Don’t Dream the Impossible Dream

Presented by Steve Kirby (Reata Pharmaceuticals) and Mario Widel (Covance)

10.10.2018

A Practical Approach to Automating End to End Standards

Agenda

1. What it would take to fully live that (impossible) dream1. Collection and tabulation level

2. Analysis and submission level

3. Process maintenance level

2. A possible dream 1. Scope (start small)

2. Start with a subset of standard TFL shells and work back

3. Pilot process

4. Roll it out

3. Examples

What would it takes to live that dream

What it takes to live that dream – Collection and Tabulation

• Protocol templates are CDISC-friendly and consistently applied

• Source data collection standards leverage CDASH and are otherwise SDTM friendly

• Source data extracts are consistently formatted

• Source to SDTM mapping is fully defined and supported by robust code

Does this describe the current state at your company?

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What it takes to live that dream – analysis and submission

• SAP templates and standard analyses are fully defined and consistently

• ADaM specifications are fully defined based on standard SAP template and associated shells

• ADaM programming is fully defined and supported by robust code

• Data documentation (for SDTM and ADaM) is fully supported by standard mapping and is automatically generated

Does this describe the current state at your company?

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What it takes to live that dream – process maintenance

• Any special needs are accounted for by a robust waiver/exception process

• Everyone always follows all company implementation standards and associated processes

• Everything works exactly as expected

Does this describe the current state at any company?.

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A possible dream

The Impossible Dream (a realistic look)

• Ain’t gonna happen*

• So let’s consider what part of that dream we can live

* Why not? What is so hard?.

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E2E standards on a budget

• We can’t live the whole dream

• Let’s focus on living part of the dream• Define some key elements from E2E

• And then automate and reuse

• After initial success:• If all is working well, expand from there.

• If not, refine the key elements (next slide, process flow)

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Define the initial scope of the E2E standards effort

• A good starting point: determine what analysis needs are the same across studies within a compound.

• Typically basic safety analyses work well for this stage.

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Start at the end and work back

• Define associated table shells,

• Work back from there to:• Associated SAP template sections,

• ADaM,

• SDTM,

• associated source data and

• related sections in the protocol.

• .

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E2E Process flow diagram

Standard

SAP Text

Standard

ADaM

Code

Standard

Table

Code

Test and

Approve

Define.xml

Standard

ADaM

DefinitionsSubset of

Std. Table

Shells

ADaM

AnnotatedSupports

Define/ARM

Based

on ARMBased on

Definitions

Accurate

and

Conformant

Beware mission creep

• Small additions can sidetrack an otherwise well-formed plan

• Start small

• Stay small.

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Pilot process for proof of concept

• Build a sand-box area to pilot.

• One simple method is to leverage content from an appropriate completed study in a work directory.

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Appropriately time initial roll-out of process

• Best to schedule initial implementation with the first study in a sequence or similar to minimize disruption. .

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Examples

Example implementation – Table Shell

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Example implementation – SAP

.

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The following demographics and baseline characteristics will be summarized descriptively for the <insert populations as applicable>:

• Age in years*

• Gender

• Ethnicity

• Race

• Height in centimeters

• Weight in kilograms

• Body mass index*

• Alcohol history (never consumed, previously consumed, currently consumes) +

• Tobacco history (never used, previously used, currently uses) +

• <insert groupings (e.g. Age Groupings, Race Groupings) and additional parameters as needed

*See General Guidance for Statistical Programming document for default computational methods; methods that differ from or are not included in that document are specified.

+ Included if relevant

Example implementation – ADaM

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Example implementation – SDTM

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Example implementation – Source Data

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Example implementation – Protocol

Demographics, Baseline Characteristics

The following demographics and baseline characteristics will be summarized descriptively for both the safety and ITT populations: age in years, gender, race, height, weight, body mass index.

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Example implementation – next steps

• Solicit feedback

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Questions?

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Thank You!