm or risk, or psychological or legal harm or risk.

Examples include, but are not limited to, breach of confidentiality, protocol violations and deviations, and complaints about the research procedures or treatments by key personnel on the research team. 

Adverse Events

  Not serious Serious

Anticipated Report in summary at time of continuing review.

Report in summary at the time of continuing review

Unanticipated Report in summary at the time of continuing review.

Report promptly in accordance with terms of this policy. (external or internal)*

  

Unanticipated Problems

Nature Action

Involves risk to subjects or others Report promptly in accordance with terms of this policy

Does not involve risk to subjects or others

No report required

  

IRB Review of Adverse EventsIRB Review of Adverse Events

IRBs usually are not equipped to IRBs usually are not equipped to adequately review AEs because adequately review AEs because

they lack full information:they lack full information:

-for double-blind studies;-for double-blind studies;-from multi-center studies (e.g. -from multi-center studies (e.g.

all AEs or the all AEs or the denominator);denominator);

-and may lack necessary -and may lack necessary statistical statistical expertiseexpertise

IRB Review of Adverse EventsIRB Review of Adverse Events

IRBs, nevertheless, are responsible IRBs, nevertheless, are responsible for receiving and reviewing AEs. for receiving and reviewing AEs. IRBs review AEs to:IRBs review AEs to:

-assess whether risk(s) can be -assess whether risk(s) can be minimized for subjects minimized for subjects experiencing an ongoing Serious AE experiencing an ongoing Serious AE (SAE);(SAE);

-assess whether the SAE alters the -assess whether the SAE alters the initial risk/benefit analysis for the initial risk/benefit analysis for the studystudy

IRB Review of Adverse EventsIRB Review of Adverse Events

IRBs review AEs to (cont’d):IRBs review AEs to (cont’d):

-assess whether risk(s) can be -assess whether risk(s) can be minimized to all subjects in the minimized to all subjects in the future;future;

-assess whether disclosure of new -assess whether disclosure of new information must be made to new information must be made to new and existing subjects.and existing subjects.

Review of Adverse EventsReview of Adverse Events

Investigator’s role in review of AEs:Investigator’s role in review of AEs:

-ensure that all results are reported -ensure that all results are reported promptly to the investigatorpromptly to the investigator

-system to ensure prompt review, -system to ensure prompt review, by a physician, of all lab results and by a physician, of all lab results and clinical data to identify AEs;clinical data to identify AEs;

Anticipated and Unanticipated Anticipated and Unanticipated Adverse EventsAdverse Events

Investigator is responsible for determining Investigator is responsible for determining when an AE exceeds its expected when an AE exceeds its expected frequency or severity.frequency or severity.

Investigator must know and keep track of a Investigator must know and keep track of a list of expected AEs and their incidence, to list of expected AEs and their incidence, to the extent possible, for each study.the extent possible, for each study.

Investigator must have a system for Investigator must have a system for determining when an AEs exceed their determining when an AEs exceed their expected frequency and/or severity and expected frequency and/or severity and report such AEs promptly to the IRB.report such AEs promptly to the IRB.