Unanticipated Problems Flashcards
Adverse Event (AE)
unfavorable change in a research subject that may occur during or after administration of IP, does not have to be cuased by the IP/Study procedure
Adverse Event as unanticipated problem
-risk is not harm, it is the possibility of harm
AE cause harm, UP incerase risk of harm
-AE can increase risk of harm without actually harming, which would be unanticipated & reportable
AE Severity
Serious
-Intensity of event-mild, moderate, severe
-Serious is not severity
Causality
-Likelihood & extent that an IP contributed to an AE
-Only an investigator can determine
-May need to report to the sponsor, IRB, and regulatory authorities
FDA Unanticpated Problems
-mirror common rule, but no definition
-promptly report to the IRB if UP has risks, including AEs
-FDA & investigators promptly informed by the sponsor for significant new AEs or risks
-Multi-center trial-better for sponsors to assess & report
HHS unanticipated problems-common rule
IRB shall establish & follow written procedures for prompt reporting to the IRB or OHRP
-unanticipated problems with risks to subjects, continuing noncompliance, suspension/termination of IRB approval
If blinding must be broken for emergency
document the date, reasons for breaking a code, name of who broke, action taken, then sign and date, and explain to the sponsor
Investigators need to report AEs from
the time a subject consents until the final study visit unless the protocol says otherwise
Minimum info for expedited reporting of SAE for drug
- Indentifiable patient
- Name of suspected medicinal product
- Identifable reporting source
- Event or outcome that can be identified as serious & unexpected which has a suspected causal relationship
- Attemt follow-up info
Noncompliance
-determine the root cause analysis (RCA)
-implement a corrective & preventative action plan (CAPA) appropriate to the situation
-if serious noncompliance persists, termination of participation should be determined & regulatory authorities notified
OHRP Adverse Events vs. unanticipated Problems
-AE is more frequent, rate of occurence is higher
-Only UP requires event is related or possibly related to research
-UP risk of harm to non-research subjects
-Only UP usually unanticipated
-Serious AE is always an UP
-AE is UP if you have to modify the IDB, protocol, or consent
OHRP Unanticipated Problems
-unexpected,
-related/possibly related to participation in the research
AND
-subjects or others at greater risk of harms then previously known
- All 3 criteria must be met
- Unexpected, related, greater risk of harm
Reporting unanticipated problems
For OHRP: Researcher reports to IRB, IRB to OHRP
For FDA: The researcher reports to sponsor & IRB
A multicenter trial, the sponsor reports to researchers, all IRBs, and the FDA
The IRB reports to FDA & OHRP
SAE Categories
- Death
- Life-threatening AE (or patient at risk of)
- Hospitalization or prolonging of already being hospitalized
- Persistent or significant incapacity or distruption of ability to control normal life functions
- Birth defect
SAE Reporting to Sponsor
-Standard within 24 hours
-Actually based on regulatory authority or IRB requirements
-Life threatning or fatal-report immediately
Serious, unexpected, associated with drug AEs
must be reported to the IRB and regulatory authorities
Sponsor Responsibilities for SUSARs
- SAEs that are unexpect & associated with the IP need to be reported to regulatory authorities
- Suspected, unexpected, serious, adverse reactions (SA reports)
- Must notify all investigators and may need to modify ICF & notify subjects
Unanticipated Problems-Device-FDA
-Unanticipated Adverse Device Effects
-Serious Adverse effect or life-threatening/death if not previously identified in nature, severity, or degree of incidence or related to rights, safety, welfare
-researcher-UADE reports to IRB & sponsor ASAP, but no later than 10 working days
-Sponsor-UADE to FDA & all reviewing IRBs & investigators within 10 working days
Unexpected AE
Adverse reaction, where the nature or severity is not consistent with the IDB
