Roy R. Estrada, PhD, PA-C, CIP Associate Director IRB UTHSCSA
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Transcript of Roy R. Estrada, PhD, PA-C, CIP Associate Director IRB UTHSCSA
Unanticipated Problems Unanticipated Problems Involving Risk to Involving Risk to
Subjects or Others Subjects or Others (UPIRSO)(UPIRSO)
Roy R. Estrada, PhD, PA-C, CIPRoy R. Estrada, PhD, PA-C, CIP
Associate Director IRBAssociate Director IRB
UTHSCSAUTHSCSA
The UTHSCSA Institutional The UTHSCSA Institutional Review Board (IRB) applies an Review Board (IRB) applies an Adverse Events reporting Adverse Events reporting process based on federal process based on federal guidanceguidance
The scope of what must be The scope of what must be reported promptly to the IRB is reported promptly to the IRB is narrow and definednarrow and defined
What?What?
Scenario #1Scenario #1
Ph II, clinical trial testing a new investigational Ph II, clinical trial testing a new investigational antihypertensive drug, at UTHSCSAantihypertensive drug, at UTHSCSA
Determined by the IRB as greater than minimal risk Determined by the IRB as greater than minimal risk No documented evidence of GERD associated with No documented evidence of GERD associated with
the drugthe drug 3 of 10 subjects had severe GERD that began 3 of 10 subjects had severe GERD that began
within one week of starting drugwithin one week of starting drug Internal or External?Internal or External? Related or Unrelated?Related or Unrelated? Anticipated or Unanticipated?Anticipated or Unanticipated? Report to IRB? If yes, what time frame?Report to IRB? If yes, what time frame?
Categories of Categories of ReportingReporting
Prompt reporting: Promptly report all adverse
events and unanticipated problems that might meet the definition of “Unanticipated Problems Involving Risks to Subjects or Others”
Non-Prompt Reporting: Not meet definition of UPIRSO Summarize Non-UPIRSO /
UPIRSO in next progress report.
Categories of EventsCategories of Events
Adverse EventsAdverse Events involve involve “physical or psychological harm” “physical or psychological harm”
Non-Adverse EventNon-Adverse Event does not does not involve physical or psychological involve physical or psychological harmharm
UNANTICIPATEDUNANTICIPATED e.g., not in the consent e.g., not in the consent form, Sponsor Brochure, or labeling; not form, Sponsor Brochure, or labeling; not expected as part of subject’s disease or expected as part of subject’s disease or conditioncondition
RELATEDRELATED e.g., (or possibly related) a result e.g., (or possibly related) a result of the research interaction/ identifiable of the research interaction/ identifiable data collectiondata collection
GREATER RISKGREATER RISK to subjects or others e.g., to subjects or others e.g., harm (including physical, psychological, harm (including physical, psychological, economic, or social harm)economic, or social harm)
SERIOUSSERIOUS e.g., severe/life threatening/fatal e.g., severe/life threatening/fatal
Categories of UPIRSO Categories of UPIRSO CriteriaCriteria
UNANTICIPATEDUNANTICIPATED in Nature, in Nature, Severity or FrequencySeverity or Frequency
RELATEDRELATED ReasonablyReasonably Sure Sure
GREATER RISKGREATER RISK Greater Risk of Greater Risk of harm than was previously known harm than was previously known or recognizedor recognized
SERIOUSSERIOUS relates to adverse events relates to adverse events
Categories of UPIRSO Categories of UPIRSO CriteriaCriteria
Scenario #1Scenario #1
Ph II, clinical trial testing a new investigational Ph II, clinical trial testing a new investigational antihypertensive drug, at UTHSCSAantihypertensive drug, at UTHSCSA
Determined by the IRB as greater than minimal risk Determined by the IRB as greater than minimal risk No documented evidence of GERD associated with No documented evidence of GERD associated with
the drugthe drug 3 of 10 subjects had severe GERD that began 3 of 10 subjects had severe GERD that began
within one week of starting drugwithin one week of starting drug Anticipated or Unanticipated?Anticipated or Unanticipated? Related or Unrelated? Related or Unrelated? Serious? If not, Greater Risk?Serious? If not, Greater Risk? Internal or External?Internal or External? Report to IRB? If yes, what time frame?Report to IRB? If yes, what time frame?
Scenario #1Scenario #1Is a UPIRSOIs a UPIRSO
Internal: Unanticipated and RelatedInternal: Unanticipated and Related Not Serious Not Serious Greater risk than previously knownGreater risk than previously known
Prompt report Prompt report Submit changes, submit UPIRSO Submit changes, submit UPIRSO
report to IRB within 7 daysreport to IRB within 7 days
Relatedness - Old WayRelatedness - Old Way
Scenario #2Scenario #2 International study -multiple countries-multiple sitesInternational study -multiple countries-multiple sites UTHSCSA is IRB for local PI and VA PIUTHSCSA is IRB for local PI and VA PI Methods: interviewing 2000 mothers (mothers and Methods: interviewing 2000 mothers (mothers and
babies are subjects) regarding breastfeeding babies are subjects) regarding breastfeeding (records)(records)
IRB determined to be minimal riskIRB determined to be minimal risk Known risks of breach of confidentiality Known risks of breach of confidentiality VA study coordinator reports that 6 babies VA study coordinator reports that 6 babies
(subjects) died of malnutrition(subjects) died of malnutrition Anticipated or Unanticipated?Anticipated or Unanticipated? Related or Unrelated? Related or Unrelated? Serious? If not, Greater Risk?Serious? If not, Greater Risk? Internal or External?Internal or External? Report to IRB? If yes, what time frame?Report to IRB? If yes, what time frame?
UTHSCSA UPIRSO Guidance Regarding Probability of Relatedness
100%
Possibility(How Convinced you are of Relatedness
0% Relatedness
UTHSCSA UPIRSO Guidance Regarding Probability of Relatedness
100% 100% sure
Possibility
(How Convinced you are of Relatedness
0%
Relatedness Could not even guess
UTHSCSA UPIRSO Guidance Regarding Probability of Relatedness
100% 100% sure
Possibility
(How Convinced you are of Relatedness
0% Not Definitely Related, Relatedness related,
but could not but could not even guess even guess
>50
%?
co
nvi
nce
dR
easo
nab
ly
sure
UTHSCSA UPIRSO Guidance Regarding Probability of Relatedness
100% 100% sure
it is not related Possibility
(How Convinced you are of Relatedness
0% Not Definitely Related, Relatedness related,
but could not but could not even guess even guess
>50
%?
co
nvi
nce
dR
easo
nab
le
sure Not Reasonably sure of relatedness
Do not report until more information
UTHSCSA UPIRSO Guidance Regarding Probability of Relatedness
100%
Possibility(How Convinced you are of Relatedness
0% Not Definitely Related, Relatedness related,
but could not but could not even guess even guess
>50
%?
co
nvi
nce
dR
easo
nab
le
sure Not Reasonably sure of relatedness
Do not report until more information
100% sure definitely related it is not related Not Related at least partially related to participation in research
100% 100% sure it is
>50
%?
co
nvi
nce
dR
easo
nab
le
sure
UTHSCSA UPIRSO Guidance Regarding Probability of Relatedness
100% 100% sure it is100% sure definitely related it is not related Not Related at least partially related to participation in research
Possibility(How Convinced you are of Relatedness
Not Reasonably sure of relatednessDo not report until more information
0% Not Definitely Related, Relatedness related,
but could not but could not even guess even guess
Scenario #2Scenario #2 International study -multiple countries-multiple sitesInternational study -multiple countries-multiple sites UTHSCSA is IRB for local PI and VA PIUTHSCSA is IRB for local PI and VA PI Methods: interviewing 2000 mothers (mothers and Methods: interviewing 2000 mothers (mothers and
babies are subjects) regarding breastfeeding babies are subjects) regarding breastfeeding (records)(records)
IRB determined to be minimal riskIRB determined to be minimal risk Known risks of breach of confidentiality Known risks of breach of confidentiality VA study coordinator reports that 6 babies VA study coordinator reports that 6 babies
(subjects) died of malnutrition(subjects) died of malnutrition Anticipated or Unanticipated?Anticipated or Unanticipated? Related or Unrelated? Related or Unrelated? Serious? If not, Greater Risk?Serious? If not, Greater Risk? Internal or External?Internal or External? Report to IRB? If yes, what time frame?Report to IRB? If yes, what time frame?
Scenario #2Scenario #2Is not a UPIRSOIs not a UPIRSO
Internal: Unanticipated and Serious Internal: Unanticipated and Serious but Unrelatedbut Unrelated
Prompt Reporting not required. Prompt Reporting not required. Follow other reporting Follow other reporting
requirements listed in protocol requirements listed in protocol (e.g., sponsored studies) as well(e.g., sponsored studies) as well
Scenario #3Scenario #3 Multi-center NCI studyMulti-center NCI study UTHSCSA one of 80 sitesUTHSCSA one of 80 sites IRB determined - greater than minimal risk - DSMPIRB determined - greater than minimal risk - DSMP Procedures include bone marrow transplant, Procedures include bone marrow transplant,
chemotherapy, blood drawing, transfusionschemotherapy, blood drawing, transfusions Risks listed in protocol documentationRisks listed in protocol documentation Subject dies in Detroit site from Subject dies in Detroit site from
complications of the chemo, UTHSCSA PI complications of the chemo, UTHSCSA PI receives IND safety reportreceives IND safety report
Anticipated or Unanticipated?Anticipated or Unanticipated? Related or Unrelated? Related or Unrelated? Serious? If not, Greater Risk?Serious? If not, Greater Risk? Internal or External?Internal or External? Report to IRB? If yes, what time frame?Report to IRB? If yes, what time frame?
UNANTICIPATEDUNANTICIPATED AND AND RELATEDRELATED (possibly(possibly RELATED) events/problems that represent a RELATED) events/problems that represent a GREATER RISK to subjects or others GREATER RISK to subjects or others
GenerallyGenerally will warrant consideration of will warrant consideration of substantive changessubstantive changes
UNANTICIPATEDUNANTICIPATED and and RELATEDRELATED (possibly RELATED)(possibly RELATED) and and SERIOUSSERIOUS adverse adverse events should also be considered to be events should also be considered to be represent GREATER RISK. represent GREATER RISK.
AlwaysAlways will warrant consideration of will warrant consideration of substantive changessubstantive changes
UPIRSOUPIRSO
Examples of corrective Examples of corrective actions or substantive actions or substantive
changeschanges Changes to eliminate apparent immediate Changes to eliminate apparent immediate
hazards to subjects (before or after IRB approval);hazards to subjects (before or after IRB approval); Modification of inclusion or exclusion criteria to Modification of inclusion or exclusion criteria to
mitigate the newly identified risks;mitigate the newly identified risks; Implementation of additional procedures for Implementation of additional procedures for
monitoring subjects; monitoring subjects; Suspension of enrollment;Suspension of enrollment; Suspension of research procedures;Suspension of research procedures; Modification of informed consent documents to Modification of informed consent documents to
include a description of newly recognized risks; include a description of newly recognized risks; Notification of previously enrolled subjects about Notification of previously enrolled subjects about
newly recognized risksnewly recognized risks
Scenario #3Scenario #3 Multi-center NCI studyMulti-center NCI study UTHSCSA one of 80 sitesUTHSCSA one of 80 sites IRB determined - greater than minimal risk - DSMPIRB determined - greater than minimal risk - DSMP Procedures include bone marrow transplant, Procedures include bone marrow transplant,
chemotherapy, blood drawing, transfusionschemotherapy, blood drawing, transfusions Risks listed in protocol documentationRisks listed in protocol documentation Subject dies in Detroit site from Subject dies in Detroit site from
complications of the chemo, UTHSCSA PI complications of the chemo, UTHSCSA PI receives IND safety reportreceives IND safety report
Anticipated or Unanticipated?Anticipated or Unanticipated? Related or Unrelated? Related or Unrelated? Serious? If not, Greater Risk?Serious? If not, Greater Risk? Internal or External?Internal or External? Report to IRB? If yes, what time frame?Report to IRB? If yes, what time frame?
Scenario #3Scenario #3Is not a UPIRSOIs not a UPIRSO
External: Related, and Serious, External: Related, and Serious, and some argue and some argue Unanticipated Unanticipated vs. Anticipatedvs. Anticipated
If confusing If confusing Substantive change required?Substantive change required?
Anticipated Anticipated
ANTICIPATEDANTICIPATED in the consent form, in the consent form, Sponsor Brochure, or labeling; expected Sponsor Brochure, or labeling; expected as part of subject’s disease or conditionas part of subject’s disease or condition
Can’t Determine if RELATEDCan’t Determine if RELATED Not Not ReasonablyReasonably sure sure
Represents a RISKRepresents a RISK But maybe not a But maybe not a Greater Risk of harm than was previously Greater Risk of harm than was previously known or recognizedknown or recognized
Clarify at each levelClarify at each level
Scenario #4Scenario #4
UTHSCSA Ph II cancer trial on biologic made UTHSCSA Ph II cancer trial on biologic made from human serafrom human sera
After 4 subjects enrolled audit revealed After 4 subjects enrolled audit revealed administered product was obtained from administered product was obtained from improperly screened donors (HIV,Hep-B risk)improperly screened donors (HIV,Hep-B risk)
IRB determined it is greater than minimal IRB determined it is greater than minimal riskrisk
Known risks: extensiveKnown risks: extensive No subject experienced any harmNo subject experienced any harm Anticipated or Unanticipated?Anticipated or Unanticipated? Related or Unrelated? Related or Unrelated? Serious? If not, Greater Risk?Serious? If not, Greater Risk? Internal or External?Internal or External? Report to IRB? If yes, what time frame?Report to IRB? If yes, what time frame?
UNANTICIPATEDUNANTICIPATED AND AND RELATEDRELATED (possibly(possibly RELATED) events/problems that represent a RELATED) events/problems that represent a GREATER RISK to subjects or others GREATER RISK to subjects or others
Only events that involve physical / Only events that involve physical / psychological harm (AKA adverse events) can psychological harm (AKA adverse events) can be be SERIOUSSERIOUS
UNANTICIPATEDUNANTICIPATED and RELATED (possibly and RELATED (possibly RELATED) and SERIOUS adverse events should RELATED) and SERIOUS adverse events should also be considered to be represent GREATER also be considered to be represent GREATER RISK). RISK).
UPIRSOUPIRSO
Scenario #4Scenario #4
UTHSCSA Ph II cancer trial on biologic made UTHSCSA Ph II cancer trial on biologic made from human serafrom human sera
After 4 subjects enrolled audit revealed After 4 subjects enrolled audit revealed administered product was obtained from administered product was obtained from improperly screened donors (HIV,Hep-B risk)improperly screened donors (HIV,Hep-B risk)
IRB determined it is greater than minimal IRB determined it is greater than minimal riskrisk
Known risks: extensiveKnown risks: extensive No subject experienced any harmNo subject experienced any harm Anticipated or Unanticipated?Anticipated or Unanticipated? Related or Unrelated? Related or Unrelated? Serious? If not, Greater Risk?Serious? If not, Greater Risk? Internal or External?Internal or External? Report to IRB? If yes, what time Report to IRB? If yes, what time
frame?frame?
Scenario #4Scenario #4Is a UPIRSOIs a UPIRSO
External: Unanticipated and External: Unanticipated and Related, although would not Related, although would not call it “Serious” as no harm call it “Serious” as no harm occurred.occurred.
Greater riskGreater risk Report to IRB promptly Report to IRB promptly
Report all internal (Report all internal (locallocal), ), unanticipated, related, unanticipated, related, life life threateningthreatening or or fatalfatal events within events within 48 48 hours hours (Submit “Fatal toxicities” only if (Submit “Fatal toxicities” only if NCI)NCI)
Report Report all othersall others within within 7 working7 working daysdays if local if local ((internalinternal) or ) or 14 working days off site 14 working days off site (external or follow-up reports)(external or follow-up reports)
How Promptly?How Promptly?
InternalInternal Events or problems experienced by Events or problems experienced by
subjects enrolled by investigators subjects enrolled by investigators approved by the UTHSCSA IRB to approved by the UTHSCSA IRB to perform research at their respective perform research at their respective institutions.institutions.
ExternalExternal Events or problems experienced by Events or problems experienced by
subjects enrolled by investigators subjects enrolled by investigators approved by IRB’s other than UTHSCSAapproved by IRB’s other than UTHSCSA
How Promptly?How Promptly?
Protocol Violations come in two flavors:Protocol Violations come in two flavors: ExceptionsExceptions are sought prior to are sought prior to
implementation implementation (Yes it deviates from the (Yes it deviates from the protocol but it is approved to do so by the IRB protocol but it is approved to do so by the IRB beforehand.)beforehand.) Exceptions are not part of the UPIRSO process Exceptions are not part of the UPIRSO process
and are requested using an and are requested using an amendment formamendment form For example a request for an exception to the For example a request for an exception to the
inclusion criteria for a single potential subjectinclusion criteria for a single potential subject DeviationsDeviations are reported after they occur are reported after they occur
Deviations are a measure of complianceDeviations are a measure of compliance Deviations may also represent a Deviations may also represent a UPIRSOUPIRSO
What about Deviations?What about Deviations?
Possible UPIRSO: AE or Non-AE UPIRSO ReportPossible UPIRSO: AE or Non-AE UPIRSO Report The report that replaces the forms used for The report that replaces the forms used for
Prompt Reporting: Adverse Event and IND Safety Prompt Reporting: Adverse Event and IND Safety Report formsReport forms
Non-Prompt ReportingNon-Prompt Reporting To report Adverse Events or IND Safety Reports To report Adverse Events or IND Safety Reports
that do not meet criteria for prompt reporting; that do not meet criteria for prompt reporting; Report in Progress Report.Report in Progress Report.
UTHSCSA Event Tracking Log - OptionalUTHSCSA Event Tracking Log - Optional Assists you in summarizing on your next Assists you in summarizing on your next
progress report: all non-prompt, non-UPIRSO progress report: all non-prompt, non-UPIRSO and UPIRSO in relation to your entire studyand UPIRSO in relation to your entire study
Forms Forms cancan be found on our website be found on our website http://research.uthscsa.edu/irbhttp://research.uthscsa.edu/irb
How?How?
Any Unanticipated Any Unanticipated Problem, Adverse Event, Problem, Adverse Event, or Deviation submitted is or Deviation submitted is considered a considered a possible possible UPIRSOUPIRSO and will be and will be reviewed by an IRB Chair reviewed by an IRB Chair or designated reviewer. or designated reviewer.
How will reports be How will reports be processed?processed?
If Promptly Reported:If Promptly Reported: Possible UPIRSO Report will be Possible UPIRSO Report will be
reviewed by expedited or full IRB reviewed by expedited or full IRB review as appropriate. review as appropriate.
PI must act on requirements of PI must act on requirements of involved institutions and requests for involved institutions and requests for more information to resolve the more information to resolve the issue.issue.
PI must submit follow-up PI must submit follow-up reports/report of resolution.reports/report of resolution.
Discovery processDiscovery process
OIRB must report, PI must act:OIRB must report, PI must act: ASAP report to involved institutions ASAP report to involved institutions
Institutions will distribute internallyInstitutions will distribute internally
PI must gather requirements and act PI must gather requirements and act
PI must submit a follow-up reportPI must submit a follow-up report
““Is the action plan fully initiated and Is the action plan fully initiated and can we call the issue resolved”can we call the issue resolved”
Determined to be a Determined to be a UPIRSOUPIRSO
IRB may act/IRB must report to OHRP:IRB may act/IRB must report to OHRP:
Failing to meet deadlines may be Failing to meet deadlines may be considered noncomplianceconsidered noncompliance
IRB can suspend enrollment, suspend IRB can suspend enrollment, suspend procedures or terminate a studyprocedures or terminate a study
Suspensions, terminations and serious Suspensions, terminations and serious or continuing noncompliance are or continuing noncompliance are reported to OHRPreported to OHRP
Final report to OHRP Final report to OHRP ((±± FDA) FDA)
UPIRSO ResolutionUPIRSO Resolution
If Prompt Reporting is not If Prompt Reporting is not required:required:The report will be returned to The report will be returned to
the PIthe PI with instructions to with instructions to summarize in their next summarize in their next progress reportprogress report
If sponsor If sponsor requiredrequired prompt prompt reporting send them a copy of reporting send them a copy of UTHSCSA policy letter.UTHSCSA policy letter.
How will reports be How will reports be processed?processed?
Scenario #5Scenario #5
UTHSCSA study of HIV patientsUTHSCSA study of HIV patients Procedures include interviews, (e.g., illicit Procedures include interviews, (e.g., illicit
drugs)drugs) Known risk of loss of confidentiality but data is Known risk of loss of confidentiality but data is
in password protected computer without in password protected computer without encryptionencryption
Event = computer with data is stolenEvent = computer with data is stolen Anticipated or Unanticipated?Anticipated or Unanticipated? Related or Unrelated? Related or Unrelated? Serious? If not, Greater Risk?Serious? If not, Greater Risk? Internal or External?Internal or External? Report to IRB? If yes, what time frame?Report to IRB? If yes, what time frame?
If an amendment is required:If an amendment is required: Submit ASAP. Submit ASAP. May qualify for expedite approval.May qualify for expedite approval.
Especially if not really a UPIRSOEspecially if not really a UPIRSO Substantive change Substantive change
Amendment associated with UPIRSO Amendment associated with UPIRSO will go to full IRBwill go to full IRB
PI must include thorough description of PI must include thorough description of event and any immediate actions event and any immediate actions taken.taken.
What if a change is What if a change is needed?needed?
Scenario #5Scenario #5
UTHSCSA study of HIV patientsUTHSCSA study of HIV patients Procedures include interviews, (e.g., illicit Procedures include interviews, (e.g., illicit
drugs)drugs) Known risk of loss of confidentiality but data is Known risk of loss of confidentiality but data is
in password protected computer without in password protected computer without encryptionencryption
Event = computer with data is stolenEvent = computer with data is stolen Anticipated or Unanticipated?Anticipated or Unanticipated? Related or Unrelated? Related or Unrelated? Serious? If not, Greater Risk?Serious? If not, Greater Risk? Internal or External?Internal or External? Report to IRB? If yes, what time frame?Report to IRB? If yes, what time frame?
Scenario #5Scenario #5Is a UPIRSOIs a UPIRSO
Internal: Unanticipated and Internal: Unanticipated and Related and represents greater Related and represents greater risk due to confidentiality of datarisk due to confidentiality of data
Changes required? Changes required? Amend protocol to add improved Amend protocol to add improved
security of data security of data Letter sent to those whose data Letter sent to those whose data
was compromised. was compromised. Submit UPIRSO report to IRB Submit UPIRSO report to IRB
within 7 dayswithin 7 days
Yes, with UPIRSO reportsYes, with UPIRSO reportsNo, (e.g., IND Safety Reports) No, (e.g., IND Safety Reports)
with progress reportswith progress reports
What about What about accompanying accompanying
documentation documentation ??
Examples of corrective Examples of corrective actions or substantive actions or substantive
changeschanges Changes to eliminate apparent immediate Changes to eliminate apparent immediate
hazards to subjects (before or after IRB approval);hazards to subjects (before or after IRB approval); Modification of inclusion or exclusion criteria to Modification of inclusion or exclusion criteria to
mitigate the newly identified risks;mitigate the newly identified risks; Implementation of additional procedures for Implementation of additional procedures for
monitoring subjects; monitoring subjects; Suspension of enrollment;Suspension of enrollment; Suspension of research procedures;Suspension of research procedures; Modification of informed consent documents to Modification of informed consent documents to
include a description of newly recognized risks; include a description of newly recognized risks; Notification of previously enrolled subjects about Notification of previously enrolled subjects about
newly recognized risksnewly recognized risks
QUESTIONS?QUESTIONS?
Roy R. Estrada, PhD, PA-C, CIPRoy R. Estrada, PhD, PA-C, CIPAssociate Director, IRBAssociate Director, IRB
UTHSCSAUTHSCSA(210) 567-3083(210) 567-3083
Fax (210) 567-2360Fax (210) [email protected]@uthscsa.edu
UDEUDE
Unanticipated is different than FDA’s Unanticipated is different than FDA’s Definition of Definition of Unexpected drug Unexpected drug experienceexperience which only includes which only includes protocol documentationprotocol documentation
This is not necessarily a problem if This is not necessarily a problem if you simply identify that you need to you simply identify that you need to report to the sponsor the unexpected report to the sponsor the unexpected adverse drug experience and not adverse drug experience and not report to the IRB since it is not a report to the IRB since it is not a UPIRSO as it is not unanticipated by UPIRSO as it is not unanticipated by the condition of the subject. the condition of the subject.
UADEUADE
For device studies, investigators are For device studies, investigators are required to submit a required to submit a reportreport of a UADE of a UADE to to the sponsorthe sponsor and the reviewing IRBand the reviewing IRB as soon as soon as possible, but in no event later than as possible, but in no event later than 10 10 working daysworking days after the investigator first after the investigator first learns of the event (§ 812.150(a)(l)).learns of the event (§ 812.150(a)(l)).
SponsorsSponsors must immediately conduct an must immediately conduct an evaluation of a UADEevaluation of a UADE, and must , and must reportreport the the results of the evaluation results of the evaluation to FDAto FDA, all , all reviewing reviewing IRBsIRBs, and participating , and participating investigatorsinvestigators within within 1010 working days after working days after the sponsor first receives notice of the the sponsor first receives notice of the effect (812.46(b), 812.150(b)(l)).effect (812.46(b), 812.150(b)(l)).
UADEUADE
So for devices you may find So for devices you may find yourselves forwarding yourselves forwarding UADE’s to the UADE’s to the IRB but not as a UPIRSOIRB but not as a UPIRSO and then and then later after investigation by the later after investigation by the sponsor forwarding the results of the sponsor forwarding the results of the sponsors investigation as a UPIRSO if sponsors investigation as a UPIRSO if they discover that it is not as you they discover that it is not as you suspected caused by the underlying suspected caused by the underlying condition but actually an effect of the condition but actually an effect of the device not previously known device not previously known