25 Understanding Adverse Events - ICSSC

1 The fundamentals of The fundamentals of International Clinical ResearchInternational Clinical ResearchUnderstanding Adverse EventsUnderstanding Adverse EventsTracy Tracy NewboldNewboldFamily Health InternationalFamily Health InternationalReason for Adverse Event Reason for Adverse Event Collection and ReportingCollection and ReportingThe most important responsibilities of The most important responsibilities of investigators and sponsors of clinical investigators and sponsors of clinical research studies:research studies: Protection of human subjectsProtection of human Collection of clean and reproducible of clean and reproducible of the PresentationGoals of the PresentationUNDERSTANDINGUNDERSTANDING:: Definition of Adverse EventDefinition of Adverse EventExpected vs.

2 Unexpected Adverse EventExpected vs. Unexpected Adverse EventDefinition of Definition of SERIOUSSERIOUSA dverse EventsAdverse EventsIntensityIntensityvs. vs. SeriousnessSeriousnessof Adverse Eventsof Adverse EventsRelationship of Adverse Event to Study ProductRelationship of Adverse Event to Study ProductReporting of Adverse EventsReporting of Adverse EventsWhat is an Adverse Event (AE)?What is an Adverse Event (AE)?Any untoward medical occurrence in a Any untoward medical occurrence in a patient or clinical investigation subject patient or clinical investigation subject administered a pharmaceutical product administered a pharmaceutical product that does not necessarily have a causal that does not necessarily have a causal relationship with this with this treatment.

3 (ICH(ICH--E2A)E2A)What is an Adverse Event (AE)?What is an Adverse Event (AE)?Any Any unfavorableunfavorableand and unintendedunintendedsign sign (including an abnormal lab finding)(including an abnormal lab finding)SymptomSymptomor or diseasedisease, , temporally associated with use of a temporally associated with use of a medicinal (investigational) product, medicinal (investigational) product, whether or not related to the medicinal whether or not related to the medicinal (investigational) product (investigational) product (ICH(ICH--E2A)E2A)What is an Adverse Event (AE)?

4 What is an Adverse Event (AE)?Unfavorable deviation from baseline Unfavorable deviation from baseline health, which includes:health, which includes: Worsening of conditions present at onset of Worsening of conditions present at onset of the studythe study Patient deterioration due to primary diseasePatient deterioration due to primary disease Intercurrent illnessIntercurrent illness Events related or possibly related to Events related or possibly related to concomitant medicationsconcomitant medicationsWhat is an Adverse Event (AE)?

5 What is an Adverse Event (AE)?Unwanted Unwanted EffectsEffects Symptoms Symptoms (headache, nausea)(headache, nausea) Syndromes of diseaseSyndromes of disease Physical findings Physical findings (elevated BP, lump)(elevated BP, lump) Abnormal lab valuesAbnormal lab values OverdosesOverdoses ToxicitiesToxicitiesAn An expectedexpectedAE is any AE is any Adverse reaction whose Adverse reaction whose nature and intensity nature and intensity have been previously have been previously observed and observed and documented for the documented for the study product study product ( in the investigator ( in the investigator brochure, product brochure, product information).)

6 Information).Expected vs Unexpected AEExpected vs Unexpected AEExpected vs Unexpected AEExpected vs Unexpected AEAn An unexpectedunexpectedAE is any Adverse AE is any Adverse reaction not reaction not observedobserved, whether or not it , whether or not it has been anticipated because of the has been anticipated because of the pharmacologic properties of the study pharmacologic properties of the study Unexpected Adverse drug experienceadverse drug experience: : Any Adverse drug experience, the Any Adverse drug experience, the specificity or severity of which is not specificity or severity of which is not previously consistent with the current previously consistent with the current investigator brochure; or, if an investigator brochure.

7 Or, if an investigator brochure is not required or investigator brochure is not required or available, the specificity or severity of available, the specificity or severity of which is not consistent with the risk which is not consistent with the risk information described in the general information described in the general investigational plan or elsewhere in the investigational plan or elsewhere in the current application, as amended. current application, as amended. 21 CFR CFR possible, Adverse Events Wherever possible, Adverse Events should be described in terms of a should be described in terms of a change in the statuschange in the statusof patientof patient s health, s health, NOT the action taken or outcome.

8 NOT the action taken or outcome. How Would You Describe an AE?How Would You Describe an AE?How Would You Describe an AE?How Would You Describe an AE?Example:Example:A patient experiences a bleeding A patient experiences a bleeding stomach ulcer that requires stomach ulcer that requires hospitalization. hospitalization. Question:Question:What event(s) should be listed on What event(s) should be listed on the Case Report Form (CRF)?the Case Report Form (CRF)? Answer:Answer:Bleeding ulcerBleeding ulcerWhat Is a What Is a SeriousSeriousAdverse Event?

9 Adverse Event?A SERIOUS Adverse Event (SAE) is A SERIOUS Adverse Event (SAE) is defined as an AE meeting one of the defined as an AE meeting one of the following conditions:following conditions: DeathDeathduring the period of protocol defined during the period of protocol defined surveillancesurveillance Life threateningLife threatening(defined as a subject at (defined as a subject at immediate risk of death at the time of the immediate risk of death at the time of the event)event)What is a What is a SeriousSeriousAdverse Event? Adverse Event?

10 Hospital admissionHospital admissionduring the period of during the period of protocol defined surveillanceprotocol defined surveillance Any event that results inAny event that results incongenital congenital anomaly or birth defectanomaly or birth defect Any event that results in aAny event that results in apersistent or persistent or significant disability/incapacitysignificant disability/incapacityWhat is a What is a SeriousSeriousAdverse Event? Adverse Event? Any other important medical eventAny other important medical eventthat that may not result in death, be life threatening, may not result in death, be life threatening, or require hospitalization, or require hospitalization, may be may be considered a serious Adverse eventconsidered a serious Adverse eventwhenwhen, based upon appropriate medical , based upon appropriate medical judgment, judgment.