Transcription
Geneva BranchCLINICAL STUDY REPORT - IN-TEXT TABLES,TABLES FIGURES AND GRAPHS, PATIENT ANDINDIVIDUAL PATIENT DATA LISTINGS:ICH E3 TECHNICAL REQUISITES ANDPOSSIBLE SOLUTION IN SASData handling and reporting in clinical trials with SASSeminario BIAS – Milano 22 / 02 /2013Angelo TinazziCytel Inc.Geneva – Switzerlandangelo.tinazzi@cytel.com
2Cytel Inc. - ConfidentialAgendaGenevaGenevaBranchBranch§ Introduction to ICH E3§ Key points in ICH E3 referring to statistical outputsproduction§ ICH E3 Additional Considerations§ Technical Solutions§ Software requirements overview§ In-house solutions§ Facilitate the work of the medical writer§ Other possible topics for discussion§ ReferencesClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
3Cytel Inc. - ConfidentialAgendaGenevaGenevaBranchBranch§ Introduction to ICH E3§ Key points in ICH E3 referring to statistical outputsproduction§ ICH E3 Additional Considerations§ Technical Solutions§ Software requirements overview§ In-house solutions§ Facilitate the work of the medical writer§ Other possible topics for discussion§ ReferencesClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
Cytel Inc. - ConfidentialIntroduction to ICH E34GenevaGenevaBranchBranchStructure and Content of Clinical Study Reports (CSR)§ CSRs describe the background, rationale, methodologyand full results for a clinical study§ Called integrated reports as they cover clinical andstatistical aspects§ Guideline ICH E3 on structure and content of CSRs: 53pages of guidance§ Other Guidances§ ICH E9 Statistical Principles for Clinical Trials§ ICH M2 EWG The Electronic Common Techincal Document(eCTD)§ FDA Portable Document Format (PDF) SpecificationsClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
Cytel Inc. - ConfidentialIntroduction to ICH E3E3 Implemention Working Group Q&A 7 June 2012§ It is a guidance not a set of rigid requirements ora template§ Modifications and adaptions that lead betterdisplay and communication of information areencouraged§ Some data in appendices are specific requirementsof individual HA and should be submitted asappropriate§ New sections could be added if appropriate§ Repetitions are allowed. E.g. deaths listing vsAE with fatal outcomeClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/20135GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialAgenda§ Introduction to ICH E3§ Key points in ICH E3 referring to statistical outputsproduction§ ICH E3 Additional Considerations§ Technical Solutions§ Software requirements overview§ In-house solutions§ Facilitate the work of the medical writer§ Other possible topics for discussion§ ReferencesClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/20136GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionObviously the TLFs programmed by biostat department arethe source of information of CSR§ In-text tables: statistical outputs inserted in the body of theCSR, i.e sections 1 to 13 as per ICH E3.§ End-text - Section 14: Tables, Figures and Graphs Referred tobut not Included in the text. When the statistical output will bepresented outside the body of the report§ Narratives: detailing deaths, other SAE and significant AE insection 12.3.2§ Subject/Patients Data Listings§ 16.1 Study Information§ 16.1.6 Listing of patients receiving test drug(s)/investigationalproduct(s) from specific batches, where more than one batch wasused§ 16.1.7 Randomisation scheme and codes (patient identification andtreatment assigned)§ 16.2 Patient Data Listings§ 16.4 Individual Patient Data ListingsClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/20137GenevaGenevaBranchBranch
8Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionGenevaGenevaBranchBranchThe guidance gave also some instructions on the required contentsof tables and listings. For example:§ 12.2.4. Listings of Adverse Events All adverse events for each patient, .,should be listed in appendix 16.2.7 the listing should be by investigator andby treatment .and should include: patient identifier, age, race .the adverseevent (preferred term, reported term) § 12.4.2.2. Laboratory Individual Patient Changes An analysis of invidual patientchanges by treatment should be given e.g. shift tables§ Some template for figures, tables and listings are also provided. For example:§ § § § Disposition of patients (figure)Listings of patients who discontinued therapyListings of patients and observations excluded from eficacy analysisNumber of patients excluded from the efficacy analysisThe guidance contains also instructions on «expected» statisticalanalysis to be taken in consideration for the SAP development (seealso section 16.1.9)Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionIn-text tablesSponsor SDOT Tool§ RTF output: a word table that can be easily inserted into the CSR§ Include CAPTION for automatic reference once they are inserted in the CSR§ Source should be also mentioned (e.g. post-text table/listing)Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/20139GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionPost-text tablesSponsor SDOT ToolComplex output summarizing information coming from different PROCse.g. LIFETEST (Median 95%CI) and PHREG (HR 95%CI) to save space andimprove readibilityClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201310GenevaGenevaBranchBranch
11Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionGenevaGenevaBranchBranchPost-text listingsAlternative solutioncan be implemented toavoid split in severalpages when there aremany information toreport. e.g. adverseevents listingSAS Proc ReportProc REPORT Tutorial. C. Zender. WUSS 2010Beyond the Basic: Advanced REPORT Procedure Tips and Tricks Updated for SAS 9.2. A. McMahill Booth. SAS Global Forum 2011Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
12Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionGenevaGenevaBranchBranchFiguresEMF, EPS, WMF and CGM arereccomended file formatsSponsor Standard Graph LibraryShould allow B&W printingwithout loosing any information.Their display should be verifiedSponsor Standard Graph LibraryClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
13Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionSubject ProfileSponsor Patient Profile ToolExtremely useful for medical review but couldbe also provided for the section 16.4Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionNarrativeGenerated with JMP ClinicalDeveloping a Complete Picture of Patient Safety in Clinical Trials. RC Zink. RD Wolfinger. SESUG 2012Usually written by the MW, but automation can be implementedespecially for big trialsClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201314GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionAs per FDA Portable Document Format (PDF) Specifications – Style Requirements§ US Letter§ Margins as recommended by FDA PDF Specification. Ingeneral settings of 1 inch on each side of the page shouldbe also enough to allow printing on A4 as well§ Font sizes ranging from 9 to 12 points§ Times New Roman 12-point font is recommended fornarrative text§ For tables generally, point sizes 9-10 are recommendedfor tables; smaller point sizes should be avoided. Ten pointfonts are recommended for footnotes.Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201315GenevaGenevaBranchBranch
16Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionGenevaGenevaBranchBranchSAS options/statements for controlling paper size and stylesPaper Size, Orientation and Margins with SAS optionsSetting fonts and size by modifying a templateZoom, Zoom: Get your document to scale on all paper size. D. O’Connor. SAS Global Forum 2010Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionSAS options/statements for controlling paper size and stylesODS Options e.g. the ‘page x of y’ dilemmaIt controls special sequence for in-line formatting(e.g. PDF, RTF, HTML)The Greatest Hits: ODS Essentials Every User Should Know. C. Zender. NESUG 2011Advanced RTF Layout with SAS. K. Glab. PhUSE 2007Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201317GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionSAS options/statements for controlling paper size and stylesOther ad-hoc style setting within a SAS proceduree.g. PROC REPORTProc REPORT Tutorial. C. Zender. WUSS 2010Beyond the Basic: Advanced REPORT Procedure Tips and Tricks Updated for SAS 9.2. A. McMahill Booth. SAS Global Forum 2011Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201318GenevaGenevaBranchBranch
19Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionGenevaGenevaBranchBranchAs per FDA Portable Document Format (PDF) Specifications – Style Requirements§ Black is the recommended font color. Any colors usedshould be tested prior to submission by printingsample pages from the document using a grayscaleprinter§ Additional rules as per eCTD guidance concerning§ File size§ File name (e.g. avoid punctuation, underscore, spaces, etc.)Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
20Cytel Inc. - ConfidentialKey points in ICH E3 referring tostatistical outputs productionGenevaGenevaBranchBranchStructure / Titles / Numbering for section 14 and 16.x§ Standard sections contents/numbering is proposed§ A hierarchical structure§ Output titles and sub-titles, and their associated bookmarks arelimited to 4 levels as per eCTD guidance.For example for section 1414.1 DEMOGRAPHICS DATA14.2 EFFICACY DATA14.3 SAFETY DATA14.3.1 Displays of Adverse Events14.3.2 Listings o deaths, other SAE and Significant Aes14.3.3 Narrative Deaths, Other serious 14.3.4 Abnormal Laboratory Value Listing (Each patient)Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
Cytel Inc. - ConfidentialAgenda§ Introduction to ICH E3§ Key points in ICH E3 referring to statistical outputsproduction§ ICH E3 Additional Considerations§ Technical Solutions§ Software requirements overview§ In-house solutions§ Facilitate the work of the medical writer§ Other possible topics for discussion§ ReferencesClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201321GenevaGenevaBranchBranch
22Cytel Inc. - ConfidentialICH E3 Additional ConsiderationsGenevaGenevaBranchBranchStill space for interpretation / individual preferencese.g. medical writer§ Duplication of outputs in section 14 and in-text§ 16.4 for all trials, 16.4 and Subjects Profiles, 16.4 and SDTM§ Duplication of outputs (listings) in section 14 and 16.x, 16.2and 16.4§ Exposure in section 14.3§ Concomitant Medications in section 14.1 or 14.3Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
Cytel Inc. - ConfidentialICH E3 Additional ConsiderationsSome reccomendations – We must do it!§ Follow the eCTD and FDA PDF Specifications§ Paper format including margins setting§ Font style and size§ Avoid use of coulors§ Adhere to key items in E3 structure§ 14.1 for all demographics / data generated prior toexperimental drug expose§ 14.2 for efficacy§ 14.3 for safety including any ‘interventions’ (e.g. exposure)§ 16.X at least listings explicetely mentioned in the ICH E3Out of scope of the presentation «non clinical» domains e.g. PKClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201323GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialAgenda§ Introduction to ICH E3§ Key points in ICH E3 referring to statistical outputsproduction§ ICH E3 Additional Considerations§ Technical Solutions§ Software requirements overview§ In-house solutions§ Facilitate the work of the medical writer§ Other possible topics for discussion§ ReferencesClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201324GenevaGenevaBranchBranch
25Cytel Inc. - ConfidentialTechinical SolutionsGenevaGenevaBranchBranchSofware requirements overview§ Combine descriptive statistics including p-values for inferential tests§ Generates totals and subtotals within specified groups§ Full control of the denominator for percentage calculations§ Automatic rounding, formatting, and decimal point alignment of results§ Manages page changing based on user-defined groupings§ Headings span (multiple columns)§ Titles and footnote management§ Places information from a single record on multiple output lines§ Full control of titles and footnotes§ Allow creation of styled RTF tables for immediate use in Publishingsoftware (e.g. WORD)§ Table of Contents Generation§ Management of template/standard librariesClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
Cytel Inc. - ConfidentialTechinical SolutionsSofware requirements overview§ SAS§ Procedures for output reporting e.g. TABULATE, REPORT,etc.§ Procedures for statistical techniques/methods e.g.LIFETEST, GLM, etc.§ ODS, Proc TEMPLATE, Proc DOCUMENT§ Macroà No end-user application, No proc CSR or proc TLF yet§ R§ Existing library for «R for Clinical Trial Reporting» FE Harrel(2007)Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201326GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialTechinical SolutionsSofware requirements overviewOthers§ Pharmastat APT Analysis Library Toold for Clinical TrialsReport Creation§ Dataceutics SAS/IntrNet based platform for ClinicalReporting§ ClinPlus§ SAS JMP Clinical§ SAS Drug and Device Development and other SAS tools forLife Science§ EntimICE§ Oracle Life ScienceStill a bit away from thepush the bottom away theoryClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201327GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialAgenda§ Introduction to ICH E3§ Key points in ICH E3 referring to statistical outputsproduction§ ICH E3 Additional Considerations§ Technical Solutions§ Software requirements overview§ In-house solutions§ Facilitate the work of the medical writer§ Other possible topics for discussion§ ReferencesClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201328GenevaGenevaBranchBranch
29Cytel Inc. - ConfidentialTechnical SolutionsGenevaGenevaBranchBranchIn-house solutions (Sponsor)Often each organization has its own tools/macro library/processGBSOS - A Guidance for statistical outputsClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
30Cytel Inc. - ConfidentialTechnical SolutionsIn-house solutions (Sponsor)GenevaGenevaBranchBranchAdditional rules / policy for outputs numbering******* Sponsor addition16.1.6 Listings of patients receiving test drug(s)/investigational product from specificbatches, where more than one batch was use16.1.9 (out of scope) SAP or description of key stats itemsFDA 0Plan.pdfClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
31Cytel Inc. - ConfidentialTechnical SolutionsGenevaGenevaBranchBranchIn-house solutions (Sponsor)SDOT - A set of SAS macro to cover standard outputs§ TABS: Continuos / Categorical Standard Analysis Outputs§ AE: Adverse Events and Concomitant Medications§ PDF: Ad-hoc outputs§ LST2PS: PDF output production with hierarchical bookmarksà Started with excel outputs.MHTM fileà Tried word outputsà PDF preferable solution for section 14 and 16.x}à Standard SAS .LST file read and transformed to PS rendered to PDF More stable Size of output file- Less space available (monospace font)- Less styling optionsClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
Cytel Inc. - ConfidentialAgenda§ Introduction to ICH E3§ Key points in ICH E3 referring to statistical outputsproduction§ ICH E3 Additional Considerations§ Technical Solutions§ Software requirements overview§ In-house solutions§ Facilitate the work of the medical writer§ Other possible topics for discussion§ ReferencesClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201332GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialTechnical Solutions33GenevaGenevaBranchBranchFacilitate the work of the medical writer§ Provide section 14 and 16.x in PDF format withbookmarks to facilitate the production of the final CSRClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
Cytel Inc. - ConfidentialTechnical SolutionsFacilitate the work of the medical writerPDF Bookmark creation – In house solution (Sponsor)Before§ Outputs where either generatedin .XLS or RTF§ Rendered to PDF§ Bookmarks where created manuallyby the MWClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201334GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialTechnical SolutionsFacilitate the work of the medical writerPDF Bookmark creation – In house solution (Sponsor)In-house solution (SAS macro)§ Standard SAS .LST output§ Rules for hierarchical titles§ .LST rendered to PDF and hierarchical titlescaptured from the .LST§ Postscript file with built-in bookmark fromhierarchical titles automatically rendered toPDFClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201335GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialTechnical Solutions36GenevaGenevaBranchBranchFacilitate the work of the medical writerPDF Bookmark creation – In house solution (Sponsor)In-house solution (SAS macro)§ LST Rules for pagesize and linesize§ Example of postscript statements to control bookmarksClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
Cytel Inc. - ConfidentialTechnical SolutionsFacilitate the work of the medical writerPDF Bookmark creation – Possible solutions with SAS 9.x§ Default PDF bookmarked file§ ODS PROCLABEL to control standard SAS proclabel (bookmark level 1)§ Proc options to control bookmark level 2 e.g.CONTENTS in PROC REPORTDESCRIPTION in SAS/GRAPH procedures§ Some procedures have more than 2 levels e.g. PROC GLM§ Control bookmarks through PROC TEMPLATE§ Full bookmarks control through PROC DOCUMENTClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201337GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialTechnical SolutionsFacilitate the work of the medical writerPDF Bookmark creation – Possible solutions with SAS 9.x - ExampleCreate a PDF file with 4 outputs with the followinghierarchical bookmarks:14.1 DEMOGRAPHICS DATA14.1.2 Subject AccrualPROC FREQTable 14.1.2.1 ITT Population14.1.6 Demographics CharacteristisPROC TABULATETable 14.1.6.1 ITT PopulationListing 14.1.6.1 Detailed Listing PROC REPORT14.2 EFFICACY DATA14.2.1 Primary EndpointPROC LOGISTICTable 14.2.1.1 ITT Populationwith ODS SELECTClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201338GenevaGenevaBranchBranch
39Cytel Inc. - ConfidentialTechnical SolutionsFacilitate the work of the medical writerGenevaGenevaBranchBranchPDF Bookmark creation – Possible solutions with SAS 9.x - ExampleThe best result with ODS statements and PROC optionsods PDF file ‘MYFILE.pdf’ style MyStyle;ods PROCLABEL '14.1 DEMOGRAPHICS DATA';proc tabulate data ptsCONTENTS "14.1.6 Demographics Characteristics";.run;ods PDF close;Other possible statements controlling bookmarksgeneration:PDFTOC n§ Control the nr. of level to be displayed (ODS option)NOPTITLE§ Suppress standard proc title (ODS option)/CONTENTS ‘Label’option of TABLES statement (proc FREQ)§ Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
Cytel Inc. - ConfidentialTechnical SolutionsFacilitate the work of the medical writerPDF Bookmark creation – Possible solutions with SAS 9.x - ExamplesThe best result with ODS statements and PROC options§ Bookmarks not controlled through title statement§ Hierarchy within PROC§ e.g. PROC LOGISTIC§ Not easy to control although further improvements arepossible with template control (PROC TEMPLATE)Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201340GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialTechnical SolutionsFacilitate the work of the medical writerPDF Bookmark creation – Possible solutions with SAS 9.x – The new DOCUMENT concept§ SAS prior to v 8PROC producing «DATA» and defining «STYLE» for only one type of output .LST§ SAS v 8§ ODS introduced the concept of DATA and STYLE object as OUTPUT object§ OUTPUT objects can be not storedClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/201341GenevaGenevaBranchBranch
Cytel Inc. - ConfidentialTechnical Solutions42GenevaGenevaBranchBranchFacilitate the work of the medical writerPDF Bookmark creation – Possible solutions with SAS 9.x – The new DOCUMENT conceptSAS 9 introduced the concept of Document§ ODS Output Objects in raw form stored in an item store§ Stored as hierarchical files§ Transform report without rerunning the analysis orrepeating the database query by modifying andreplaying an item store§ Control the report structure§ Absolute control over Table of Contents (e.g. PDFbookmarks)§ ODS DOCUMENT, PROC DOCUMENT, ODSDOCUMENTWINDOWClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
43Cytel Inc. - ConfidentialTechnical SolutionsGenevaGenevaBranchBranchFacilitate the work of the medical writerPDF Bookmark creation – Possible solutions with SAS 9.x – The new DOCUMENT conceptODS DOCUMENT NAME TLF(WRITE); SAS Proc Statement generating outputs ODS DOCUMENT CLOSE;proc document name TLF;list / levels all;run;quit;PROC FREQ OutputPROC TABULATE OutputPROC REPORT OutputPROC LOGISTIC OutputClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
44Cytel Inc. - ConfidentialTechnical SolutionsGenevaGenevaBranchBranchFacilitate the work of the medical writerPDF Bookmark creation – Possible solutions with SAS 9.x – The new DOCUMENT conceptAn interactive environment tomodify the document§ Adding a node§ Modifying a node§ Rename a node§ Move a node§ Same actions for a tableClinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
45Cytel Inc. - ConfidentialTechnical SolutionsGenevaGenevaBranchBranchFacilitate the work of the medical writerPDF Bookmark creation – Possible solutions with SAS 9.x – The new DOCUMENT conceptDocument modified withODSDOCUMENT point andclick toolPDF recreatedods pdf file " my file "style MYSTYLE;proc document name TLF;replay ;run;ods pdf close;Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution in SAS – A. Tinazzi – Seminario BIAS – Milano 22/02/2013
Cytel Inc. - ConfidentialTechnical SolutionsFacilitate the work of the medical writerPDF Bookmark creation – Possib
FDA Portable Document Format (PDF) Specifications Geneva BranchGeneva Branch Clinical Study Report - In-text tables, Tables Figures and Graphs, Patient and Individual Patient Data Listings: ICH E3 technical requisites and possible solution
