Copyright © 2013, SAS Institute Inc. All r ights reserved.
LEVERAGE THE CDISC DATA MODEL TO STREAMLINE ANALYTICAL
WORKFLOWS
KELCI J. MICLAUS, PH.D.RESEARCH AND DEVELOPMENT MANAGERJMP LIFE SCIENCESSAS INSTITUTE, INC.
Copyright © 2013, SAS Institute Inc. All r ights reserved.
INTRODUCTION SAS CLINICAL RESEARCH INFORMATION FLOW
EDC (Rave)
EDC (Other)
Adapters / Interfaces
ePRO and others
Labs and other external sources
Raw data
Internal systems
Metadata, integration and standardization management
SAS Clinical Data Integration
External metadata (RDF, OWL, etc.)
SAS Drug Development
Data and analytics platform
SDTMADaMOthers
Real-world data Raw data
Metadata
Submission data sets
Tables, figures and listings
Pooled analyses
Patient Profiles/ Medical Review/RBM
CDISC
JMP Clinical
SAS Visual
Analytics
Exploration across and beyond trials
Transparency initiatives
Adapters / Interfaces
Adapters / Interfaces
Dictionary coding(TMS)
Copyright © 2013, SAS Institute Inc. All r ights reserved.
JMP CLINICAL LEVERAGING CDISC IN ANALYTICAL WORKFLOWS
• Integrated solution of JMP and SAS platforms
• All analyses built on SDTM/ADaM standards.
• Build Clinical Reviews for variety of consumers: • Medical Monitoring• Signal Detection • Data Quality and Fraud Detection• Risk Based Monitoring
• Patient Profiles and auto-generated Adverse Event Narratives
• Open system of SAS programming macros to allow for consumer
customization
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JMP CLINICAL SOLUTION PROVIDES…
• Statistically-driven, dynamic data visualization that is key to efficient
clinical review
• Data standards support for streamlined/standardized analyses that
enable clinicians, data monitors, data managers, and statisticians
• Tools for snapshot comparison accelerate reviews
• Integrations with broader SAS solutions (Metadata Server, CDI, SDD)
Copyright © 2013, SAS Institute Inc. All r ights reserved.
JMP CLINICAL DATA MANAGEMENT
EFFICIENT REVIEWS THROUGH SNAPSHOT COMPARISON
• Comparisons between current and previous data snapshot accelerate
clinical review to avoid redundant work effort
• Keys allow record-level and subject-level categorization to flag new
and updated data• Record-level: New, Modified, Stable, Dropped, Non-Unique (Duplicate)• Subject-level: New Records, Modified Records, Stable, Introduced
• Keys are system-defined based on CDISC Key recommendation or
user-generated
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JMP CLINICAL INTEGRATION WITH SAS DRUG DEVELOPMENT (SDD)
• Enable JMP Clinical users to access study data stored in SDD• No web login or drive-mapping required
• Snapshot of most current version of files in SDD• Future version will enable users to select “as-of” date
• Supports SDD 3.x • future version of integration to support 4.x
Copyright © 2013, SAS Institute Inc. All r ights reserved.
JMP CLINICAL LEVERAGING THE STANDARDS
• CDISC variable usage architecture:• Tracks all SDTM/ADaM variable usage (required and optional) in analysis reports
• Documents variable specifications with pre-/post- study data tables and reports,
variable narratives, and in analysis report dialogs
• Executes algorithmic logic to restrict availability of analysis reports for studies based
on variable requirements
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• Live Demonstration• CDISC Variable Usage• Clinical Starter Menu• Review Builder• Patient Profile and Narratives
Copyright © 2013, SAS Institute Inc. All r ights reserved.
PATIENT PROFILE REPORT
Profile
VISIT
NIC .15
DATE OF SAHRANDOMIZED
DEATH
HydrocephalusHyperglycaemia
HypokalaemiaHypotension
Status asthmaticusVomiting
Pulmonary oedemaDisorientation
IsosthenuriaMyocardial infarction
CoagulopathyOedema peripheral
Respiratory disorderAnaemia
Hepatic function abnormalHypertension
VasoconstrictionBrain oedema
Intracranial pressure increased
ACETAMINOPHENCODEINE COMPOUND 1/2
DEXAMETHASONEDOCUSATE SODIUM
PHENOBARBITALPOTASSIUM SUPPLEMENTS
RANITIDINEINSULINS
FUROSEMIDEBENZODIAZAPINE
DOPAMINEFENTANYL
VANCOMYCINLABETALOL HCL
PRMEANQRSDURQTMEANRTMEAN
KSODIUM
ALTASTALPBILI
GLUCCREAT
HCTHGBRBC
PLATWBCAPTTBUN
CACKCL
CO2LDH
PCO2PH
PHOSPO2
PROTPT
URATE
SYSBPDIABP
HR
1 2 3 4 5 6 7 8 9 10 11 12 13 14
0 100
120 17350 100
280 436540 1000
3.4 4.5133 145
12 16715 9345 165
0 05.2 12
0 0.128 439.3 14
3 4.7138 4317.9 2121 322.5 10
2 2.527 60397 11187 122
147 5333591 5719
7.4 7.50.6 1.4
8911 216795.3 7.511 130.1 0.3
112 17460 9064 108
Adverse Events
Concomitant Medications
Disposition
ECG Test Results
Exposure
Laboratory Test Results
Visits
Vital Signs
0 7 14Study Day
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JMP CLINICAL REPORTS AUTO-GENERATED AE PATIENT NARRATIVES
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JMP CLINICAL SIGNAL DETECTION
SAFETY SIGNAL DETECTION
• Statistically-driven volcano plots
(Jin et al. 2001, Zink et al. 2013)
• Space-constrained view of several
hundred AE events
• Difference in observed AE risk vs.
statistical significance
• Color illustrates direction of effect
• Bubble size reflects AE frequency
• Traditional relative risk plot (Amit et al.
2008) to display interesting signals
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JMP CLINICAL SIGNAL DETECTION
ANALYSIS COMPLEXITIES ADDRESSED WITH JMP CLINICAL
• Abundance of endpoints (multiplicity)• False discovery rate (FDR) Benjamini & Hochberg (1995)• Double FDR (Mehrotra & Heyse 2004, Mehrotra & Adewale, 2012)• Bayesian Hierarchical Models
• Repeated/recurrent events• Inclusion of time windows across analyses
• Trial design complexity • Crossover analysis and visualization
• Limited population and understanding of biological underpinnings• Cross-domain predictive models• Subgroup analysis• Pharmacogenomics
Copyright © 2013, SAS Institute Inc. All r ights reserved.
JMP CLINICAL DATA MANAGEMENT
SNAPSHOT COMPARISON ANALYSIS TOOLS
• Domain Data Viewing• Use of color/annotate New, Modified, and Stable records• System-generated record-level notes describe changes in variables
Copyright © 2013, SAS Institute Inc. All r ights reserved.
JMP CLINICAL DATA MANAGEMENT
SNAPSHOT COMPARISON ANALYSIS TOOLS
• Track data/record updates and review status at subject level patient profile
Copyright © 2013, SAS Institute Inc. All r ights reserved.
JMP CLINICAL DATA MANAGEMENT
SNAPSHOT COMPARISON ANALYSIS TOOLS
• Use derived flags to filter analysis views to see modified/new data• Compare distributions of new versus previous records
AE Counts Graph
Sub
ject
Co
un
t
0
5
10
15
20
Vaso
cons
trictio
n
Anaem
ia
Intrac
rania
l pre
ssure
incr
ease
d
Hydro
cepha
lus
Hyper
tensio
n
Pyre
xia
Hepatic
func
tion
abno
rmal
Pulm
onar
y oede
ma
Hypot
ension
Hyper
glyca
emia
Alveo
litis
Oed
ema
perip
hera
l
Brain
oed
ema
Atele
ctas
is
Urinar
y trac
t infe
ctio
n
Hypok
alaem
ia
Vom
iting
Phlebiti
s
Heart r
ate in
crea
sed
Isos
thenu
ria
Cerebr
al in
farc
tion
Dictionary-Derived Term ordered by Total Count (descending)
AE Review Flag
Modifiednew
Where(5947 rows excluded)