Larix – a full service Clinical Research Organisation N o r d i c • r o b u s t • f l e x i b l e

Protocol Deviations – How we do it, challenges and solutions Presenters: Maria Weibull (Sr DM) and Lisa Thell (Director DM, Sweden))

Responsibility Clinical Trial Manager (CTM) - Maintenance of PD log - Preliminary assessment of PD (minor/major) - Planning/conduct of any corrective action needed Clinical Research Associate (CRA) - Identifying and reporting, as they occur - Support CTM in maintaining the PD log Data Manager (DM) - Ensuring the reviewed and assessed PD log is available prior to Database lock

How we do it Protocol Deviation Form (Word) / Log (Excel) Information collected: Level (Subject, Site, Study), Collection/Start/Stop date, Category (IC, IE…), Classification (assessment), Description, Corrective/Preventive actions, Reason for deviation, Signatures Unresolved discrepancies list (By-passed checks) Presented at the latest at the Database Lock meeting SDTM dataset Excel sheet is read into SAS

How we do it Define logical checks in DVP – Only covers data errors, clinical findings are not detected. Query PD discrepancies / Missing data Offer listings of PD discrepancies / Missing data Ensure PD log is received and available at Database lock meeting Deliver PD log to SDTM team

Challenges CRO process - DM assignment with CO at different CRO/Sponsor Sponsor processes - CTMS Definitions – What is considered to be a PD Reporting – Who should report and to whom Reporting format – Excel, Word, eCRF

Challenges Review of PD – Why, Who, When DM not always part of review. Lack of review could lead to: Loss of information, No time for corrective/preventive actions, delay of DB Lock, affects data quality, safety concerns, PD misclassified or even lost Assessment – Who, When – What if sponsor/investigator disagrees? Study, Country, Site and Subject PDs – eCRF, SDTM

Solutions Specify PDs and assessment thereof in protocol Clear routines and timelines for reporting Training – CRA and Site Continuous review as a part of oversight Specify all PDs as checks in Data Validation Plan (DVP) – allow listings to be created during study Harmonize form and PD log with SDTM Collect PDs in eCRF, per subject

Thank you for your attention