Preparing an eSubmission based on multiple trials, some of which - - PowerPoint PPT Presentation

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Preparing an eSubmission based

• n multiple trials, some of which

are ongoing

– challenges for statistical programming

Åsa Carlsheimer, Statistical Programming Director PhUSE October 9-11, 2011

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Outline

• 1. Introduction
• 2. Data standards
• 3. Data repository
• 4. Output programs
• 5. Planning and communication
• 6. Key message

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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 8 ongoing phase IIIb trials Scope of new eSubmission Combined safety & efficacy analysis for FER123

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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

5(12) . . . . . Study 1 Study 10 Study 2 Study Analysis Database Compound Analysis Database (CAD)

*.SAS

Study 11 Study 12 Study 17 CAD

Studies included in the previous submission

Migration process CAD

Migration to ADaM

*.SAS

Validation of repository Integrate repository

*.SAS

Submission repository MedDRA dictionary

Harmonize MedDRA codes

Study 18 Study 14 Study 25 Cut-off

*.SAS

Repository Database

*.SAS

Create combined treatment codes

Data repository

. . . .

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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

7(12) ISS/ISE Statistical Analysis Plan (SAP) Output specification *.SAS Grouping macros *.SAS Standard programs *.SAS ISS/ISE unique programs *.TAB *.CGM ISS/ISE

• utput

Subgroups (age, weight, race, geographic region, disease severity) Pooled trials (phase 2/3, phase IIIb), dose/regimens, controlled/uncontrolled

Output program set-up

(>1100 TLFs)

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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)

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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

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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

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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

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Questions/comments?

Contact information: asa.carlsheimer@ferring.com

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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?