Trials and Tribulations of SDTM Trial Design Mary Lenzen Octagon Research Solutions

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Trials and Tribulationsof SDTM Trial Design

Mary Lenzen Octagon Research Solutions

ESUG TeleconJuly 26, 2011



Why Do Trial Design

• Rapidly understanding the design of the study • Standard and relatively simple data structures• Relatively small number of rows of data and

easy to comprehend• Useful for both FDA reviewers and internal

sponsor use• Information can be centrally accessible and

searchable



Ordered by Complexity• Trial Inclusion/Exclusion Criteria (Lookup table)• Trial Summary (Descriptive attributes of trial)• Trial Visits (Planned)• Trial Arms (Planned)• Trial Elements (Planned)

Trial Design: Overview



Creating Trial Inclusion/Exclusion

• Challenge of 200 character limit• Truncation – potential for duplicate IETEST

values• Need protocol or CRF for complete IETEST

values• Subject IETEST/IETESTDC must match Trial

Inclusion/Exclusion IETEST/IETESTCD



Creating Trial Summary

• Key details about the trial• One record per parameter value

• TSGRPID used to group multiple related parameters such as Dose, Units, Frequency etc

• TSSEQ used as a key for multiple records with the same parameters



Creating Trial Visits

• Planned schedule of Visits• Timing variables: VISITNUM, VISIT, and

VISITDY• What is really the start and end of a visit? • Create Subject Visits dataset from Visit based

SDTM datasets



STUDYID DOMAIN VISITNUM VISIT VISITDY ARMCD ARM TVSTRL TVENRL

1999001 TV 1 Visit 1 Signing of informed consent

Completion of lab draw

1999001 TV 2 Visit 2 30 minutes before receipt of Run-In drug

1999001 TV 3 Visit 3 30 minutes before receipt of blinded treatment

30 minutes after receipt of blinded treatment

1999001 TV 4 Visit 4 1 week after receipt of blinded treatment

1999001 TV 5 Visit 5 2 weeks after

receipt of blinded treatment

Completion of final disposition page

Creating Trial Visits (2)

• Planned schedule of Visits• Challenge is in defining start and end of a visit• ARM/ARMCD can be used if schedule varies by Arm



STUDYID DOMAIN USUBJID VISITNUM VISIT VISITDY SVSTDTC SVENDTC SVUPDES

1999001 SV 145-011 0 2003-04-01 2003-04-01

1999001 SV 145-011 1 2003-04-16 2003-04-16

1999001 SV 145-011 2 2003-05-01 2003-05-02

1999001 SV 145-011 4 2003-06-01 2003-06-01

1999001 SV 145-011 5 2003-06-16 2003-06-16

1999001 SV 145-011 5.1 2003-06-17 2003-06-17 Evaluate severe rash

Creating Subject Visits

Subject Visits comes from the data, rather than the Visit Start and End Rules.



Trial Visits describes the planned Visits for each Arm, and any start and end rules.

Screen Run-In Drug A

Screen Run-In Drug B

Screening

Screen Run-In Placebo

Drug A

Drug B

Trial Arms describes the Elements in each Arm, their order and Epoch, and any branching or transition rules.

Screen Run-in Placebo

Drug A Drug B

Trial Elements describes the Elements and the rules for the start and end of each.

Placebo

Run-In TreatmentEpochs are described only in Trial Arms, and have no separate table.

Visit 1 Visit 2 Visit 3 Visit 4 Visit 5

Trial Arms and Elements Overview



Screen Run-In Drug A

Screen Run-In Drug B

Screen Run-In Placebo

Drug A

Drug B

Placebo

STUDYID DOMAIN ARMCD ARM TAETORD ETCD TABRANCH EPOCH

1999001 TA P Placebo 1 SCRN Screen

1999001 TA P Placebo 2 RUNIN Randomized to Placebo

Run-In

1999001 TA P Placebo 3 PLAC Treatment

1999001 TA A Drug A 1 SCREEN Screen

1999001 TA A Drug A 2 RUNIN Randomized to Drug A

Run-In

1999001 TA A Drug A 3 DRUGA Treatment

1999001 TA A Drug B 1 SCREEN Screen

1999001 TA A Drug B 2 RUNIN Randomized to Drug B

Run-In

1999001 TA A Drug B 3 DRUGB Treatment

Creating Trial Arms (1)



Creating Trial Arms (2)

• High level treatment plan• Composed of Elements from Trial Elements• Planned ARM values in DM correspond to

ARM values in Trial Arms• Names of ARM should reflect the protocol



Creating Trial Elements (1)

• Usually the most challenging dataset• Not a duplication of EX (Exposure)• Start rules are the most important

– Subject data must exist to support the creation of these

– Start of next element defines end of previous




• Simple as possible• Screening Element – use date of informed

consent for Start Rule• First Treatment Element - date/time of the

first administration of that treatment.• End of the last Element usually coincides with

the date/time the subject completes the study• Use pseudocode to facilitate and ensure

creation of Subject Elements data



Screen Run-in Placebo

Drug A Drug B

Trial Elements describes the Elements and the rules for the start and end of each.

STUDYID DOMAIN ETCD ELEMENT TESTRL TEENRL TEDUR

1999001 TE SCRN Screen Informed consent signed

Start of next element or date subject dropped

P2W

1999001 TE RUNIN Run-in First dose of run-in drug

Start of next element or date subject dropped

P1W

1999001 TE PLAC Placebo First dose of placebo

Start of next element or date subject dropped or completed

P2W


Example pseudocode: DSSTDTC where DSDECOD = INFORMED CONSENT

Example pseudocode: EXSTDTC where EXTRT = RUN-IN DRUG



STUDYID DOMAIN USUBJID SESEQ ETCD ELEMENT SESTDTC SEENDTC SEUPDES

1999001 SE 145-011 1 SCRN Screen 2003-04-01 2003-04-15

1999001 SE 145-011 2 RUNIN Run-In 2003-04-15 2003-04-22

1999001 SE 145-011 3 PLAC Placebo 2003-04-22 2003-05-06

Creating Subject Elements (3)

DSSTDTC where DSDECOD = INFORMED CONSENT

EXSTDTC where EXTRT = RUN-IN DRUG



Trial Design Challenges

Retrospective creation can be difficult – Finding the information

• Protocol• CRFs• Actual Subject Data

– Inconsistency in information

– Authored by different people

– Interpretation



TDM Best Practices

• SIMPLE and informative• Create Trial Summary first to become familiar

with the Study• Use a Trial Design Template• Use Controlled Terminology

Documents

Trials and Tribulations of SDTM Trial Design Mary Lenzen Octagon Research Solutions