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ADaM Implementation Guide Status Update

John K. Troxell John Troxell Consulting LLC

Bridgewater, NJ [email protected]

June 17, 2013

Current CDISC ADaM Documents • 2009

– Analysis Data Model (ADaM), Version 2.1 – Analysis Data Model (ADaM) Implementation Guide, Version

1.0

• 2010-2012 – CDISC ADaM Validation Checks, Version 1.2

• 2011 – Analysis Data Model (ADaM) Examples in Commonly Used

Statistical Analysis Methods

• 2012 – Analysis Data Model (ADaM) Data Structure for Adverse

Event Analysis, Version 1.0 – The ADaM Basic Data Structure for Time-to-Event Analyses,

Version 1.0 – IG compliance update of CDISC-FDA Pilot I

2013-06-17 John Troxell - ADaM IG Status Update 2

ADaMIG to Date

• ADaM team started working on IG in 2006

• Concentrated effort in 2009, published IG in Dec.

• Multiple work streams 2010-2012

– Published Validation Checks, Examples in Stat. Analysis, AE, TTE, compliance update of CDISC-FDA Pilot I

– Worked on metadata guide, general occurrences, integration, multivariate, PK, contributed to Define 2.0

• Started to refocus on IG in 2H 2012

– Learning from implementation experience

– Recently dedicating team meetings to IG, doubled frequency


ADaMIG Update • Primarily driven by Cathy Barrows, GSK (retired)

– minor assistance from colead John Troxell

• Compiled list of suggestions/issues/deferred items • Triaged: reject, do first, do later • IG 1.1 draft for public comment targeted 2013*

– typos, error fixes – clarifications (requires thought and discussion) – some relatively easier issues and enhancements (but really none of them are easy and there is lots of deep thought and debate)

• IG 1.2 targeted 2014+* – issues requiring deepest thought and extended debate – more extensive document restructuring

* Guaranteed by the ADaM Team or double your money back.


Processing of Implementation Experience • Clarify, clarify, clarify

– The scrutiny of the text by implementers is intense – Impossible to be too precise

• Implementers’ misunderstandings – Re-examine original thinking, clarify

• Objections to constraints – Re-examine fundamental aspects of the model or data structure – Can we ring-fence a proposed relaxation or exception without

breaking the model and inviting chaos? – Deep thought process and debate

• Additional features desired – Debate, consider impacts, design

• Typos, errors – Fix, considering backwards compatibility


Types of “Clarification”

1. We agree on what we meant and we need to express it more clearly.

2. We agreed on some language but now we realize we understood it differently.

– We need to agree on the meaning before we can clarify the text.

3. We realize we had not thought things through well enough to begin with.

– We need to clarify our thinking first.

– We may need to make some changes here and/or elsewhere in the standard, as well as clarify the text.


Example of a Needed Clarification: 1:1 Map of AVAL:AVALC

• QS1 is a BDS parameter from a standard questionnaire.

• QSSTRESC contains the coded value of the answer.

• We copy the answer from QSORRES into AVALC.

• We copy (or derive) the score and put it into AVAL.

• Within QS1, AVAL and AVALC map 1:1 as required by IG

In SDTM In ADaM

QSORRES QSSTRESC QSSTRESN AVISIT PARAMCD AVAL AVALC DTYPE

VERY BAD 1 1 Week 8 QS1 1 VERY BAD

BAD 2 2 Week 8 QS1 2 BAD

GOOD 4 4 Week 8 QS1 4 GOOD



• Per the SAP, we need to analyze the average Score for Week 8, so we derive a record for it.

In SDTM In ADaM





Week 8 QS1 2.333 AVERAGE

• This looks good so far – still 1:1 – but what happens when we add more data….?


AVAL:AVALC In SDTM In ADaM






OK 3 3 Week 8 QS1 3 OK




Now we don’t have a 1:1 correspondence between AVAL and AVALC: AVAL=2.333 / AVALC=null AVAL=2.0 / AVALC=null

This is a topic for clarification by the ADaM team.



• Solution: clarify the scope of the 1:1 mapping requirement

• Clarify that AVAL and AVALC must be a one-to-one map within a parameter on the rows on which both AVAL and AVALC are populated

• We are making many scope clarifications in IG 1.1

– A statement applies within a study? dataset? parameter? subject? Often this was unstated in IG 1.0.


Common Misunderstandings and Impacts on Next Versions of IG

• Sometimes we observe people (including us) misunderstanding the IG or authors’ intent

• Misunderstandings point to places where the IG can be improved

• See “Common Misunderstandings about ADaM Implementation,” PharmaSUG 2012.

– N. Freimark, S. Kenny, J. Shostak, J. Troxell

– a snapshot of personal opinions of the authors

– not a complete list


Example of a Misunderstanding: Mistaking PARCATy as a Qualifier

• Parameter PARAM has no qualifiers • Parameter Category PARCATy groups parameters into categories • PARCATy does not subdivide or qualify PARAM • ADaM Validation Check Error:

– There is more than one value of PARCATy for a given value of PARAMCD.

• Some have misunderstood PARCATy to be a qualifier of PARAM • Misunderstanding often results from carrying over SDTM thinking

ADaM ≠ SDTM

PARCATy ≠ --CAT

Basic Data Structure ≠ Findings Domain +

AVAL/AVALC ≠ --STRESN/--STRESC



PARAM AVAL

Cumulative Dose of Drug A (mg) 1,234

Cumulative Dose of Drug B (mg) 8,765

PARAM PARCAT1 AVAL

Cumulative Dose (mg) Drug A 1,234

Cumulative Dose (mg) Drug B 8,765

Compliant but not scalable:

Non-compliant but scalable:

For a company core controlled terminology for PARAM, it would be nice if we could have one parameter, not dozens. SO, wouldn’t it be nice to misunderstand PARCATy?



• How should ADaM IG be modified?

– Clarify and emphasize that PARCATy is not a qualifier on PARAM and re-emphasize that PARAM has no qualifiers?

– Find a carefully ring-fenced way to permit limited qualifier functionality without permitting degeneration to SDTM TEST + qualifiers approach?

Is this even possible?

Deeper question than just PARCATy

– Need to address one way or the other


What you really wanted to hear about: Exactly what is changing?

• Not appropriate to publicize details until release for public comment • Still evolving • Some clues about 1.1

– corrections of typos and minor errors – clarifications (e.g. scopes, definitions, text) – additional timing and other variables – some features useful for oncology – more Word tables – minor restructuring of document

• 1.2 – more profound issues addressed – more restructuring – coordinated model document update


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