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

This section illustrates example analysis datasets for the following endpoints:

The Analysis dataset (ADaM) is created from the collected data stored in SDTM. It should have full traceability back to the input datasets. For this example we show the following endpoints:

...

Percent change in ejection fraction over time (1 year)
Decline in ejection fraction over a time period (yearly1 year) grouped by a decline greater than x.x%.From the LB domain-5.0%
Percent change in NTproBNP over a period of NT-proBNP over time (yearly).1 year)

Source Data

The SDTM example datasets from which this data is drawn are in the section "Basic CMR tests -Systolic Function" (make link) . The example datasets show visits 1 and 6 for one subject. As mentioned in the SDTM text, for the purposes of this example, the participant was enrolled in the study on 20-May-2021 and the study visits were every two months. Visit 1 represents the visit at day 1 of the study, and visit 6 represents the visit at month 12 of the study. The associated laboratory test, N-Terminal ProB-type Natriuretic Peptide, is used in conjunction with ejection fraction as a biomarker and is important for diagnosis and treatment. It is also used separately to identify the percent change over a period of time.

The analysis dataset also includes treatment and demographic information drawn from the ADSL. In this example, we only show some of the required variables plus important stratification variables from ADSL. One variable mentioned body surface area (BSA), can be computed and added to ADSL. However, since the subjects are children their body surface area changes over time. Therefore it would probably be better to have a separate dataset to capture this. In this example, we will show one variable for BSA with the label "BASELINE Body Surface Area".

Questions.

Is screening considered visit 1, or is it to include the subject into the study? SDTM team agreed to change to VISIT 1 instead of SCREENING.

Are these Real World Evidence (RWE) studies only or clinical trials?

Should both endpoints be shown in one efficacy dataset or two? I will be showing 3 datasets.

bWhat is a good surface area to use for the child subject?

Should i use Male and 6 years? please advise.

Analysis Datasets

Below is the table of analysis datasets and unique parameters created for the example. The ADSL is required as part of the process of creating the subsequent analysis datasets.

ADCVEF is a dataset capturing only the tests required for this analysis, selecting for CVTESTCD equal to "LVEF_C" or "LVCO". The relationship dataset RELREC is merged in with ADCVEF in preprarion to add the tests from LB to the efficacy dataset.
ADLBNTRP is a subset of LB selecting for LBTESTCD equal to "BNPPRONT", and LBLINKID not missing. In this case, many lab draws may occur throughout the year, but we are only interested in the ones linked to a specific visit.

examples used as the source data are from Section 2.1, Basic Systolic Function. The records in the CV dataset for which CVTESTCD = "LVEF_C" and "RVEF_C" were selected for analysis. The records in the LB dataset where LBTESTCD = "BNPPRONT" were used to compute the percent change over time and as a potential covariate. 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.

-ADCMRI is an efficacy analysis dataset with only a few records for more complex modeling of changes in ejection fraction plus the ProB-type test results. It is a Basic Structure dataset with additional variables added from ADCVEF.

Definexmltable

Multiple	true
Level	Dataset
Purpose	Analysis

Dataset Name	Dataset Description	Class of Dataset	Structure	LocationPurpose	Keys	Location	Documentation
ADSL	Subject-Level Analysis Dataset	SUBJECT LEVEL ANALYSIS DATASETadsl.xpt	One record per subject.	Analysis	USUBJID	ADaMIG v1.3 section 3.1.1	adsl.xpt	ADSL.SAS
ADEFNTP	CV MRI EF and NT-proBNP Analysis	ADCVEF	Cardiac Ejection Fraction Analysis Dataset	BASIC DATA STRUCTURE	One record per subject per analysis visit per parameter.	adcvef.xptAnalysis	USUBJID, AVISITN, PARAMCD	Analysis Dataset	PARAMN	adefntp.xpt	ADEFNTP.SAS/SAP
ADEFMRI	CV MRI Ejection Fraction Analysis	ADLBNTRP	Cardiac NTproBNP Laboratory Analysis Dataset	BASIC DATA STRUCTURE	One record per subject per analysis visit per parameter.	adntpro.xptAnalysis	USUBJID, AVISITN, PARAMCD	Analysis Dataset
ADCMRI	Cardiac Magnetic Resonance Imaging Measurements Analysis Dataset	BASIC DATA STRUCTURE	One record per subject per analysis visit per parameter.	adcmri.xpt	USUBJID, AVISITN, PARAMCD	Analysis Dataset

Definexmltable

Multiple	true
Dataset	ADCEF, ADLBNTRP
Level	Value
Purpose	Analysis
OID	AVAL

Dataset

Variable

Where

Type

Origin

Derivation/Comment

ADCEF

AVAL

PARAMCD = " LVEFC"

Num

Predecessor

Set to CV. CVSTRESN where CV.CVTESTCD ="LVEFC".

ADCEF

AVAL

PARAMCD = "RVEFC"

Num

Predecessor

Set to CV. CVSTRESN where CV.CVTESTCD ="LVEFC".

ADLBNTRP

AVAL

PARAMCD = "BNPPRONT"

Num

Predecessor

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

Analysis Datasets

The following are the data structures for the example ADaM dataset. Note that the columns for derived variables, BASE, and CHG, PCHG and CHGCAT1 have been added for the efficacy analysis of endpoints. The example demographics for ADSL were created for a xx year old male child.

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

Number records 1 to n after sorting by keys.

Definexmltable

Dataset	ADEFNTP

Definexmltable

Dataset	ADCV
Level	Variable
Purpose	Analysis
Name	Variable

Variable Name	Variable Label	Type	Codelist/Controlled Terms

/Format

	Source

/Derivation/Comment
STUDYID	Study Identifier

Char

text		Predecessor: CV.STUDYID
USUBJID	Unique Subject Identifier

Char

text

Predecessor: CV.USUBJID

Select for records with RE data.

ASEQ

Analysis Sequence Number

Num

CV.CVSEQ


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

Char

text

"Treatment A"

Drug A; Drug B

Predecessor: ADSL.TRT01P

For this example we are putting "Treatment A". In a Real World Evidence study this could be non-treatment related, e.g. "Group A".


TRT01A	Actual Treatment for Period 01	text	Drug A; Drug B	Predecessor: ADSL.TRT01A
ITTFL	Intent-To-Treat Population Flag	text

COMPLFL

Completers Population Flag

Char

Y; N

Predecessor: ADSL.

COMPLFL

Pick other population? for RWE this does not apply

AGEAgeNumADSL.AGEAGEUAge UnitsChar(AGEU)ADSL.AGEUSEXSexChar(SEX)ADSL.SEXBSABASEBody Surface Area at Baseline (m2)NumADSL.BSABSECompute in ADSL where VS.VSTESTCD = "BSA".

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

PARAMParameterChar

Left Ventricular Ejection Fraction,

Calculated

Cal (%);

Right Ventricular Ejection Fraction,

Calculated

Cal (%);

N-Terminal ProB-type Natriuretic Peptide (

pg

ng/

mL

L)

For tests from CV, set to the values of

Predecessor:

CV.CVTEST

plus CV.CVTESTU with spaces and parentheses as shown.

For tests from

LB

, set to the value of LB

.LBTEST

plus LB.LBTESTU with spaces and parentheses as shown.


PARAMCD	Parameter Code

Char

LVEFC

RVEFC

If CV.CVTESTCD = "LVEF_C" then PARAMCD = "LVEFC"

If CV.CVTESTCD = "RVEF_C" then PARAMCD = "RVEFC".

If LB.LBTESTDC = "BNPPRONT" then PARAMCD = "BNPPRONT.

Note: for this example dataset, select the records where the test values shown above are included.

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

Num

float

See Parameter Value

List

Metadata
AVISIT	Analysis Visit

Char

text

Visit 1 (Baseline); Visit 6 (1 Year)

If CV.VISIT = "VISIT 1" then AVISIT = "Visit 1 (Baseline)".

Else if

If CV.VISIT = "VISIT 6" then AVISIT = "Visit 6 (1 Year)".
AVISITN	Analysis Visit (N)

Num

integer

1

,

; 6

Set to value of

Predecessor:

CV.VISITNUM

LB.VISITNUM

VISIT

Visit

Char

integer

VISIT 1; VISIT 6

Predecessor:

CV.VISIT

LB.VISIT

ADT

Analysis Date

Num

integer

date9

yymmdd10.

Date portion of CV.CVDTC or LB.LBDTC converted to numeric and displayed in a format such as

date9

yymmdd10.
ABLFL	Baseline Record Flag

Char

text	Y	Derived: If CV.VISIT = "VISIT 1" then ABLFL = "Y".
BASE	Baseline Value

Num

float

Derived: Set BASE to AVAL from the record for that subject and parameter where ABLFL = "Y".

Populate BASE for additional

visit

visits by merging

by USUJID and ADT. (Or by AVISIT if ADT varies for labs, and windowing is applied to select record closest to the visit)

the value of BASE in the baseline record by USUBJID and PARAMCD.
CHG	Change from Baseline

Num

float		Derived: Compute CHG = AVAL - BASE for that record. Only compute for post-baseline records.
PCHG	Percent Change from Baseline

Num

float		Derived: Compute PCHG = (CHG / BASE) * 100. Only compute for post-baseline records.
CHGCAT1	Change from Baseline Category 1

>1.0 g/dL;

text

Decline >=-5.0%; Decline <-5.0%; No Decline

See Parameter Value Metadata

<=1.0 g/dL


SRCDOM	Source Data

Char

text

CV

LB

Set

; 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

Num

CV.CVSEQ

LB.LBSEQ

integer

Predecessor: Set to the SDTM domain sequence number that relates to the analysis value, CV.CVSEQ or LB.LBSEQ.

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Source Data

Analysis Datasets

Example Analysis Datasets

Analysis Datasets

ADSL

ADEFNTP

ADEFMRI