Paula Peyrani, MDDivision of Infectious Diseases

University of Louisvillep0peyr01@louisville.edu

Performing the Study

OUTLINE

AE, SAE, UPIRSO

Follow-up visits

Data collection and Data quality

AE, SAE, UPIRSO AND MORE

Adverse event

Any untoward or unfavorable medical occurrence

in a human subject, including any abnormal sign (for

example, abnormal physical exam or laboratory finding),

symptom, or disease, temporally associated with the

subject’s participation in the research, whether or not

considered related to the subject’s participation in the

research.

AE, SAE, UPIRSO AND MORE

Adverse event

External Internal

AE experienced by subjects enrolled by

investigators in other study sites

AE experienced by subjects enrolled at the

investigator’s sites

AE, SAE, UPIRSO AND MORE

Serious Adverse Event Results in death Life-threatening Requires inpatient hospitalization or prolongation of

existing hospitalization Results in a persistent or significant disability/incapacity Results in a congenital anomaly/birth defect

AE, SAE, UPIRSO AND MORE

Serious Adverse Event Any other adverse event that may jeopardize the

subject’s health and may require medical or surgical

intervention to prevent one of the other outcomes listed

in this definition (e.g. allergic bronchospasm requiring

intensive treatment in the emergency room or at home)

AE, SAE, UPIRSO AND MORE

Unanticipated Problem Involving Risks to Subjects or Others

Any incident, experience, or outcome that meets all

of the following criteria:Unexpected (not in the consent form, sponsor

brochure, or labeling; not expected as part of subject’s

disease or conditionRelated or possibly related to study participationResearch places subjects or others at a greater risk of

harm

AE, SAE, UPIRSO AND MORE

Unexpected event

Any adverse event occurring in study subjects where

the specificity and severity of the event are NOT consistent

with the information provided in the IRB-approved research

protocol, any applicable investigator brochure, the current

IRB-approved informed consent document, and any other

relevant sources of information, such as product labeling

and package inserts

WHAT NEEDS TO BE REPORTED TO THE IRB?

Only when a particular local adverse event or series

of adverse events is determined to meet the criteria

for an UPIRTSO should a report of the adverse event(s) be

submitted to the UofL IRBs under the HHS

regulations.

AE that are NOT unanticipated problems

Unanticipated

problems that are not AE

AE that are unanticipated

problems

Unanticipated problems

A BC

WHAT NEEDS TO BE REPORTED TO THE IRB?

AAE that are NOT unanticipated problems

Unanticipated

problems that are not AE

AE that are unanticipated

problems

Unanticipated problems

Do not report REPORT

BC

WHAT NEEDS TO BE REPORTED TO THE IRB?

AE, incident, experience or outcome

Is the event unexpected in nature, severity of frequency?

NO

Is the event related or possibly related to participation in the

study?

NO

Does the event suggest that the research places subject or others

at a greater risk of harm?

NOSTOPNot a

UPIRSOYES

SAE

This is a UPIRTSO

WHAT NEEDS TO BE REPORTED TO THE IRB?

REPORT

Do adverse event that are not unexpected

need to be reported to the IRB?

WHAT NEEDS TO BE REPORTED TO THE IRB?

Do adverse event that are not unexpected

need to be collected?

Most of the adverse events seen during clinical trials will not be

a SAE or UPIRTSO Although not reported to the IRB, still need to be collected in

CRFs and they will be reviewed by study monitor

WHAT NEEDS TO BE REPORTED TO THE IRB?

Promptly report UPIRSO Incorrect labeling of study medication/test article Incorrect dosing of study medication/test article Incarceration of a subject while participating in research Suicide attempt related to participation in a research study

WHAT NEEDS TO BE REPORTED TO THE IRB?

Key items Definitions:

What is an AE, SAE? Related? Expected/Unexpected?

Event collection period: Pre-treatment, during treatment, during follow-up?

Unresolved AEs at end of study: Follow until resolution? Follow for 30 days?

WHAT DO I NEED TO KNOW FROM THE STUDY PROTOCOL?

Key items Timing:

SAE: as soon as possible (within 24 hrs of becoming aware)

Even if details are not available (follow-ups can be done) Expected/Unexpected?

Non-serious AE: Collected in CRF No real timing specified.

WHAT DO I NEED TO KNOW FROM THE STUDY PROTOCOL?

Scheduling subjects for visits If missed, may be a problem for data analysis If missed, sponsor may not pay for the visit Try to schedule visits at the beginning of the window

period Develop a reminder system: email, calendar, excel, phone Complete CRF including med log and adverse events Develop a reminder system: email, calendar, excel, phone

Maximize retention: reminder calls, goodies, thank you notes,

bonus gift certificates, birthday cards…

FOLLOW-UP VISITS

Keep in mind… if you want to avoid future queries Data entered should be accurate, complete and legible Check that answers are within range, dates are correct Make sure that information makes sense If source documents will be reviewed and collected, they need

to agree with the CRF Remember that if CRF is modified, this may have an impact on

other data Take errors as learning tools and make sure that you

understand why the modification is requested

DATA COLLECTION AND DATA QUALITY

Internal quality assurance May have a person solely dedicated to review CRF internally Should be someone different from the person who collected

the information Prepare for the monitor visit: check CRF and source document

(all or part of them) Request to have a monitor visit soon after the first case/s

DATA COLLECTION AND DATA QUALITY

Unanticipated Problems that Do Not Involve Adverse Events and Need to be Reported

As a result of a processing error by a pharmacy technician, a

subject enrolled in a multicenter clinical trial receives a dose of

an experimental agent that is 10-times higher than the dose

dictated by the IRB-approved protocol. While the dosing error increased the risk of toxic

manifestations of the experimental agent, the subject

experienced no detectable harm or adverse effect after an

appropriate period of careful observation.

Adverse Events that Do Not Represent Unanticipated Problems and Do Not Need to be

Reported

Phase 3, randomized, double-blind, placebo-controlled clinical

trial evaluating the safety and efficacy of a new investigational

anti-inflammatory agent for management of osteoarthritis Subject develops severe abdominal pain and nausea one

month after randomization (gastric ulcers) The IRB-approved protocol and IC indicated that the there was

a 10% chance of developing mild to moderate gastritis and a

2% chance of developing gastric ulcers for subjects assigned to

the active investigational agent Subject is withdrawn from the study

Adverse Events that Represent Unanticipated Problems and Need to be Reported

Subject with chronic gastroesophageal reflux disease enrolls in

a randomized, placebo- controlled, double-blind, phase 3

clinical trial evaluating a new investigational agent that blocks

acid release in the stomach Two weeks after being randomized and started on the study

intervention the subject develops acute kidney failure Known risk profile of the investigational agent does not include

renal toxicity, and the IRB-approved protocol and IC for the

study does not identify kidney damage as a risk of the

research.

References

1. Woodin K. The CRC’s Guide to Coordinating Clinical Research.

Thompson Centerwatch. 2004

2. University of Louisville. Investigator’s Guide for Human

Research. Version November 29, 2010.