2Overview 1. What is a serious adverse event? (SAE) 2. Where does our event information come from?3. How do we process an SAE?4. MedDRA coding5. Final points
3An event is serious if it results in... DeathHospitalisation/prolonging an existing hospitalisationSignificant loss of function or disabilityCongenital malformationLife threatening in any wayIV antibiotics/anti-fungals/anti-virals
4Where does adverse event data come from? From data which has been entered at follow-up onto the live system (including patient diaries)From the NHS IC (deaths and malignancies)
5Pharmacovigilance inbox - screenshot In this example, this has not been ticked as being an ESI. However it is a Psoriasis flare so we would ask for an ESI form for this.
6Pharmacovigilance - process All events checked by the PV teamReportingEvents coded using MedDRAFurther information requestsFurther information forwarded
7ReportingThe following information must be present in order to report an event:Legible & recognised disorder/signs/symptoms(bad examples: ‘thyroid’, ‘pt hospitalised’)Date of eventBiologic therapy details at time of eventThis is to ensure that the event is reported to the correct company.
8Examples“Attended GP (15/03/2011) with chest pain referred to Cardiac clinic. Diagnosis 1. Coronary Artery Disease. 2. Typical angina type II, referred for angiogram.”“Intrepid carcinoma left wrist lesion, ongoing from ?patch impetigo left thenar eminence and wrist”“Menia”“Ovarian cyst requiring hospitalisation and IV antibiotics”“Histology shows an area of invasive squamous cell carcinomna (left lower leg) which is well differentiated. SCC Excised and skin grafted”“SCC/Yca”
9ReportingBiologic therapy at time of event decides which company an SAE is reported toSAEs are reported whether they are considered to be related to the drug or notIf an event occurs after the patient has stopped a biologic we follow the 90 day guidelines
10Exceptions to the 90 Day Rule PregnancySend to all applicable companiesMalignancy- Send to all applicable companiesDeath- Send to last company
11Requests for further information to clinicianDiagnosisOutcomeConfirm date/biologic if unknownCausalityEvents of Special Interest (ESI) formsgather event specific informationE.g. – clinician twice, one month apart. Then call. ESI forms come from the website. Specific events which are relevant to biologics
12Events of Special Interest (ESI) forms Aplastic anaemiaDemyelinationLymphoproliferative diseaseMalignancyMyocardial infarctionPregnancy (Outcome)Hepatic dysfunctionCongestive Heart FailureSerious InfectionTuberculosis (TB)SurgeryESIs without formsCerebrovascular accidentPulmonary embolismMisuse, abuse, overdose and medication errorProgressive Multifocal LeucoencephalopathyHypersensitivity
13Follow Up ReportingIf/when we receive more information on an event, a follow-up report is sentESI received after initial report – sent along with a follow up report
14MedDRA Medical Dictionary for Regulatory Activities Computer programme which allows individual adverse outcomes to be coded and stored on database in specific groupsThese groups can be pulled out, cross referenced, counted and comparedMedDRA is now the internationally accepted coding dictionary for use by all international regulatory authorities and drug companies It was devised to increase consistency in adverse event reporting between different countries
15Structural Hierarchy of the MedDRA Terminology System Order Class(SOC)High Level Group Term(HLGT)High Level Term(HLT)MedDRA provides a hierarchy of 5 levels of groups of medical terms into which an Adverse Event can be classified. Each level is linked to the one above and below. The medical terms in the groups at the lower end of the hierarchy are very specific descriptors of the adverse event. The ones at the top include the adverse event in groups of medical terms which are very general.Every Adverse Event is entered at the LLT. This represents the event as reported by the patient or nurse eg heart attackEach LLT is linked by MedDRA to ONE PT. This represents the medical term for the event. Eg myocardial infarctionPreferred Term(PT)Lowest Level Term(LLT)
16Structural Hierarchy of the MedDRA Terminology System Order ClassCardiac DisordersCoronary artery disordersHigh Level Group TermIschaemic coronaryartery disordersHigh Level TermPreferred TermMyocardial infarctionLowest Level TermHeart attack
17MedDRA coding issues Example: Chest Pain Lowest Level Term Chest Pain Ischaemic coronary artery disordersHigh Level Group TermPain and discomfort NECRespiratory signs and symptoms NEC