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Measuring LVEF regularly can show the rate of decline in left ventricle function for a patient with DMD. Thus it was selected as an example endpoint to measure whether a course of therapy provides a slowing of the progression to heart failure for the patient. The second endpoint chosen, NT-proBNP, is a biomarker that is 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%
  • 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" and "RVEF_C" were selected for analysis. 

The NT-proBNP test is stored 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 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 TAUGDMDCIS-2 - Getting issue details... STATUS 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 TAUGDMDCIS-3 - Getting issue details... STATUS and parameters used for this example.

Analysis Datasets

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.

ADSL Variable Metadata

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adsl.xpt

RowSTUDYIDUSUBJIDBRTHDTAAGEAGEAGEUSEXRACETRTSDTRFICDTDTHDTDTHFLTRT01PITTFLACEINHFLHEIGHTSCWEIGHTSCBSASC
1DMD-EFLGEDMD-EF-01-10107FEB201012.312YEARSMBLACK OR AFRICAN AMERICAN16JUN202216JUN2022

Drug AYY119200.82
2DMD-EFLGEDMD-EF-01-10101MAY200814.114YEARSMASIAN13JUN202213JUN2022

Drug AYY115300.95
3DMD-EFLGEDMD-EF-01-10110JUL200319.019YEARSMNATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER15JUL2202215JUL2022

Drug BYN140451.30
4DMD-EFLGEDMD-EF-01-10115JAN199923.723YEARSMWHITE06SEP202206SEP202223NOV2023YDrug BYY132421.21
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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.

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

Parameter Value List - ADCVNTP [ADCVNTP]

ADCVNTP Variable Metadata

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adcvntp.xpt

RowSTUDYIDUSUBJIDAAGEAGEUSEXRACETRT01PTRT01AITTFLHEIGHTWEIGHTBSAACEINHFLPARAMPARAMCDPARAMNAVALAVISITAVISITNVISITADTABLFLBASECHGPCHGCHGCAT1SRCDOMSRCVARSRCSEQ
1DMD-EFLGEDMD-EF-01-10112.3YEARSMBLACK OR AFRICAN AMERICANDrug ADrug AY119200.82YLeft Ventricular Ejection Fraction, Cal (%)LVEF_C167Visit 1 (Baseline)1VISIT 116MAY2022Y67


CVCVTESTCD3
2DMD-EFLGEDMD-EF-01-10112.3YEARSMBLACK OR AFRICAN AMERICANDrug ADrug AY119200.82YRight Ventricular Ejection Fraction, Cal (%)RVEF_C274Visit 1 (Baseline)1VISIT 116MAY2022Y74


CVCVTESTCD7
3DMD-EFLGEDMD-EF-01-10112.3YEARSMBLACK OR AFRICAN AMERICANDrug ADrug AY119200.82YN-Terminal ProB-type Natriuretic Peptide (ng/L)BNPPRONT340Visit 1 (Baseline)1VISIT 116MAY2022Y40


LBLBTESTCD1
4DMD-EFLGEDMD-EF-01-10112.3YEARSMBLACK OR AFRICAN AMERICANDrug ADrug AY132321.08YLeft Ventricular Ejection Fraction, Cal (%)LVEF_C160Visit 6 (1 Year)6VISIT 606APR2023
67-7-10.447761Decline >=5.0%CVCVTESTCD11
5DMD-EFLGEDMD-EF-01-10112.3YEARSMBLACK OR AFRICAN AMERICANDrug ADrug AY132321.08YRight Ventricular Ejection Fraction, Cal (%)RVEF_C261Visit 6 (1 Year)6VISIT 606APR2023
74-13-17.567568Decline >=5.0%CVCVTESTCD15
6DMD-EFLGEDMD-EF-01-10112.3YEARSMBLACK OR AFRICAN AMERICANDrug ADrug AY132321.08Y

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

BNPPRONT3900Visit 6 (1 Year)6VISIT 606APR2023
408602,150Increase >100 ng/LLBLBTESTCD2
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ADCVCMR

The ADCVMR 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 an ADaM Basic Data Structure (BDS) dataset, with additional variables added from ADCVNTP.

The dataset can provide multivariate analyses by taking the lab tests of interest (PARAMCD = "BNPPRONT") or other analysis datasets, and merging variables of interest with the ADCVNTP dataset. This summary dataset is created from other ADaM datasets and only variables used in the analysis are kept.

ADCVCMR Variable Metadata

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adcvcmr.xpt

RowSTUDYIDUSUBJIDBRTHDTTRT01PAAGEAGUSEXRACETRT01AITTFLBSAACEINHFLBNPPRONTPARAMPARAMCDPARAMNAVALAVISITAVISITNADTABLFLBASECHGPCHGCHGCAT1
1DMD-EFLGEDMD-EF-01-10107FEB2010Drug A12.3YEARSMBLACK OR AFRICAN AMERICANDrug AY0.82Y40Left Ventricular Ejection Fraction, Cal (%)LVEF_C170Visit 1 (Baseline)116MAY2022Y70


2DMD-EFLGEDMD-EF-01-10107FEB2010Drug A12.3YEARSMBLACK OR AFRICAN AMERICANDrug AY0.82Y40Right Ventricular Ejection Fraction, Cal (%)RVEF_C275Visit 1 (Baseline)116MAY2022Y75


3DMD-EFLGEDMD-EF-01-10107FEB2010Drug A12.3YEARSMBLACK OR AFRICAN AMERICANDrug AY1.08Y900Left Ventricular Ejection Fraction, Cal (%)LVEF_C165Visit 6 (1 Year)606APR2023
70-5-10.447761Decline >=5.0%
4DMD-EFLGEDMD-EF-01-10107FEB2010Drug A12.3YEARSMBLACK OR AFRICAN AMERICANDrug AY1.08Y900Right Ventricular Ejection Fraction, Cal (%)RVEF_C270Visit 6 (1 Year)606APR2023
75-5-17.567568Decline >=5.0%
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