Lesson:ICH GCP E6: Reporting Responsibilities Of The Investigator Flashcards
ICH E6 Investigator Responsibilities
1-Investigator’s Qualification and Agreement
2-Adequate Resources
3-Medical Care of Trial Subject
4-Communications with IRB/ICE
5-Compliance with Protocol
6-IP
7-Randomization Procedures unblinding
8-ICF
9-Records and Reports
10-Progress Reports
11-Safety Reporting
12-Premature Termination or Suspension of a Trial
13-Final Report by investigators
Adverse Events can be ??
Unexpected
Related or possibly related to the research intervention and may put subject at a greater risk or harm
What are Internal AEs?
-are those AEs experienced by subjects enrolled by the Investigators at that institution.
-inform Investigators via patient, provider or study coordinator.
-In a single center clinical trial all AEs would be considered internal AEs
**All adverse events you will report at your site will be IAEs those that you receive would be EAEs
What are External AEs?
-are those AEs experienced by subjects enrolled by investigators at other institutions engaged in the clinical trial.
-Inform outside investigators via report sent by sponsor/main center
When do I report an AEs?
1-is the AE unexpected?
2-is the AEs related or possibly related to participation in the research?
3-Does the AE suggest that the research place subject or others at a greater risk of harm than was previously know or recognized?
** Yes to all 3, then the AE is an unanticipated problem and must be reported to appropriate entities under the HHS regulations at 45 CRF 46.103 and 46.103(b)(5)
Do I have to report an anticipated AEs?
Do not report
AEs severity fall into one of the following categories?
Mild: does not influence performance or functioning. Doesn’t require intervention or treatment. Do not limit or interfere with daily activities, resolve quickly, without consequences
Moderate: patient uncomfortable, may include worsening of condition present at the onset. Treatment may be needed, expected to resolve in short term but consequences are possible.
Severe: significant symptoms that prevent normal daily activities, may require hospitalization or intervention. Long term consequences are possible
What is the severity/ grade of the AEs?
CTCAE grades.?
Grade 1: mild
Grade 2: moderate
Grade 3:severe or medical significant but immediately life-threatening.
Grade 4: Life-threatening consequences
Grade 5: Death relate to AE.
What is the timeline for reporting IAEs to the IRB?
AEs that meet the IRB’s reporting requirement must be reported to the IRB office/ sponsor as fallows:
-Internal AEs which are:
1-unexpected
2-fatal
3-Life-threatening
4-Related to the research
Must be report to the IRB within 24 hr of learning of the event
Is it a fatal/life threatening?
No—> sponsor report to the FDA within 15 days calendar (21 CFR 312.32 (o)(1))
Yes—> report to the FDA within 7 days calendar
Reporting time frame associated single case
Events that are interpretable as single case (strongly associated with drugs exposure) should be reported to FDA within 15 days from initial receipt
Reporting time frame: fatal/life threatening 7 days
Unexpected fatal or life threatening suspected Adverse reaction to FDA is not later than 7 calendar days (after the sponsor’s initial receipt of the information (21 CFR 312.32(c)(2))
When to report AE with variable severity/frequency?
1-An AE that is described/addressed in the investigator’s brochure, protocol or ICF document but occurs at a specificity or severity that is inconsistent with prior observation.
Ex: transaminase elevation is listed in the investigator’s brochure and hepatic necrosis is observed in study subject hepatic necrosis would be considered an unanticipated problem involving risk to human subject.
How to determine AE is an Unanticipated problem that needs to be reported?
AE involving risk to human subject and report to the IRB only if it were unexpected, serious and would have implications for the conduct of the study, changes in the protocol.
Individual AE occurrence does not meet these criteria bc as an isolated event, implications for the study cannot be understood.
Examples of type of unanticipated problems that must be reported to the IRB include:
-deviation from approved protocol that involves risks (missed safety labs, incorrect dosing or labeling)
-deviation from the protocol taken without prior IRB review to eliminate apparent immediate hazard to a subject
- lost or stolen research data
