This section illustrates example analysis datasets for the following endpoints:
- Percent change in ejection fraction over time
- Decline in ejection fraction over a time period (1 year) grouped by a decline greater than 10.0%
- Percent change in NTproBNP over a period of time (1 year)
Source Data
The SDTM examples used as the source data are from Section 2.1, Basic CMR Tests for Systolic Function. The CV dataset contains 16 rows, 1-8 for visit 1 and 9-16 for visit 6. Of these rows, the CVTESTCD = "LVEF_C" and CVTESTCD = "RVEF_C" representing the Ventricular Ejection Fraction, Calculated (%) for left and right were selected for the analysis. The LB dataset test where LBTESTCD = "BNPPRONT" was used to add the value of BNPPRONT to compute the percent change over time, and then it was added as a potential covariate in each row for the last analysis. As in all ADaM datasets, the Subject Level Analysis Dataset (ADSL) was merged in to the SDTM datasets to capture all the necessary demographics, treatments and other required variables for analysis of the data.
Example Analysis Datasets
The analysis datasets for this example include treatment and demographic information drawn from the Subject Level Analysis Dataset (ADSL), defined in the Metadata Tables below. Only some of the required variables from ADSL are shown for illustrative purposes. The ADSL incorporates demographics, treatment groups, study dates, and stratification variables. Additional information on the ADSL can be found in Section 2.3.1 of the ADaM Implementation Guide (ADaMIG) v1.3.
The ADSL is combined with other SDTM dataset to create the analysis datasets. More than one SDTM dataset can be combined in this way. Also, stratification variables can be created in the ADSL to subset by, or to add variables needed in the analyses. For instance, stratification variable might be type of concomitant medications, such as an ACE inhibitors. for this we added a flag ACEMEDFL, which is coded Y or N. Another variable added; body surface area (BSABL), is derived from the LB dataset at the baseline visit and added to ADSL. However, when the subjects are children, the body surface area changes over time. Therefore, an additional non-standard variable is added to the analysis dataset with the subject's current BSA by visit.
The ADCVNTP dataset includes tests pertinent to these analyses. The record LB are selected where CVTESTCD is equal to "LVEF_C" or "RVEF_C". It also includes a subset of the Laboratory Results (LB) SDTM dataset, for which LBTESTCD is equal to "BNPPRONT". The relationship dataset RELREC illustrates the relationship between datasets. In this case, many lab draws may occur throughout the year, but only those linked to a specific visit are included. By subsetting the LB dataset with 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 the example, only two LB records are shown which are linked to CV where CVTESTCD = "LVEF_C" or CVTESTCD = "R.VEF_C"
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 tableS below showsthe example analysis dataset metadata and parameters used for the analysis.
Analysis Datasets
Dataset Name | Dataset Description | Class of Dataset | Structure | Location | Keys | Documentation |
|---|---|---|---|---|---|---|
ADSL | Subject-Level Analysis Dataset | SUBJECT LEVEL ANALYSIS DATASET | One record per subject | adsl.xpt | USUBJID | ADaMIG |
| ADCVNTP | Cardiac Ejection Fraction and NTproBNP Analysis Dataset | BASIC DATA STRUCTURE | One record per subject per analysis visit per parameter | adcvntp.xpt | USUBJID, AVISITN, PARAMN | Analysis Dataset |
| ADCVCMR | Cardiovascular CMR Ejection Fraction Analysis Dataset | BASIC DATA STRUCTURE | One record per subject per analysis visit per parameter | adcvcmr.xpt | USUBJID, AVISITN, PARAMN | Analysis Dataset |
ADSL Analysis Dataset
This is a simplified example ADSL dataset; it is expected that additional variables for stratification or of interest for analysis would be included.
ADSL Variable Metadata
| Variable Name | Variable Label | Type | Codelist/Controlled Terms/Format | Source | Derivation/Comment |
|---|---|---|---|---|---|
| STUDYID | Study Identifier | Char | DM.STUDYID | ||
| USUBJID | Unique Subject Identifier | Char | DM.USUBJID | ||
| BRTHDT | Date of Birth | Num | date9. | ADSL.BRTHDTC | Convert BRTHDTC from ISO 8601 format to numeric date. (Note that if exact date is not found then use two variables to capture year and month.) |
| 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. | |
| TRT01P | Planned Treatment for Period 01 | Char | Treatment A | ADSL.TRT01P | For this example we are using "Treatment A". In a Real World Evidence study this could be non-treatment related, e.g. "Group A". |
ITTFL | Intent-To-Treat Population Flag | Char | Y; N | ADSL.ITTFL | Derive the intent-to-treat population as per the protocol and SAP. |
| BSABASE | Body Surface Area (m2) at Baseline | Num | ADSL.BSABASE | Set to VS.VSSTRESN in ADSL where VS.VSTESTCD = "BSA" and select for baseline visit. | |
ACEINHFL | ACE Inhibitor Medications Flag | Char | Y | Select a list of ACE inhibitor medications from concomitant medications (CM) domain, and from treatment (EX or EC) domains. Code 'Y' if the medication was taken during the study. Can be used to subset or to exclude the population who took ACE inhibitors. |
adsl.xpt
| Row | STUDYID | USUBJID | BRTHDT | TRTSDT | TRT01P | ITTFL | BSABASE | ACENHFL |
|---|---|---|---|---|---|---|---|---|
| 1 | DMD-EFLGE | DMD-EFLGE-101 | 15FEB2021 | 16MAY2022 | Treatment A | Y | 0.65 | Y |
Parameter Value List - ADCVNTP [ADCVNTP]
| Dataset | Variable | Where | Type | Origin | Derivation/Comment |
|---|---|---|---|---|---|
| ADCVNTP | AVAL | PARAMCD = "LVEFC" | Num | Predecessor | Set to CV.CVSTRESN where CV.CVTESTCD = "LVEF_C" |
| ADCVNTP | AVAL | PARAMCD = "RVEFC" | Num | Predecessor | Set to CV.CVSTRESN where CV.CVTESTCD = "RVEF_C" |
| ADCVNTP | AVAL | PARAMCD = "BNPPRONT" | Num | Predecessor | Set to LB.LBSTRESN where LB.LBTESTCD = "BNPPRONT" |
Analysis Datasets for Ejection Fraction
The subsequent section provides the data structures for the example ADaM datasets. 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 (BSABASE), and an example of a stratification variable for subjects with was added from ADSL.
ADCVNTP Variable Metadata
| 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 | Select for records with RE data. | |
| ASEQ | Analysis Sequence Number | Num | CV.CVSEQ | Number records 1 to n after sorting by keys. | |
| BRTHDT | Date of Birth | Num | Date9. | ADSL.BRTHDTC | Convert BRTHDTC from ISO 8601 format to numeric date. (Note that if exact date is not found then use two variables to capture year and month.) |
| TRT01P | Planned Treatment for Period 01 | Char | Treatment A | ADSL.TRT01P | For this example we are using "Treatment A". In a Real World Evidence study this could be non-treatment related, e.g. "Group A". |
ITTFL | Intent-To-Treat Population Flag | Char | Y; N | ADSL.ITTFL | |
| BSABASE | Body Surface Area (m2) at Baseline | Num | ADSL.BSABASE | Compute in ADSL where VS.VSTESTCD = "BSA". | |
ACEINHFL | ACE Inhibitor Medications Flag | Char | Y | Select a list of ACE inhibitor medications from concomitant medications (CM) domain, and from treatment (EX or EC) domains. Code 'Y' if the medication was taken during the study. Can be used to subset or to exclude the population who took ACE inhibitors. | |
| BSA | Body Surface Area (m2) by Visit | Num | Compute from VS.HEIGHT and VS.WEIGHT by visit, using the Du Bois method. Note that there are multiple methods to compute, and the study protocol should describe which one to use. (e.g. other methods may be Mosteller, Haycock, Gehan & George, Boyd, Fujimoto, Takahira, and Schlich) | ||
| PARAM | Parameter | Char | Left Ventricular Ejection Fraction, Calculated (%); Right Ventricular Ejection Fraction, Calculated (%); N-Terminal ProB-type Natriuretic Peptide (pg/mL) | For tests from CV, set to the values of 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; BNPPRONT | 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. | |
| PARAMN | Parameter (N) | Num | Number PARAMCD as follows: LVEFC = "1" RVEFC = "2" BNPPRONT = "3" | ||
| AVAL | Analysis Value | Num | See Parameter Value List | ||
| AVISIT | Analysis Visit | Char | If CV.VISIT = "VISIT 1" then AVISIT = "Visit 1 (Baseline)". Else if CV.VISIT = "VISIT 6" then AVISIT = "Visit 6 (1 Year)". | ||
| AVISITN | Analysis Visit (N) | Num | Set to value of CV.VISITNUM or LB.VISITNUM | ||
| VISIT | Visit | Num | CV.VISIT LB.VISIT | ||
| ADT | Analysis Date | Num | date9. | Date portion of CV.CVDTC or LB.LBDTC converted to numeric and displayed in a format such as date9. | |
| ABLFL | Baseline Record Flag | Char | Y | If CV.VISIT = 1 then ABLFL = "Y". | |
| BASE | Baseline Value | Num | Set BASE to AVAL from the record for that subject and parameter where ABLFL = "Y". Populate BASE for additional visits by copying the value of BASE in the baseline record by USUBJID and ADT. (Or by AVISIT if ADT varies for labs, where windowing is applied to select record closest to the visit) | ||
| CHG | Change from Baseline | Num | Compute CHG = AVAL - BASE for that record. Only compute for post-baseline records. | ||
| PCHG | Percent Change from Baseline | Num | Compute PCHG = (CHG / BASE) * 100. Only compute for post-baseline records. | ||
| CHGCAT1 | Change from Baseline Category 1 | Char | Decline >=10.0; Decline < 10.0; Increase | Categorize the value of CHG for Left Ventricular Ejection Fraction, and Calculated (%) (LVEFC) and for Right Ventricular Ejection Fraction, Calculated (%) (RVEFC) | |
| CHGCAT2 | Change from Baseline Category 2 | Chart | Categorize the value of CHG for N-Terminal ProB-type Natriuretic Peptide (pg/mL) (BNPPRONT) | ||
| SRCDOM | Source Data | Char | CV; LB | Set to the SDTM domain name that relates to the analysis value. | |
| SRCSEQ | Source Sequence Number | Num | CV.CVSEQ LB.LBSEQ | Set to the SDTM domain sequence number that relates to the analysis value. |
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 Wrapper Debug Message
Please add a row column to your dataset.
The dataset above can also be set up to provide multivariate analyses by taking the lab tests of interest, transposing and merging with the ADCVNTP dataset. In that case, the records from LB are not needed as a row.
| Dataset | Value | Where | Variable | Variable Label |
|---|---|---|---|---|
| ADCVCMR | AVAL | PARAMCD = "BNPPRONT" | BNPPRONT | N-Terminal ProB-type Natriuretic Peptide (IU/L) |
| ADCVCMR | CHG | PARAMCD = "BNPPRONT" | BNPCHG | N-Term ProB-type N Pep Change Category |
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
Display | Table 14.xx.xx Percent Change in Left Ventricular Ejection Fraction Over Time |
|---|---|
| Analysis Result | Comparison of Percent Change of Ejection Fraction for the Treatment Groups Over Time (quarterly or yearly) |
| Analysis Variables(s) | PCHG |
| Analysis Reason | Primary efficacy endpoint as prespecified in the SAP |
| Analysis Purpose | Primary outcome measure |
Data References (incl. selection criteria) | PARAMCD = "LVEFC" Where ITTFL = "Y" |
| Documentation | The mixed model using lsmeans to compare treatment groups |
Programming Statements (Add programming language statements here: SAS, R, etc.) | PROC MIXED DATA=ADCVCMR; CLASS STUYDID TRT01P AVISITN; MODEL PCHG=AVISITN*TRT01P/Solution; RANDOM INTERCEPT / SUBJECT=STUYDID TYPE=UN; LSMEANS TRT01P*AVISITN/ CL PDIFF; RUN; |
Table 2, ADD SOME COVARIATES TO THE MODEL
Display | Table 14.xx.xx Percent Change in Left Ventricular Ejection Fraction Over Time |
|---|---|
| Analysis Result | Comparison of Percent Change of Ejection Fraction for the Treatment Groups Over Time (quarterly or yearly) |
| Analysis Variables(s) | PCHG |
| Analysis Reason | Primary efficacy endpoint as prespecified in the SAP |
| Analysis Purpose | Primary outcome measure |
Data References (incl. selection criteria) | PARAMCD = "LVEFC" Where ITTFL = "Y" |
| Documentation | The mixed model using lsmeans to compare treatment groups |
Programming Statements (Add programming language statements here: SAS, R, etc.) | PROC MIXED DATA=ADCVNTP; CLASS STUYDID TRT01P AVISITN; MODEL PCHG=AVISITN*TRT01P/Solution; RANDOM INTERCEPT / SUBJECT=STUYDID TYPE=UN; LSMEANS TRT01P*AVISITN/ CL PDIFF; RUN; |
Move to table 3 This example uses the dataset ADCVNTP, selecting for the parameter "N-Terminal ProB-type Natriuretic Peptide (IU/L)".
Display | Table 14.xx.xx Percent change in NTproBNP over a period of time (yearly) |
|---|---|
| Analysis Result | Comparison of Percent Change of NTproBNP for the Treatment Groups Over Time (yearly) |
| Analysis Variables(s) | PCHG |
| Analysis Reason | Primary efficacy endpoint as prespecified in the SAP |
| Analysis Purpose | Primary outcome measure |
Data References (incl. selection criteria) | PARAMCD = "BNPPRONT" Where ITTFL = "Y" |
| Documentation | The mixed model using lsmeans to compare treatment groups |
Programming Statements (Add programming language statements here: SAS, R, etc.) | PROC MIXED DATA=ADCVNTP; WHERE PARAMCD = "BNPPRONT"; CLASS STUYDID TRT01P AVISITN; MODEL PCHG=AVISITN*TRT01P/Solution; RANDOM INTERCEPT / SUBJECT=STUYDID TYPE=UN; LSMEANS TRT01P*AVISITN/ CL PDIFF; RUN; |
Ejection Fraction
- change in ejection fraction, would expect a decline in EF 2-3% per year, would prefer an improvement or no change. Concerning if rapid progression, 10% decline or more, for example.
NTproBNP
- % change over a period of time – a decrease would mean improvement, annually is appropriate
SDTM Examples: Basic CMR Tests for Systolic Function