Index
A
ABLFL variable 139
ADAE (Adverse Event Analysis datasets) 139–141
ADaM (Analysis Data Model)
about 3, 4, 127
ADAE (Adverse Event Analysis dataset) 139–141
ADSL (Subject-Level Analysis dataset) 134–137, 210–213
ADTTE (Time-to-Event Analysis dataset) 141–144
Analysis Results metadata 120–122
Basic Data Structure (BDS) 8, 137–139
considerations 7–8
datasets 200–202
define.xml 117
metadata 117
Pinnacle 21 Community 181
spreadsheets 118–123
tools 128–134
traceability checks 182–184
Variable-Level metadata 118–119
ADAMLIB parameter 183
ADEF (efficacy dataset), creating 137–139
&ADEFKEEPSTRING macro 139
ADSL (Subject-Level dataset) 134–137, 191, 210–213
&ADSLKEEPSTRING macro 136
ADTTE (Time-to-Event Analysis dataset) 141–144
Adverse Event Analysis datasets (ADAE) 139–141
Adverse Events events domain (AE), creating 48–50, 104–106
ADY variable 129
AE (Adverse Events events domain), creating 48–50, 104–106
AESEV codelist 17
ALGORITHM variable 68
ALT (alanine aminotransferase) 191
"Amendment 1 to the Study Data Tabulation Model (SDTM) v 1.2 and the SDTM Implementation Guide: Human Clinical Trials V3.1.2" 227
Analysis Data Model
See ADaM (Analysis Data Model)
Analysis Parameter Value-Level metadata 119–120
Analysis Results metadata 120–122
ANALYSISDATASET metadata 121
ANALYSISVARIABLES metadata 121
AnnotateCRF metadata 25
ARCHIVELOCATIONID metadata 12
ARM variable 66
ARMCD variable 66
ARM_DEMOGRAPHIC_TRT format 32
AST (aspartate transaminase) 191
AVAL variable 124, 139
AVALCAT variable 139
B
Base SAS
about 9, 29–30
background 57–58
building SDTM datasets 61–66
clinical standards setup for Study XYZ123 58–61
creating empty SDTM domain dataset 32–35
creating SDTM codelist SAS format catalog 30–32
creating SDTM study day variable 36–37
creating SDTM--DTC date variable 35–36
define.xml 66–77
implementing CDISC SDTM with 30–56
macros and tools for SDTM conversions 29–39
sorting final SDTM domain dataset 37–39
BASE variable 139
BDS (Basic Data Structure) 8, 137–139
bilirubin (BILI) 191
BLAs (Biologic License Applications) 2
BRIDG (Biomedical Research Integrated Domain Group) 225–226
building
See also creating
SDTM datasets 32–35, 39–55, 61–66
special purpose DM 39–42, 63–66, 95–103
SUPPDM domains 39–42, 63–66, 95–103
BY variable 192
C
case report form (CRF) 1–2
CDASH (Clinical Data Acquisition Standards Harmonization) Standard 4–5
CDER Common Issues document 3
CDISC
benefits of using data 187
data review and analysis 187–205, 200–202
future directions 227
implementing SDTM with Base SAS 30–56, 159–165
model versioning 227
reasons for using 1–3
validation, Pinnacle 21 Community 168–170
website 7–8, 15, 117
wiki 224
CDISC-Published metadata 79–80
%CFB macro 139
challenges, with data integration 208–209
character variable 17
CHG variable 139
CLASS metadata 11
Clinical Data Acquisition Standards Harmonization (CDASH) Standard 4–5
clinical standards setup, for Study XYZ123 58–61
clinical studies, defining 85–87
Clinical Trials Repository (CTR) 226
CNSR variable 141
CODEDVALUE metadata 16
CODEDVALUENUM variable 68
Codelist metadata 15–17
CODELISTCODE metadata 16
CODELISTDESCRIPTION variable 68
CODELISTDICTIONARY metadata 16
CODELISTITEMCODE metadata 16
CODELISTNAME metadata 14, 16, 19
codelists metadata dataset, creating 68–69
CODELISTVERSION metadata 17
coding dictionaries 214–215
column-level metadata datasets, creating 67
COMMENT metadata 24
COMMENT variable 68
COMMENTOID metadata 12, 14, 19, 22, 24
Comments metadata 24
company-specific metadata 81
COMPARATOR metadata 21
COMPLETED STUDY variable 142
Computational Method metadata 22–24
COMPUTATIONMETHOD metadata 23
COMPUTATIONMETHODOID metadata 14, 19, 23
CONTENTS procedure 34–35, 102
CONTEXT metadata 121
converting between native SAS and version 5.0 transport files 219–220
copying SDTM 3.2 standard to XYZ123 58
CQ01NAM variable 140, 141
creating
See also building
Adverse Events events domain (AE) 48–50, 104–106
codelists metadata dataset 68–69
column-level metadata datasets 67
define file generation programs 67–77, 69–77
define file metadata 66–67
define.xml 26–27, 66–77, 113–114, 122–123
document reference metadata datasets 69
efficacy dataset (ADEF) 137–139
empty SDTM domain dataset 32–35
EX (Exposure Interventions) domain 50–52, 108
LB (Laboratory Findings) domain 42–45, 109
SAS format catalog 30–32
SDTM domains 95–112
SDTM study day variable 36–37
SDTM--DTC date variable 35–36
study level metadata dataset 67
table-level metadata datasets 67
Trial Design Model domains 52–55, 109–110
value-level metadata datasets 67–68
XP (Pain Scale Customized Findings) domain 45–48, 106–107
CRF (case report form) 1–2
CRIT1 text string 119–120, 124
CRIT1FL variable 124, 139, 201
CROs 2, 4
CTR (Clinical Trials Repository) 226
customized code, using in SDTM production 110–111
D
data integration
challenges 208–209
strategies 209–216
submission tools and 216–220
DATA step code 111, 129, 139
&DATALIST macro 218
dataset creator, emptying via SAS clinical standards toolkit 62
DATASETORDER metadata 11
datasets
ADaM (Analysis Data Model) 200–202
EMPTY_** 34
Empty SDTM domain 32–35
EMPTY_ADEF 139
FORMATDATA 89, 99
Subject-Level (ADSL) 134–137, 210–213
SUPP 134
SUPPQUAL 134
Time-to-Event Analysis (ADTTE) 141–144
Validation Control 148
WORK 134
DATASETS parameter 183
Dataset-XML 224–225
date conversions 128–129
date variable 13, 18
datetime conversions 128–129
datetime variable 13, 18
define.xml
ADaM (Analysis Data Model) 117
Base SAS 66–77
building 26–27, 66–77, 113–114, 122–123
creating generation programs 67–77
defining file creation SAS program 27
defining file header metadata 26–27
generation programs 69–77
metadata 66–67
navigation 123–125
rendering 123–125
SAS Clinical Standards Toolkit 66–77
using SAS Clinical Data Integration to create 113–114
validation, with Pinnacle 21 Community 184–185
Define-XMLfinal version 2.0 10–11
defining
clinical studies and subfolders 85–87
file creation SAS program 27
file header metadata 26–27
target SDTM datasets 91–93
DEMOGRAPHIC TRT variable 32
DILI (drug-induced liver injury) 191
%DIRDELIM macro 219
DISPLAYFORMAT metadata 9, 14, 19
DISPLAYID metadata 121
DISPLAYNAME metadata 121
document reference metadata datasets, creating 69
DOCUMENTATION metadata 118, 121
DOMAIN metadata 13, 18, 19
domain sorting, via SAS clinical standards toolkit 62–63
DOMAINS parameter 130–134
DO-WHILE loop 218
drug-induced liver injury (DILI) 191
"Drug-Induced Liver Injury: Premarketing Clinical Evaluation" (FDA) 191
%DTC2DT macro 136, 139, 141
E
eCTD (FDA) 3
EDC (electronic data capture) systems 4
editing
XYZ123 metadata 58–59
XYZ123 SAS clinical standards toolkit control files 59–60
efficacy dataset (ADEF), creating 137–139
electronic data capture (EDC) systems 4
EMPTY_** dataset 34
Empty SDTM domain dataset, creating 32–35
EMPTY_ADEF dataset 139
event narratives 197–200
EVNTDESC variable 141
EVS (NCI Enterprise Vocabulary Services) 15
EX (Exposure Interventions) domain, creating 50–52, 108
exchanging non-clinical data 223
EXTENDEDVALUE variable 68
External Links metadata 24–25
Extract transformation 96–97
F
FDA
documents and events in support of data standards 2–3
Janus 226
use of Pinnacle 21 Community by 167–168
file creation SAS program, defining 27
file header metadata, defining 26–27
FILEOID metadata 26
final SDTM domain dataset, sorting 37–39
float variable 13, 16, 18
FORMATDATA dataset 89, 99
%FROMEXP macro 219–220
G
governance, need for 5–6
Guidance for Industry: Integrated Summary of Effectiveness (FDA) 208
Guidance for Industry: Premarketing Risk Assessment (FDA) 208
H
Healthcare Link (website) 227
HL7 (Health Level Seven International) 225–226
%horizontalize macro 203–204
HREF variable 68
Hy's Law Screening routine 191–192
I
ICH M4E(R1)-Clinical Overview and Clinical Summary of Module 2 208
IDVAR variable 134
IHE (Integrating the Healthcare Enterprise) 227
implementation strategies
ADaM considerations 7–8
CDASH 4–5
CDISC 1–3
models 4
need for governance 5–6
SDTM considerations 6–7
implementing
ADaM 127–145
CDISC SDTM with Base SAS 30–56
IMPORT procedure 109
INDEX variable 107
integer variable 13, 16, 18
integrated summary of efficacy 207
integrated summary of safety 207
Integrating the Healthcare Enterprise (IHE) 227
integration 207
ISO 8601 date/datetime conversions 128–129
ISREFERENCEDATA metadata 11
ITEMOID metadata 21
J
Janus 226
JMP Clinical
event narratives 197–200
getting started 188–191
patient profiles 195–197
safety analyses 191–195
safety evaluations with 187–200
K
Kaplan Meier estimates 202
**KEEPSTRING macro 34
L
LABEL metadata 11, 13, 18, 23
LB (Laboratory Findings) domain, creating 42–45, 109
LBCAT variable 109
LBTEST variable 109
LBTESTCD variable 109
LeafID metadata 24
LEAFID variable 122
LeafPageRef metadata 24
LeafPageRefType metadata 25
LeafRelPath metadata 24
LENGTH metadata 13, 18
library 31, 39, 42, 46, 48, 50, 63
LIFETEST procedure 201–202
LLT (lower-level term) 214
Lookup transformation 98–100
M
macros
&ADEFKEEPSTRING 139
&ADSLKEEPSTRING 136
%CFB 139
&DATALIST 218
%DIRDELIM 219
%DTC2DT 136, 139, 141
%FROMEXP 219–220
**KEEPSTRING 34
make_codelist_format.sas 30
make_dtc_date.sas 30
make_empty_dataset.sas 30
%MAKE_EMPTY_DATASET 135, 136
%MAKE_SORT_ORDER 136
make_sdtm_dy.sas 30
make_sort_order.sas 30
MAXLENGTH 216–219
%MAXLENGTH2 219, 220
%MERGSUPP 130–134, 135, 219–220
%run_p21 221
for SDTM conversions 29–39
%TOEXP 219, 221
&VARLIST 218
website 224
make_codelist_format.sas macro 30
make_dtc_date.sas macro 30
make_empty_dataset.sas macro 30
%MAKE_EMPTY_DATASET macro 135, 136
%MAKE_SORT_ORDER macro 136
make_sdtm_dy.sas macro 30
make_sort_order.sas macro 30
MANDATORY metadata 14, 19
MAXLENGTH macro 216–219
%MAXLENGTH2 macro 219, 220
MedDRA codes 214–215
merging supplemental qualifiers 130–134
%MERGSUPP macro 130–134, 135, 219–220
metadata
See also specific types
in ADaM (Analysis Data Model) 118–119
Analysis Parameter Value-Level 119–120
Analysis Results 120–122
CDISC-Published 79–80
Codelist 15–17
Comments 24
company-specific 81
External Links 24–25
file header 26–27
Reference dataset 149
SAS clinical data integration 80–85
SDTM (Study Data Tabulation Model) 10–25
Source dataset 149
Value-Level 18–21
Where Clause 21–22
metadata folder 66
model document (ADaM version 2.1) 7–8
model versioning 227
models 4
MONTH3DT variable 107
MONTH6DT variable 107
N
NAME metadata 11
navigation, in define.xml 123–125
NCI Enterprise Vocabulary Services (EVS) 15
NDAs (New Drug Applications) 2
non-clinical data, exchanging 223
number variable 17
O
OID metadata 11
OpenCDISC Validator 147
ORDERNUMBER metadata 16, 17
ORIGIN metadata 14, 19, 118
OUTLIB parameter 134
P
PAIN ADVERSE EVENT variable 142
PAIN RELIEF variable 142
Pain Scale Customized Findings (XP) domain, creating 45–48, 106–107
PAIN WORSENING variable 142
PAIN3MO variable 107
PAINBASE variable 107
PAN6MO variable 107
PARAM variable 119
PARAMCD metadata 121
PARAMCD variable 119
parameter invariant 139
parameters
ADAMLIB 183
DATASETS 183
DOMAINS 130–134
OUTLIB 134
REFDT 129, 139, 141
SOURCELIB 134
SRCLIB 183
patient profiles, in JMP Clinical 195–197
PDUFA (Prescription Drug User Fee Act) 2
PhaseForward's WebSDM 148–150
Pinnacle 21 Community
about 168–170
controlling terminology 176–177
Define.xml validation with 184–185
evaluating reports 170–173
modifying configuration files 174–176
running 168–170, 177–181
Points to Consider on Application with 1. Meta-Analyses; 2. One Pivotal Study (EMA) 208
Prescription Drug User Fee Act (PDUFA) 2
PRM (Protocol Representation Model) 226
PROBLEM metadata 184
PROBTYPE metadata 184
procedures
about 200–202
CONTENTS 102
IMPORT 109
LIFETEST 201–202
TRANSPOSE 102, 107
PROGRAMLEAFID metadata 122
PROGRAMMINGCODE metadata 121
Protocol Representation Model (PRM) 226
PROTOCOLNAME metadata 26
Providing Regulatory Submissions in Electronic Format - Standardized Study Data (FDA) 3
PURPOSE metadata 11, 121
Q
QLABEL variable 103
QNAM value 103, 134
QVAL variable 103
R
RACE variable 66
RANDOMIZEDT variable 107
RANK metadata 16
REASON metadata 121
REF variable 68
REFDT parameter 129, 139, 141
Reference dataset metadata 149
Reference Information Model (RIM) 225
REFLEAFID metadata 121
registering
source datasets 88–93
XYZ123 standard 60–61
regulatory submissions
about 207–208
data integration and 216–220
guidance 208
preparing 220–221
RENAME clause 65
rendering, in define.xml 123–125
REPEATING metadata 11
REPORT procedure 158
results folder 66
RFENDTC variable 65
RFSTDTC variable 65
RIM (Reference Information Model) 225
ROLE metadata 14, 19
ROLECODELIST metadata 14, 19, 118
"root" folder 66
%run_p21 macro 221
S
safety evaluations, with JMP Clinical 187–200
SAFETY flag 192
SAS Clinical Data Integration tool
about 159–165
creating define.xml 113–114
creating SDTM domains 95–112
implementing CDISC SDTM with 79–115
metadata 80–85
setting defaults 94
study setup 81–85
using to create define.xml 113–114
SAS Clinical Standards Toolkit
about 147–148
background 57–58
building SDTM datasets 61–66
clinical standards setup for Study XYZ123 58–61
define.xml 66–77
domain sorting via 62–63
emptying dataset creator via 62
setup 148–150
validation program 150–158
SAS Clinical Standards Toolkit 1.6: User's Guide 58, 60, 148, 158
SAS format catalog, creating 30–32
SASFIELDNAME metadata 14
SCHEMALOCATION metadata 26
SDTM (Study Data Tabulation Model)
about 1, 4, 39
AE (Adverse Events) events domain 48–50, 104–106
Base SAS macros and tools for conversions 61–63
building datasets 32–35, 39–55, 61–66
Codelist metadata 15–17
Comments metadata 24
Computational Method metadata 22–24
considerations 6–7
copying 3.2 standard to XYZ123 58
creating domains 95–112
EX (Exposure Interventions) domain 50–52, 108
External Links metadata 24–25
LB (Laboratory Findings) domain 42–45, 109
metadata 10–25
special purpose DM 39–42
SUPPDM domains 39–42
Table of Contents metadata 11–12
TDM (Trial Design Model) domains 52–55, 109–110
templating conversion jobs for reuse 112–113
using customized code in production 110–111
Value-Level metadata 18–21
Variable-Level metadata 12–15
Where Clause metadata 17–22
XP (Pain Scale Customized Findings) domain 45–48, 106–107
SDTM study day variable, creating 36–37
SDTM validation
about 147
SAS Clinical Data Integration 159–165
SAS Clinical Standards toolkit 147–158
SDTM--DTC date variable, creating 35–36
SE (Subject Elements) domain 109
SENDIG (SEND Implementation Guide) 223
SEQ metadata 21
SET statement 65
setting
SAS clinical data integration defaults 94
variable lengths 216–219
setup
SAS clinical data integration metadata 81–85
SAS clinical data integration study 85–94
SAS Clinical Standards Toolkit 148–150
SEX variable 66
SIGNIFICANTDIGITS metadata 13, 18
SOFTHARD metadata 21
sorting final SDTM domain dataset 37–39
**SORTSTRING variable 62–63
source 39, 42, 46, 48, 50, 63
Source dataset metadata 149
source datasets, registering 88–93
sourcedata folder 66
SOURCEDATASET metadata 17
SOURCELIB parameter 134
SOURCETYPE metadata 17
SOURCEVALUE metadata 17
SOURCEVARIABLE metadata 17
sourcexml folder 66
special purpose DM
building 39–42, 63–66
creating 95–103
spreadsheets (ADaM metadata) 118–123
SQL Join transformation 97–98
SRCDOM variable 144, 182
SRCLIB parameter 183
SRCSEQ variable 144, 182
SRCVAR variable 182
Standard for Exchange of Non-Clinical Data 223
STANDARD metadata 26
statements
SET 65
WHERE 98, 192, 200
strategies, data integration
about 209–210
choosing data 213–214
coding dictionaries 214–215
subject-level datasets 210–213
strategies, implementation
ADaM considerations 7–8
CDASH 4–5
CDISC 1–3
models 4
need for governance 5–6
SDTM considerations 6–7
STRUCTURE metadata 11
Study Data Tabulation Model
See SDTM (Study Data Tabulation Model)
study level metadata dataset, creating 67
Study XYZ123
clinical standards setup for 58
copying 3.2 standard to 58
editing metadata 58–59
editing SAS clinical standards toolkit control files 59–60
registering standard 60–61
study-based custom codelist format catalog 149
STUDYDESCRIPTION metadata 26
STUDYID variable 102
STUDYNAME metadata 26
STUDYOID metadata 26
stylesheet 67
STYLESHEET metadata 26
subfolders, defining 85–87
Subject Elements (SE) domain 109
Subject Sequence Generator transformation 105–106
SUBJECT variable 96
Subject Visits (SV) domain 109
Subject-Level dataset (ADSL) 134–137, 210–213
SUBJID variable 65
submissions, regulatory
about 207–208
data integration and 216–220
guidance 208
preparing 220–221
SUPP dataset 134
SUPPDM domain 39–42, 63–66, 95–1037
supplemental qualifiers, merging 130–134
SupplementalDoc metadata 25
SUPPQUAL dataset 134
SV (Subject Visits) domain 109
T
TA (Trial Arms) 109
Table of Contents metadata 11–12
table-level metadata datasets, creating 67
target SDTM datasets, defining 91–93
TD (Trial Disease Assessments) 109
TDM (Trial Design Model) domains, creating 52–55, 109–110
TE (Trial Elements) 109
templating SDTM conversion jobs for reuse 112–113
TESTCD variable 216
text variable 13, 16, 18
TI (Trial Inclusion) 109
time variable 13, 18
Time-to-Event Analysis dataset (ADTTE) 141–144
Title metadata 25
%TOEXP macro 219, 221
tools
ADaM (Analysis Data Model) 128–134
data integration and submission 216–220
for SDTM conversions 29–39
traceability checks 182–184
TRANSLATED metadata 16
transport files, converting between native SAS and Version 5.0 219–220
TRANSPOSE procedure 102, 107
Transpose transformation 100–103
transposing data stucture 202–205
Trial Arms (TA) 109
Trial Design Model (TDM) domains, creating 52–55, 109–110
Trial Disease Assessments (TD) 109
Trial Elements (TE) 109
Trial Inclusion (TI) 109
Trial Summary (TS) 109
Trial Visits (TV) 109
trialdesign.xlsx 52
TRTSEQA variable 212
TRTSEQP variable 211
TS (Trial Summary) 109
TV (Trial Visits) 109
TYPE metadata 13, 16, 18, 23
U
UML (Unified Modeling Language) 225
UNIQUEID variable 65, 96
"up version" 209
USUBJID variable 65, 102, 109, 209
V
validation, CDISC
Pinnacle 21 Community 168–170
validation, Define.xml
with Pinnacle 21 Community 184–185
validation, SDTM
about 147
SAS Clinical Data Integration 159–165
SAS Clinical Standards toolkit 147–158
Validation Control dataset 148
Validation Properties file 150
VALUE variable 68
Value-Level metadata 18–21
value-level metadata datasets, creating 67–68
VALUELISTOID metadata 19
VALUENAME metadata 18, 19
VALUES metadata 21
VALUEVAR metadata 18, 19
variable lengths, setting 216–219
VARIABLE metadata 13, 18, 19
Variable-Level metadata
ADaM (Analysis Data Model) metadata 118–119
SDTM (Study Data Tabulation Model) 12–15
variables
BY 192
ABLFL 139
ADY 129
ALGORITHM 68
ARM 66
ARMCD 66
AVAL 124, 139
AVALCAT 139
BASE 139
character 17
CHG 139
CNSR 141
CODEDVALUENUM 68
CODELISTDESCRIPTION 68
COMMENT 68
COMPLETED STUDY 142
CQ01NAM 140, 141
CRIT1FL 124, 139, 201
date 13, 18
datetime 13, 18
DEMOGRAPHIC TRT 32
EVNTDESC 141
EXTENDEDVALUE 68
float 13, 16, 18
HREF 68
IDVAR 134
INDEX 107
integer 13, 16, 18
LBCAT 109
LBTEST 109
LBTESTCD 109
LEAFID 122
MONTH3DT 107
MONTH6DT 107
number 17
PAIN ADVERSE EVENT 142
PAIN RELIEF 142
PAIN WORSENING 142
PAIN3MO 107
PAINBASE 107
PAN6MO 107
PARAM 119
PARAMCD 119
QLABEL 103
QNAME 103
QVAL 103
RACE 66
RANDOMIZEDT 107
REF 68
RFENDTC 65
RFSTDTC 65
SEX 66
**SORTSTRING 62–63
SRCDOM 144, 182
SRCSEQ 144, 182
SRCVAR 182
STUDYID 102
SUBJECT 96
SUBJID 65
TESTCD 216
text 13, 16, 18
time 13, 18
TRTSEQA 212
TRTSEQP 211
UNIQUEID 65, 96
USUBJID 65, 102, 109, 209
VALUE 68
VISIT 109
VISITNUM 107
WHERECLAUSECOMMENT 68
&VARLIST macro 218
VARNUM metadata 13, 18
VERSION metadata 26
VISIT variable 109
VISITNUM variable 107
W
WebSDM 148–150
websites
ADaM Basic Data Structure for Time-to-Event Analyses document 141
Biomedical Research Integrated Domain Group (BRIDG) 225
CDASH (Clinical Data Acquisition Standards Harmonization) Standard 4
CDISC 7–8, 15, 117
Define-XMLfinal version 2.0 10–11
macros 224
%MAXLENGTH2 macro 219, 220
Pinnacle 21 Community 167
PRM (Protocol Representation Model) 226
SAS transport files 219
SENDIG (SEND Implementation Guide) 223
traceability checks 183
Where Clause metadata 17–22
WHERE statement 98, 192, 200
WHERECLAUSECOMMENT variable 68
WHERECLAUSEOID metadata 18, 19, 21, 22, 121
WORK dataset 134
X
XP (Pain Scale Customized Findings) domain, creating 45–48, 106–107
Z
Zimmerman, Hy, Dr. 191