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:
- 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 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.
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
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 TAUGDMDCIS-4 - Getting issue details... STATUS |
| 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.
ADSL Variable Metadata
| 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 | date9. | Derived: Date portion of DM.BRTHDTC converted to numeric and displayed in a format, such as date9. TAUGDMDCIS-5 - Getting issue details... STATUS |
| 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 | date9. | Derived: Date portion of DM.RFSTDTC converted to numeric and displayed in a format such as date9. |
| RFICDT | Date of Informed Consent | integer | date9. | Derived: Date portion of DM.RFICDTC converted to numeric and displayed in a format such as date9. |
| DTHDT | Date of Death | integer | date9. | Derived: Date portion of DM.DTHDT TAUGDMDCIS-6 - Getting issue details... STATUS converted to numeric and displayed in a format such as date9. |
| DTHFL | Subject Death | 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 × W0.425 × H0.725 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. |
adsl.xpt
| 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 | 07FEB2010 | 12.3 | 12 | YEARS | M | BLACK OR AFRICAN AMERICAN | 16JUN2022 | 16JUN2022 | Drug A | Y | Y | 119 | 20 | 0.82 | ||
| 2 | DMD-EFLGE | DMD-EF-01-101 | 01MAY2008 | 14.1 | 14 | YEARS | M | ASIAN | 13JUN2022 | 13JUN2022 | Drug A | Y | Y | 115 | 30 | 0.95 | ||
| 3 | DMD-EFLGE | DMD-EF-01-101 | 10JUL2003 | 19.0 | 19 | YEARS | M | NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | 15JUL2022 | 15JUL2022 | Drug B | Y | N | 140 | 45 | 1.30 | ||
| 4 | DMD-EFLGE | DMD-EF-01-101 | 15JAN1999 | 23.7 | 23 | YEARS | M | WHITE | 06SEP2022 | 06SEP2022 | 23NOV2023 | Y | Drug B | Y | Y | 132 | 42 | 1.21 |
Dataset Debug Message
When the JIRA issue(s) present in the dataset have been resolved, and their resolution has been confirmed by governance, please remove them.
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.).
TAUGDMDCIS-8 - Getting issue details... STATUS
ADEFNTP Variable Metadata
| 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 | date9. | Predecessor: ADSL.BRTHDT |
| AAGE | Analysis Age | float | Predecessor: ADSL.AAGE | |
| AGEU | Age Unit | text | Predecessor: ADSL.AGEU | |
SEX | Sex | text | (SEX) | Predecessor: ADSL.SEX TAUGDMDCIS-16 - Getting issue details... STATUS |
RACE | Race | text | (RACE) | Predecessor: ADSL.RACE |
| TRTSDT | Date of First Exposure to Treatment | integer | date9 | 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 × W0.425 × H0.725 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 | date9. | Date portion of CV.CVDTC or LB.LBDTC converted to numeric and displayed in a format such as date9. |
| 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%; Decline <5%; 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. TAUGDMDCIS-12 - Getting issue details... STATUS |
| SRCSEQ | Source Sequence Number | integer | Predecessor: Set to the SDTM domain sequence number that relates to the analysis value, CV.CVSEQ or LB.LBSEQ. |
Example Parameter [CL.PARAM.ADCVNTP]
| Permitted Value (code) |
|---|
Left Ventricular Ejection Fraction, Cal (%); |
| Right Ventricular Ejection Fraction, Cal (%); |
| N-Terminal ProB-type Natriuretic Peptide (ng/L) |
Example Parameter Code [CL.PARAMCD.ADEFNTP]
| Permitted Value (code) | Display Value (Decode) |
|---|---|
LVEF_C | Left Ventricular Ejection Fraction, Cal (%); |
| RVEF_C | Right Ventricular Ejection Fraction, Cal (%); |
| BNPPRONT | N-Terminal ProB-type Natriuretic Peptide (ng/L) |
ADCVNTP Variable Metadata
| Variable | Where | Type | Controlled Terms or Format | Origin | Derivation/Comment |
|---|---|---|---|---|---|
| AVAL | CV.CVSTRESN IN("LVEF_C", "RVEF_C") | float | Predecessor | CV.CVSTRESN | |
| AVAL | LB.LBTESTCD = "BNPPRONT" | float | Predecessor | LB.LBSTRESN |
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Parameter Value List - ADCVNTP [CHGCAT1]
| Variable | Where | Type | Controlled Terms or Format | Origin | Derivation/Comment |
|---|---|---|---|---|---|
| CHGCAT1 | PARAMCD in ("LVEF_C", "RVEF_C") | text | Decline >=5% Decline <5% No Decline | Derived | Categorize the value of CHG as follows: If CHG >= 5.00 THEN CHGCAT1 = "Decline >=5%". TAUGDMDCIS-9 - Getting issue details... STATUS Else if CHG GT 0 and CHG < 5.00 THEN CHGCAT1 = "Decline <5%" Else if CHG <0 then CHGCAT1 = "No Decline" TAUGDMDCIS-10 - Getting issue details... STATUS |
| CHGCAT1 | PARAMCD = "BNPPRONT" | text | Increase >100 ng/L Increase <=100 ng/L No increase | Derived | Categorize the value of CHCAT1 as follows: "Increase >100 ng/L"; "Increase <=100 ng/L"; "No increase" TAUGDMDCIS-11 - Getting issue details... STATUS |
adcvntp.xpt
| Row | STUDYID | USUBJID | AAGE | AGEU | SEX | RACE | TRT01P | TRT01A | ITTFL | HEIGHT | WEIGHT | BSA | ACEINHFL | PARAM | PARAMCD | PARAMN | AVAL | AVISIT | AVISITN | VISIT | ADT | ABLFL | BASE | CHG | PCHG | CHGCAT1 | SRCDOM | SRCVAR | SRCSEQ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | DMD-EFLGE | DMD-EF-01-101 | 12.3 | YEARS | M | BLACK OR AFRICAN AMERICAN | Drug A | Drug A | Y | 119 | 20 | 0.82 | Y | Left Ventricular Ejection Fraction, Cal (%) | LVEF_C | 1 | 67 | Visit 1 (Baseline) | 1 | VISIT 1 | 16MAY2022 | Y | 67 | CV | CVTESTCD | 3 | |||
| 2 | DMD-EFLGE | DMD-EF-01-101 | 12.3 | YEARS | M | BLACK OR AFRICAN AMERICAN | Drug A | Drug A | Y | 119 | 20 | 0.82 | Y | Right Ventricular Ejection Fraction, Cal (%) | RVEF_C | 2 | 74 | Visit 1 (Baseline) | 1 | VISIT 1 | 16MAY2022 | Y | 74 | CV | CVTESTCD | 7 | |||
| 3 | DMD-EFLGE | DMD-EF-01-101 | 12.3 | YEARS | M | BLACK OR AFRICAN AMERICAN | Drug A | Drug A | Y | 119 | 20 | 0.82 | Y | N-Terminal ProB-type Natriuretic Peptide (ng/L) | BNPPRONT | 3 | 40 | Visit 1 (Baseline) | 1 | VISIT 1 | 16MAY2022 | Y | 40 | LB | LBTESTCD | 1 | |||
| 4 | DMD-EFLGE | DMD-EF-01-101 | 12.3 | YEARS | M | BLACK OR AFRICAN AMERICAN | Drug A | Drug A | Y | 132 | 32 | 1.08 | Y | Left Ventricular Ejection Fraction, Cal (%) | LVEF_C | 1 | 60 | Visit 6 (1 Year) | 6 | VISIT 6 | 06APR2023 | 67 | -7 | -10.447761 | Decline >=5.0% | CV | CVTESTCD | 11 | |
| 5 | DMD-EFLGE | DMD-EF-01-101 | 12.3 | YEARS | M | BLACK OR AFRICAN AMERICAN | Drug A | Drug A | Y | 132 | 32 | 1.08 | Y | Right Ventricular Ejection Fraction, Cal (%) | RVEF_C | 2 | 61 | Visit 6 (1 Year) | 6 | VISIT 6 | 06APR2023 | 74 | -13 | -17.567568 | Decline >=5.0% | CV | CVTESTCD | 15 | |
| 6 | DMD-EFLGE | DMD-EF-01-101 | 12.3 | YEARS | M | BLACK OR AFRICAN AMERICAN | Drug A | Drug A | Y | 132 | 32 | 1.08 | Y | N-Terminal ProB-type Natriuretic Peptide (ng/L) | BNPPRONT | 3 | 900 | Visit 6 (1 Year) | 6 | VISIT 6 | 06APR2023 | 40 | 860 | 2,150 | Increase >100 ng/L | LB | LBTESTCD | 2 |
Dataset Debug Message
When the JIRA issue(s) present in the dataset have been resolved, and their resolution has been confirmed by governance, please remove them.
ADEFMRI
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 TAUGDMDCIS-15 - Getting issue details... STATUS , with additional variables added from ADEFNTP dataset.
The dataset can can be used for multivariate analyses TAUGDMDCIS-14 - Getting issue details... STATUS by taking the lab tests of interest (PARAMCD = "BNPPRONT") or other analysis datasets, and merging variables of interest with the ADEFNTP dataset. This summary dataset is created from other ADaM datasets and only variables used in the analysis are kept.
ADCVCMR Variable Metadata
| Variable Name | Variable Label | Type | Codelist/Controlled Terms | Source/Derivation/Comment |
|---|---|---|---|---|
| STUDYID | Study Identifier | text | Predecessor: ADEFNTP.STUDYID | |
| USUBJID | Unique Subject Identifier | text | Predecessor: ADEFNTP.USUBJID | |
| BRTHDT | Date of Birth | integer | date9. | Predecessor: ADEFNTP.BRTHDT |
| AAGE | Analysis Age | float | Predecessor: ADEFNTP.AAGE | |
| AGEU | Age Unit | text | YEARS | Predecessor: ADEFNTP.AGEU |
SEX | Sex | text | (SEX) | Predecessor: ADEFNTP.SEX |
RACE | Race | text | (RACE) | Predecessor: ADEFNTP.RACE |
| TRTSDT | Date of First Exposure to Treatment | Num | date9. | Predecessor: ADEFNTP.TRTSDT |
| TRT01P | Planned Treatment for Period 01 | text | Drug A; Drug B | Predecessor: ADEFNTP.TRT01P |
ITTFL | Intent-To-Treat Population Flag | text | Y; N | Predecessor: ADEFNTP.ITTFL |
| BSA | Body Surface Area (m2) | float | Predecessor: ADEFNTP.BSA | |
ACEINHFL | ACE Inhibitor Medications Flag | text | Y; N | Predecessor: ADEFNTP.ACEINHFL |
BNPPRONT | integer | Derived: BNPPRONT = AVAL where PARAMCD = ADEFNTP.BNPPRONT, and merge by USUBJID and AVISITN. Note: There are many ways to add this including transposing the data. | ||
| PARAM | Parameter | text | Left Ventricular Ejection Fraction, Cal (%); Right Ventricular Ejection Fraction, Cal (%) | Predecessor: ADEFNTP.PARAM |
| PARAMCD | Parameter Code | text | LVEF_C; RVEF_C | Predecessor: ADEFNTP.PARAMCD |
| PARAMN | Parameter (N) | integer | Predecessor: ADEFNTP.PARAMN | |
| AVAL | Analysis Value | float | Predecessor: ADEFNTP.AVAL | |
| AVISIT | Analysis Visit | text | Visit 1 (Baseline); Visit 6 (1 Year) | Predecessor: ADEFNTP.AVISIT |
| AVISITN | Analysis Visit (N) | integer | 1; 6 | Predecessor: ADEFNTP.AVISITN |
| ADT | Analysis Date | float | date9. | Predecessor: ADEFNTP.ADT |
| ABLFL | Baseline Record Flag | text | Y | Predecessor: ADEFNTP.ABLFL |
| BASE | Baseline Value | float | Predecessor: ADEFNTP.BASE | |
| CHG | Change from Baseline | float | Predecessor: ADEFNTP.CHG | |
| PCHG | Percent Change from Baseline | float | Predecessor: ADEFNTP.PCHG | |
| CHGCAT1 | Change from Baseline Category 1 | text | Decline >=5.0%; Decline <5.0%; Increase >100 ng/L | Predecessor: ADEFNTP.CHGCAT1 |
adefmri.xpt
| Row | STUDYID | USUBJID | BRTHDT | TRT01P | AAGE | AGU | SEX | RACE | TRT01A | ITTFL | BSA | ACEINHFL | BNPPRONT | PARAM | PARAMCD | PARAMN | AVAL | AVISIT | AVISITN | ADT | ABLFL | BASE | CHG | PCHG | CHGCAT1 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | DMD-EFLGE | DMD-EF-01-101 | 07FEB2010 | Drug A | 12.3 | YEARS | M | BLACK OR AFRICAN AMERICAN | Drug A | Y | 0.82 | Y | 40 | Left Ventricular Ejection Fraction, Cal (%) | LVEF_C | 1 | 70 | Visit 1 (Baseline) | 1 | 16MAY2022 | Y | 70 | |||
| 2 | DMD-EFLGE | DMD-EF-01-101 | 07FEB2010 | Drug A | 12.3 | YEARS | M | BLACK OR AFRICAN AMERICAN | Drug A | Y | 0.82 | Y | 40 | Right Ventricular Ejection Fraction, Cal (%) | RVEF_C | 2 | 75 | Visit 1 (Baseline) | 1 | 16MAY2022 | Y | 75 | |||
| 3 | DMD-EFLGE | DMD-EF-01-101 | 07FEB2010 | Drug A | 12.3 | YEARS | M | BLACK OR AFRICAN AMERICAN | Drug A | Y | 1.08 | Y | 900 | Left Ventricular Ejection Fraction, Cal (%) | LVEF_C | 1 | 65 | Visit 6 (1 Year) | 6 | 06APR2023 | 70 | -5 | -10.447761 | Decline >=5.0% | |
| 4 | DMD-EFLGE | DMD-EF-01-101 | 07FEB2010 | Drug A | 12.3 | YEARS | M | BLACK OR AFRICAN AMERICAN | Drug A | Y | 1.08 | Y | 900 | Right Ventricular Ejection Fraction, Cal (%) | RVEF_C | 2 | 70 | Visit 6 (1 Year) | 6 | 06APR2023 | 75 | -5 | -17.567568 | Decline >=5.0% |