Clinical Submission - Integrated Statistical Analysis Plan (SAP)

For your clinical - regulatory filing, FDA requires an integrated SAP. An integrated SAP is a harmonization of data and terms, data coding, data guidelines, data requirements, data CDISC version and data otherwise of all clinical studies for safety, efficacy and clinical pharmacology, performed during the clinical examination and lifetime of the investigational drug. The Integrated SAP must be compliant and up to date with all requirements and guidelines for the year the file is to be submitted to FDA.

It is strongly recommended that at the completion of your Phase 2 studies, a Briefing Document is prepared for FDA that will include the overall Submission "Integrated" SAP and Analysis Plan for the following:

• Develop a Integrated Clinical Submission SAP for Clinical Phases 1,2,3
  
• Choose how the Integrated Safety Data will be presented and then develop your Integrated Safety SAPs accordingly - for example, a SAP for Phase 1, a SAP for Phase 2, a SAP for Phase 3, or a SAP for Phase 2 and 3 combined
• Develop a separate Integrated SAP for Efficacy - usually pooling Phase 2 and Phase 3 clinical studies
• Develop a separate SAP for Clinical Pharmacology
• File the SAPs early with FDA as a component of the sponsor's End of Phase 2 Briefing Document
• Request a date with FDA to review and comment and discuss the End of Phase 2 Briefing Document especially the SAPs
• Make sure to finalize agreements with FDA on the SAP methodology early so preparation for the Integrated Global Database , the GIDB can begin
• DO NOT unblind the last Pivotal Phase 3 Clinical Study before finalizing and receiving agreement on the Integrated SAPs for Safety, Efficacy and Clinical Pharmacology
• Ask FDA for meeting minutes pertaining to the End of Phase 2 Briefing Document Meeting to ensure comprehension and confirm agreements of what is to be filed pertaining to data presentation, integration and pooling
• Review the meeting minutes and debrief notes and all correspondence from FDA - it is important to archive all correspondence from FDA - follow the correspondence and make sure that all items of the correspondence from FDA are addressed - if this is not done - a RTF - REFUSAL TO FILE will be triggered by FDA at the time of filing - the RTF will be issued for "filing an incomplete clinical submission". Ramifications, costs, loss of timelines, submission integrity, questioning perception with FDA and delays are huge and can be easily avoided with properly managing FDA correspondence and follow-up.