congenital disorders have as their primary SOC assignment SOC Congenital, familial and genetic disorders absence of bile ducts has a primary SOC assignment of SOC Congenital, familial and genetic disorders and a secondary SOC assignment of SOC Hepatobiliary disorders assignment for these terms is their “site of manifestation” SOC Neoplastic All terms for malignant and benign neoplasms (except cysts and polyps) have as their primary SOC assignment SOC Neoplasms benign, malignant and unspecified (incl cysts and polyps) PT Skin cancer has a primary SOC assignment of SOC Neoplasms benign, malignant and unspecified (incl cysts and polyps) and a secondary SOC assignment of SOC Skin and subcutaneous tissue disorders Cyst and polyp terms are an exception to this rule. The primary SOC assignment for cyst and polyp terms is the “site of manifestation” SOC, and the secondary SOC is SOC Neoplasms benign, malignant and unspecified (incl cysts and polyps) Infectious All terms for infectious disorders have as their primary SOC assignment SOC Infections and infestations PT Enterocolitis infectious has a primary SOC assignment of SOC Infections and infestations and a secondary SOC assignment of SOC Gastrointestinal disorders The secondary SOC assignment for these terms is their “site of manifestation” SOC If a PT links to more than one of these three SOCs, the following priority is used to determine the primary SOC: SOC Congenital, familial and genetic disorders SOC Neoplasms benign, malignant and unspecified (incl cysts and polyps) SOC Infections and infestations Non multiaxial SOCs Terms in the following three SOCs do not have multiaxial links: SOC Investigations SOC Surgical and medical procedures
HLT Bullous conditions PT Stevens-Johnson syndrome PT Toxic epidermal necrolysis HLT Exfoliative conditions PT Dermatitis exfoliative PT Dermatitis exfoliative generalised PT Nikolsky's sign PT Skin exfoliation The frequency of a medical concept may be underestimated if the above points are not considered; this may impact interpretation of data (see Section 3.2). MedDRA SOCs group terms by body systems, aetiologies and specialised purposes. Data may be coded to terms in SOCs that had not been anticipated by the user. Keep in mind the potential impact of multiaxiality on frequencies of the medical condition of interest. Example Preferred Term Primary SOC Post procedural haemorrhage Injury, poisoning and procedural complications Chest pain General disorders and administration site conditions MedDRA Versioning MedDRA is updated twice yearly. Version “X.0” contains both simple and complex changes; version “X.1” contains only simple changes. Organisations should be aware of the types of MedDRA changes for their possible impact on data output. Types of MedDRA Changes Simple Changes Complex Changes Add a PT (new medical concept) Move an existing PT from one HLT to another Demote a PT to LLT level Add or remove a link to an existing PT Add an LLT Move an existing LLT from one PT to another Promote an LLT to PT level Add or change multiaxial links Add new grouping terms Merge existing grouping terms Restructure a SOC
check the documentation in the SMQ Introductory Guide to understand the purpose and definition of the SMQ. The user may also wish to review the term contents of the SMQ. Following application of the selected SMQ on coded data, search results (i.e., retrieved data) should then be evaluated against the question originally posed. The search output alone may not be sufficient for data assessment (e.g., frequency of a condition). Define and document criteria for case evaluation. Generally, more cases/events will be retrieved than will eventually be subjected to analysis due to “noise”. This is a more significant consideration for “broad” searches but in principle also applies to “narrow” searches (see Section 4.10.1). Clinical trials SMQs may be applied in the clinical trial setting – especially for aggregate data – where the safety profile has yet to be fully established. In this instance, most (if not all) available SMQs may be used, possibly on a routine basis. Alternatively, a user can apply an SMQ (or SMQs) that relates to a previously identified area of interest (e.g., from pre-clinical data or class effect) for further evaluation. Example Targeted Safety Study When developing a data analysis plan for a targeted safety study, consider using the narrow terms of an SMQ to aggregate events of interest. Post-marketing Focused searches A specific SMQ or a selection of SMQs may be used to retrieve relevant cases for subsequent medical review. Example Emerging Safety Signal A company suspects an emerging signal of pancreatitis for a new HIV product. SMQ Acute pancreatitis can be applied to the data. Signal detection The entire set of SMQs may be used on the database for signal detection. The user may wish to use the narrow terms or more specific levels of hierarchical SMQs (i.e., a SMQ) to minimise dilution of the signal. Single case alert SMQs may be used to create a “watch list” (e.g., an automated notification system) to alert the user of incoming cases needing urgent review.
ICH E2E: Pharmacovigilance Planning Membership of the ICH Points to Consider Working Group Current members of the ICH Points to Consider Working Group Affiliation Member Commission of the European Communities Maria Luisa Casini Kavita Chadda European Federation of Pharmaceutical Industries and Associations Hilary Vass* Christina Winter† Health Canada Alison Bennett Polina Ostrovsky Lynn Macdonald Japanese Maintenance Organization Yutaka Nagao Kazuyuki Sekiguchi Mitsuru Takano Reiji Tezuka Japan Pharmaceutical Manufacturers Association Yo Tanaka Hitomi Takeshita MedDRA MSSO Judy Harrison Ministry of Health, Labour and Welfare/Pharmaceuticals and Medical Devices Agency Yuhei Fukuta Miki Ohta Daisuke Sato Makiko Isozaki Kiyomi Ueno Pharmaceutical Research and Manufacturers of America Milbhor D’Silva JoAnn Medbery US Food and Drug Administration Sonja Brajovic#