Adverse Event (AE) SAE Categories

Transcription

1 Adverse Event (AE) Adverse Event (AE) Standard Course in Clinical Trials March 2013 Faculty of Medicine, Chulalongkorn University Kulvadee Soontrapornchai Integrated Medical Safety Manager Novartis Definition Any untoward medical occurrence in a patient or clinical-trial subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Non-Serious AE (NSAE) Serious AE (SAE) Data captured in SAE only Serious Adverse Event (SAE) Categories Adverse event which results in death is life-threatening requires in-patient hospitalization or prolongation of existing hospitalization results in persistent or significant disability/incapacity is congenital anomaly/birth defect medically significant Death Death is an outcome and should not be an event unless death is sudden and cannot be clearly attributed to any cause The cause of a fatal SAE should be the condition that led to the subject s death A life-threatening event places the patient, in the view of the investigator, at immediate risk of death from the event as it occurred Hospitalizations an adverse event caused the patient to be hospitalized the hospitalization is related to deterioration of the disease state under investigation the hospitalization is related to deterioration of a preexisting condition Prolongation of existing hospitalization 1

2 Not SAE Hospitalization specified as part of the protocol specific requirements planned prior to patient entering trial for social reasons and respite care in the absence of any deterioration in the patient s general condition regular treatment for the disease under study / there is NO deterioration elective in nature and not related to worsening of an underlying condition ONLY treatment in the emergency room /casualty department (NO admission as an inpatient) AND no other criteria of seriousness apply Persistent or Significant Disability or Incapacity An event resulting in persistent or significant disability or incapacity is one which: substantially interferes with a person s ability to conduct normal ordinary life functions does not need to be permanent Congenital anomaly or birth defect A congenital anomaly or birth defect which can be related to trial treatment given to one of the parents during pregnancy. Other significant medical event This category requires the s medical and scientific judgement Includes important medical events which may jeopardise the patient or require intervention to prevent one of the other seriousness criteria being met SAE Report Completion Completion according to GCP print legibly in English - black ink, block letters use only standard abbreviations: - enter NA in fields that are not applicable - enter ND in fields that were not done - enter Unk when appropriate (eg. unk-jan-2014) ensure the SAE data are consistent with the CRF data (all AEs recorded in CRF) sign and date the report Sponsor provides: SAE forms, SAE Fax Cover Sheet, Completion guideline SAE Report Completion Minimum information for reporting an SAE Patient Identification number Investigational product Seriousness criteria (e.g. hospitalization, lifethreatening) A serious adverse event in medical terms assessment of causality (suspected or not) Pre-printed name/address/phone Protocol number Centre number SAE Report Completion Other required information: Total daily dose Start date, End date Outcome (follow-up) Brief description of the event: nature, severity, course, other relevant information, etc. relevant medical history, concomitant medication (including SAE treatment) Lab values: units, ranges, significant changes 2

3 Assessment of Causality To assess CAUSALITY, carefully consider: time interval between SAE and trial drug administration effects of other drugs or therapeutic interventions effect of study indication effect of co-existent medical conditions Assessment of Causality Suspected of being related to trial drug the temporal relationship of the clinical event to trial drug administration makes a causal relationship possible, and other drugs, therapeutic interventions or underlying conditions do not provide a sufficient explanation for the observed event Not suspected of being related to trial drug the temporal relationship of the clinical event to trial drug administration makes a causal relationship unlikely, or other drugs, therapeutic interventions or underlying conditions provide a sufficient explanation for the observed event Relationship/Causality Determine relationship between drug and SAE Unrelated: clearly not related to study drug Unlikely related: doubtfully related to study drug Possibly related: may be related to study drug Probably related: likely related to study drug Definitely related: clearly related to study drug ICH GCP Guideline responsibilities 4.11 Safety Reporting All SAEs should be reported immediately to the sponsor... The immediate reports should be followed promptly by detailed, written reports... should identify subjects by unique code numbers assigned to the trial subjects comply with the applicable regulatory requirement(s) related to the reporting of unexpected serious adverse drug reactions to the regulatory authority(ies) and the IRB/EC. ICH GCP Guideline (cont.) reponsibilities AEs &/ lab. abnormalities identified in the protocol as critical to safety evaluations should be reported to sponsor. within the time periods specified by the sponsor in the protocol For reported deaths, the investigator should supply the sponsor and the IRB/IEC with any additional requested information. Responsibilities & Timeline SAE report sent to Sponsor within 24 hours of receiving the new / follow-up information CIOMS-I sent to EC: timeline according to EC / company requirements The CIOMS-I form has been a widely accepted standard for expedited adverse event reporting. However, no matter what the form or format used, it is important that certain basic information/data elements, when available, be included with any expedited report, whether in a tabular or narrative presentation. 3

4 CIOMS Council for International Organizations of Medical Sciences is an international, non-governmental, non-profit organization established jointly by WHO and UNESCO in CIOMS Distribution & Handling s (worldwide) When will the SAE be on CIOMS-I form to notify ( Notification)? Serious, Unexpected (SAE not in s Brochure/ other safety documents), Suspected SUSAR Sponsor keep in folder IRB/EC CIOMS/ Notification is issued to: keep s aware of potential safety issues enable sponsor to meet global regulatory requirements CIOMS does not necessarily mean that the SAE was caused by the trial drug. CIOMS / Notification Standard Reporting Timelines Death / Life threatening: day 7 Other SAE: day 15 What Company do with the SAE? Local Drug Safety receives the case Check completeness & accuracy Local Drug Safety Central Drug Safety Forward the SAE form to Central Drug safety Forward a copy of the original SAE form to CRA for SDV Archive source documents Note: Each IRB/IEC has different reporting timeline. 4

5 Central Drug Safety Evaluate and process Summary Question # 1 Review clarity and completeness, identify any missing contact local Drug Safety responsible to obtain the necessary information Review investigator's causality assessment (if missing, report as suspected) Determine seriousness according to the pre-defined criteria Evaluate labeling/expectedness according to the current product labeling (e.g. IB, package insert) and specific HA requirements Unblind appropriate blinded serious, unexpected and suspected (SUSAR) cases according to the Unblinding Procedures Review for medical accuracy and company assessment Add medical comments where required Potentially reportable case generated and distributed to local Drug Safety in order to meet the HA regulatory requirements SAE reported to Sponsor within 24 hrs. Completeness of report is quality of patient safety Causality assessment (suspected/related or not) is crucial. Suspected, Unexpected, Serious adverse reaction (SUSAR) in CIOMS notified to investigator. sent to EC. A subject in a cancer treatment study was hospitalized with severe headache, fever, nausea, seizures. A CT scan reviewed intracranial hemorrhage. The subject recovered with sequelae. a. Life Threatening b. Hospitalisation c. Disability d. Other medical event e. Not report as SAE Question # 2 A patient with a history of renal failure has peritoneal dialysis catheter. The patient receives transplant and enters a study for an immunosuppressant drug. After entering the study, the patient is admitted for surgery to remove the catheter. a. Life Threatening b. Hospitalisation c. Disability d. Other medical event e. Not report as SAE Question # 3 Patient enrolled in a breast cancer study is diagnosed with metastatic tumor in left hip. The investigator reported this diagnosis in an initial SAE (medically significant). Two weeks later, the patient was admitted to the hospital for surgery to excise the tumor. What should the investigator do? a. File a follow-up report for treatment of the previously report condition. b. Sent within 48 hours c. Enter the additional information on the original SAE report. d. Do not file a SAE report since hospitalization was for treatment of the previous diagnosed condition. e. Call CRA for help Question # 4 When may an investigator s SAE reporting responsibilities start? (select all that apply) a. After first dose of study drug is administered. b. After informed consent is administered. c. After initiation of any protocol-specified procedures. d. After all subjects have been enrolled in the study. e. After end of study for data analysis 5

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