© 2014 PerkinElmer

HUMAN HEALTH • ENVIRONMENTAL HEALTH

Innovations in Clinical AnalyticsAccelerating Insights & Data-Driven Decisions

Mark Demesmaeker

Contents

IntroductionIntroductionIntroductionIntroduction

•Innovating to accelerate insights: Workflow, Advanced Analytics, Data Provisioning

Innovation Spotlight: CDRInnovation Spotlight: CDRInnovation Spotlight: CDRInnovation Spotlight: CDR

•Guided workflow, SDTM standardization

Innovation Spotlight: RBMInnovation Spotlight: RBMInnovation Spotlight: RBMInnovation Spotlight: RBM

•Closed-loop integrated monitoring workflow, leveraging legacy data

Innovation Roadmap: Clinical Application FrameworkInnovation Roadmap: Clinical Application FrameworkInnovation Roadmap: Clinical Application FrameworkInnovation Roadmap: Clinical Application Framework

•Single framework, modular solutions

Safe Harbor Statement

• This document shows current intentions regarding product features,

behavior, schedules and support; these intentions may change

without notice as we respond to customer requirements.

• Any unreleased products, services or features referenced herein are

not currently available and may not be delivered on time or at all.

Customers who purchase PerkinElmer informatics applications

should make their purchase decisions based upon products, features,

and services that are currently available.

IntroductionAccelerate Insights with PerkinElmer Innovations in Clinical Analytics

Clinical/Medical Clinical/Medical Clinical/Medical Clinical/Medical Data ReviewData ReviewData ReviewData Review

Safety and PVSafety and PVSafety and PVSafety and PV RiskRiskRiskRisk----Based MonitoringBased MonitoringBased MonitoringBased Monitoring

Clinical OperationsClinical OperationsClinical OperationsClinical Operations

Spotfire in Clinical Development

Health Outcomes & RWEHealth Outcomes & RWEHealth Outcomes & RWEHealth Outcomes & RWE

The Workflow Challenge:

Where is the Actionable Data?

• How do find the analysis I need?

• How do I know the data is current and actionable?

• How do I navigate the analysis to find the data points I’m looking for?

• How do I act on the data?

The Analytics Challenge:

The Need for Faster, Smarter, Data-Driven Decisions

Competitive pressure for: • Smarter decisions: pervasive advanced analytics beyond the data science community

• Faster decisions: both human and automated

Need for agile analytics:• Data questions and answers change rapidly

• Analytics must be adaptive

The Data Challenge:

There’s More to Data Insights than Analytics

• Clinical Analytics Clinical Analytics Clinical Analytics Clinical Analytics

• Can studies be set up automatically?

• Are the data sets compatible?

• Can they be standardized?

• Can they be integrated?

• Can I look across historical snapshots of data?

• Can I perform analysis across multiple studies?

• How quickly can I access the data?

• …

Clinical Innovation Focus Areas

PersonaPersonaPersonaPersona----Driven Guided WorkflowsDriven Guided WorkflowsDriven Guided WorkflowsDriven Guided Workflows� Integrated role-based insights to reduce drug development duration

� Curated analytics experience to streamline root-cause analysis

� Immediate access to actionable data for faster data-driven decisions

Advanced Advanced Advanced Advanced AnalyticsAnalyticsAnalyticsAnalytics� TERR for advanced statistics and predictive modeling

� Legacy data analysis to unlock value of legacy data assets

� Alignment with TIBCO Roadmap for fastest analytics innovation

Holistic Data ProvisioningHolistic Data ProvisioningHolistic Data ProvisioningHolistic Data Provisioning� Ability to normalize and standardize clinical data

� Manage data extracts

� Easily provision data for analytics from multiple data sources

Clinical and Medical Clinical and Medical Clinical and Medical Clinical and Medical Data ReviewData ReviewData ReviewData Review RiskRiskRiskRisk----Based MonitoringBased MonitoringBased MonitoringBased Monitoring

Innovation Spotlight: CDR & RBM

PersonaPersonaPersonaPersona----Driven Driven Driven Driven Guided Guided Guided Guided WorkflowsWorkflowsWorkflowsWorkflows

� Alerts Workflow

� Exploratory Workflow

� Line Listing Review

� CRA Dashboard

� Central Monitor View

� Closed-Loop Monitoring

Holistic Data ProvisioningHolistic Data ProvisioningHolistic Data ProvisioningHolistic Data Provisioning

� Study setup automation

� Extracts Management and Versioning

� SDTM Data Standardization

� Study setup automation

� Data Source Identification

� Data Normalization

Advanced AnalyticsAdvanced AnalyticsAdvanced AnalyticsAdvanced Analytics

� Predictive risk modeling

� Adaptive monitoring

� Legacy data analysis and tolerance limits

� Signal detection

� Time to event analysis

� Risk difference

Clinical Data ReviewAlerts Workflow Option, Extract Management, Data Standardization

Clinical Data Review

� Provides access to a Provides access to a Provides access to a Provides access to a 360 degree view 360 degree view 360 degree view 360 degree view into

Patient Demographics, Adverse Events,

Labs, Vitals/ECG results and other safety

domains

� Increases agility Increases agility Increases agility Increases agility by allowing interactive

exploration of unexpected trends & hidden

relationships

� Enables rapid Enables rapid Enables rapid Enables rapid medical review medical review medical review medical review of clinical data

through intuitive navigation of population

and subject-level data

� Provides fast and accurate fast and accurate fast and accurate fast and accurate data quality data quality data quality data quality

assessmentassessmentassessmentassessment through fraud detection and

visibility into data quality issues

� Facilitates process improvement Facilitates process improvement Facilitates process improvement Facilitates process improvement by allowing

early identification of study issues and

dimension-free data exploration

Navigate populationNavigate populationNavigate populationNavigate population----level and level and level and level and

domaindomaindomaindomain----level viewslevel viewslevel viewslevel views

Select subSelect subSelect subSelect sub----populations for analysispopulations for analysispopulations for analysispopulations for analysis

Easily navigate to subjectEasily navigate to subjectEasily navigate to subjectEasily navigate to subject----level level level level

data with Patient Profiledata with Patient Profiledata with Patient Profiledata with Patient Profile

Workflow Configuration:

Alerts-Driven and Exploratory Workflows

Explore trends in populationExplore trends in populationExplore trends in populationExplore trends in population----level data level data level data level data

to select a subto select a subto select a subto select a sub----population for analysis population for analysis population for analysis population for analysis

…or follow configurable therapeutic…or follow configurable therapeutic…or follow configurable therapeutic…or follow configurable therapeutic----

area “Alerts” directly to the Patient area “Alerts” directly to the Patient area “Alerts” directly to the Patient area “Alerts” directly to the Patient

Profiles of relevant subjectsProfiles of relevant subjectsProfiles of relevant subjectsProfiles of relevant subjects

� Reduce drug development durationReduce drug development durationReduce drug development durationReduce drug development duration

� SSSStreamline roottreamline roottreamline roottreamline root----cause analysiscause analysiscause analysiscause analysis

� Save costs by identifying issues earlySave costs by identifying issues earlySave costs by identifying issues earlySave costs by identifying issues early

View all alerts or filter based View all alerts or filter based View all alerts or filter based View all alerts or filter based

on status or timelineon status or timelineon status or timelineon status or timeline

Line Listing Review and Queries

Mark records as “read” or “reviewed”Mark records as “read” or “reviewed”Mark records as “read” or “reviewed”Mark records as “read” or “reviewed”

Raise queries about specific data pointsRaise queries about specific data pointsRaise queries about specific data pointsRaise queries about specific data points

Access full review history and audit trailAccess full review history and audit trailAccess full review history and audit trailAccess full review history and audit trail

� Mark records directly in analysis Mark records directly in analysis Mark records directly in analysis Mark records directly in analysis

for accelerated datafor accelerated datafor accelerated datafor accelerated data----driven driven driven driven

decisionsdecisionsdecisionsdecisions

� Access review history audit trail Access review history audit trail Access review history audit trail Access review history audit trail

for 21 CFR part 11 compliance and for 21 CFR part 11 compliance and for 21 CFR part 11 compliance and for 21 CFR part 11 compliance and

meet validation requirementsmeet validation requirementsmeet validation requirementsmeet validation requirements

Automate Study Setup, Manage Data Extracts, Expedite

Data Standardization

� Reduce cycle time and medical Reduce cycle time and medical Reduce cycle time and medical Reduce cycle time and medical

monitoring costs with study setup monitoring costs with study setup monitoring costs with study setup monitoring costs with study setup

automationautomationautomationautomation

� Enable CRO oversight and Enable CRO oversight and Enable CRO oversight and Enable CRO oversight and leverage leverage leverage leverage

historical data with historical analysis historical data with historical analysis historical data with historical analysis historical data with historical analysis

across data “snapshots”across data “snapshots”across data “snapshots”across data “snapshots”

� RRRReduce cycle time to analysis with educe cycle time to analysis with educe cycle time to analysis with educe cycle time to analysis with

expedited SDTM standardizationexpedited SDTM standardizationexpedited SDTM standardizationexpedited SDTM standardization

MMMMerging and versioning of study data erging and versioning of study data erging and versioning of study data erging and versioning of study data

extracts to enable historical analysisextracts to enable historical analysisextracts to enable historical analysisextracts to enable historical analysis

SDTM data standardization for study SDTM data standardization for study SDTM data standardization for study SDTM data standardization for study

pooling and crosspooling and crosspooling and crosspooling and cross----study analysisstudy analysisstudy analysisstudy analysis

Study setup automation Study setup automation Study setup automation Study setup automation

PerkinElmer PerkinElmer PerkinElmer PerkinElmer

Data ServicesData ServicesData ServicesData Services

PerkinElmer PerkinElmer PerkinElmer PerkinElmer

SignalsSignalsSignalsSignalsTMTMTMTM

PerspectivesPerspectivesPerspectivesPerspectives

PerkinElmer PerkinElmer PerkinElmer PerkinElmer

SignalsSignalsSignalsSignalsTMTMTMTM

PerspectivesPerspectivesPerspectivesPerspectives

Risk-Based MonitoringClosed-loop Monitoring Workflow, Adaptive Monitoring, and Data Normalization

Why Risk-Based Monitoring

• Traditional 100% SDV-based, scheduled monitoring approaches are costly and not effective in identifying issues with critical data and processes

◦ Mostly transcription errors are discovered ◦ Resources are not directed where they are most needed

• Risk-based monitoring shifts the focus from scheduled site visits to a targeted and adaptive monitoring and SDV approach, increasing patient safety and data quality while decreasing unnecessary resource costs

• RBM is recommended by regulatory bodies and the focus on RBM will increase with the upcoming GCP guidance, ICH E6 R2

• An effective RBM strategy should include a flexible, data-agnostic visualization platform, an integrated workflow solution, and advanced analytics to leverage the value of historical data assets in enhancing the monitoring strategy and trial design

Risk Based Monitoring Overview

Risk Based Monitoring approach to Clinical Trial Monitoring is

“recommended” by FDA, EMA and MHRA

TransCelerate Vision

• KRI Reference Library

with TransCelerate’ s

RACT (Risk Assessment

categorization Tool)

and IQRMP (Integrated

Quality Risk

Management Plan) in

vision

• Utilization of Overall

Risk levels to establish

Monitoring levels Reference: Risk Based Monitoring Methodology Position Paper by TransCelerate BioPharma, 30 May 2013

ICH E6 R2- coming Nov 2016/early 2017

• Increased focus on Sponsor responsibilities for vendor

oversight

• First mention of risk-based approach to quality in a GxP

guidance

• Focus on traceability in decision making and a metrics-

based approach

• Need for tolerance limits for specific risk areas- what is

the tolerated, systemic level of risk for a particular risk

area

Risk-Based Monitoring

� Simplifies RiskSimplifies RiskSimplifies RiskSimplifies Risk----Based Based Based Based MMMMonitoring onitoring onitoring onitoring with

intuitive dashboard displays

� Enables flexibility Enables flexibility Enables flexibility Enables flexibility by providing a vendor

and data-agnostic solution designed to

work with multiple clinical data sources

� Supports adaptive design and adaptive Supports adaptive design and adaptive Supports adaptive design and adaptive Supports adaptive design and adaptive

monitoring monitoring monitoring monitoring through modeling of KRI

algorithms, thresholds, weightings, and

recommended actions

� Provides risk model assessment and Provides risk model assessment and Provides risk model assessment and Provides risk model assessment and

feedback loop feedback loop feedback loop feedback loop through timeline

analysis, geographic views, and

regression modeling

� Leverages historical data assets Leverages historical data assets Leverages historical data assets Leverages historical data assets

through the analysis of legacy data to

establish tolerance limits for risk

categories

Dashboard view into TransCelerateDashboard view into TransCelerateDashboard view into TransCelerateDashboard view into TransCelerate----aligned aligned aligned aligned

Risk Indicators, CategoryRisk Indicators, CategoryRisk Indicators, CategoryRisk Indicators, Category----Level Indicators, Level Indicators, Level Indicators, Level Indicators,

and Overall Site Indicatorsand Overall Site Indicatorsand Overall Site Indicatorsand Overall Site Indicators

Timeline view to assess the impact of Timeline view to assess the impact of Timeline view to assess the impact of Timeline view to assess the impact of

recommended actions on risk signals recommended actions on risk signals recommended actions on risk signals recommended actions on risk signals

Geographic view of indicators and Geographic view of indicators and Geographic view of indicators and Geographic view of indicators and

risk levels for resource management risk levels for resource management risk levels for resource management risk levels for resource management

and rootand rootand rootand root----cause assessmentcause assessmentcause assessmentcause assessment

Persona-Driven Views� Simplify RBM through roleSimplify RBM through roleSimplify RBM through roleSimplify RBM through role----based guided workflows, users only see what they need based guided workflows, users only see what they need based guided workflows, users only see what they need based guided workflows, users only see what they need

� Reduce monitoring cycle time through fastest access to actionable dataReduce monitoring cycle time through fastest access to actionable dataReduce monitoring cycle time through fastest access to actionable dataReduce monitoring cycle time through fastest access to actionable data

The CRA is able to view and investigate The CRA is able to view and investigate The CRA is able to view and investigate The CRA is able to view and investigate

risk Indicators for assigned sites risk Indicators for assigned sites risk Indicators for assigned sites risk Indicators for assigned sites

The Central Monitor is able to The Central Monitor is able to The Central Monitor is able to The Central Monitor is able to

navigate the overall risk model and navigate the overall risk model and navigate the overall risk model and navigate the overall risk model and

drill down to sitedrill down to sitedrill down to sitedrill down to site----level detailslevel detailslevel detailslevel details

Closed-Loop Monitoring� Save time by following up on recommended actions directly in the analysis Save time by following up on recommended actions directly in the analysis Save time by following up on recommended actions directly in the analysis Save time by following up on recommended actions directly in the analysis

� Use the feedback loop to learn what is working and easily adjust recommended actionsUse the feedback loop to learn what is working and easily adjust recommended actionsUse the feedback loop to learn what is working and easily adjust recommended actionsUse the feedback loop to learn what is working and easily adjust recommended actions

� Optimize trial design and QbD by leveraging historical data on recommended actionsOptimize trial design and QbD by leveraging historical data on recommended actionsOptimize trial design and QbD by leveraging historical data on recommended actionsOptimize trial design and QbD by leveraging historical data on recommended actions

CRA updates status and comments CRA updates status and comments CRA updates status and comments CRA updates status and comments

for recommended actionsfor recommended actionsfor recommended actionsfor recommended actions

Status is automatically updatedStatus is automatically updatedStatus is automatically updatedStatus is automatically updated

Action status can be reviewed Action status can be reviewed Action status can be reviewed Action status can be reviewed

and actions modeled according and actions modeled according and actions modeled according and actions modeled according

to impact assessmentto impact assessmentto impact assessmentto impact assessment

Advanced Analytics:

Unlock the Value of Historical Data Assets

Regression modeling and advanced Regression modeling and advanced Regression modeling and advanced Regression modeling and advanced

statistics offer a feedback loop on the statistics offer a feedback loop on the statistics offer a feedback loop on the statistics offer a feedback loop on the

historical performance of the risk model historical performance of the risk model historical performance of the risk model historical performance of the risk model

Adjust KRI algorithms, weightings, Adjust KRI algorithms, weightings, Adjust KRI algorithms, weightings, Adjust KRI algorithms, weightings,

thresholds, and recommended actions thresholds, and recommended actions thresholds, and recommended actions thresholds, and recommended actions

based on risk model assessmentbased on risk model assessmentbased on risk model assessmentbased on risk model assessment

Apply outApply outApply outApply out----ofofofof----the box regression the box regression the box regression the box regression

analysis, advanced statistics, analysis, advanced statistics, analysis, advanced statistics, analysis, advanced statistics,

historical analysis and predictive historical analysis and predictive historical analysis and predictive historical analysis and predictive

modeling to:modeling to:modeling to:modeling to:

� Apply adaptive monitoring, Apply adaptive monitoring, Apply adaptive monitoring, Apply adaptive monitoring,

adjusting risk model in adjusting risk model in adjusting risk model in adjusting risk model in

response to dataresponse to dataresponse to dataresponse to data

� Derive statistically meaningful Derive statistically meaningful Derive statistically meaningful Derive statistically meaningful

tolerance limits for risk tolerance limits for risk tolerance limits for risk tolerance limits for risk

categories (an ICH E6 R2 categories (an ICH E6 R2 categories (an ICH E6 R2 categories (an ICH E6 R2

requirement)requirement)requirement)requirement)

� Assess site feasibility Assess site feasibility Assess site feasibility Assess site feasibility

� Improve trial designImprove trial designImprove trial designImprove trial design

Data Normalization and Provisioning

� Enable crossEnable crossEnable crossEnable cross----study analysis and study study analysis and study study analysis and study study analysis and study

pooling by expediting the normalization pooling by expediting the normalization pooling by expediting the normalization pooling by expediting the normalization

of source data of source data of source data of source data

� Lower cost of ownership and reliance on Lower cost of ownership and reliance on Lower cost of ownership and reliance on Lower cost of ownership and reliance on

IT with SignalsIT with SignalsIT with SignalsIT with SignalsTMTMTMTM Perspectives, providing a Perspectives, providing a Perspectives, providing a Perspectives, providing a

lightweight, virtual alternative to lightweight, virtual alternative to lightweight, virtual alternative to lightweight, virtual alternative to

traditional warehousingtraditional warehousingtraditional warehousingtraditional warehousing

� Reduce time to analytics insights by Reduce time to analytics insights by Reduce time to analytics insights by Reduce time to analytics insights by

provisioning data to analytics without provisioning data to analytics without provisioning data to analytics without provisioning data to analytics without

impacting source system performanceimpacting source system performanceimpacting source system performanceimpacting source system performance

� Discover joins between data sources to Discover joins between data sources to Discover joins between data sources to Discover joins between data sources to

explore the “full picture” view of risk explore the “full picture” view of risk explore the “full picture” view of risk explore the “full picture” view of risk

across multiple clinical source systems, across multiple clinical source systems, across multiple clinical source systems, across multiple clinical source systems,

trackers, etc. trackers, etc. trackers, etc. trackers, etc.

The Adaptive Risk Model: Beyond Visualization

Risk Trigger

Recommended Action

Action Follow-up

Action Impact Assessment

Risk Model Evaluation

Risk Model Adjustment

Site 104 is in the red category for the Protocol Deviations KRI because while the count of minor violations is below the average, there is a high proportion of major violations.

A Site Visit has been recommended for the CRA based on the Protocol Deviation Indicator. The CRA completes the Action and adds Comments.

The Central Monitor is notified that the Recommended Action has been completed.

The Central Monitor can assess whether the Action had an impact on the Protocol Deviation Indicator.

The Central Monitor evaluates the Risk Model.

What is the historical correlation between:

o Visits at Site 104 and the Protocol Deviation Indicator?

o Between Visits and other Key Risk Indicators?

o Between Visits and the Protocol Deviation Indicator across Sites?

Regression modeling and predictions based on:

o Analysis of Indicators and other Indicatorso Analysis of Indicators and Actionso Analysis of Indicators and Monitor

Commentso Analysis against baseline and legacy

data

The Central Monitor adjusts Indicator Thresholds, KRI Weightings, and Recommended Actions. The Risk Model evolves based on monitoring impact and adapts based on changing risk.

Clinical Application FrameworkLooking Ahead: Combining Workflow, Holistic Data Provisioning, and Advanced Analytics

PerkinElmer Clinical Application Framework:

“One Stop Shop” for Clinical Data insights

Key Framework Features

PersonaPersonaPersonaPersona----Driven Guided WorkflowsDriven Guided WorkflowsDriven Guided WorkflowsDriven Guided Workflows• Integrated role-based insights to reduce drug development duration

• Curated analytics experience to streamline root-cause analysis

• Immediate access to actionable data for faster data-driven decisions

Advanced Advanced Advanced Advanced AnalyticsAnalyticsAnalyticsAnalytics• TERR for advanced statistics and predictive modeling

• Legacy data analysis to unlock value of legacy data assets

• Alignment with TIBCO Roadmap for fastest analytics innovation

Holistic Data ProvisioningHolistic Data ProvisioningHolistic Data ProvisioningHolistic Data Provisioning• Ability to normalize and standardize clinical data

• Manage data extracts

• Easily provision data for analytics from multiple data sources

Secure Secure Secure Secure Cloud Cloud Cloud Cloud InfrastructureInfrastructureInfrastructureInfrastructure• Multi-tenant and virtual private cloud options for secure, scalable architecture

Unified FrameworkUnified FrameworkUnified FrameworkUnified Framework• Single web application, modular clinical solutions to accelerate adoption

Streamlined Workflow, Curated Analytics

With PerkinElmer’s new Clinical Application Framework:

� Convenience:Convenience:Convenience:Convenience: single, hosted web application for all clinical analytics modules

� Process Efficiency: Process Efficiency: Process Efficiency: Process Efficiency: intuitive analytics workflows tailored to user role

� Cost Savings: Cost Savings: Cost Savings: Cost Savings: agile and automatic data normalization and provisioning

� Smart Insights: Smart Insights: Smart Insights: Smart Insights: built-in advanced and predictive analytics

� Faster Decisions: Faster Decisions: Faster Decisions: Faster Decisions: direct access to actionable data, closed-loop workflow

� Quality by Design:Quality by Design:Quality by Design:Quality by Design: leverage data to enhance trial design, site selection, analytics workflows

� Security and Compliance: Security and Compliance: Security and Compliance: Security and Compliance: secure cloud infrastructure, 21 CFR part 11 compliance

Persona-Driven

Workflow

Automatic study

setup and data

normalization

TIBCO Spotfire

visualizations, enhanced

with advanced analytics

Actionable Data Insights

Advanced Analytics:

Enhance Clinical Data Review with Advanced Analytics Built in R

TIBCO Enterprise Runtime for R (TERR) allows you to code openTIBCO Enterprise Runtime for R (TERR) allows you to code openTIBCO Enterprise Runtime for R (TERR) allows you to code openTIBCO Enterprise Runtime for R (TERR) allows you to code open----

source R directly in Spotfire with many builtsource R directly in Spotfire with many builtsource R directly in Spotfire with many builtsource R directly in Spotfire with many built----in analytics methods in analytics methods in analytics methods in analytics methods

and supported R packagesand supported R packagesand supported R packagesand supported R packages

Embed advanced analytics directly into the Embed advanced analytics directly into the Embed advanced analytics directly into the Embed advanced analytics directly into the

analysis to extend advanced data insights analysis to extend advanced data insights analysis to extend advanced data insights analysis to extend advanced data insights

beyond the data science communitybeyond the data science communitybeyond the data science communitybeyond the data science community

Smarter data insights with advanced analytics, including: Smarter data insights with advanced analytics, including: Smarter data insights with advanced analytics, including: Smarter data insights with advanced analytics, including:

� Relative RiskRelative RiskRelative RiskRelative Risk

� Time to Response AnalysisTime to Response AnalysisTime to Response AnalysisTime to Response Analysis

� Survival AnalysisSurvival AnalysisSurvival AnalysisSurvival Analysis

� Time to AE AnalysisTime to AE AnalysisTime to AE AnalysisTime to AE Analysis

Holistic Data Provisioning

This document shows current intentions regarding product features, behavior, schedules and support;

these intentions may change without notice as we respond to customer requirements.

Thank You!

mark.demesmaeker@perkinelmer.com