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To EC or not to EC…that is the Question! Roche Products Ltd Hiren Naygandhi Acknowledgements: Colin Brown, Jim Elder & James Gallagher GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 1 Contents Ø Introduction Ø What is Executable Code? ü Guidelines ü Why do it? Ø What we did ü Process Overview ü Methodology ü Challenges Ø Feedback Ø Conclusion GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 2 Introduction Ø Drug Development Ø Reduction in amount of time taken in drug approval process Ø Submitting Executable Code (EC) may be a way to achieve this GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 3 What is EC? Ø Essentially, our programs! Ø Our definition: ü Standalone – no external dependencies e.g. macros, formats. ü Produce one output – per program ü Compatible with Windows SAS Ø Provides a window on the detailed steps taken to produce the analysis GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 4 Guidelines Ø FDA: Not Mandatory Ø Unclear guidelines: ü What to submit: efficacy and/or safety; analysis and/or TFLs ü How many programs ü New process within Legacy Roche, hence little experience Ø If not mandatory, why go through the effort? GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 5 Why do it? Ø Facilitate an accelerated decision making process Ø Reduce risk of program-specific requests Ø Moving towards globalized standards GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 6 What we did Ø Need arose: ü Global ü Submission Ø EC requirements ü Standalone – macros/formats being called externally ü Produce one output – programs produced multiple outputs ü Compatible with Windows SAS – used UNIX platform Ø Tool was required GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 7 Process Overview CSV Lists (1) Compare against original analysis (6) Build list of resources (3) EC (5) Xpt Files (2) Build Xpt file converting code (4) Create TOC document (7) Ø Ø Ø Ø Ø Ø Ø Ø (1) Input list of programs (2) Input list of datasets (3) Build list of resources (RTRACE) (4) Build Xpt à Dataset conversion code (5) Consisting of: Header; libnames*; datasets; compile macros; code; output (6) QC (7) Documentation * Manual step incl. Formats GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 8 Methodology Ø MPRINT ü Generate program from the contents of the LOG ü Required all external dependencies to be within a macro ü Considered too complex and time consuming Ø RTRACE ü Generate list of resources read from SAS ü List would be used to generate EC ü Considered as most time-saving option GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 9 Challenges Ø Identifying programs required for submission Ø E-Submission requiring further datasets Ø Formats Ø Incomplete resources ü NOSOURCE Ø Too many resources ü SASHELP.VCOLUMN Ø Using First-line reporting programs GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 10 Feedback Ø Metrics ü Took 4 weeks to build tool ü Included submission of 6 programs ü Recommended timelines to develop 2 programs per day Ø Feedback ü EC tool used in 6 submissions to FDA ü No feedback received – no news is good news J Ø Future ü Global tool to incorporate EC functionality GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 11 Conclusion Ø Tool developed to provide EC in submissions to FDA Ø Challenges faced, however, proved to be time-saver ü From producing EC manually ü FDA requests Ø No follow-up comments from FDA ü Would be desirable to receive feedback Ø We can make a difference GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 12 Further Reading Ø Todd, M. Using SAS Enterprise Guide to Create Standalone Programs, North East SAS Users Group (2010) Ø Vachal, R. FDA Reviewers as Ultimate End Users: Using the SAS System to Construct e-Submissions that Actually Facilitate the NDA / BLA Review Process, PharmaSug (2001) Ø Widel M. & Zhou. J. Techniques for creating reviewer-friendly SAS programs, PharmaSug (2006) GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 13 Questions GLOBAL BIOMETRICS Biostatistics Clinical Data Management Epidemiology & Patient Reported Outcomes Statistical Programming and Analysis Strategic Planning, Operations and Collaborations 14