Supplemental Update Report CR Number: 2012319113 Implementation Date: 16-Jan-19 Related CR: 2012319113 MedDRA Change Requested Add a new SMQ Final Disposition Final Placement Code # Proposed SMQ Infusion related reactions Rejected After Suspension MSSO The proposal to add a new SMQ Infusion related reactions is not approved after suspension. The ICH Advisory Panel did approve this SMQ topic to go into the development phase and it Comment: underwent testing in three databases (two regulatory authorities and one company). However, there were numerous challenges encountered in testing and the consensus decision of the CIOMS SMQ Implementation Working Group was that the topic could not be developed to go into production as an SMQ. Most notably, in contrast to other SMQs, this query could not be tested using negative control compounds because it was not possible to identify suitable compounds administered via infusion that were not associated with some type of reaction. In addition, there is no internationally agreed definition of an infusion related reaction and the range of potential reactions associated with the large variety of compounds given by infusion is very broad and heterogenous. Testing was conducted on a set of around 500 terms, the majority of which was already included in Anaphylactic reaction (SMQ), Angioedema (SMQ), and Hypersensitivity (SMQ). It proved difficult to identify potential cases of infusion related reactions in post-marketing databases where the temporal relationship of the event to the infusion is typically not available. In clinical trial databases where this information is more easily available, users are encouraged to provide more specificity about the event, e.g., by reporting “Anaphylactic reaction” when it is known that this event is temporally associated with the infusion. In summary, this topic was too broad and non-specific to be developed into an SMQ without the benefit of suitable negative controls for testing. Users could consider using or modifying existing SMQs such as Anaphylactic reaction (SMQ), Angioedema (SMQ), and Hypersensitivity (SMQ) to address this query. CR Number: 2018337001 Implementation Date: 09-Jan-19 Related CR: 2018337001 MedDRA Change Requested Add a New Term Final Disposition Final Placement Code # Proposed Term Aorto-bronchial fistula Approved as Requested Proposed PT Aorto-bronchial fistula 10082565 HLT primary Bronchial conditions NEC 10006429 SOC primary Respiratory, thoracic and mediastinal 10038738 disorders HLT secondary Haemorrhages NEC 10018987 SOC secondary Vascular disorders 10047065 MSSO The proposal to add a new term Aorto-bronchial fistula is approved as requested. An aorto-bronchial fistula (ABF) is a connection between the aorta and the tracheobronchial tree. The Comment: main symptom of ABF is coughing up blood or bloodstained mucus from the lungs, a condition known as hemoptysis, which may result in a life-threatening haemorrhage. ABF may develop as a complication of an aneurysm of the aorta, whether atherosclerotic, syphilitic, dissecting, or in association with inflammation. More often it is a surgical complication from procedures such as valve replacement, aortocoronary bypass, interruption of persistent ductus arteriosus and reconstructive procedures of the aorta. Aorto-bronchial fistula will be added as a PT to primary HLT Bronchial conditions NEC, to secondary HLT Haemorrhages NEC and to secondary HLT Cardiac and vascular procedural complications. Jun-12-2019 Page 1 of 486 Supplemental Update Report CR Number: 2018365142 Implementation Date: 09-Jan-19 Related CR: 2018337001 MedDRA Change Requested Link a PT to a HLT Final Disposition Final Placement Code # Proposed PT Aorto-bronchial fistula Approved as Requested Proposed PT To HLT Cardiac and vascular procedural complications Aorto-bronchial fistula 10082565 To HLT Cardiac and vascular procedural 10007602 complications MSSO Comment: CR Number: 2018338001 Implementation Date: 09-Jan-19 Related CR: 2018338001 MedDRA Change Requested Add a New PT Final Disposition Final Placement Code # Proposed PT Nasolaryngoscopy Approved as Requested Proposed PT HLT primary Respiratory tract and thoracic imaging procedures Nasolaryngoscopy 10082566 SOC primary Investigations HLT primary Respiratory tract and thoracic imaging 10006476 procedures SOC primary Investigations 10022891 MSSO The proposal to add a new PT Nasolaryngoscopy to primary HLT Respiratory tract and thoracic imaging procedures in SOC Investigations is approved as requested. Nasolaryngoscopy Comment: (fiberoptic laryngoscopy) uses a small flexible video scope. The instrument is passed through the nose and into the pharynx and laryngeal area while the patient is conscious. This is the most common means for the visual examination of the larynx. Jun-12-2019 Page 2 of 486 Supplemental Update Report CR Number: 2018338006 Implementation Date: 09-Jan-19 Related CR: 2018338006 MedDRA Change Requested Add a New PT Final Disposition Final Placement Code # Proposed PT Plasminogen activator inhibitor deficiency type 1 Approved Not as Requested Proposed PT HLT primary Acquired gene mutations and other alterations Plasminogen activator inhibitor deficiency type 1 SOC primary General disorders and administration site conditions HLT primary Coagulation disorders congenital 10009735 SOC primary Congenital, familial and genetic disorders 10010331 HLT secondary Coagulopathies 10053567 SOC secondary Blood and lymphatic system disorders 10005329 MSSO The proposal to add a new PT Plasminogen activator inhibitor deficiency type 1 to primary HLT Acquired gene mutations and other alterations in SOC General disorders and Comment: administration site conditions and secondary HLT Coagulopathies in SOC Blood and lymphatic system disorders is approved but not as requested. Plasminogen inhibitor-1 deficiency is a rare autosomal recessive hematologic disorder characterized by increased bleeding after trauma, injury, or surgery. Affected females have menorrhagia. The bleeding defect is due to increased fibrinolysis of fibrin blood clots due to deficiency of PAI1, which inhibits tissue (PLAT; 173370) and urinary (PLAU; 191840) activators of plasminogen (PLG; 173350). Plasminogen activator inhibitor deficiency type 1 will be added as a PT to primary HLT Coagulation disorders congenital and secondary HLT Coagulopathies. CR Number: 2018338009 Implementation Date: 09-Jan-19 Related CR: 2018338009 MedDRA Change Requested Add a New Term Final Disposition Final Placement Code # Proposed Term Adenoid ameloblastoma with dentinoid Approved as Requested Proposed LLT Adenoid ameloblastoma with dentinoid 10082568 Current To PT Ameloblastoma 10066796 MSSO The proposal to add a new term Adenoid ameloblastoma with dentinoid is approved as requested. Adenoid ameloblastoma with dentinoid is a rare lesion. Due to the diverse Comment: histopathological presentation and also the paucity of reported cases, pathologists may face diagnostic confusion on many occasions. Hence, it can be considered as rare hybrid variants of ameloblastoma. Adenoid ameloblastoma with dentinoid will be added as a sub-concept LLT to PT Ameloblastoma. Jun-12-2019 Page 3 of 486 Supplemental Update Report CR Number: 2018340002 Implementation Date: 09-Jan-19 Related CR: 2018340002 MedDRA Change Requested Add a New PT Final Disposition Final Placement Code # Proposed PT Dysdialysis syndrome Rejected HLT primary Dialysis related complications SOC primary Injury, poisoning and procedural complications MSSO The proposal to add a new PT Dysdialysis syndrome to primary HLT Dialysis related complications in SOC Injury, poisoning and procedural complications and secondary HLT Vascular Comment: hypotensive disorders in SOC Vascular disorders is not approved. Dysdialysis syndrome does not appear to be an internationally recognized concept. References describing Dysdialysis syndrome were only identified in Japanese articles. CR Number: 2018340003 Implementation Date: 09-Jan-19 Related CR: 2018340003 MedDRA Change Requested Add a New Term Final Disposition Final Placement Code # Proposed Term Diaphragm resection Approved as Requested Proposed LLT Diaphragm resection 10082564 Current To PT Diaphragmatic operation 10061817 MSSO The proposal to add a new term Diaphragm resection is approved as requested. Resection, or excision of the diaphragm is performed for a variety of indications, including neoplastic Comment: invasion or metastasis involving the diaphragmatic tissue. Diaphragm resection will be added as a subconcept LLT to PT Diaphragmatic operation. CR Number: 2018340005 Implementation Date: 09-Jan-19 Related CR: 2018340005 MedDRA Change Requested Add a New PT Final Disposition Final Placement Code # Proposed PT Penile rash Approved Not as Requested Proposed LLT HLT primary Penile disorders NEC (excl erection and Penile rash 10082571 ejaculation) To PT SOC primary Reproductive system and breast disorders Genital rash 10018175 MSSO The proposal to add a new PT Penile rash to primary HLT Penile disorders NEC (excl erection and ejaculation) in SOC Reproductive system and breast disorders is approved but not as Comment: requested. Penile rash will be added as anatomical sub-concept LLT to the broad PT Genital rash. Jun-12-2019 Page 4 of 486 Supplemental Update Report CR Number: 2018340006 Implementation Date: 09-Jan-19 Related CR: 2018340006 MedDRA Change Requested Promote an LLT Final Disposition Final Placement Code # Proposed LLT Rash acneiform Rejected From PT Dermatitis acneiform MSSO The proposal to promote the LLT Rash acneiform