CDISC SDTM and ADaM for survival data

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

Cytel Inc. - Confidential
The information contained in this presentation is based on personal research of the author and does not necessarily represent Cytel Inc.

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.

CDISC Intro Available Standards
Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References

CDISC Intro Standards in Submission
Data Analysis Data Tabulations Data Collection Planning CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Protocol CDASH SDTM ADaM Study Design LAB SEND NCI CT

CDISC Intro A World of Clinical Standards
Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References

CDISC Intro Traceability
Primary Overall Survival Analysis CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References ADTTE aCRF ADaM define.xml SDTM define.xml DM

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. 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. Progression-free survival (PFS) Time from randomization until objective tumor progression or death. Time to progression (TTP) Time from randomization until objective tumor progression (does not include deaths) Time to treatment failure (TTF) Time from randomization to treatment discontinuation for any cause, including drug toxicity. 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 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. 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. Progression-free survival (PFS) Time from randomization until objective tumor progression or death. Time to progression (TTP) Time from randomization until objective tumor progression (does not include deaths) Time to treatment failure (TTF) Time from randomization to treatment discontinuation for any cause, including drug toxicity. 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

Efficacy Endpoint in Oncology Solid Tumors
CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Off TRT Death / Alive RAN SD SD PR CR PD ORR PFS TTP DOR TTF OS

CDISC SDTM SDTM Domains (as per Version 3.2)
CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References

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

Date of death CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References DM Patient died (DTHFL=Y) the 17JAN2013 (DTHDTC) Patient is alive (DTHFL=NULL) DS Patient died (DSSCAT=REPORT OF DEATH) because of Progressive Disease (DSTERM) on 14DEC2010 (DSSTDTC)

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 CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Survival Status (available from version 3.2) SS SUBJID SSORRES SSSTRESC VISIT SSDTC 001001 ALIVE FUP 1 07JAN13 FUP 2 25MAY13 001002 DECEASED DEAD 08JUN13 001003 01JAN12 05AUG12 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)

CDISC SDTM Oncology Domains 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 CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References 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

CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Source: Oncology Legacy Data => SDTM.

CDISC ADaM Foundation Models
CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References 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 ADaM ADTTE – Analysis Dataset for Time to Event – Variables of Interest
CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References 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 ADaM ADTTE – Analysis Dataset for Time to Event – Variables of Interest
CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References 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

ADTTE Examples Case 1: Single Endpoint with Multiple Values for Censoring
CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References A study with 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

Time to Event Parameter
ADTTE Examples Case 1: Single Endpoint with Multiple Values for Censoring CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Endpoint: Overall Survival ; Cut-off Date Applied: 08APR2014 SUBJID TR TP PARAMCD PARAM AVAL START DT ADT ADTF CNSR EVNTDESC 001001 PBO OS Overall Survival (Months) 16.8 15AUG11 07JAN13 DEATH 001002 EXP 8.4 12SEP11 25MAY12 D 1 LAST FOLLOW-UP DATE 001003 7.2 02SEP13 08APR14 FINAL ANALYSIS CUT-OFF DATE Treatment Received Time to Event Parameter Time part of the TTE event (ADT-STARTDT+1)/30.42 *30.42 Standard for nr. of days in a month Start Date Randomisation Event/Censor Date 0=Event 1..n=Censor Event/Censor Description

CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Endpoint: Overall Survival ; Cut-off Date Applied: 08APR2014 SUBJID TR TP PARAMCD PARAM AVAL START DT ADT ADTF CNSR EVNTDESC 001001 PBO OS Overall Survival (Months) 12.1 01APR13 07JAN13 DEATH 001002 EXP 17.2 04APR13 25MAY12 D 1 LAST FOLLOW-UP DATE 001003 17.5 08APR13 08APR14 FINAL ANALYSIS CUT-OFF DATE 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 This is also traceability!!!!!!

CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Endpoint: Overall Survival ; Cut-off Date Applied: 08APR2014 SUBJ ID TR TP PARAMCD … ADT ADTF CNSR EVNTDESC SRC DOM SRCVAR SRCSEQ 001001 PBO OS 07JAN13 DEATH DM DTHDTC . 001002 EXP 25MAY12 D 1 LAST FOLLOW-UP DATE ADSL LASTVSDT 001003 08APR14 FINAL ANALYSIS CUT-OFF DATE SDTM.DM ADAM.ADSL This is also traceability!!!!!!

ADTTE Examples Case 2: Composite Endpoint with multiple value for Event and Censoring
CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Progression Free Survival Definition Time from randomization until radiological tumor progression or death which ever come first Censor Last date radiological tumor assessment

ADTTE Examples Case 2: Composite Endpoint with multiple value for Event and Censoring
CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Endpoint: Progression Free Survival SUBJ ID TR TP PARAMCD PARAM AVAL START DT ADT CNSR EVNTDESC CNSDTDSC 001001 P B O PFS Progression Free Survival (Months) 16.8 15AUG11 07JAN13 RADIOLOGICAL PROGRESSION 001002 E X 8.4 12SEP11 25MAY12 1 STUDY COMPLETED LAST RADIOLOGICAL ASSESSMENT 001003 7.2 02SEP13 08APR14 2 NO BASELINE ASSESSMENT RANDOMIZATION 001004 DEATH

ADTTE Examples Case 3: One ADTTE with several time-to-event Endpoints
CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References 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

ADTTE Examples Case 3: One ADTTE with several time-to-event Endpoints
CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References SUBJ ID TR TP PARAMCD PARAM AVAL ADT CNSR EVNTDESC CNSDTDSC 001001 P B O AML Susbsequent AML Therapies (Months) 0.6 31AUG11 SUBSEQUENT AML NON PROTOCOL THERAPY TRA Post Treatment Transplantation (Months) 16.8 07JAN13 1 NO EVENT LAST VISIT DATE OS Overal Survival (Months) DEATH OSTR OS Censored for Transpl. (Months) OSAML OS Censored for Subsequent AML Therapy (Months) SUBSEQUENT AML NON PROTOCOL THERAPY DATE The Subsequent AML therapy started on 31st August The death occurred the 7th January 2013 was censored for OSAML

ADTTE Examples ADaM Define.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

ADTTE Examples Analysis Results Metadata
CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References Analysis Results Metadata Fields Description Display Identifier Tables Display Name Overall Survival (months) by Treatment Result Identifier Overall Survival (months) PARAM 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 Programming Statements PROC LIFETEST DATA=ADTTE; TIME AVAL*CNSR(1); STRATA TRTP; WHERE PARAMCD=‘OS’; RUN;

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

RECIST and OTHER NON SOLID TUMOR REFERENCES
CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples 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: , 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 ,

ONCOLOGY RELATED REGULATORY GUIDANCE
References CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples 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 es/CancerDrugs/ucm htm

CDISC SDTM References CDISC Standards
CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References CDISC SDTM CDISC Standards 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 A Tinazzi - Looking for SDTM Migration Specialist – PhUSE - London 2014

References CDISC Intro Efficacy Endp. Onco CDISC SDTM CDSIC ADaM ADTTE Examples References CDISC ADaM 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

Angelo Tinazzi – Associate Director – Statistical Programming
Thank you for your time! Angelo Tinazzi – Associate Director – Statistical Programming

Cytel Global Reach USA France Switzerland India UK
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 UK London (sales office) >400 FTEs worldwide Low turnover rate (7% in 2011, 2012)

CDISC SDTM and ADaM for survival data

Similar presentations

Presentation on theme: "CDISC SDTM and ADaM for survival data"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

CDISC SDTM and ADaM for survival data

Similar presentations

Presentation on theme: "CDISC SDTM and ADaM for survival data"— Presentation transcript:

Similar presentations

About project

Feedback