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CDISC SDTM and ADaM for survival data

This document discusses CDISC standards for representing survival data from oncology clinical trials. It provides an overview of CDISC and describes the SDTM and ADaM domains that are useful for capturing efficacy endpoints involving survival, such as overall survival, progression-free survival and tumor response. Examples are given of how survival data from different patients would be represented in an ADTTE (Analysis Dataset for Time to Event) dataset according to CDISC ADaM standards.

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Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] CDISC SDTM and ADaM for survival data VI BIAS Annual Conference Analisi della sopravvivenza ed applicazioni in Oncologia: un percorso dalle basi agli ultimiaggiornamenti Genoa – 30-31/10/2014 Angelo Tinazzi Cytel Inc., Wilmington Del. USA Succursale de Meyrin – Geneva – Switzerland angelo.tinazzi@cytel.com 1
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 2 The information contained in this presentation is based on personal research of the author and does not necessarily represent Cytel Inc.
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 3 CDISC Intro CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References CDISC is a global, open, multidisciplinary, non-profit organization that has established standards to support the acquisition, exchange, submission and archive of clinical research data and metadata. The CDISC mission is to develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare. CDISC standards are vendor-neutral, platform-independent and freely available via the CDISC website.
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 4 CDISC Intro Available Standards CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 5 CDISC Intro Standards in Submission Data Analysis Data Tabulations Data Collection Planning SDTM ADaM SEND CDASH LAB Protocol Study Design NCI CT CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 6 CDISC Intro A World of Clinical Standards CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 7 CDISC Intro Traceability CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Primary Overall Survival Analysis ADTTE ADaM define.xml DM aCRF SDTM define.xml
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 8 Efficacy Endpoints in Oncology Solid Tumors CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Clinical Trial Endpoint Definition Source Overall Survival (OS) Time from randomization to death from any cause. FDA Objective Response Rate (ORR) Proportion of patients achieving either a partial or complete response for a minimum duration of time. FDA Disease-free survival (DFS) Time from randomization until recurrence of tumor or death from any cause. DFS is typically used in clinical trials of adjuvant cancer therapy. FDA Progression-free survival (PFS) Time from randomization until objective tumor progression or death. FDA Time to progression (TTP) Time from randomization until objective tumor progression (does not include deaths) FDA Time to treatment failure (TTF) Time from randomization to treatment discontinuation for any cause, including drug toxicity. FDA Progression-free survival 2 (PFS2) Same as PFS with some indication variant. E.g. in Prostate cancer - Duration of Response (DOR) Time from documentation of tumor response to disease progression EMA Clinical Benefit Response Rate (CBR) Patients achieving either a complete response, partial response or absence of progression at 6 months EMA
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 9 Efficacy Endpoint in Oncology Solid Tumors RAN SD SD PR CR PD DOR ORR OS PFS TTP Death / Alive TTF Off TRT CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 10 CDISC SDTM SDTM Domains (as per Version 3.2) CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 11 CDISC SDTM Domains/Items Useful for Overall Survival Date of Origin / Starting point Randomization date Treatment Start date CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References DS DM
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 12 CDISC SDTM Domains/Items Useful for Overall Survival Date of death DM DS Patient 101001 died (DTHFL=Y) the 17JAN2013 (DTHDTC) Patient 101006 is alive (DTHFL=NULL) Patient died (DSSCAT=REPORT OF DEATH) because of Progressive Disease (DSTERM) on 14DEC2010 (DSSTDTC) CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 13 CDISC SDTM Domains/Items Useful for Overall Survival Date of last follow-up  Any date documenting patient is still alive  Visit date, AEs, CM, Lab Samples, ECG, etc.  In SDTM we have a lot of «administrative» date that should be not considered (--DTC)  Investigate for date in Supplemental Qualifiers SUBJID SSORRES SSSTR ESC VISIT SSDTC 001001 ALIVE ALIVE FUP 1 07JAN13 001001 ALIVE ALIVE FUP 2 25MAY13 001002 DECEASED DEAD FUP 1 08JUN13 001003 ALIVE ALIVE FUP 1 01JAN12 001003 ALIVE ALIVE FUP 2 05AUG12 001003 PATIENT LOST TO FOLLOW UP LOST FUP 3 20NOV12 Last follow-up Date when death was reported. Date of death in DM At this follow-up the patient was known to be lost, date of last follow-up is therefore 05AUG12 (previous visit) Survival SS Status (available from version 3.2) CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 14 CDISC SDTM OncologyDomains for Tumor Response TU/TR/RS Tumor Identification Unique identification of tumors for that patient Tumor Results Quantitative measurements and/or qualitative assessments of the tumors identified in the TU Disease Response Clinical response evaluations determined from the TR data and other SDTM domains TU TR RS  Overcoming Difficulties in Implementing RECIST criteria, PhUSE 2013, G. Ruhnke  CDISC Journey on Solid Tumor Studies using RECIST 1.1., PhUSE 2013, K. Lee  SDTM Oncology Domains From Patients to Data to Narrative, PhUSE 2013, K. Stoltzfus CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 15 CDISC SDTM OncologyDomains for Tumor Response TU/TR/RS CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 16 CDISC SDTM OncologyDomains for Tumor Response TU/TR/RS CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 17 CDISC SDTM OncologyDomains for Tumor Response TU/TR/RS Source: Oncology Legacy Data => SDTM. CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 18 CDISC ADaM FoundationModels • One record per subject • Demographics, Baseline Chars • Study Population (ITTFL, SAFFL, ..) • Study Arm, Treatment Periods ADSL Analysis Subject Level Dataset • Vertical Structure • One or more record per subject/time-point BDS Basic Data Structure • Counting of subjects with a record for each term • It often includes a structured hierarchy of dictionary ODS Occurrence Data Structure • Based on BDS • Time to the Event of Interest • One or more time-to-event endpoint per ADTTE dataset TTE Time to Event CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 19 CDISC ADaM ADTTE – Analysis Dataset for Time to Event – Variables of Interest  Description of time-to-event (PARAMCD/PARAM)  E.g. OS/Overall Survival  Date Origin (STARTDT) E.g. Randomization Date  Censor (CNSR) 0=Event  Analysis date of event or censoring (ADT)  E.g. Death Date / Last follow-up  Elapsed time to the event of interest from the origin (AVAL)  E.g. (ADT-STARTDT)+1 (days) CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 20 CDISC ADaM ADTTE – Analysis Dataset for Time to Event – Variables of Interest  Event or Censoring Description (EVNTDESC)  E.g. DEATH  Censor Date Description (CNSDTDSC)  E.g. LAST FOLLOW-UP DATE  Imputation Date Flag (ADTF)  E.g. D/M/Y CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 21 ADTTE Examples Case 1: Single Endpoint with Multiple Values for Censoring A studywith Overall Survival as Primary Endpoint Definition Time from randomization until death from any cause Censor Last date subject was seen alive Cut-off Date Applied: 08APR2014 CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 22 ADTTE Examples Case 1: Single Endpoint with Multiple Values for Censoring SUBJID TR TP PARA MCD PARAM AVAL START DT ADT A D T F C N S R EVNTDESC 001001 PBO OS Overall Survival (Months) 16.8 15AUG11 07JAN13 0 DEATH 001002 EXP OS Overall Survival (Months) 8.4 12SEP11 25MAY12 D 1 LAST FOLLOW-UP DATE 001003 EXP OS Overall Survival (Months) 7.2 02SEP13 08APR14 1 FINAL ANALYSIS CUT-OFF DATE Endpoint: Overall Survival ; Cut-off Date Applied: 08APR2014 Treatment Received Time to Event Parameter − Start Date Randomisation - Event/Censor Date Time part of the TTE event (ADT-STARTDT+1)/30.42 *30.42 Standard for nr. of days in a month Event/Censor Description 0=Event 1..n=Censor CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 23 ADTTE Examples Case 1: Single Endpoint with Multiple Values for Censoring SUBJID TR TP PARA MCD PARAM AVAL START DT ADT A D T F C N S R EVNTDESC 001001 PBO OS Overall Survival (Months) 12.1 01APR13 07JAN13 0 DEATH 001002 EXP OS Overall Survival (Months) 17.2 04APR13 25MAY12 D 1 LAST FOLLOW-UP DATE 001003 EXP OS Overall Survival (Months) 17.5 08APR13 08APR14 1 FINAL ANALYSIS CUT-OFF DATE Endpoint: Overall Survival ; Cut-off Date Applied: 08APR2014 A partial date (--MAY12) where the day part has been imputed. Valid values are D,M,Y More details about censoring date. This patient either die or had a follow-up>cut-off date and therefore censored at the time of analysis cut-off date CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References This is also traceability!!!!!!
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 24 ADTTE Examples Case 1: Single Endpoint with Multiple Values for Censoring Endpoint: Overall Survival ; Cut-off Date Applied: 08APR2014 SUBJ ID TR TP PARA MCD … ADT A D T F CN SR EVNTDESC SRC DOM SRCVAR SRCS EQ 001001 PBO OS … 07JAN13 0 DEATH DM DTHDTC . 001002 EXP OS … 25MAY12 D 1 LAST FOLLOW-UP DATE ADSL LASTVSDT . 001003 EXP OS … 08APR14 1 FINAL ANALYSIS CUT-OFF DATE ADSL LASTVSDT . SDTM.DM ADAM.ADSL CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References This is also traceability!!!!!!
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 25 ADTTE Examples Case 2: Composite Endpoint with multiple value for Event and Censoring Progression Free Survival Definition Time from randomization until radiological tumor progression or death which ever come first Censor Last date radiological tumor assessment CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 26 ADTTE Examples Case 2: Composite Endpoint with multiple value for Event and Censoring Endpoint: Progression Free Survival SUBJ ID T R T P PA RA MC D PARAM AVAL START DT ADT C N S R EVNTDESC CNSDTDSC 001001 P B O PFS Progression Free Survival (Months) 16.8 15AUG11 07JAN13 0 RADIOLOGI CAL PROGRESSI ON 001002 E X P PFS Progression Free Survival (Months) 8.4 12SEP11 25MAY12 1 STUDY COMPLETED LAST RADIOLOGIC AL ASSESSMENT 001003 E X P PFS Progression Free Survival (Months) 7.2 02SEP13 08APR14 2 NO BASELINE ASSESSMEN T RANDOMIZAT ION 001004 P B O PFS Progression Free Survival (Months) 8.4 12SEP11 25MAY12 0 DEATH CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 27 ADTTE Examples Case 3: One ADTTE with several time-to-event Endpoints  Phase III study  First Relapsed or Refractory Acute Myeloid Leukemia  Primary Endpoint: Overall Survival  Sensitivity Analysis  Overall Survival censored for Susbsequent AML Therapies  Overall Survival censored for Post Treatment Transplantation CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 28 ADTTE Examples Case 3: One ADTTE with several time-to-event Endpoints SUBJ ID T R T P PAR AMC D PARAM AVAL ADT C N S R EVNTDESC CNSDTDSC 001001 P B O AML Susbsequent AML Therapies (Months) 0.6 31AUG11 0 SUBSEQUENT AML NON PROTOCOL THERAPY 001001 P B O TRA Post Treatment Transplantation (Months) 16.8 07JAN13 1 NO EVENT LAST VISIT DATE 001001 P B O OS Overal Survival (Months) 16.8 07JAN13 0 DEATH 001001 P B O OST R OS Censored for Transpl. (Months) 16.8 07JAN13 0 DEATH 001001 P B O OSA ML OS Censored for Subsequent AML Therapy (Months) 0.6 31AUG11 1 NO EVENT SUBSEQUENT AML NON PROTOCOL THERAPY DATE The Subsequent AML therapy started on 31st August 2011. The death occurred the 7th January 2013 was censored for OSAML CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 29 ADTTE Examples ADaMDefine.xml CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Variable Value Label Type Format Source/Computational Method PARAMCD PFS Progression Free Survival (Months) FLOAT 8.1 Analysis Date (ADT) used for Progression Free Survival will be the earliest date of radiologically documented disease progression (RS.RSDTC where RS.RSTESTCD=OVRLRESP and RSORRES=PD) or death (DM.DTHDTC) If none of these events occurred Analysis Date (ADT) is the last post-baseline tumour assessment (Max RS.RSDTC). Progression Free Survival (months)=(ADT - STARTDT+1)/30.42
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 30 ADTTE Examples Analysis ResultsMetadata CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Analysis Results Metadata Fields Description Display Identifier Tables 14.2.1 Display Name Overall Survival (months) by Treatment Result Identifier Overall Survival (months) PARAM Overall Survival (months) PARAMCD OS Analysis Variables AVAL, CNSR Reason Primary Efficacy Endpoint as per Protocol Dataset ADTTE Selection Criteria ITTFL=‘Y’ and PARAMCD=‘OS’ Documentation SAP Section 10.1.1 Programming Statements PROC LIFETEST DATA=ADTTE; TIME AVAL*CNSR(1); STRATA TRTP; WHERE PARAMCD=‘OS’; RUN;
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 31 ADTTE Examples The Analysis Reviewer Guide: The ideal place where to clarify potential source of misinterpretation not enough explained in the SAP CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 32 References RECIST and OTHER NON SOLID TUMOR REFERENCES  P Therasse et al, "New response evaluation criteria in solid tumors: Revised RECIST guideline (version 1.1)," European Journal of Clinical Oncology, pp. 45: 228-247, 2009.  Overcoming Difficulties in Implementing RECIST criteria, PhUSE 2013, G. Ruhnke  CDISC Journey on Solid Tumor Studies using RECIST 1.1., PhUSE 2013, K. Lee  SDTM Oncology Domains From Patients to Data to Narrative, PhUSE 2013, K. Stoltzfus  D Cheson et al, "Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia," Journal of Clinical Oncology, pp. Vol 21, No 24: pp 4642-4649, 2003 CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 33 References ONCOLOGY RELATED REGULATORY GUIDANCE  Clinical Trial Endpoints for the Approval of Non-Small Cell Lung Cancer Cancer Drugs and Biologics, FDA, 2011  Cancer Drug Approval Endpoints http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResourc es/CancerDrugs/ucm094586.htm CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 34 CDISC SDTM  CDISC Standards References  CDISC Study Data Tabulation Model (SDTM) v1.4  Study Data Tabulation Model Implementation Guide (SDTMIG) v3.2  Associated Persons Implementation Guide (SDTMIG-AP) v1.0  Released Therapeutic Area Standards:  Diabetes, Alzheimer, Asthma, Multiple Sclerosis, Pain, Parkinson Disease, Polycystic Kidney Disease, Tuberculosis and Virology  Oncology for Tumor Response domains (integrated into SDTMIG 3.1.3)  CDISC/NCI-EVE Standard Controlled Terminology  FDA Guidance and Technical Documents:  CDER and CBER: Guidance for Industry - Providing Regulatory Submissions in Electronic Format - Standardized Study Data (Draft)  Study Data Specifications (soon replaced by Study Data Technical Conformance Guide)  CDER Common Data Standards Issues  C Holland J Shostak - Implementing CDISC Using SAS, SAS 2012  F Wood - Creating SDTM Datasets from Legacy Data - PharmaSUG - 2011  A Tinazzi - Looking for SDTM Migration Specialist – PhUSE - London 2014 CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 35 CDISC ADaM References  Analysis Data Model (ADaM) Implementation Guide v1.0  The ADaM Basic Data Structure for Time-to-Event Analyses v1.0  Analysis Data Model (ADaM) Data Structure for Adverse Event Analysis  G Cappellini - ADaM and traceability: Chiesi experience. BIAS Seminar «Data handling and reporting in clinical trials with SAS» - Milan 2013  A Tinazzi - Interpreting CDISC ADaM IG through Users Interpretation. PhUSE - Bruxelles 2013 CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 36 Thank you for your time! Angelo Tinazzi – Associate Director – Statistical Programming angelo.tinazzi@cytel.com
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 37 Cytel Global Reach USA • Cambridge, MA (HQ) • Philadelphia, PA • Waltham, MA Sales Offices • New York, NY • San Francisco, CA France • Paris (sales office) Switzerland • Geneva India • Pune • Hyderabad • Bangalore • >400 FTEs worldwide • Low turnover rate (7% in 2011, 2012) UK • London (sales office)
Cytel Inc. - Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 38

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CDISC SDTM and ADaM for survival data

  • 1.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] CDISC SDTM and ADaM for survival data VI BIAS Annual Conference Analisi della sopravvivenza ed applicazioni in Oncologia: un percorso dalle basi agli ultimiaggiornamenti Genoa – 30-31/10/2014 Angelo Tinazzi Cytel Inc., Wilmington Del. USA Succursale de Meyrin – Geneva – Switzerland angelo.tinazzi@cytel.com 1
  • 2.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 2 The information contained in this presentation is based on personal research of the author and does not necessarily represent Cytel Inc.
  • 3.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 3 CDISC Intro CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References CDISC is a global, open, multidisciplinary, non-profit organization that has established standards to support the acquisition, exchange, submission and archive of clinical research data and metadata. The CDISC mission is to develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare. CDISC standards are vendor-neutral, platform-independent and freely available via the CDISC website.
  • 4.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 4 CDISC Intro Available Standards CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 5.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 5 CDISC Intro Standards in Submission Data Analysis Data Tabulations Data Collection Planning SDTM ADaM SEND CDASH LAB Protocol Study Design NCI CT CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 6.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 6 CDISC Intro A World of Clinical Standards CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 7.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 7 CDISC Intro Traceability CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Primary Overall Survival Analysis ADTTE ADaM define.xml DM aCRF SDTM define.xml
  • 8.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 8 Efficacy Endpoints in Oncology Solid Tumors CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Clinical Trial Endpoint Definition Source Overall Survival (OS) Time from randomization to death from any cause. FDA Objective Response Rate (ORR) Proportion of patients achieving either a partial or complete response for a minimum duration of time. FDA Disease-free survival (DFS) Time from randomization until recurrence of tumor or death from any cause. DFS is typically used in clinical trials of adjuvant cancer therapy. FDA Progression-free survival (PFS) Time from randomization until objective tumor progression or death. FDA Time to progression (TTP) Time from randomization until objective tumor progression (does not include deaths) FDA Time to treatment failure (TTF) Time from randomization to treatment discontinuation for any cause, including drug toxicity. FDA Progression-free survival 2 (PFS2) Same as PFS with some indication variant. E.g. in Prostate cancer - Duration of Response (DOR) Time from documentation of tumor response to disease progression EMA Clinical Benefit Response Rate (CBR) Patients achieving either a complete response, partial response or absence of progression at 6 months EMA
  • 9.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 9 Efficacy Endpoint in Oncology Solid Tumors RAN SD SD PR CR PD DOR ORR OS PFS TTP Death / Alive TTF Off TRT CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 10.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 10 CDISC SDTM SDTM Domains (as per Version 3.2) CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 11.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 11 CDISC SDTM Domains/Items Useful for Overall Survival Date of Origin / Starting point Randomization date Treatment Start date CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References DS DM
  • 12.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 12 CDISC SDTM Domains/Items Useful for Overall Survival Date of death DM DS Patient 101001 died (DTHFL=Y) the 17JAN2013 (DTHDTC) Patient 101006 is alive (DTHFL=NULL) Patient died (DSSCAT=REPORT OF DEATH) because of Progressive Disease (DSTERM) on 14DEC2010 (DSSTDTC) CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 13.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 13 CDISC SDTM Domains/Items Useful for Overall Survival Date of last follow-up  Any date documenting patient is still alive  Visit date, AEs, CM, Lab Samples, ECG, etc.  In SDTM we have a lot of «administrative» date that should be not considered (--DTC)  Investigate for date in Supplemental Qualifiers SUBJID SSORRES SSSTR ESC VISIT SSDTC 001001 ALIVE ALIVE FUP 1 07JAN13 001001 ALIVE ALIVE FUP 2 25MAY13 001002 DECEASED DEAD FUP 1 08JUN13 001003 ALIVE ALIVE FUP 1 01JAN12 001003 ALIVE ALIVE FUP 2 05AUG12 001003 PATIENT LOST TO FOLLOW UP LOST FUP 3 20NOV12 Last follow-up Date when death was reported. Date of death in DM At this follow-up the patient was known to be lost, date of last follow-up is therefore 05AUG12 (previous visit) Survival SS Status (available from version 3.2) CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 14.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 14 CDISC SDTM OncologyDomains for Tumor Response TU/TR/RS Tumor Identification Unique identification of tumors for that patient Tumor Results Quantitative measurements and/or qualitative assessments of the tumors identified in the TU Disease Response Clinical response evaluations determined from the TR data and other SDTM domains TU TR RS  Overcoming Difficulties in Implementing RECIST criteria, PhUSE 2013, G. Ruhnke  CDISC Journey on Solid Tumor Studies using RECIST 1.1., PhUSE 2013, K. Lee  SDTM Oncology Domains From Patients to Data to Narrative, PhUSE 2013, K. Stoltzfus CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 15.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 15 CDISC SDTM OncologyDomains for Tumor Response TU/TR/RS CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 16.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 16 CDISC SDTM OncologyDomains for Tumor Response TU/TR/RS CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 17.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 17 CDISC SDTM OncologyDomains for Tumor Response TU/TR/RS Source: Oncology Legacy Data => SDTM. CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 18.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 18 CDISC ADaM FoundationModels • One record per subject • Demographics, Baseline Chars • Study Population (ITTFL, SAFFL, ..) • Study Arm, Treatment Periods ADSL Analysis Subject Level Dataset • Vertical Structure • One or more record per subject/time-point BDS Basic Data Structure • Counting of subjects with a record for each term • It often includes a structured hierarchy of dictionary ODS Occurrence Data Structure • Based on BDS • Time to the Event of Interest • One or more time-to-event endpoint per ADTTE dataset TTE Time to Event CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 19.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 19 CDISC ADaM ADTTE – Analysis Dataset for Time to Event – Variables of Interest  Description of time-to-event (PARAMCD/PARAM)  E.g. OS/Overall Survival  Date Origin (STARTDT) E.g. Randomization Date  Censor (CNSR) 0=Event  Analysis date of event or censoring (ADT)  E.g. Death Date / Last follow-up  Elapsed time to the event of interest from the origin (AVAL)  E.g. (ADT-STARTDT)+1 (days) CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 20.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 20 CDISC ADaM ADTTE – Analysis Dataset for Time to Event – Variables of Interest  Event or Censoring Description (EVNTDESC)  E.g. DEATH  Censor Date Description (CNSDTDSC)  E.g. LAST FOLLOW-UP DATE  Imputation Date Flag (ADTF)  E.g. D/M/Y CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 21.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 21 ADTTE Examples Case 1: Single Endpoint with Multiple Values for Censoring A studywith Overall Survival as Primary Endpoint Definition Time from randomization until death from any cause Censor Last date subject was seen alive Cut-off Date Applied: 08APR2014 CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 22.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 22 ADTTE Examples Case 1: Single Endpoint with Multiple Values for Censoring SUBJID TR TP PARA MCD PARAM AVAL START DT ADT A D T F C N S R EVNTDESC 001001 PBO OS Overall Survival (Months) 16.8 15AUG11 07JAN13 0 DEATH 001002 EXP OS Overall Survival (Months) 8.4 12SEP11 25MAY12 D 1 LAST FOLLOW-UP DATE 001003 EXP OS Overall Survival (Months) 7.2 02SEP13 08APR14 1 FINAL ANALYSIS CUT-OFF DATE Endpoint: Overall Survival ; Cut-off Date Applied: 08APR2014 Treatment Received Time to Event Parameter − Start Date Randomisation - Event/Censor Date Time part of the TTE event (ADT-STARTDT+1)/30.42 *30.42 Standard for nr. of days in a month Event/Censor Description 0=Event 1..n=Censor CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 23.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 23 ADTTE Examples Case 1: Single Endpoint with Multiple Values for Censoring SUBJID TR TP PARA MCD PARAM AVAL START DT ADT A D T F C N S R EVNTDESC 001001 PBO OS Overall Survival (Months) 12.1 01APR13 07JAN13 0 DEATH 001002 EXP OS Overall Survival (Months) 17.2 04APR13 25MAY12 D 1 LAST FOLLOW-UP DATE 001003 EXP OS Overall Survival (Months) 17.5 08APR13 08APR14 1 FINAL ANALYSIS CUT-OFF DATE Endpoint: Overall Survival ; Cut-off Date Applied: 08APR2014 A partial date (--MAY12) where the day part has been imputed. Valid values are D,M,Y More details about censoring date. This patient either die or had a follow-up>cut-off date and therefore censored at the time of analysis cut-off date CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References This is also traceability!!!!!!
  • 24.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 24 ADTTE Examples Case 1: Single Endpoint with Multiple Values for Censoring Endpoint: Overall Survival ; Cut-off Date Applied: 08APR2014 SUBJ ID TR TP PARA MCD … ADT A D T F CN SR EVNTDESC SRC DOM SRCVAR SRCS EQ 001001 PBO OS … 07JAN13 0 DEATH DM DTHDTC . 001002 EXP OS … 25MAY12 D 1 LAST FOLLOW-UP DATE ADSL LASTVSDT . 001003 EXP OS … 08APR14 1 FINAL ANALYSIS CUT-OFF DATE ADSL LASTVSDT . SDTM.DM ADAM.ADSL CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References This is also traceability!!!!!!
  • 25.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 25 ADTTE Examples Case 2: Composite Endpoint with multiple value for Event and Censoring Progression Free Survival Definition Time from randomization until radiological tumor progression or death which ever come first Censor Last date radiological tumor assessment CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 26.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 26 ADTTE Examples Case 2: Composite Endpoint with multiple value for Event and Censoring Endpoint: Progression Free Survival SUBJ ID T R T P PA RA MC D PARAM AVAL START DT ADT C N S R EVNTDESC CNSDTDSC 001001 P B O PFS Progression Free Survival (Months) 16.8 15AUG11 07JAN13 0 RADIOLOGI CAL PROGRESSI ON 001002 E X P PFS Progression Free Survival (Months) 8.4 12SEP11 25MAY12 1 STUDY COMPLETED LAST RADIOLOGIC AL ASSESSMENT 001003 E X P PFS Progression Free Survival (Months) 7.2 02SEP13 08APR14 2 NO BASELINE ASSESSMEN T RANDOMIZAT ION 001004 P B O PFS Progression Free Survival (Months) 8.4 12SEP11 25MAY12 0 DEATH CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 27.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 27 ADTTE Examples Case 3: One ADTTE with several time-to-event Endpoints  Phase III study  First Relapsed or Refractory Acute Myeloid Leukemia  Primary Endpoint: Overall Survival  Sensitivity Analysis  Overall Survival censored for Susbsequent AML Therapies  Overall Survival censored for Post Treatment Transplantation CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 28.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 28 ADTTE Examples Case 3: One ADTTE with several time-to-event Endpoints SUBJ ID T R T P PAR AMC D PARAM AVAL ADT C N S R EVNTDESC CNSDTDSC 001001 P B O AML Susbsequent AML Therapies (Months) 0.6 31AUG11 0 SUBSEQUENT AML NON PROTOCOL THERAPY 001001 P B O TRA Post Treatment Transplantation (Months) 16.8 07JAN13 1 NO EVENT LAST VISIT DATE 001001 P B O OS Overal Survival (Months) 16.8 07JAN13 0 DEATH 001001 P B O OST R OS Censored for Transpl. (Months) 16.8 07JAN13 0 DEATH 001001 P B O OSA ML OS Censored for Subsequent AML Therapy (Months) 0.6 31AUG11 1 NO EVENT SUBSEQUENT AML NON PROTOCOL THERAPY DATE The Subsequent AML therapy started on 31st August 2011. The death occurred the 7th January 2013 was censored for OSAML CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 29.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 29 ADTTE Examples ADaMDefine.xml CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Variable Value Label Type Format Source/Computational Method PARAMCD PFS Progression Free Survival (Months) FLOAT 8.1 Analysis Date (ADT) used for Progression Free Survival will be the earliest date of radiologically documented disease progression (RS.RSDTC where RS.RSTESTCD=OVRLRESP and RSORRES=PD) or death (DM.DTHDTC) If none of these events occurred Analysis Date (ADT) is the last post-baseline tumour assessment (Max RS.RSDTC). Progression Free Survival (months)=(ADT - STARTDT+1)/30.42
  • 30.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 30 ADTTE Examples Analysis ResultsMetadata CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Analysis Results Metadata Fields Description Display Identifier Tables 14.2.1 Display Name Overall Survival (months) by Treatment Result Identifier Overall Survival (months) PARAM Overall Survival (months) PARAMCD OS Analysis Variables AVAL, CNSR Reason Primary Efficacy Endpoint as per Protocol Dataset ADTTE Selection Criteria ITTFL=‘Y’ and PARAMCD=‘OS’ Documentation SAP Section 10.1.1 Programming Statements PROC LIFETEST DATA=ADTTE; TIME AVAL*CNSR(1); STRATA TRTP; WHERE PARAMCD=‘OS’; RUN;
  • 31.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 31 ADTTE Examples The Analysis Reviewer Guide: The ideal place where to clarify potential source of misinterpretation not enough explained in the SAP CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 32.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 32 References RECIST and OTHER NON SOLID TUMOR REFERENCES  P Therasse et al, "New response evaluation criteria in solid tumors: Revised RECIST guideline (version 1.1)," European Journal of Clinical Oncology, pp. 45: 228-247, 2009.  Overcoming Difficulties in Implementing RECIST criteria, PhUSE 2013, G. Ruhnke  CDISC Journey on Solid Tumor Studies using RECIST 1.1., PhUSE 2013, K. Lee  SDTM Oncology Domains From Patients to Data to Narrative, PhUSE 2013, K. Stoltzfus  D Cheson et al, "Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia," Journal of Clinical Oncology, pp. Vol 21, No 24: pp 4642-4649, 2003 CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 33.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 33 References ONCOLOGY RELATED REGULATORY GUIDANCE  Clinical Trial Endpoints for the Approval of Non-Small Cell Lung Cancer Cancer Drugs and Biologics, FDA, 2011  Cancer Drug Approval Endpoints http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResourc es/CancerDrugs/ucm094586.htm CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 34.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 34 CDISC SDTM  CDISC Standards References  CDISC Study Data Tabulation Model (SDTM) v1.4  Study Data Tabulation Model Implementation Guide (SDTMIG) v3.2  Associated Persons Implementation Guide (SDTMIG-AP) v1.0  Released Therapeutic Area Standards:  Diabetes, Alzheimer, Asthma, Multiple Sclerosis, Pain, Parkinson Disease, Polycystic Kidney Disease, Tuberculosis and Virology  Oncology for Tumor Response domains (integrated into SDTMIG 3.1.3)  CDISC/NCI-EVE Standard Controlled Terminology  FDA Guidance and Technical Documents:  CDER and CBER: Guidance for Industry - Providing Regulatory Submissions in Electronic Format - Standardized Study Data (Draft)  Study Data Specifications (soon replaced by Study Data Technical Conformance Guide)  CDER Common Data Standards Issues  C Holland J Shostak - Implementing CDISC Using SAS, SAS 2012  F Wood - Creating SDTM Datasets from Legacy Data - PharmaSUG - 2011  A Tinazzi - Looking for SDTM Migration Specialist – PhUSE - London 2014 CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
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    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 35 CDISC ADaM References  Analysis Data Model (ADaM) Implementation Guide v1.0  The ADaM Basic Data Structure for Time-to-Event Analyses v1.0  Analysis Data Model (ADaM) Data Structure for Adverse Event Analysis  G Cappellini - ADaM and traceability: Chiesi experience. BIAS Seminar «Data handling and reporting in clinical trials with SAS» - Milan 2013  A Tinazzi - Interpreting CDISC ADaM IG through Users Interpretation. PhUSE - Bruxelles 2013 CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References
  • 36.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 36 Thank you for your time! Angelo Tinazzi – Associate Director – Statistical Programming angelo.tinazzi@cytel.com
  • 37.
    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 37 Cytel Global Reach USA • Cambridge, MA (HQ) • Philadelphia, PA • Waltham, MA Sales Offices • New York, NY • San Francisco, CA France • Paris (sales office) Switzerland • Geneva India • Pune • Hyderabad • Bangalore • >400 FTEs worldwide • Low turnover rate (7% in 2011, 2012) UK • London (sales office)
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    Cytel Inc. -Confidential [A. Tinazzi – CDISC SDTM and ADaM for survival data – BIAS 2014 Genoa 30-31 October 2014] 38