Page History

Measuring LVEF regularly can show the rate of decline in left ventricle function for a patient with DMD. Thus Therefore, it was selected as an endpoint for this example endpoint to measure whether a course of therapy provides a slowing of may slow the progression to of heart failure for the patient. The second endpoint chosen, NT-proBNP, is a biomarker that is may be used to predict or diagnose heart failure.

This section illustrates example analysis datasets for the following endpoints:

Percent change in ejection fraction over time (1 year)
Decline in ejection fraction over time (1 year) grouped by a decline greater than 5%-5.0%
Percent change in NT-proBNP over time (1 year)

Source Data

The SDTM examples used as the source data are from Section 2.1, Basic Systolic Function. The readings chosen to analyze ejection fraction are the Left Ventricular Ejection Fraction, Cal, with the unit of percent. The example dataset also shows the Right Ventricular Ejection Fraction, Cal which can be used to confirm the result. The SDTM data are stored in the CV domain. The example dataset in Section 2.1 shows 2 visits for subject DMD-EF-01-101. The records for CVTESTCD = "LVEF_C The records in the CV dataset for which CVTESTCD = "LVEF_C" and "RVEF_C" were selected for analysis. The NT-proBNP test is stored The records in the LB domain. The example dataset in Section 2.1 shows the test in the example LB dataset (LBTESTCD = "BNPPRONT"). The lab value was dataset where LBTESTCD = "BNPPRONT" were used to compute the percent change over time for the third endpoint and as a potential covariate for the ejection fraction models.

The example Adam

Jira

showSummary	false
server	Issue Tracker (JIRA)
serverId	85506ce4-3cb3-3d91-85ee-f633aaaf4a45
key	TAUGDMDCIS-2

Subject-level Analysis (ADSL) dataset draws from the DM dataset for demographics and study dates. It draws from Vital Signs (VS) for height and weight at screening. The VS is also used for height and weight at each visit, which in turn is used to compute body surface area (BSA), an important measure used in calculations for basic systolic functions. A flag for angiotensin-converting enzyme (ACE) inhibitor medications was added to the example. The source for this data would be concomitant medications (CM) or dosing information (EX, EC), not shown.

Example Analysis Datasets

The following tables show the analysis dataset metadata

Jira

showSummary	false
server	Issue Tracker (JIRA)
serverId	85506ce4-3cb3-3d91-85ee-f633aaaf4a45
key	TAUGDMDCIS-3

and parameters used for this example.

...

Multiple	true
Level	Dataset
Purpose	Analysis

...

Dataset Name

...

Dataset Description

...

Structure

...

Keys

...

Location

...

ADSL

...

Subject-Level Analysis Dataset

...

One record per subject

...

BASIC DATA STRUCTURE

...

Analysis Dataset

...

BASIC DATA STRUCTURE

...

Analysis Dataset

...

ADSL

The ADSL contains subject characteristics and covariates that are important for analyses. Stratification variables can be created in the ADSL to subset the data. More than one SDTM dataset may be used as input to the ADSL. This is a simplified example ADSL dataset; the ADaMIG should be referenced for additional variables.

For this example:

Analysis age (AAGE) was included to provide age with more precision.
A flag indicating the use of ACE inhibitors (ACEINHFL) is shown with example derivation from the CM dataset.
Body surface area at screening (BSASC) was derived from the VS dataset using height and weight at the screening visit. There are many possible calculations for BSA; for this example, the Du Bois method was used.[11] Note that the screening visit and visit 1 occurred at the same time in this example.

...

Dataset	ADSL
Level	Variable
Purpose	Analysis
Name	Variable

...

DM.STUDYID

...

DM.USUBJID

...

Jira

showSummary	false
server	Issue Tracker (JIRA)
serverId	85506ce4-3cb3-3d91-85ee-f633aaaf4a45
key	TAUGDMDCIS-5

...

DM.AGE

...

DM.AGEU

...

SEX

...

DM.SEX

...

RACE

...

DM.RACE

...

Date of Informed Consent

...

Date of Death

...

Jira

showSummary	false
server	Issue Tracker (JIRA)
serverId	85506ce4-3cb3-3d91-85ee-f633aaaf4a45
key	TAUGDMDCIS-6

...

Subject Death
Flag

...

Planned Treatment for Period 01

...

Predecessor: DM.ARM.

May be changed to lower case or more descriptive term for use in tables and listings.

...

Actual Treatment for Period 01

...

Predecessor: DM.ACTARM.

Note: Actual treatment matches planned treatment unless there is a reason subject does not take planned drug.

...

ITTFL

...

Intent-To-Treat Population Flag

...

Char

...

Y; N

...

ACEINHFL

...

ACE Inhibitor Medications Flag

...

Char

...

Y; N

...

Select a list of ACE inhibitor medications from concomitant medications (CM) domain as per SAP or protocol. Set to "Y" if these medications were taken during the study, and "N" if they are absent. Can be used to subset or to exclude the population who took ACE inhibitors.

...

HEIGHTSC

...

Height (cm) at Screening

...

Num

...

Set to VS.VSSTRESN where VS.VSTESTCD = "HEIGHT" and VISITNUM= 1 (or screening visit).

...

WEIGHTSC

...

Weight (kg) at Screening

...

Num

...

Set to VS.VSSTRESN where VS.VSTESTCD = "WEIGHT" and VISITNUM = 1 (or screening visit).

...

BSASC

...

Body Surface Area at Screening

...

Num

...

Select where VISITNUM = 1 (or screening visit). Compute from HEIGHT and WEIGHT, using the Du Bois method. BSA = 0.007184 × W^0.425 × H^0.725

There are multiple methods for calculating BSA (e.g., Du Bois, Mosteller, Haycock, Gehan & George, Boyd, Fujimoto, Takahira, Schlich); the study protocol should describe which to use.

. Both SDTM domains are used in one analysis dataset to demonstrate the flexibility of ADaM and to show that the various SDTM domains can be combined into one dataset both as rows and also as covariates.

Example Analysis Datasets

The following tables show the analysis dataset metadata and parameters used for this example.

-

Definexmltable

Multiple	true
Level	Dataset
Purpose	Analysis

Dataset Name	Description	Class	Structure	Purpose	Keys	Location	Documentation
ADSL	Subject-Level Analysis Dataset	SUBJECT LEVEL ANALYSIS DATASET	One record per subject.	Analysis	USUBJID	adsl.xpt	ADSL.SAS
ADEFNTP	CV MRI EF and NT-proBNP Analysis	BASIC DATA STRUCTURE	One record per subject per analysis visit per parameter.	Analysis	USUBJID, AVISITN, PARAMN	adefntp.xpt	ADEFNTP.SAS/SAP
ADEFMRI	CV MRI Ejection Fraction Analysis	BASIC DATA STRUCTURE	One record per subject per analysis visit per parameter.	Analysis	USUBJID, AVISITN, PARAMN	adefmri.xpt	ADEFMRI.SAS/SAP

ADSL

The ADSL contains subject characteristics and covariates that are important for analyses. Stratification variables can be created in the ADSL to subset the data. More than one SDTM dataset may be used as input to the ADSL. This is a simplified example ADSL dataset; the ADaMIG should be referenced for additional variables.

For this example:

Analysis age (AAGE) was included to provide age with more precision.
A flag indicating the use of ACE inhibitors (ACEINHFL) is shown with example derivation from the CM dataset.
Body surface area at screening (BSASC) was derived from the VS dataset using height and weight at the screening visit. There are many possible calculations for BSA; for this example, the Du Bois method was used.[11] Note that the screening visit and visit 1 occurred at the same time in this example.

Definexmltable

Dataset	ADSL
Level	Variable
Purpose	Analysis
Name	Variable

Variable Name	Variable Label	Type	Codelist/Controlled Terms	Source/Derivation/Comment
STUDYID	Study Identifier	text		Predecessor: DM.STUDYID
USUBJID	Unique Subject Identifier	text		Predecessor: DM.USUBJID
BRTHDT	Date of Birth	integer	yymmdd10.	Derived: Date portion of DM.BRTHDTC converted to numeric and displayed in a format, such as yymmdd10.
AAGE	Analysis Age	float		Derived: Age as screening, computed by DM.RFICDTC - BRTHDTC as continuous variable. Note that some countries do not allow capturing date of birth, so this could be computed by capturing age in years and months on a CRF.
AGE	Age	integer		Predecessor: DM.AGE
AGEU	Age Units	text	YEARS	Predecessor: DM.AGEU
SEX	Sex	text	(SEX)	Predecessor: DM.SEX
RACE	Race	text	(RACE)	Predecessor: DM.RACE
TRTSDT	Date of First Exposure to Treatment	integer	yymmdd10.	Derived: Date portion of DM.RFSTDTC converted to numeric and displayed in a format such as yymmdd10.
RFICDT	Date of Informed Consent	integer	yymmdd10.	Derived: Date portion of DM.RFICDTC converted to numeric and displayed in a format such as yymmdd10.
DTHDT	Date of Death	integer	yymmdd10.	Derived: Date portion of DM.DTHDT converted to numeric and displayed in a format such as yymmdd10.
DTHFL	Subject Death Flag	text	Y	Predecessor: DM.DTHFL
TRT01P	Planned Treatment for Period 01	text	Drug A; Drug B	Predecessor: DM.ARM. May be changed to lower case or more descriptive term for use in tables and listings.
TRT01A	Actual Treatment for Period 01	text	Drug A; Drug B	Predecessor: DM.ACTARM. Note: Actual treatment matches planned treatment unless there is a reason subject does not take planned drug.
ITTFL	Intent-To-Treat Population Flag	text	Y; N	Derived: Derive the intent-to-treat population as per the protocol and SAP.
ACEINHFL	ACE Inhibitor Medications Flag	text	Y; N	Derived: Select a list of ACE inhibitor medications from concomitant medications (CM) domain as per SAP or protocol. Set to "Y" if these medications were taken during the study, and "N" if they are absent. Can be used to subset or to exclude the population who took ACE inhibitors.
HEIGHTSC	Height (cm) at Screening	float		Predecessor: Set to VS.VSSTRESN where VS.VSTESTCD = "HEIGHT" and VISITNUM= 1 (or screening visit).
WEIGHTSC	Weight (kg) at Screening	float		Predecessor: Set to VS.VSSTRESN where VS.VSTESTCD = "WEIGHT" and VISITNUM = 1 (or screening visit).
BSASC	Body Surface Area at Screening	float		Derived: Select where VISITNUM = 1 (or screening visit). Compute from HEIGHT and WEIGHT, using the Du Bois method. BSA = 0.007184 × W^0.425 × H^0.725 There are multiple methods for calculating BSA (e.g., Du Bois, Mosteller, Haycock, Gehan & George, Boyd, Fujimoto, Takahira, Schlich); the study protocol should describe which to use.

Dataset wrap

Show	true
Name	ADSL

Dataset2

tableid	adsl

Row	STUDYID	USUBJID	BRTHDT	AAGE	AGE	AGEU	SEX	RACE	TRTSDT	RFICDT	DTHDT	DTHFL	TRT01P	ITTFL	ACEINHFL	HEIGHTSC	WEIGHTSC	BSASC
1	DMD-EFLGE	DMD-EF-01-101	2010-02-07	12.3	12	YEARS	M	BLACK OR AFRICAN AMERICAN	2022-06-16	2022-06-16			Drug A	Y	Y	119	20	0.82
2	DMD-EFLGE	DMD-EF-01-101	2008-05-01	14.1	14	YEARS	M	ASIAN	2022-06-13	2022-06-13			Drug A	Y	Y	115	30	0.95
3	DMD-EFLGE	DMD-EF-01-101	2003-07-10	19.0	19	YEARS	M	NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	2022-07-15	2022-07-15			Drug B	Y	N	140	45	1.30
4	DMD-EFLGE	DMD-EF-01-101	1999-01-15	23.7	23	YEARS	M	WHITE	2022-09-06	2022-09-06	2023-11-23	Y	Drug B	Y	Y	132	42	1.21

ADEFNTP

The ADEFNTP includes tests pertinent to analyses. The records from CV (CVTESTCD = "LVEF_C" and "RVEF_C") and the records from LB (LBTESTCD = "BNPPRONT") were selected. Many lab draws may occur throughout the year, but only those linked to a specific visit were included. By subsetting the LB dataset by LBLNKID not missing, laboratory data that aligns with CV data can be filtered out and sorted using USUBJID and VISIT. If LBLNKID is not available or the LB dataset does not contain VISIT, a windowing strategy could be used to select the laboratory draw closest to that visit using date of lab draw (LB.LBDTC.).

Jira

showSummary	false
server	Issue Tracker (JIRA)
serverId	85506ce4-3cb3-3d91-85ee-f633aaaf4a45
key	TAUGDMDCIS-8

Definexmltable

Dataset	ADEFNTP
Level	Variable
Purpose	Analysis
Name	Variable

Variable Name	Variable Label	Type	Codelist/Controlled Terms	Source/Derivation/Comment
STUDYID	Study Identifier	text		Predecessor: CV.STUDYID
USUBJID	Unique Subject Identifier	text		Predecessor: CV.USUBJID
BRTHDT	Date of Birth	integer	yymmdd10.	Predecessor: ADSL.BRTHDT
AAGE	Analysis Age	float		Predecessor: ADSL.AAGE
AGEU	Age Unit	text		Predecessor: ADSL.AGEU
SEX	Sex	text	(SEX)	Predecessor: ADSL.SEX
RACE	Race	text	(RACE)	Predecessor: ADSL.RACE
TRTSDT	Date of First Exposure to Treatment	integer	yymmdd10.	Predecessor: ADSL.TRTSDT
TRT01P	Planned Treatment for Period 01	text	Drug A; Drug B	Predecessor: ADSL.TRT01P
TRT01A	Actual Treatment for Period 01	text	Drug A; Drug B	Predecessor: ADSL.TRT01A
ITTFL	Intent-To-Treat Population Flag	text	Y; N	Predecessor: ADSL.ITTFL
HEIGHT	Height (cm)	float		Set to VS.VSSTRESN where VS.VSTEST = "HEIGHT" by visit.
WEIGHT	Weight (kg)	float		Set to VS.VSSTRESN where VS.VSTEST = "WEIGHT" by visit.
BSA	Body Surface Area (m2)	float		Derived: Compute from HEIGHT and WEIGHT at each visit, using the Du Bois method. BSA = 0.007184 × W^0.425 × H^0.725 There are multiple methods for calculating BSA; the study protocol should describe which to use.
ACEINHFL	ACE Inhibitor Medications Flag	text	Y; N	Predecessor: ADSL.ACEINHFL
PARAM	Parameter	text	Left Ventricular Ejection Fraction, Cal (%); Right Ventricular Ejection Fraction, Cal (%); N-Terminal ProB-type Natriuretic Peptide (ng/L)	Predecessor: CV.CVTEST LB.LBTEST
PARAMCD	Parameter Code	text	LVEF_C; RVEF_C; BNPPRONT	Predecessor: CV.CVTESTCD LB.LBTESTCD
PARAMN	Parameter (N)	integer	1; 2; 3	Assigned: Number PARAMCD as follows: LVEF_C = "1" RVEF_C = "2" BNPPRONT = "3"
AVAL	Analysis Value	float		See Parameter Value Metadata
AVISIT	Analysis Visit	text	Visit 1 (Baseline); Visit 6 (1 Year)	If CV.VISIT = "VISIT 1" then AVISIT = "Visit 1 (Baseline)". If CV.VISIT = "VISIT 6" then AVISIT = "Visit 6 (1 Year)".
AVISITN	Analysis Visit (N)	integer	1; 6	Predecessor: CV.VISITNUM LB.VISITNUM
VISIT	Visit	integer	VISIT 1; VISIT 6	Predecessor: CV.VISIT LB.VISIT
ADT	Analysis Date	integer	yymmdd10.	Date portion of CV.CVDTC or LB.LBDTC converted to numeric and displayed in a format such as yymmdd10.
ABLFL	Baseline Record Flag	text	Y	Derived: If CV.VISIT = "VISIT 1" then ABLFL = "Y".
BASE	Baseline Value	float		Derived: Set BASE to AVAL from the record for that subject and parameter where ABLFL = "Y". Populate BASE for additional visits by merging the value of BASE in the baseline record by USUBJID and PARAMCD.
CHG	Change from Baseline	float		Derived: Compute CHG = AVAL - BASE for that record. Only compute for post-baseline records.
PCHG	Percent Change from Baseline	float		Derived: Compute PCHG = (CHG / BASE) * 100. Only compute for post-baseline records.
CHGCAT1	Change from Baseline Category 1	text	Decline >=-5.0%; Decline <-5.0%; No Decline	See Parameter Value Metadata
SRCDOM	Source Data	text	CV; LB	Assigned: Set to the SDTM domain name that relates to the analysis value.
SRCVAR	Source Variable	text	CVSTRESN; LBSTRESN	Assigned: Set to the SDTM variable that relates to the analysis value.
SRCSEQ	Source Sequence Number	integer		Predecessor: Set to the SDTM domain sequence number that relates to the analysis value, CV.CVSEQ or LB.LBSEQ.

In this example, variables BASE, CHG, PCHG, and CHGCAT1 were added to facilitate analyses of the efficacy endpoints. the variables SRCDOM, SRCVAR, and SRCSEQ provide traceability to the combined source datasets. The tables below represent parameter value level lists for applicable variables.

Definexmltable

Dataset	ADEFNTP
Example	true
Level	Codelist
Purpose	Analysis
OID	PARAM.ADEFNTP
Name	Parameter

Permitted Value (code)
Left Ventricular Ejection Fraction, Cal (%)
Right Ventricular Ejection Fraction, Cal (%)
N-Terminal ProB-type Natriuretic Peptide (ng/L)

Definexmltable

Dataset	ADEFNTP
Example	true
Level	Codelist
Purpose	Analysis
OID	PARAMCD.ADEFNTP
Name	Parameter Code

Permitted Value (code)	Display Value (Decode)
LVEF_C	Left Ventricular Ejection Fraction, Cal (%)
RVEF_C	Right Ventricular Ejection Fraction, Cal (%)
BNPPRONT

...

Show	true
Name	ADSL

...

tableid	adsl

...

Jira

showSummary	false
server	Issue Tracker (JIRA)
serverId	85506ce4-3cb3-3d91-85ee-f633aaaf4a45
key	TAUGDMDCIS-7

...

ADCVNTP

The ADCVNTP includes tests pertinent to analyses. The records from CV (CVTESTCD = "LVEF_C" and "RVEF_C") and the records from LB (LBTESTCD = "BNPPRONT") were selected. Many lab draws may occur throughout the year, but only those linked to a specific visit were included. By subsetting the LB dataset by LBLNKID not missing, laboratory data that aligns with CV data can be filtered out and sorted using USUBJID and VISIT. If LBLNKID is not available, a windowing strategy could be used to select the laboratory draw closest to that visit for merging with CV, computed in AVISIT

Jira

showSummary	false
server	Issue Tracker (JIRA)
serverId	85506ce4-3cb3-3d91-85ee-f633aaaf4a45
key	TAUGDMDCIS-8

.

In this example, variables BASE, CHG, PCHG, and CHGCAT1 were used to facilitate analyses of the efficacy endpoints.

Left Ventricular Ejection Fraction, Cal (%);

Right Ventricular Ejection Fraction, Cal (%);

Definexmltable

Dataset	ADCVNTP
Level	Value
Purpose	Analysis
OID	AVAL

Dataset

Variable

Where

Type

Origin

Derivation/Comment

ADCVNTP

AVAL

PARAMCD in ("LVEF_C", "RVEF_C")

Num

Predecessor

Set to CV.CVSTRESN

ADCVNTP

AVAL

PARAMCD = "BNPPRONT"

Num

Predecessor

Set to LB.LBSTRESN where LB.LBTESTCD = "BNPPRONT"

ADCVNTP

CHGCAT1

PARAMCD in ("LVEF_C", "RVEF_C")

Char

Categorize the value of CHGCAT1 as follows: If CHG >= 5.00 THEN CHGCAT1 = "Decline >=5%

Jira

showSummary	false
server	Issue Tracker (JIRA)
serverId	85506ce4-3cb3-3d91-85ee-f633aaaf4a45
key	TAUGDMDCIS-9

".

Else if CHG not missing and CHG < 5.00 THEN CHGCAT1 = "Decline <5%

Jira

showSummary	false
server	Issue Tracker (JIRA)
serverId	85506ce4-3cb3-3d91-85ee-f633aaaf4a45
key	TAUGDMDCIS-10

"

ADCVNTP

CHGCAT1

PARAMCD = "BNPPRONT"

Char

Categorize the value of CHCAT1 as follows: "Increase >100 ng/L"; "Increase <=100 ng/L"; "No increase

Jira

showSummary	false
server	Issue Tracker (JIRA)
serverId	85506ce4-3cb3-3d91-85ee-f633aaaf4a45
key	TAUGDMDCIS-11

"

Definexmltable

Dataset	ADCVNTP
Level	Variable
Purpose	Analysis
Name	Variable

Variable Name

Variable Label

Type

Codelist/Controlled Terms/Format

Source

Derivation/Comment

STUDYID

Study Identifier

Char

CV.STUDYID

USUBJID

Unique Subject Identifier

Char

CV.USUBJID

BRTHDT

Date of Birth

Num

Date9.

ADSL.BRTHDT

AAGE

Analysis Age

Num

ADSL.AAGE

AGEU

Age Unit

Char

YEARS

ADSL.AGEU

SEX

Sex

Char

(SEX)

DM.SEX

RACE

Race

Num

(RACE)

DM.RACE

TRTSDT

Date of First Exposure to Treatment

Num

date9

ADSL.TRTSDT

TRT01P

Planned Treatment for Period 01

Char

Drug A; Drug B

ADSL.TRT01P

TRT01A

Actual Treatment for Period 01

Char

Drug A; Drug B

ADSL.TRT01A

ITTFL

Intent-To-Treat Population Flag

Char

Y; N

ADSL.ITTFL

HEIGHT

Height (cm)

Num

Set to VS.VSSTRESN where VS.VSTEST = "HEIGHT" by visit.

WEIGHT

Weight (kg)

Num

Set to VS.VSSTRESN where VS.VSTEST = "WEIGHT" by visit.

BSA

Body Surface Area (m2)

Num

Compute from HEIGHT and WEIGHT at each visit, using the Du Bois method. BSA = 0.007184 × W^0.425 × H^0.725

There are multiple methods for calculating BSA; the study protocol should describe which to use.

ACEINHFL

ACE Inhibitor Medications Flag

Char

Y; N

ADSL.ACEINHFL

PARAM

Parameter

Char

N-Terminal ProB-type Natriuretic Peptide (ng/L

)

CV.CVTEST

LB.LBTEST

PARAMCDParameter CodeChar

LVEF_C;

RVEF_C;

BNPPRONT

CV.CVTESTCD

LB.LBTESTCD

PARAMNParameter (N)Num

Number PARAMCD as follows:

LVEF_C = "1"

RVEF_C = "2"

BNPPRONT = "3"

AVALAnalysis ValueNum

See Parameter Value Metadata

)

Space shortcuts

Page tree

Versions Compared

Old Version 139

New Version Current

Key

Source Data

Example Analysis Datasets

ADSL

Example Analysis Datasets

ADSL

ADEFNTP

ADCVNTP

ADEFMRI

	text		Predecessor: ADEFNTP.STUDYID
USUBJID	Unique Subject Identifier

Predecessor: ADEFNTP.RACE
TRTSDT	Date of First Exposure to Treatment	Num

Predecessor: ADEFNTP.TRTSDT
TRT01P	Planned Treatment for Period 01

Predecessor: ADEFNTP.TRT01P
ITTFL	Intent-To-Treat Population Flag

	Predecessor: ADEFNTP.BSA
ACEINHFL	ACE Inhibitor Medications Flag

	Predecessor: ADEFNTP.PCHG
CHGCAT1	Change from Baseline Category 1