Copyright © 2013, SAS Institute Inc. All rights reserved. LEVERAGE THE CDISC DATA MODEL TO STREAMLINE ANALYTICAL WORKFLOWS KELCI J. MICLAUS, PH.D. RESEARCH

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.


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



Dictionary coding(TMS)


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


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)


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


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


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


• Live Demonstration• CDISC Variable Usage• Clinical Starter Menu• Review Builder• Patient Profile and Narratives


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


PATIENT PROFILE TABLES REPORT


JMP CLINICAL REPORTS AUTO-GENERATED AE PATIENT NARRATIVES


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


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



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




• Track data/record updates and review status at subject level patient profile




• 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)