High Quality or Poor Quality DB

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2 The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. ( DIA ), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated. These PowerPoint slides are the intellectual property of the individual presenter and are protected under the copyright laws of the United States of America and other countries. Used by permission. All rights reserved. Drug Information Association, DIA and DIA logo are registered trademarks or trademarks of Inc. All other trademarks are the property of their respective owners. 2

3 Goal Electronic clinical database (DB) that accurately reflects the data collected and is able to be used for purposes of analyzing study data for regulatory submissions 3

4 High Quality or Poor Quality DB Accuracy data in DB equal to source documents (e.g., > 95% CI) Timeliness data provided for decision-making activities Relevance data useful for decision-making activities Completeness data in DB 100% accounted for in source Understood data generated supported by sound procedures and methods Trusted confidence in programming efforts and data in DB 4

5 Objectives 1. Describe FDA ABCs when it comes to receiving an inspection 2. Identify key activities when establishing an Inspection-Ready database 3. Establish tools to mitigate quality and compliance issues with final delivery of the database 5

6 The ABCs of an FDA Inspection A The A s in Auditing Accurate study data verified by comparing the data filed with the agency (CRFs)* with actual source documentation at the site Authentic and attributable original records *case report forms (CRFs) 6

7 The ABCs of an FDA Inspection B Bioresearch Monitoring Program (BIMO) CP , Sponsor, CRO and Monitors Roles of the FDA Field Investigator and BIMO Reviewer Verify the accuracy and reliability of clinical trial data submitted to FDA Assess compliance with statutory requirements and FDA s regulations governing the conduct of clinical trials 7

8 The ABCs of an FDA Inspection C Conduct of an inspection In response to Sponsor concerns (i.e., data issues, personnel) Upon termination of a clinical site At the request of an FDA review division Form 482 (notice of inspection) is issued upon arrival Inspection of documents contemporaneously recorded Interviews with key personnel, key roles and decision-making process FDA investigator conducts an exit interview with most responsible person Form 483 is issued if deficiencies are identified 8

9 Key Activities for Inspection-Ready DB Monitoring 21 CFR Part 11 Compliance Data Management Plan (DMP) maintenance Clinical Data Lifecycle Evaluation eligibility and reporting adverse events QA/QC Activities Quality System Documentation 9

10 Monitoring Inter-disciplinary Roles Traditional versus Nontraditional Risk-based or 100% SDV Identify system limitations and mitigate with manual QC such as monitoring or data listing reviews 10

11 Part 11 Compliance Electronic systems that create, modify, maintain, archive, retrieve, or transmit clinical data for purposes of analysis and reporting of FDA regulated studies must also adhere to 21 CFR Part 11 regulations for data management systems. 11

12 Effective Data Management Plan (DMP) Describes all DM activities to include Description of data sources Data handling processes Data transfer formats and process Quality Control (QC) procedures Cross-walks DM activities with validated processes Substantiates all DM activities with supporting documentation Identifies all decision-making gateways and all unanticipated problems and changes during the course of the study 12

13 Clinical Data Lifecycle Initial programming, validation and QC of data Additional programming, validation and QC of data Ongoing data validation (cleaning) activities 13

14 Eligibility and Reporting AEs Ensure study was conducted according to the investigational plan, whether all adverse events were recorded, and whether the subjects met the inclusion/exclusion criteria outlined in the study protocol. 14

15 QA/QC Activities Quality Assurance Gap analysis: Clinical Data Management System (CDMS) Import and Export Data Validation Source to ecrf audit CRF to database audit DB to Clinical Line Listing audit Clinical Line Listing to SDTM Listing audit Programmatic (SAS) Validation Quality Control Edit Checks Query process 15

16 DB/DM Assessment Checklist Evaluate a group s ability to electronically capture, maintain and report clinical research data At study completion for a complete and tidy final DB deliverable package 16

17 The Checklist

18 The Checklist 18

19 The Checklist 19

20 The Checklist 20

21 The Checklist 21

22 3 Principles of Sound DM Infrastructure 1. The more you rely upon your system (CDMS), the more data handling activities can be automated and the more validation needs to be done. 2. The more you rely up on your procedures, the more specifications and documented evidence of correct performance you need to generate along the way. 3. And the more you rely on your people, the more important quality control activities are to guarantee quality clinical data. 22

23 Final Recommendations Re-familiarize yourself with the protocol and any unusual circumstances affecting quality clinical data Good documentation practices (GDPs) prevents NTFs* Identify procedural gaps and data management problems in the DMP Deploy standardized processes Document initial and ongoing training Cross-walk Hard-Lock deliverables with approved documents *Note-to-files (NTFs) retrospective application 23