Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download MedDRA Term Groupings: Use in clinical, drug safety and regulatory
Document related concepts
Transcript
MedDRA Term Groupings: Use in clinical, drug safety and regulatory departments INTRODUCTION Christina Winter GlaxoSmithKline MedDRA hierarchy • MedDRA hierarchy: – SOCs, HLGTs, HLTs and PTs gather terms below them so could be considered “groupings” – LLT is the lowest level and there are no official MedDRA terms below LLT – However some browsers use synonyms behind the scenes to aid retrieval (e.g. If synonyms are used, searching for “hepatic necrosis” will also retrieve LLT Liver necrosis.) Synonym Lists • Synonym lists – Some users maintain synonym lists within their own systems – linked to LLTs – aid consistency of coding – aid the autoencoder function – need maintenance for each MedDRA version Paediatric / Gender Lists MSSO maintains • Paediatric adverse event list • Gender adverse event list – Intended to improve data quality of adverse event reporting – May be used in conjunction with database fields – Unlike SMQs, these lists are not intended to identify a medical condition or area of interest. Standardised MedDRA Queries Standardised MedDRA Queries (SMQs) – Produced by CIOMS and MSSO collaboration; tested on regulatory and company databases prior to release – Maintained by MSSO; guidance available in – Introductory guide for SMQs – Data Retrieval and Presentation: Points to Consider – Intended to identify a medical condition or area of interest – Recommended by regulatory authorities as first strategy for searching safety data – May be applied to signal detection – Medical review of data retrieved is necessary – Quality of data retrieved is highly dependent on accurate coding In-house MedDRA groupings (1) • • • • Created and maintained by individual users/companies Used globally or tailored for product Generally topics not covered by SMQs Constructed with any level of MedDRA hierarchy, sub-SMQs, modified SMQs etc – “Home grown queries” – In-house searches (MedDRA terms with/without database fields) – “Drug/Event pairs” – Refer to group(s) of terms reflecting condition(s) of interest for specified drug – Incoming data: alert for expedited manual review – If term coded, alert case handler that special follow up questionnaire is needed In-house MedDRA groupings (2) – Grouping terms for labelling – Narrow list of search terms to aggregate safety data to create labelling (regulatory use) – Narrow list of terms to interpret labelling – E.g. “Myocardial infarction” in product label: PTs Myocardial infarction, Acute myocardial infarction, Post procedural myocardial infarction, Silent myocardial infarction considered “listed/expected” – Designated Medical Events (DMEs) – Grouping of terms reflecting serious medical conditions that are – typically due to drug – lead to benefit/risk review – DME medical concepts include Stevens Johnson syndrome, Aplastic anaemia, Seizure EMA’s Important Medical Events Topic for later presentation at this meeting Thank you E<EMA Important Medical Events list Identification of serious events in Drug Safety Christina Winter GlaxoSmithKline EMA’s Important Medical Events (IME) • EMA’s Eudravigilance expert working group created and maintain IME list • IME List (PTs) and inclusion/exclusion criteria on EMA Eudravigilance website http://eudravigilance.ema.europa.eu/human/textforIME.asp • Very large list (>7,900 PTs in v19.0) • Intended as aid to select events of higher priority for pharmacovigilance Use by Drug Safety Departments • Post marketing reports require expedited reporting if they are serious • Serious includes regulatory serious criteria and “medically serious” if none of the regulatory serious criteria applied to the case • Post marketing reports from any source; reporter may not be healthcare professional • Medically serious judgement varied between drug safety physicians • For consistency of “medically serious”, drug safety departments may apply a medically serious list in the database. • In addition to expedited reporting, list may be applied to periodic reports (separating non-serious from serious) Use by Drug Safety Departments • GSK initially maintained its own list • High maintenance effort • Always of interest in audits by regulatory agencies (who may have different opinions on terms selected) • GSK now uses the entire IME list • Adds a few terms that are specifically required for vaccine expedited reporting (e.g. Vaccination failure) • Simpler (only need to maintain vaccine list) • Less likely to have queries in regulatory audits • Other companies remove terms from the IME list • Requires maintenance Thank you EMA Important Medical Event list for the identification of serious adverse events in clinical studies Carol-Ann Wilson MedDRA User Group Meeting Hamburg April 5, 2016 Scope of IME list • A serious adverse event is any untoward medical occurrence in clinical studies that: 1. Results in death 2. Is life-threatening 3. Requires in-patient hospitalization or prolongation of existing hospitalization 4. Results in persistent or significant disability or incapacity 5. Is a congenital anomaly or birth defect 6. Is another medically important serious event as judged by the investigator, i.e. 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 definitions above • The IME list includes MedDRA PTs that represent these outcomes. It is quite broad because it also intends to cover the last outcome category Page 2 MedDRA User Group meeting• 5 April 2016 Use of IME list in clinical studies • The IME list is provided and maintained by the EMA and was created to facilitate the seriousness classification of suspected adverse reactions and to support aggregated data analysis and case assessment in day to day pharmacovigilance activities of stakeholders in the EU • Consistent classification of seriousness of adverse events/reactions is difficult to achieve when relying on Investigator assessment alone • It has a guidance purpose only and is not a mandatory requirement for seriousness assessment and regulatory reporting. Thus, organizations have the option to use it for their purposes depending on their individual needs • Within Bayer, the IME list is used in clinical trials to support the medical review process in terms of consistency of the seriousness definition of adverse events Page 3 MedDRA User Group meeting• 5 April 2016 Use of IME list in clinical studies Process (1) • The IME list can be adapted on a project and study level by excluding PTs that are already covered by e.g. study inclusion criteria or study endpoints • The IME list with justification for exclusion of specific PTs is attached to the Medical Review Plan and has to be approved by the responsible medical experts in Clinical and Drug Safety • The Study Data Manager regularly runs an IME based macro on non-serious AEs and provides listings of potentially serious AEs that were identified by the (adapted) IME list • An additional tab identifies excluded PTs in the study • A complementary medical history listing will provide information about medical history findings that have the same MedDRA PT assignment as the listed AEs for the relevant patients • Another tab lists all documented AEs for the respective patients with grading/ severity information Page 4 MedDRA User Group meeting• 5 April 2016 Process: Use of IME list in clinical studies (2) • The Study Medical Expert regularly performs the medical review of the listing of potentially serious AEs • After each review, queries to the Investigator are raised for the upgrading of non-serious AEs to serious AEs, where medically appropriate • A listing with the acceptable non-serious adverse events is sent back to the Study Data Manager • Any further created report will be up-to-date concerning latest comments by Study Medical Expert • The creation of the IME derived listing will be cumulative. New records will be highlighted and AEs classified as serious will be removed • The Study Medical Expert evaluates the Investigator’s response and either closes the query or posts a re-query • If the site disagrees with the upgrading, the adverse event will remain classified as non-serious Page 5 MedDRA User Group meeting• 5 April 2016 Process: Use of IME list in clinical studies (3) • New versions of the IME list are implemented in each study when a new MedDRA version is released into production • All processes will be run for all subjects as described before, based on the new version of the IME list • If a query was posted before implementation of the new version of the IME list, the query will not be withdrawn • If the Investigator has classified an AE as serious based on a previous version of the IME list but the PT has been removed from its new version, the previous classification will not be re-queried or revised • The process is iterative until study completion and all queries are resolved • Study Medical Expert confirms the final status of the IME derived listing as part of the confirmation of completion of medical review • Any non-serious AE that is upgraded to an SAE near data base closure will require SAE reconciliation macros to be re-run Page 6 MedDRA User Group meeting• 5 April 2016 Process: Use of IME list in clinical studies (4) Subject Number Investigator verbatim 180060002 LIVER INJURY 180090016 HEART FAILURE WORSENING Real No. (Diff. since EudraVigilance Important 09FEB Medical Event (IME) Term 2016) (MedDRA PT) 1(0) Liver Injury 1(0) Cardiac Failure To Clinical Trial be Trial unit queri Comments Number Country number ed Queries 15626 POLAND 18006 Y It was non serious adverse event 15626 POLAND 18009 Y this is not serious AE EPIDERMOID CARCINOMARIGHT 300030003 CHEST 1(0) Squamous Cell Carcinoma Of Skin 15626 400010002 BCC LEFT INFRACLAVICULAR 1(+1) Basal Cell Carcinoma 15626 420030004 THORACIC TRAUMA 1(0) Chest Injury 15626 560040002 GASTRIC ULCER 1(0) Gastric Ulcer 15626 CRUSHING INJURY OF THE FIFTH FINGER OF THE RIGHT 820110005 HAND 890040004 HYPERTENSION CRISIS 1(0) 1(+1) 710050010 UPPER GI BLEEDING 400040004 PULMONARY ASPERGILLOSIS Page 7 MedDRA User Group meeting• 5 April 2016 NETHERL ANDS AUSTRALI A PORTUGA L SOUTH KOREA Y no serious, It was operable and no further treatment is necessary 42003 Y REPLY is PENDING 56004 Y confirmed not serious """We confirm that the event was not serious. It was an accidental injury of the finger which did not require hospitalization." 30003 40001 15626 15626 ROMANIA 82011 SERBIA 89004 Y 1(0) Limb Crushing Injury Hypertensive Crisis Upper Gastrointestinal Haemorrhage 15626 Y 1(0) Bronchopulmonary Aspergillosis 15626 THAILAND 71005 AUSTRALI A 40004 Y Confirmed this event is not SAE. Further investigator review determined to be Not Serious Thank you! Servier Sabine Bayle Medical Data Quality and Tools Project Manager Claudine Gontier Medical Data Coding Project Manager Topic 1: Ontological thesaurus Topic 2: How do we use MedDRA to carry out medical data cleaning Topic 1 Ontological thesaurus Guidelines Semiologic thesaurus Clinical Knowledge For human consultation Semiological Ontology Artificial intelligence For IT purposes MedDRA Terms selection-Points to consider for multiple diagnosis Inspection findings Major findings regarding 5 adverse events (on > 17000 AEs) where a symptom was not coded Adverse events in our Clinical database 330 000 AEs in our clinical trials 3 300 PT used in these studies 756 PT corresponding to 80% of AEs 490 PT diagnosis 90 medical concepts Semiologic thesaurus 10 medical areas represented including 3 principal ones: -Cardiovascular -Psychiatry -Neurology 90 Medical Concepts (diagnosis ) 2248 characteristic signs and symptoms (PT) Semiologic Thesaurus Today we have 90 medical conditions with characteristic signs/symptoms NOT to be coded in addition to the medical condition if reported as part of a verbatim by investigator Medical condition Not to be coded in addition to the corresponding medical condition Bradycardia • Heart rate decreased • Dizziness • Thoracic discomfort/pain • Asthenia (weakness), fatigue, malaise From Thesaurus to Ontology Creation of an Ontology structured database with links between Diagnosis PT and their main Signs and Symptoms PT Syncope exertional Aortic valve stenosis Dyspnoea on effort Aortic valve calcification Left ventricular hypertrophy Angina on exercise Palpitation Systolic murmur 9 Text Mining reminder Medical Concept1, MC2, MC3, MC4 PT1, PT2, PT3, PT4 Reported Terms Split Coded Terms by Text Mining Reported Terms ATRIAL FIBRILATION / DISPNEA, PALPITATION / WHEN TACHIACARDIA (ATRIAL FIBRILATION ) PERSISTED, A PATIENT FELT PALPITATION SO HE CAME TO THE HOSPITAL Split coded Terms by Text Mining PTcod1 : ATRIAL FIBRILLATION PTcod2 : DYSPNOEA PTcod3 : PALPITATIONS PTcod4 : TACHYCARDIA Each medical concept of a reported adverse event is coded Splitting methodology (not recommended !) Text mining to Ontology Medical Concept1, MC2, MC3, MC4 PT1, PT2, PT3, PT4 Ontology Reported Terms Split Coded Terms by Text Mining PT1, PT4 Recommended Diagnosis: Bradycardia S&S: blurred vision and dizziness Today Tomorrow Manual selection of terms to be coded with help of thesaurus Identification of medical concepts (Text mining) Translation of all detected terms (Medical ontology) Selection of terms to be coded CODING Bradycardia/ 10006093 Blurred vision / 10005886 Semiological ontology: « MetaDRA » How did we fill in the « MetaDRA » ? Translated the 90 medical conditions from the semiologic thesaurus into MedDRA terms to supply the MetaDRA database. The MetaDRA interface A dropdown list of medical conditions is available: The MetaDRA interface Medical concept: The Diagnosis LLT are the codes that are considered as medical concepts. Any characteristic sign or symptom reported in a verbatim would not be coded in addition Topic 2 How do we use MedDRA in our daily work in addition to our coding activities? Medical data cleaning Medical data cleaning The medical data cleaning is set up by our department in order to detect potential medical inconsistencies in the clinical trials database using automated and manual checks. Medical data cleaning Checks developed for: •AEs, medical and surgical histories, •Previous and concomitant medications, •biological data and vital signs. And run on MedDRA lists of codes. Medical data cleaning Patient Patient number Country Center identification Type of control 1646 40 402 Liver disorder Liver disorder Coding process 40040201646 AE_X Discrepancy message Detection date PT ‘Liver disorder' is a vague PT and has to be checked 06NOV2015 Satuts Comments Medical data cleaning Patient number Country Center 1717 112 4005 Type of control MR_AE_04_S TD Event number E01 Discrepancy message The event is not related to study drug but the action taken regarding study drug is Dose increased Detection date 06NOV2015 Satuts Comments Medical data cleaning Type 2 diabetes mellitus Drugs used in diabetes Patient Patient Disease number identification Type of control verbatim 1717 Type 2 400501717 MR_MH_05_STD diabetes PT code Discrepancy message Type 2 diabetes This event is reported as treated but there mellitus is no corresponding treatment reported Detection date 06NOV2015 Satuts Comments Review and handling of discrepancies NEW Discrepancy Inconsistency Inconsistency ‘Not real’ ‘Real’ Change code List of codes Not correct or DB error No query needed No action Needed Resolved internally + comments No query Wait + comments Query already sent + open Query already answered Explanation No action Needed + comments No query New Wait Check if new query needed Sent +/- Sent Query Sent 22 Medical validation cleaning Example : Coherence between hematology and MH pages For hemoglobin values below 90g/l in eCRF. Check presence of medical history using MedDRA list of codes Discrepancy message: « The HEMOGLOBIN(37 g/L) is less than 90 g/L but no corresponding medical history is reported » Step1: Verify if medical history reported in eCRF No MH Step2: Issue a query in eCRF Step3: Change status of discrepancy once query issued Medical validation cleaning Example : Coherence between hematology and MH pages Step 4: Query answer reporting error. Data corrected in eCRF by investigator Step5: discrepancy closed automatically PATIENT IDENTIFICA STUDY COUNTRY CENTRE TION 10 76 525 4198 VISIT M000 BIOP HGB STATUSME COMMENTS D PANEL The HEMOGLOBIN (37g/L) is less than 90g/L but no corresponding medical history is reported CLOSED HEM1VAL COMSTAT Q sent How we deal with Important Medical Events (IME) EMA provides a list of MedDRA codes (Preferred Terms) called Important Medical Events Non serious Adverse events coded with a PT from the IME list have to be reviewed according to predefined seriousness upgrade rules. Any AE that is upgraded is transferred to the pharmacovigilance for declaration purposes IME Process AE3 AE2 AE1 AE1 PV DB Upgrade rules criteria IME PT ? No Yes medical review Criteria fulfilled Missing data Criteria not fulfilled Tripartite meeting interface Yes Wait No Clinical Data Base Thank you for your attention!
