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.
| Info |
|---|
Ejection Fraction - change in ejection fraction, would expect a decline in EF of 2-3% per year, concerning if rapid progression
, i.e., 10% decline or more - Use absolute change, updated to 5% decline for 1 year
NTproBNP - % change over a period of time – a decrease is correlated with improvement, measured annually
SDTM Examples: Basic Systolic Function |
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 ADSL draws from the DM dataset. The CV dataset shows two visits for subject DMD-EF-01-101. The records 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 below show the analysis dataset metadata and metadata and parameters used for this example.
-
| Definexmltable |
|---|
| Multiple | true |
|---|
| Level | Dataset |
|---|
| Purpose | Analysis |
|---|
|
Dataset Name | Dataset Description | Class of Dataset | Structure | Purpose | Keys | Location | Documentation | Location |
|---|
ADSL | Subject-Level Analysis Dataset | SUBJECT LEVEL ANALYSIS DATASET | One record per subject. | Analysis | USUBJID | ADaMIG | adsl.xpt | ADSL.SAS | | ADEFNTP | CV MRI EF and NT-proBNP Analysis | ADCVNTP | Cardiac Ejection Fraction and NTproBNP Analysis Dataset | BASIC DATA STRUCTURE | One record per subject per analysis visit per parameter. | Analysis | USUBJID, AVISITN, PARAMN | | adcvntp.xpt | adefntp.xpt | | | ADEFMRI | CV MRI | ADCVCMR | Cardiovascular CMR Ejection Fraction Analysis Dataset | BASIC DATA STRUCTURE | One record per subject per analysis visit per parameter. | Analysis | USUBJID, AVISITN, PARAMN | | adcvcmr.xpt | adefmri.xpt | |
|
ADSL
The ADSL contains subject characteristics and The ADaM model requires a one-record-per-subject analysis dataset, ADSL, which contains subject characteristics and covariates that are important for analyses. Also, stratification Stratification variables can be created in the ADSL to subset the data. More than one SDTM dataset is may be used as input to the ADSL. As an example, a flag indicating concomitant medication 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
...
...
- 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 | | integer | yymmdd10. | Derived: Date portion of DM.RFICDTC |
|
The ADCVNTP dataset includes tests pertinent to these analyses. The records from CV where CVTESTCD = "LVEF_C" and "RVEF_C" and the records from LB where 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.
The ADCVMR dataset 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.
ADSL Analysis Dataset
This is a simplified example ADSL dataset; it is expected that the ADaMIG is referenced. Analysis age (AAGE) was included to provide age with more precision. The Body Surface Area (BSA) at screening is named BSASC as per the ADAMIG v1.2. There are many possible calculations for BSA; for this example, the Du Bois method was used (ref: https://www.calculator.net/body-surface-area-calculator.html).
| Definexmltable |
|---|
| Dataset | ADSL |
|---|
| Level | Variable |
|---|
| Purpose | Analysis |
|---|
| Name | Variable |
|---|
|
| Variable Name | Variable Label | Type | Codelist/Controlled Terms/Format | Source | Derivation/Comment |
|---|
STUDYID | Study Identifier | Char | DM.STUDYID | USUBJID | Unique Subject Identifier | Char | | BRTHDT | Date of Birth | Num | date9. | Date portion of DM.BRTHDTC | converted to numeric and displayed in a format such as |
date9.from ISO 8601 format to numeric date.9 AAGE | Analysis Age | Num | 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 | Num | DM.AGE | AGEU | Age Units | Char | YEARS | DM.AGEU | SEX | Sex | Char | (SEX) | DM.SEX | RACE | Race | Num | (RACE) | DM.RACE | TRTSDT | Date of First Exposure to Treatment | Num | date9. | Date portion of DM.RFSTDTC converted to numeric and displayed in a format such as date9. | RFICDT | | Num | date9. | Date portion of DM.RFICDTC converted to numeric and displayed in a format such as date9. | DTHDT | | Num | date9. | Date portion of DM.RFSTDTC converted to numeric and displayed in a format such as date9. | DTHFL | | Char | Y | DM.DTHFL | TRT01P | Planned Treatment for Period 01 | Char | 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 | Char | 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 | Char | Y; N | Derive the intent-to-treat population as per the protocol and SAP. | ACEINHFL | ACE Inhibitor Medications Flag | Char | Y; N | Select a list of ACE inhibitor medications from concomitant medications (CM) domain as per Statistical Analysis Plan 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 for your study). | WEIGHTSC | Weight (kg) at Screening | Num | Set to VS.VSSTRESN where VS.VSTESTCD = "WEIGHT" and VISITNUM = 1 (or screening visit for your study). | BSASC | Body Surface Area at Screening | Num | Select where VISITNUM = 1 (or screening visit for your study). Compute from HEIGHT and WEIGHT, using the Du Bois method. BSA = 0.007184 × W0.425 × H0.725 There are multiple methods and the study protocol should describe which one to use (e.g., Du Bois, Mosteller, Haycock, Gehan & George, Boyd, Fujimoto, Takahira, and Schlich). | | yymmdd10. | | DTHDT | | integer | yymmdd10. | Derived: Date portion of DM.DTHDT converted to numeric and displayed in a format such as yymmdd10. | | DTHFL | | 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. |
|
| Dataset wrap |
|---|
|
|
| Dataset wrap |
|---|
|
| Dataset2 |
|---|
| | Row | STUDYID | USUBJID | BRTHDT | AAGE | AGE | AGEU | SEX | RACE | TRTSDT | RFICDT | DTHDT | DTHFL | TRT01P | ITTFL | ACEINHFL | HEIGHTSC | WEIGHTSC | BSASC |
|---|
1 | | 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 |
07FEB2010 | 12.3 | 12BLACK OR AFRICAN AMERICAN | 16JUN2022 | 16JUN2022 | Drug A| NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | | 2022-07-15 |
|
| Drug B | Y |
Y11920082201MAY2008 | 14.1 | 14ASIAN | 13JUN2022 | 13JUN2022 | Drug A| WHITE | 2022-09-06 | 2022-09-06 | 2023-11-23 | Y | Drug B | Y | Y |
11530 | 0,95 | 3 | DMD-EFLGE | DMD-EF-01-101 | 10JUL2003 | 19.0 | 19 | YEARS | M | NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | 15JUL22022 | 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 | |
|
ADCVNTP Analysis Dataset
In this example, columns for derived variables BASE, CHG, PCHG and CHGCAT1 have been added to facilitate analyses of the efficacy endpoints. Specifically, example demographic data for ADSL were created for an 8 year old male. Also, a custom variable for BSA at baseline (BSABL), and an example of a stratification variable for subjects with was added from ADSL.
...
| Dataset | ADCVNTP |
|---|
| Level | Value |
|---|
| Purpose | Analysis |
|---|
| OID | AVAL |
|---|
...
Categorize the value of CHGCAT1 as follows: If CHG >= 5.00 THEN CHGCAT1 = "Decline >=5%".
Else if CHG not missing and CHG < 5.00 THEN CHGCAT1 = "Decline <5%"
...
Categorize the value of CHCAT1 as follows: "Increase >100 pg/mL"; "Increase <=100 pg/mL"; "No increase"
...
| Dataset | ADCVNTP |
|---|
| Level | Variable |
|---|
| Purpose | Analysis |
|---|
| Name | Variable |
|---|
...
CV.STUDYID
...
...
ADSL.BRTHDT
...
ADSL.AAGE
...
ADSL.AGEU
...
SEX
...
DM.SEX
...
RACE
...
DM.RACE
...
Date of First Exposure to Treatment
...
Planned Treatment for Period 01
...
Actual Treatment for Period 01
...
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.
...
Compute from HEIGHT and WEIGHT at each visit, using the Du Bois method. BSA = 0.007184 × W0.425 × H0.725
There are multiple methods and the study protocol should describe which one to use (e.g., Mosteller, Haycock, Gehan & George, Boyd, Fujimoto, Takahira, and Schlich).
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) | | 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 | | 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 | 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 | N-Terminal ProB-type Natriuretic Peptide (ng/L) |
|
| Definexmltable |
|---|
| Dataset | ADEFNTP |
|---|
| Level | Value |
|---|
| Purpose | Analysis |
|---|
| Name | AVAL |
|---|
|
| 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 |
|
In this table the ADaM parameters are used rather than the source SDTM data.
| Definexmltable |
|---|
| Dataset | ADEFNTP |
|---|
| Level | Value |
|---|
| Purpose | Analysis |
|---|
| Name | CHGCAT1 |
|---|
|
| Variable | Where | Type | Controlled Terms or Format | Origin | Derivation/Comment |
|---|
| CHGCAT1 | PARAMCD in ("LVEF_C", "RVEF_C") | text | Decline >=-5.0%; Decline <-5.0%; No Decline | Derived | Categorize the value of CHG as follows: If CHG >= 5.00 THEN CHGCAT1 = "Decline >=-5.0%". | Jira |
|---|
| showSummary | false |
|---|
| server | Issue Tracker (JIRA) |
|---|
| serverId | 85506ce4-3cb3-3d91-85ee-f633aaaf4a45 |
|---|
| key | TAUGDMDCIS-9 |
|---|
|
Else if CHG GT 0 and CHG < 5.00 THEN CHGCAT1 = "Decline <-5.0%" Else if CHG <0 then CHGCAT1 = "No Decline" | Jira |
|---|
| showSummary | false |
|---|
| server | Issue Tracker (JIRA) |
|---|
| serverId | 85506ce4-3cb3-3d91-85ee-f633aaaf4a45 |
|---|
| key | TAUGDMDCIS-10 |
|---|
|
| | 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" | Jira |
|---|
| showSummary | false |
|---|
| server | Issue Tracker (JIRA) |
|---|
| serverId | 85506ce4-3cb3-3d91-85ee-f633aaaf4a45 |
|---|
| key | TAUGDMDCIS-11 |
|---|
|
|
|
| Dataset wrap |
|---|
|
| Dataset2 |
|---|
| | 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 |
|
|
...
ACEINHFL
...
ACE Inhibitor Medications Flag
...
Char
...
Y; N
...
ADSL.ACEINHFL
...
Left Ventricular Ejection Fraction, Calculated (%);
Right Ventricular Ejection Fraction, Calculated (%);
N-Terminal ProB-type Natriuretic Peptide (pg/mL)
...
CV.CVTEST
LB.LBTEST
...
LVEF_C;
RVEF_C;
BNPPRONT
...
CV.CVTESTCD
LB.LBTESTCD
...
Number PARAMCD as follows:
LVEF_C = "1"
RVEF_C = "2"
BNPPRONT = "3"
...
See Parameter Value Metadata
...
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)".
...
CV.VISITNUM
LB.VISITNUM
...
VISIT 1; VISIT 6
...
CV.VISIT
LB.VISIT
...
If CV.VISIT = "VISIT 1" then ABLFL = "Y".
...
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.
...
Decline >=5%; Decline <5%; Increase GT 100 pg/mL
...
CV; LB
...
CV.CVSEQ
LB.LBSEQ
...
Efficacy Analysis Example 1
This example dataset shows the findings and additional analysis variables associated with:
- Left Ventricular Ejection Fraction, Calculated (%)
- Right Ventricular Ejection Fraction, Calculated (%)
- N-Terminal ProB-type Natriuretic Peptide (pg/mL)
| Dataset wrap |
|---|
|
| Rowcaps |
|---|
| Rows 1-2: | Show the baseline ejection fraction measurements at VISIT 1. | | Row 3: | Shows the baseline N-Terminal ProB-type Natriuretic Peptide test results at VISIT 1. | | Rows 4-5: | Show the baseline ejection fraction measurements at VISIT 6. | | Row 6: | Shows the baseline N-Terminal ProB-type Natriuretic Peptide test results at VISIT 6. | | Dataset2 |
|---|
| | 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, Calculated (%) | 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, Calculated (%) | 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 (IU/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 |
13232108| 82 | Y | Left Ventricular Ejection Fraction, |
Calculated 60 6 1 Year6 606APR2023 | 67 | -7 | -10.447761 | Decline >=5.0% | CV | CVTESTCD | 11 | | 1 | 2022-05-16 | Y | 67 |
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| CV | CVTESTCD| Jira |
|---|
| showSummary | false |
|---|
| server | Issue Tracker (JIRA) |
|---|
| serverId | 85506ce4-3cb3-3d91-85ee-f633aaaf4a45 |
|---|
| key | TAUGDMDCIS-13 |
|---|
|
| 3 | | 2 |
5 | DMD-EFLGE | DMD-EF-01-101 | 12.3 | YEARS | M | BLACK OR AFRICAN AMERICAN | Drug A | Drug A | Y |
13232108| 82 | Y | Right Ventricular Ejection Fraction, |
Calculated 61 6 1 Year6 606APR2023 | 74 | -13 | -17.567568 | Decline >=5.0%156| 3 | DMD-EFLGE | DMD-EF-01-101 | 12.3 | YEARS | M | BLACK OR AFRICAN AMERICAN | Drug A | Drug A | Y |
13232108| 82 | Y | N-Terminal ProB-type Natriuretic Peptide ( |
IU900 6 1 Year6 106APR2023 | 40 | 860 | 2,150 | Increase GT 100 pg/mL2 | |
|
ADCVCMR Analysis Dataset
The dataset above can also be set up to 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 as the source and only variable used in the analysis are kept.
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| Dataset | ADCVCMR |
|---|
| Level | Variable |
|---|
| Purpose | Analysis |
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| Name | Variable |
|---|
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ADCVNTP.STUDYID
...
...
ADCVNTP.BRTHDT
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ADCVNTP.AAGE
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ADCVNTPL.AGEU
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SEX
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ADCVNTPL.SEX
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RACE
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ADCVNTPL.RACE
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Date of First Exposure to Treatment
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Planned Treatment for Period 01
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ITTFL
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Intent-To-Treat Population Flag
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Char
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Y; N
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ADCVNTP.ITTFL
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ADCVNTP.BSA
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ACEINHFL
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ACE Inhibitor Medications Flag
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Char
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Y; N
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ADCVNTP.ACEINHFL
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BNPPRONT
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Num
...
BNPPRONT = AVAL where PARAMCD = ADCVNTP.BNPPRONT, and merge by USUBJID and AVISITN.
Note: there are many ways to add this including transposing the data.
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Left Ventricular Ejection Fraction, Calculated (%);
Right Ventricular Ejection Fraction, Calculated (%);
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ADCVNTP.PARAM
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LVEF_C;
RVEF_C;
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ADCVNTP.PARAMCD
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ADCVNTP.PARAMN
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ADCVNTP.AVAL
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Visit 1 (Baseline);
Visit 6 (1 Year)
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ADCVNTP.AVISIT
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ADCVNTP.AVISITN
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Decline >=5%; Decline <5%; Increase GT 100 pg/mL
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ADCVNTP.CHGCAT1
Efficacy Analysis Example 2
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...
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Example Analysis Results Metadata (ARM) Tables
For more details on ARM, see the ADaMIG and the Analysis Results Metadata (ARM) v1.0 for Define-XML v2.0 (https://www.cdisc.org/standards/foundational/adam).
Table 1. A simple comparison of change by treatment groups over one year.
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Display
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Table 14.xx.xx Change in Left Ventricular Ejection Fraction Percent Over 1 Year
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Data References
(incl. selection criteria)
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PARAMCD = "LVEF_C"
Where ITTFL = "Y" and AVISITN = 6;
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Comparison of Means with 95% confidence interval
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Programming Statements
(Add programming language statements here: SAS, R, etc.)
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Proc means DATA=ADCVNTP N MEAN clm STDERR;
/* Subset the data. Can run again selecting for paramcd="RVEF_C"*/
Where PARAMCD = 'LVEF_C' and ITTFL = "Y" and AVISITN = 6 ;
Class TRT01P;
Var CHG;
run;
Table 2. This table demonstrates a model over multiple time points, adding some of the covariates that were retained in the analysis dataset.
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Display
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Table 14.xx.xx Percent Change in Left Ventricular Ejection Fraction Percent Over Time (Yearly)
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Data References
(incl. selection criteria)
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PARAMCD = "LVEF_C"
Where ITTFL = "Y"
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The mixed model using lsmeans to compare treatment groups
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Programming Statements
(Add programming language statements here: SAS, R, etc.)
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/* Note that CHG is only computed post-baseline, so subset for the yearly visits, i.e. 6, 12, 18 etc. */
Proc mixed DATA=ADCVNTP;
Class TRT01P AVISITN;
/* Subset by param, as there are two parameters with CHG calculated*/
Where ITTFL = "Y" and AVISITN IN(6,12,18,24,36,48) and PARAMCD = "LVEF_C";
Model PCHG=AVISITN*TRT01P/Solution;
RANDOM INTERCEPT / SUBJECT=STUYDID TYPE=UN;
LSMEANS TRT01P*AVISITN/ CL PDIFF;
RUN;
| 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 | 2023-04-23 |
| 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 | 2023-04-23 |
| 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 | 2023-04-23 |
| 40 | 860 | 2,150 | Increase >100 ng/L | LB | LBTESTCD | 2 |
|
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ADEFMRI
The ADEFMRI 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| Jira |
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| showSummary | false |
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| server | Issue Tracker (JIRA) |
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| serverId | 85506ce4-3cb3-3d91-85ee-f633aaaf4a45 |
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| key | TAUGDMDCIS-15 |
|---|
|
, with additional variables added from ADEFNTP dataset.
The dataset can can be used for analyses with multiple covariates
| Jira |
|---|
| showSummary | false |
|---|
| server | Issue Tracker (JIRA) |
|---|
| serverId | 85506ce4-3cb3-3d91-85ee-f633aaaf4a45 |
|---|
| key | TAUGDMDCIS-14 |
|---|
|
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.| Definexmltable |
|---|
| Dataset | ADEFMRI |
|---|
| Level | Variable |
|---|
| Purpose | Analysis |
|---|
| Name | Variable |
|---|
|
| 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 | yymmdd10. | 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 | yymmdd10. | 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 | yymmdd10. | 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 |
|
| Dataset wrap |
|---|
|
| Dataset2 |
|---|
| | 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 | 2010-02-07 | 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 | 2022-05-16 | Y | 70 |
|
|
| | 2 | DMD-EFLGE | DMD-EF-01-101 | 2010-02-07 | 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 | 2022-05-16 | Y | 75 |
|
|
| | 3 | DMD-EFLGE | DMD-EF-01-101 | 2010-02-07 | 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 | 2023-04-23 |
| 70 | -5 | -10.447761 | Decline >==5.0% | | 4 | DMD-EFLGE | DMD-EF-01-101 | 2010-02-07 | 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 | 2023-04-23 |
| 75 | -5 | -17.567568 | Decline >==5.0% |
|
|
Table 3. This example uses the dataset ADCVCMR, with BNPPRONT as an additional covariate.
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Display
...
Table 14.xx.xx Percent change in NTproBNP over 1 Year
...
Data References
(incl. selection criteria)
...
PARAMCD = L_VEFC;
ITTFL = "Y" and AVISIT GE 6;
...
Multiple Regression Model
Proc reg data=ADCVCMR ;
Where PARAMCD = L_VEFC and ITTFL = "Y" and AVISIT GE 6;
Model PCHG = AAGE SEX RACE BNPPRONT;
...