CDISC ADaM 2.1 Implementation: A Challenging Next Step …€¦ · 1 CDISC ADaM 2.1 Implementation:...

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CDISC ADaM 2.1 Implementation:A Challenging Next Step in the Process

Presented by Tineke Callant

2014-03-14

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Agenda

n CDISC - Introduction

n CDISC - Foundational standards

n CDISC ADaM V2.1 - Analysis data flow

n CDISC ADaM V2.1 - ADaM data structures

n CDISC ADaM V2.1 - Traceability

n CDISC ADaM V2.1 - ADaM metadata

n CHKSTRUCT macro

n Linear method - Challenges and solutions

n Take home messages

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Clinical Data Interchange Standards Consortium - Introduction

n 1997 - Inception

n 2000 - 32 global companies

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.

n 2014 - ± 200 organizations• biotechnology and pharmaceutical development companies• device and diagnostic companies• CROs and technology providers• government institutions, academic research centers and other non-profit

organizations

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n Mission statement

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.

Data standards to improve clinical research

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- 2001: Biomedical Research Integrated Domain Group (BRIDG) Model

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Agenda







n CHKSTRUCT macro



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CDISC - Foundational standards

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content

transport

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n Study Data Tabulation Model (SDTM)

The content standard for regulatory submission of case report form data tabulations from clinical research studies.

Datasets containing data collected during the study and organized by clinical domain.

n Analysis Data Model (ADaM)

The content standard for regulatory submission of analysis datasets and associated files.

Datasets used for statistical analysis and reporting by the sponsor, submitted in addition to the SDTM domains.

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Agenda







n CHKSTRUCT macro



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CDISC ADaM V2.1 - Analysis data flow

ADaM

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Agenda







n CHKSTRUCT macro



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CDISC ADaM V2.1 - ADaM data structures

n The Subject-Level Analysis Dataset (ADSL) structure

n The Basic Data Structure (BDS)

n Other

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CDISC ADaM V2.1 - ADaM data structuresThe Subject-Level Analysis Dataset (ADSL) structure

n One record per subject

n Variables (required + other)• Study identifiers (e.g. DM.STUDYID)• Subject demographics (e.g. DM.AGE)• Population indicator(s) (e.g. RANDFL)• Treatment variables (e.g. DM.ARM)• Trial dates (e.g. RANDDT)

n Required in a CDISC-based submission

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n Other

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CDISC ADaM V2.1 - ADaM data structuresThe Basic Data Structure (BDS)

n One or more records per subject, per analysis parameter, per analysis time point (conditionally required)

n Variables• e.g. PARAM and related variables• e.g. AVAL and AVALC and related variables• e.g. the subject identification• e.g. DTYPE• e.g. treatment variables, covariates

n Supports the majority of statistical analyses

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n Other

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CDISC ADaM V2.1 - ADaM data structuresOther

n CDISC ADaM Basic Data Structure for Time-to-Event Analysis Version 1.0 - May 8, 2012

n CDISC ADaM Data Structure for Adverse Event Analysis Version 1.0 - May 10, 2012

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n CHKSTRUCT macro



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CDISC ADaM V2.1 - Analysis data flow

ADaM

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n Understanding the relationship of element vs. predecessor

n Enabling transparancy

n Analysis results → Analysis datasets → SDTM

CDISC ADaM V2.1 - Traceability

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CDISC ADaM V2.1 - TraceabilityStrategies for implementing SDTM and ADaM standardsSusan Kenny – Michael Litzsinger

n Parallel method

SDTM DomainsDBMS Extract

Analysis Datasets

n Retrospective method

DBMS Extract → Analysis Datasets → SDTM Domains

n Linear method

DBMS Extract → SDTM Domains → Analysis Datasets

n Hybrid method

DBMS Extract → SDTM Draft Domains → Analysis Datasets → SDTM Final Domains

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n Traceability

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n CDISC ADaM V2.1 • Fundamental principles

– Provide traceability between the analysis data and its source data

• Practical considerations– Maintain the values and attributes of SDTM variables

n CDISC ADaM implementation guide (IG) V1.0• General variable naming conventions

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CDISC ADaM V2.1 - TraceabilityGeneral variable naming conventions

Any ADaM variable whose name is the

same as an SDTM variable must be a

copy of the SDTM variable, and its label,

meaning, and values must not be

modified

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n Parallel method

SDTM DomainsDBMS Extract

Analysis Datasets

n Retrospective method

DBMS Extract → Analysis Datasets → SDTM Domains

n Linear method


n Hybrid method



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n Linear method


• Traceability• CDISC SDTM/ADaM Pilot Project• Recommended


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n Hybrid method


• Traceability• Amendment 1 SDTM V1.2 and SDTM IG V3.1.2• Future?!?


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n Traceability → Recommended: Linear method

n Flexible

n Delivery of consistent analysis datasets

n Easy to use (Excel file)

n Easy to maintain (Excel file)


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Agenda







n CHKSTRUCT macro



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CDISC ADaM V2.1 - ADaM metadata

n Microsoft Office Excel spreadsheet as framework

n Metadata

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n analysis dataset

n %CHKSTRUCT(ds_ = )• Automatization • Compliance

n define.xml

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n Analysis dataset metadata

n Analysis variable metadata

n Analysis parameter value-level metadata

n Analysis results metadata

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CDISC ADaM V2.1 - ADaM metadataAnalysis dataset metadata

n Illustration from CDISC ADaM V2.1

n Practical consideration: ADxxxxxx

! ≠ SDTM !The key variables should define uniqueness

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Analysis dataset naming convention

n ADxxxxxx

n The subject-level analysis dataset is named ADSL

n max. 8 characters

CDISC ADaM V2.1 - ADaM metadataAnalysis dataset metadata

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CDISC ADaM V2.1 - ADaM metadataAnalysis variable metadata

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CDISC ADaM V2.1 - ADaM metadataAnalysis parameter value-level metadata

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n Analysis results metadata (not required)

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CDISC ADaM V2.1 - ADaM metadataAnalysis variable metadata in practice

n Analysis dataset metadatan Analysis variable metadata

Dataset name Display formatVariable name Codelist / Controlled termsVariable label Source / DerivationVariable type

Parameter identifier (Basic Data Structure (BDS))

n Analysis results metadata (not required)

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n Metadata

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n SAS variable attributes

n To work in a SAS environment– NAME– TYPE– LENGTH– FORMAT– INFORMAT– LABEL– POSITION IN

OBSERVATION– INDEX TYPE

n Analysis variable metadata fields

– DATASET NAME– VARIABLE NAME– VARIABLE LABEL– VARIABLE TYPE– DISPLAY FORMAT– CODELIST /

CONTROLLED TERMS– SOURCE / DERIVATION– BASIC DATA STRUCTURE:

PARAMETER IDENTIFIER

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n Example


...

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CDISC ADaM V2.1 - ADaM metadataAnalysis variable metadata in practice -Subposition in observation

n Example• ADSL – SITEGR* (Char) and SITEGR*N (Num)

* = a single digit [1-9]

• SITEID

• SITEID grouped together by city in the variable SITEGR1 (SITEGR1N)

• SITEID grouped together by province in the variable SITEGR2 (SITEGR2N)

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%CHKSTRUCT(ds_ = ADSL)

1 21 2ORDER

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ORDER 1 2 1 2

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n Example• ADSL – SITEGR* (Char) and SITEGR*N (Num)

* = a single digit [1-9]

POSITION IN OBSERVATION

SUBPOSITION IN OBSERVATION

VARIABLE NAME

1 STUDYID

2 USUBJID

3 SITEID

4 1 SITEGR*

4 2 SITEGR*N

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n Example


n Example

...

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CDISC SDTM CDISC ADaMReq - Required

The variable must be included in the dataset and cannot be null for any record.

Req - Required

The variable must be included in the dataset.

Exp - Expected

... and may contain some null values.

Cond - Conditionally required

... in certain circumstances.Perm - Permissible

The variable should be used in a domainas appropriate when collected or derived.

Perm - Permissible

The variable may be included in the dataset, but is not required.

CDISC ADaM V2.1 - ADaM metadataAnalysis variable metadata in practice - Core

n Nulls are allowed

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Agenda







n CHKSTRUCT macro



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CHKSTRUCT macro


n analysis dataset

n %CHKSTRUCT(ds_ = )• Automatization • Compliance

n define.xml

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CHKSTRUCT macro - Automatization


Before

After

4 6 5 7 1 2 3

1 2 3 4 5 6 7

ORDER THE ANALYSIS VARIABLES

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Before

After

LABEL THE ANALYSIS VARIABLES

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Key variables

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2134

5698

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1234

6789

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Key variables

Before

After

SORT THE ANALYSIS DATASET

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CHKSTRUCT macro – Compliance

Analysis dataset Analysis variable metadata

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CHKSTRUCT macro

n Excel spreadsheet as framework

n Purpose• Reference • Automatization• Compliance

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Agenda







n CHKSTRUCT macro



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Linear method - Challenges and solutions

Step 1

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Linear method - Challenges and solutionsStep 1 - CDISC SDTM Implementation Guide

...

...

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Linear method - Challenges and solutionsStep 1 - CDISC SDTM Implementation Guide

Any ADaM variable whose name is the

same as an SDTM variable must be a

copy of the SDTM variable, and its label,

meaning, and values must not be

modified

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Linear method - Challenges and solutionsStep 1 - CDISC SDTM Implementation GuideChallenge: Flexible variable length

...

...

...

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n CDISC SDTM IG• Variables of the same name in split datasets should have the same

SAS Length attribute• Version 5 SAS transport file format: max. 200 characters• -- TESTCD and QNAM: max. 8 characters• -- TEST and QLABEL: max. 40 characters

n Example: DM.RACE: $41, $50, and $200

n Amendment 1 to SDTM V1.2 and SDTM IG V3.1.2• Version 5 SAS transport file format: max. 200 characters

! only if necessary !

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n Traceability

n Flexible


n Easy to use

n Easy to maintain


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Linear method - Challenges and solutionsStep 1 - CDISC SDTM Implementation GuideSolution: [sdtm] ↔ %CHKSTRUCT(ds_ = )

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Example: LB.LBSCAT

Linear method - Challenges and solutionsStep 1 - CDISC SDTM Implementation GuideChallenge: Permissible variables

Solution: [sdtm] ↔ %CHKSTRUCT(ds_ = )

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Step 2

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Linear method - Challenges and solutionsStep 2 - SUPP--

n QNAM → variable name

n QLABEL → variable label

n QVAL → variable type

→ variable length

e.g. SUPPDM SDTM dataset e.g. ADSL ADaM dataset

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Linear method - Challenges and solutionsStep 2 - SUPP--Challenge: Flexible code list

n QLABEL is different for the same QNAM– Example

ELIGCONF Subject Still EligibleELIGCONF Still Fulfill Eligibility Criteria

n QLABEL format– Example

RANDNO RANDOMIZATION NUMBERRANDNO Randomization Number

n QLABEL changes during the course of a study– Example

ELIGIBLE Suject Eligible For Dosing ELIGIBLE Subject Eligible For Dosing

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Linear method - Challenges and solutionsStep 2 - SUPP--Solution: [supp] ↔ %CHKSTRUCT(ds_ = )

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Step 3

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Linear method - Challenges and solutions - Step 3

ADaM

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Linear method - Challenges and solutions - Step 3Challenge: 12 SDTM → 12 ADaM?!?

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910

SDTM

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ADaM

?

?

??

??

??

??

??

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Linear method - Challenges and solutions - Step 3Solution: 1 central model + sponsor specific add-ons

sponsorspecificadd-on

centralADaMmodel

domlist.sas7bdat

varlist.sas7bdat

codelist.sas7bdat

domlist.sas7bdat

varlist.sas7bdat

codelist.sas7bdat

domlist.sas7bdat

varlist.sas7bdat

codelist.sas7bdat

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1 Convert Excel file to SAS datasets (by ADaM administrator)

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2 Combine central model and sponsor specific add-on (by study programmer)

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n Traceability

n Flexible


n Easy to use

n Easy to maintain

Linear method - Challenges and solutions - Step 3Solution: 1 central model + sponsor specific add-ons

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Step 4

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Linear method - Challenges and solutions - Step 4Challenge: SDTM model no. 1, 2, 3 ... ?

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910

SDTM

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ADaM

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Linear method - Challenges and solutions - Step 4 Solution: Central metadata repository

n CDISC metadata• SDTM version• SDTM metadata• ...

n Study characteristics • Therapeutic area• Clinical phase • Trial design characteristics• ...

n Project metadata• Study timelines• Key Performance Indicators• ...

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Step 5

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Linear method - Challenges and solutions – Step 5Challenge: Future

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Linear method - Challenges and solutions – Step 5Challenge: Future

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Agenda







n CHKSTRUCT macro



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Take home messagesMessage no. 1

ADaM SDTM

n SDTM and ADaM go hand in hand

n Thus, without a CDISC compliant SDTM database to start from, ADaM cannot exist

n But do realize a strong analysis data model needs more than a CDISC compliant SDTM database alone

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n Linear method:• Recommended• Challenging

n Solution:• SDTM: Central metadata repository• ADaM: Automatization, e.g. [sdtm], [supp] …

Study medata differences are handled efficiently

Take home messagesMessage no. 2

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E-mail:[email protected]

Internet:www.sgs.com/cro

CDISC ADaM 2.1 Implementation: A Challenging Next Step …€¦ · 1 CDISC ADaM 2.1 Implementation:...

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