paula peyrani, md division of infectious diseases university of louisville [email protected]...
TRANSCRIPT
Paula Peyrani, MDDivision of Infectious Diseases
University of [email protected]
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.