Chapter 10 - Serious Adverse Event (SAE)

1 Chapter 10 - Serious Adverse Event (SAE) Serious Adverse Event (SAE) reporting constitutes one of the most important safety elements of any clinical trial. It is the joint responsibility of investigator(s) and sponsor(s) to report all the valid SAE to the respective IRB/IEC/EC and regulatory body (ies) in a timely and accurate fashion as per the applicable Adverse Event has been defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a casual relationship with this treatment.

2 An Adverse Event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) Adverse Event refers to any untoward medical occurrence that at any dose:lresults in deathlis life-threateninglrequires inpatient hospitalization or prolongation of existing hospitalization,lresults in persistent or significant disability/incapacity, orlis a congenital anomaly/birth defectlis considered Serious by the investigator for a reason other than those.

3 The term "life-threatening" in the definition of " Serious " refers to an Event in which the patient is at risk of death at the time of the Event , it does not refer to an Event , which hypothetically might have caused death if it were more severe. Medical and scientific judgment should be exercised in deciding whether expedited reporting is appropriate in other situations, such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the other outcomes listed in the definition above.

4 These should also usually be considered Serious . Examples of such events are intensive treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; or development of drug dependency or drug abuse. A distinction should be drawn between Serious and severe experience. A severe experience is a major experience of its type. A severe experience need not necessarily be Serious . For example, nausea, which persists for several hours, may be considered severe but not a Serious Adverse experience.

5 On the other hand, a stroke, which results in, only a limited degree of disability may be considered a mild stroke but would be a Serious Adverse experience. The investigator is responsible for ensuring that there are procedures and expertise available to cope with medical emergencies during the study. In the Event of an occurrence of any Serious Adverse reaction , the patient shall be withdrawn from the study immediately. He/She will be followed up for the Adverse Event even after the date of therapy discontinuation if the Adverse Event or its sequel persist.

6 Follow up shall be done until the Event or its sequel resolves or stabilize at a level acceptable to the investigator. ,,, Copyright Catalyst Clinical Services Pvt. considering any clinical incident for submission to the FDA in an expedited or periodic safety report, applicants, manufacturers, and licensed manufacturers should have knowledge of the following four data identifiable patient; identifiable reporter; suspect drug or biological product; Adverse Event or fatal outcomeSAE Reporting Timelines1.

7 Investigator Site to Sponsor/CRO;lICH-GCP recommendations: Immediately2. Investigator Site to Ethics Committee;lICH-GCP recommendations: As per the applicable regulations3. Sponsor/CRO to Regulatory Agency;lICH-GCP recommendations: a) Fatal or life-threatening unexpected Adverse drug reactions- Within 7 calendar days (initial report) and within 8 additional calendar days (complete report)b) All other Serious , unexpected Adverse drug reactions- Within 15 calendar days Copyright Catalyst Clinical Services Pvt.

8 Reporting Process Flow - Investigator's ResponsibilitiesSAE takes place at the siteSite undertakes the medical management of the eventSite reports the SAE to the sponsor immediately in a prescribed formatSite confirms the receipt of SAE by the sponsorSite follow-up the patient until the Event is resolvedSite report follow-up information to the sponsor within stipulated timeframeSite resolves all the queries raised by the sponsor's pharmacovigilance departmentSite reports all SAEs and follow-up information to the respective IRB/IEC/ECSite file all the relevant documents in the respective sections of the site's trial binder/file.

9 Copyright Catalyst Clinical Services Pvt. Reporting Process Flow - Sponsor's ResponsibilitiesSponsor's designee gives training to the site on SAE reporting requirementsSponsor's designee receives the SAE and document the date and time of receiptSponsor's designee performs the medical review of the SAE and seeks clarification from investigator site (if any)Sponsor's designee discuss the Event with the investigator and assist in ascertaining the severity and relatedness (if required)

10 Sponsor's designee document all the discussion/clarification on SAE with the siteSponsor's designee report all SAEs to the applicable regulatory authorities as per the stipulated timelines Sponsor's designee share the information with other trial sitesSponsor's designee performs the source data verification (SDV) of the SAE and all discussion/clarification during the monitoring visitSponsor's designee performs the review of IRB/IEC/EC communications for ensuring complianceSponsor's designee undertakes the re-training of the site on SAE reporting (if required)