Preparing an eSubmission based on multiple trials, some of which are ongoing – challenges for statistical programming Åsa Carlsheimer, Statistical Programming Director PhUSE October 9-11, 2011 1(12)
Outline 1. Introduction 2. Data standards 3. Data repository 4. Output programs 5. Planning and communication 6. Key message 2(12)
Introduction Drug FER123 was approved by FDA and EMEA in 2009 Different dose and longer treatment duration now investigated 1 pivotal phase III trial 17 completed phase II-IIIb trials Scope of new eSubmission 8 ongoing phase IIIb trials Combined safety & efficacy analysis for FER123 3(12)
Data standards l Implementation – Early 2009 based on draft CDISC ADaM 2.1 l Maintenance – All new trials across all projects and therapeutic areas l Benefits – One common standard – Customization, recognition, facilitating communication with other functions – Easy to integrate in a repository – Submission ready 4(12)
Data repository Study Analysis Compound Analysis Migration Repository Database Database (CAD) process Database Study 1 . Study 2 . CAD CAD *.SAS . . Migration Study 10 Studies included . in the previous to ADaM submission Study 11 Create combined *.SAS treatment codes Study 12 Submission . repository Integrate . repository *.SAS Study 17 Cut-off Validation of *.SAS Study 18 Harmonize repository *.SAS MedDRA codes Study 14 . . MedDRA dictionary Study 25 5(12)
Repository learnings Ø Discuss expectations on level of data cleaning for cut-off Ø Include time for coding of ongoing trials after cut-off in timelines Ø Agree on version of MedDRA dictionary for pivotal trial and Integrated Summary of Safety (ISS) Ø Document outcome of repository validation together with actions and responsible programmer Ø Easy to underestimate the resources & time needed for cleaning up the ongoing trials 6(12)
Output program set-up ISS/ISE Statistical Analysis Plan (SAP) Standard Output specification programs *.SAS ISS/ISE *.TAB output *.CGM ISS/ISE Grouping unique macros *.SAS *.SAS programs (>1100 TLFs) Subgroups (age, weight, race, geographic region, disease severity) Pooled trials (phase 2/3, phase IIIb), dose/regimens, controlled/uncontrolled 7(12)
Output program learnings Ø Include an option to present data by multiple trials when developing standard programs (for ISS/ISE) Ø >1100 TLFs need to split in to several documents (consider numbering) Ø Test transfer to eCTD tool (pdf-size, templates, bookmarks, hyperlinks) 8(12)
Planning and communication Submission team 13 statistical programmers (including biostatisticians and off-shore) Weekly internal programming/biostat meetings (status, issues, validation strategies, assign tasks to person) One representative in the regulatory led cross-functional team Structured programming approach using planning tools 9(12)
Delivery times after database lock ü Pivotal phase III trial (500 TLF) within 1 week ü ISE (200 TLF) within 2 weeks ü ISS (900 TLF) within 3 weeks 10(12)
Key message To prepare for a submission based on multiple trials, some of which are ongoing is a complex and challenging task! Utilizing the following will facilitate the work and ensure timely deliveries: • Implemented ADaM standards • Maintaining data repository • Clear programming and validation strategy • Good communication & planning 11(12)
Questions/comments? Contact information: asa.carlsheimer@ferring.com 12(12)
Data format considerations Read eCTD to FDA “ Study Data Specifications 1.5 ” Define file (metadata and logic) generated from ADaM specifications in Word Format SAS transport files *.xpt maximum 400 MB Ferring eCTD system limitation of 100 MB ADLB > 830 MB = ADLB1, ADLB2,----,ADLB10 Split by subject, site, X number of observations? 13(12)
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