Serious Adverse Events

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Serious Adverse Events
GCP Workshop Ethics Committee Members
C.Adithan
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Objectives

• To make the EC members understand the
• importance of adverse event (AE)
• differences between AE and ADR
• importance of serious adverse event (SAE)
• regulatory requirements in reporting SAE
• Investigators responsibility in SAE
• sponsors responsibility in SAE
• timelines for SAE reporting
• responsibilities of IEC in case of SAE

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Adverse Event (AE)

• Any untoward medical occurrence including
• undesirable signs symptoms
• disease or accidents
• abnormal lab. finding ( leading to dose reduction
  / discontinuation / intervention )
• during treatment with a pharmaceutical product in
• a patient or a human volunteer that does not
• necessarily have a relationship with the
  treatment
• given.

• After signing the Informed Consent Form
• Related / unrelated to the study drug

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Adverse Events Sources

• Hospital / physician / nurses notes
• Patients diaries
• Assessment forms
• Concomitant medications (indications)
• Abnormal lab. results
• Reasons for withdrawal and drop outs
• Missed visits

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Adverse Events Why to report ?

• Ethical requirements
• Regulatory requirements
• Legal requirements

A joint responsibility of the sponsor the
investigator
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Adverse Drug Reaction (ADR)

• For approved pharmaceutical product A noxious
• and unintended response at doses normally used
• or tested in humans
• For a new unregistered pharmaceutical product
• A noxious and unintended response at any dose

A response to a drug which is noxious
unintended and which occurs at doses normally
used for prophylaxis, diagnosis or therapy of a
disease or for modification of a physiological
function. --- WHO
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What is the difference between AE and ADR?

• AE event does NOT imply Causality

ADR A causal role is suspected
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Serious Adverse Event (SAE)

• An AE or ADR that is associated with
• Death
• Inpatient hospitalization
• Prolonged hospitalization
• Persistent or significant disability or
  incapacity
• Congenital anomaly or birth defect
• Otherwise life threatening
• ---- GCP guidelines

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What is a life threatening event?

• Places the patient , in the view of the
• investigator, at immediate risk of
• death from the event as it occurred

Does not include an event that, had it occurred
in a more severe form, might have caused death
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AE is reported What next?

• Evaluate AE based on protocol seriousness of
  the event
• Medical care for the subject
• Document appropriately
• Notify sponsor others
• Verify and maintain all data contained in CRF
  supporting source documents

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Adverse Event Recording

• Duration (Date of onset resolution)
• Severity (Mild, Moderate, Severe)
• Assessment (Serious / Non serious)
• Relationship to study medication
• (Suspected / Not
  suspected)
• Action taken (discontinued/dose )
• Outcome (Recovered, Improving, Unchanged,
• Deteriorated, Permanent
  Disability,
• Death, Unknown)

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When to record AE?

• Do complete an SAE form if
• an adverse event caused the patient
• to be hospitalized
• the hospitalization is related to a
• deterioration of the disease state
• under investigation or a pre-existing
• condition

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When not to record AE?

• Do not complete an SAE form if the
  hospitalization
• was planned prior to the patient entering the
  study
• is part of the regular treatment for the disease
  under study and there is no deterioration e.g.
  seizure monitoring
• occurs for a situation that is elective in nature
• involved only treatment in the emergency room and
  no admission as an in-patient, unless other
  criteria of seriousness are met

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SAEs What to report ?

• Minimal information for regulatory
  reporting
• an identifiable patient
• an investigational drug
• an identifiable reporter
• a serious adverse event
• Initial SAE form to be sent as soon as the
  above minimum information is available
• Recurrent episodes or complication of a
  previous reported SAE occurring at different time
  intervals should be always reported as a
  follow-up ( regulatory requirement)

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Data Elements for reporting SAE

• Patient details Pt. identifier, initials, sex,
  age, Wt. etc
• Suspected drug generic name, indication, dates
  of
• admin., dose, starting stopping date
  and time
• Other treatments
• Details of suspected ADR
• Outcome
• Details about the investigator
• Date reporting to Licensing authority
• Date reporting to Ethics Committee
• Signature of the Investigator
• Schedule Y, 20, January 2005

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WHO causality algorithm

• Certain

• Temporal relationship

• Probable

• Concomitant Medication

• Possible

• Concurrent Illness

• Unlikely

• Ve De-Challenge

• Unclassifiable

• Ve Re-Challenge

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Investigator Notification / Alert

• If an SAE is
• serious
• unlabelled (i.e. not noted in the
  Investigators Brochure)
• and suspected of being related to trial drug
• An Investigator Notification may be issued to
• keep the investigator aware of potential safety
  issues
• enable sponsor to meet its global regulatory
  requirements
• (An IN does not necessarily mean that the
• SAE was caused by the trial drug)

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Investigators responsibilities

• Record all AEs in the CRF
• Report all SAEs immediately to sponsor
• Ensure adequate follow-up and
• inform sponsor
• Report the event to IEC
• Report any Investigator Notifications to IEC

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Sponsors responsibilities

• Adequate training of investigator and team
• Expeditious reporting of all SAEs to HA
• verification of the SAE Form data against
• source documents
• Consistency of SAE Form data with the CRF data
• Generate Investigator Notifications
• when required
• Generate periodic safety updates

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Timelines for Reporting SAE
I E C
Sponsors
Investigator notices SAE
7 days
24 h
14 calendar days
DCGI
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What Ethics Committee can do?

• Modification of Protocol
• Updating the clinical IB
• Obtaining additional consent from
• ongoing Patients
• Stopping the study

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Group Exercises
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Thank you...