Sunday, December 27, 2009

SAS Programming Points to Consider in Clinical Submission

Remember, there is SAS programming performed at two levels in a clinical submission.
  • One: There is programming which occurs at the clinical study level. At the completion of all clinical studies, each clinical study database is reviewed, cleaned and closed. Each clinical study SAP (Statistical Analysis Plan) will direct the generation and programming of clinical study TLGFs - SAS output of programmed tables, listings, graphs and figures to be incorporated intext and EOT (End of Text) located in the appendix of the CSR.
  • Two: At the completion of the last pivotal clinical study or before, depending on the MSPP, and according to an Integrated, Global SAP, a GIDB (Global Integrated Database) is created which integrates all data from all clinical studies, in particular for clinical safety, clinical efficacy and clinical pharmacology. SAS programming off the GIDB will serve as the data source of integrated TGLFs that will be used by medical writers and clinical team members to develop CTD Module Clinical Summaries (2.7.1, 2.7.2, 2.7.3, 2.7.4), Clinical Overview (2.5.), ISS (Integrated Summary of Safety) and ISE (Integrated Summary of Efficacy. Note: There is a separate, additional ClinPharm Database at the Global Integrated level of programming.
  1. All clinical study databases and the GIDB must be CDISC compliant for the year the filing is to be submitted to FDA.
  2. It is strongly recommended that Subject or Patient Profiles (PP) are developed and programmed for Clinical Phase 2 and 3 studies. With communication and logic, FDA will negotiate with the sponsor to program PPs only for pivotal Phase 2 and 3 clinical studies, refer to the Integrated SAP as to whether the programmed TLGFs will be pooled in some way, for example, for Phase 2 and 3 clinical studies, data is often combined.
  3. Before creating the GIDB, CSR databases must be validated and checked for quality, accuracy, consistency, completeness, coding, compliance, nomenclature, CDISC version, etc. The GIDB must be harmonized when combining databases from all clinical studies worldwide. Standards, metrics, terms, units, calibrations, measures must be standardized for labs, AEs, medical history, eligibility, etc.
  4. FDA will most certainly ask the sponsor to submit a ISS (Integrated Summary of Safety), which is similar but not exact in content and data presentation to CTD M 2.7.4, the Clinical Summary of Safety.
  5. FDA will most certainly ask the sponsor to submit a ISE (Integrated Summary of Efficacy), which is similar but not exact in content and data presentation to CTD M 2.7.3, the Clinical Summary of Efficacy.
  6. TLGFs for CTD Modules 2.7.3 (CSE), 2.7.4 (CSS) and the ISE and the ISS, respectively, will be programmed in SAS output from the GIDB.
  7. All document summaries, all PPs, all CSRs, all TLGFs, whether at the clinical study level or the GIDB level must be QC. Quality Control of data is essential at the CSR and GIDB levels.
  8. Remember that the ISS, ISE, CTD Module GIDB TLGFs must be compliant and compatible with the clinical submission writing system and "que" and the publishing tool, especially for format considerations.
  9. All GIDB SAS programs are submitted at the time of filing to FDA for Phase 2 and 3 clinical studies and ClinPharm studies.
  10. If requested, Phase 1 SAS programs are also filed at the time of the clinical submission with FDA.
Much more to come...

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