Presentation on theme: "FDA/Industry Statistics Workshop - 29 September 2006"— Presentation transcript:
1FDA/Industry Statistics Workshop - 29 September 2006 An Update on the CDISC SDTM/ADaM Pilot ProjectCathy Barrows, Ph.D.GlaxoSmithKlineCo-Leader of CDISC Pilot ProjectCDISC ADaM TeamFDA/Industry Statistics Workshop - 29 September 2006
3CDISC Pilot Project was to… Demonstrate that data submitted to the FDA using the CDISC Standard will meet the needs and expectations of both medical and statistical FDA reviewers.Produce a worked example implementation of the available CDISC standards.
4How? By conducting a case study legacy data (real clinical trial data, warts and all) CDISC SDTM domains and ADaM datasets and associated metadatasubmission of case study package to FDA for mock reviewAnd in the process, identify any issues to be resolved in SDTM and ADaM models
5FOCUS: the package not the process Choices/decisions guided bytimelinerealities of a team of volunteers from multiple companiesquick, efficient, effective - not necessarily the most preferred optionare not making recommendations re process!
6Pilot Submission Deliverables Submission packageIncludes SDTM datasets, analysis datasets, all relevant metadata, analysis results, abbreviated reportReview package tied together using metadata in DEFINE.XMLSummary report of the pilot submission projectissues encountered, strengths and weaknessesincorporate what we learned from the FDA feedbackBoth to be made available to the public on the CDISC website
7Criteria for success of the Pilot Project FDA statistical and medical reviewers will evaluate the submitted datasets (SDTM and AdaM), metadata and documentationUsable with their tools?Reproducibility of analyses, derivations?Navigable?Contents – what and where are OK?etc.
8And the verdict?We DID produce an electronic submission that met the reviewers’ needsThe overall tone of the reviewers’ feedback was very positivenoted easier learning curveThe FDA review was very thorough and they provided constructive criticismIssues encountered both by team and in FDA feedback are already beginning to be addressed by CDISC teams
10Who? 15 core team members from industry FDA involvement Interactions: Unprecedented level of involvementProvided co-leadership18-20 employees involved 12 consistently in contact with teamincludes medical and statistical reviewersInteractions:regular team teleconferencesFeb. face-to-face meeting to define the project (expectations/requirements)Pre-submission encounterFeedback from review
11FDA representatives - expectations, requirements, wish list Key messages:Consistency, accuracy, completeness are extremely important - follow the specifications!Define file crucial, but needs to be accurateClear mapping between the plans for analysis, the tabulation data, the analysis data, and the analyses performedSDTM and Analysis datasets should be available for both medical and statistical reviewers
12Presubmission “Encounter” Important opportunity to communicate about those crucial data-type issues that we run out of time for at “usual” meetingsDiscussed data to be submitted - structures, variablesFDA was able to make specific requests, for example:Hy’s Law analysis dataset (liver hepatotoxicity)
13Legacy data used in the pilot submission Real clinical trial data, provided by Eli LillyData de-identified, documents redactedIndication: Alzheimer’sRandomized, double-blind, placebo-controlled, parallel-group studyThree treatment arms: low dose, high dose, placeboApproximately 300 patients, multiple centersRepresentative set of endpoints and analyses included in package
14CDISC Pilot Submission Package Content PDF TOCs and eCTD folder structure
15Building the CDISC Pilot LegacydocumentsreceivedBuilding the CDISC PilotSubmission PackageDecisionsregarding dataanalysisNote that “create” includes QC steps.Map blank CRFto SDTM(aCRF)Write SAPReceive legacydataCoding ofevents data &con.med. dataCreate SDTMdata metadataCreate analysisdata metadataCreate SDTMdatasets (littlederived data)Write reviewer’sguideCreate 0-obsSDTM datasetsCreate 0-obsanalysisdatasetsCreate analysisdatasetsGenerateanalysesWrite coverletterDerived datato SDTMWrite studyreportCreate DEFINECreate XPT filesFinalizeSDTM datasetsCreate analysisresults metadata
16Presentation of the Define FDA expectation: Pilot package in Define.xmlThe Define file integratestabulation dataset (SDTM) metadataanalysis dataset (ADaM) metadataanalysis results (ADaM) metadataNew implementation! Exciting!
27Inclusion of Programs? Elected to not include entire “program” Included program code in metadata for repeated measures analysisThis WAS used in the review
28Next Steps: Wrap up tasks for this iteration Some revisions to current packageImplement some of the FDA feedbackFix a few things that are errors or oversightsIncorporate some things we wish we had doneComplete the project reportPublish the package and the project report
29Future iterations might: Fully and completely work this example (rather than a subset)More fully develop the metadataInclude datasets in the DEFINE file, instead of separately XPT filesUse studies from other therapeutic areasGo beyond a single studyTest submitting different sets of sponsor data (e.g., NDA, safety update)Address how to send updates (e.g. additional derived variables) effectivelyTest newer versions of models, e.g.:ADaMPK dataPre-clinical dataODMTest other analysis strategies
30Wisdom is scar tissue in disguise Our Advice -It’s worth it!Or, as one FDA Review Team member said:In order to get a standard we have to suffer