A DYNAMIC APPROACH TO MANAGINGRISKS WITH XCELLERATE® MONITORING

Understanding the Value of Advanced Monitoring in Clinical Trials

SUMMARY

Risks are always inherent in any clinical trial, especially as studies have become more complex to accommodate multiple protocols and data sources. As a result, biophar-maceuticals are recognizing that they must change the way risks are identified and managed. A comprehensive, central monitoring approach offers a more accurate and efficient method to oversee modern clinical trials while maintaining data quality and patient safety.

At Covance, Xcellerate® Monitoring is our “intelligent monitoring” solution to help our clients manage the increasing complexities of clinical trials. Designed to tightly align with regulatory guidance, Xcellerate Monitoring centralizes and consolidates clinical trial data to deliver near real-time insights so sponsors can proactively identify and mitigate risks that can negatively impact the success of a study.

Learn how our risk-based monitoring solution differs from traditional approaches as we discuss strategies to profile risk and increase monitoring efficiencies.

A new perspective on risk

TABLE OF CONTENTS

▶ Understanding the Monitoring Landscape

▶ The Adaptive Focus of Risk-Based Monitoring

▶ Pillars to Proactively Mitigate Risk

▶ Profiling Risks at the Study, Site and Operational Level

▶ Improving Decisions with Advanced Technology: Xcellerate® Monitoring

▶ Observed Results with Xcellerate Monitoring

▶ About the Authors

UNDERSTANDING THE MONITORING LANDSCAPEThe difference between current and historical methods

Every clinical trial requires careful monitoring to protect subjects and ensure reliable results, but methods to monitor trials can differ greatly.

Historical monitoring practices have involved:

▶ On-site Monitoring – typical frequency of 8-12 weeks▶ 100% Source Data/Document Verification

Contemporary monitoring practices have expanded to include:▶ Less frequent on-site Monitoring▶ Reduced Source Data/Document Verification▶ Source Data Review▶ Remote Monitoring▶ Central Monitoring

TransCelerate BioPharma have challenged the value of SDV in their paper “Evaluating Source Data Verification as a Quality Control Measure in Clinical Trials”1. This paper concludes that “SDV has a negligible impact on data quality” and that “other monitoring methods such as central monitoring and SDR should be used to focus on what matters most to the study.”

Given that traditional methods can account for up to 20-30% of clinical trial costs, many sponsors are revisiting their monitoring strategies to find more efficient strategies through solutions like Xcellerate Monitoring.

▶ More countries involved▶ More complex & disparate sources▶ More challenging protocol designs (e.g. adaptive protocols)

Evolving Complexity of Clinical Trials

1. Therapeutic Innovation and Regulatory Science, 2014, Vol. 48(6) 671-680.

THE ADAPTIVE FOCUS OF RISK-BASED MONITORING The value of building more accurate monitoring measures

From pharma to biotech, Clinical Research Organizations (CRO) to Academic Research Organizations (ARO), many groups are now embracing guidance by the regulatory bodies to implement holistic risk-based approaches to better support patient safety.

Risk-based monitoring (RBM) principles built into Xcellerate Monitoring can be implemented in customized ways, but the overall strategy focuses on:

Reducing non-value-added SDV transcription checks

Decreasing efforts and time needed for on-site monitoring visits

Focusing on value-added SDR compliance anddocumentation checks

Increasing the use of remote monitoring

Increasing use of central monitoring technologies for managing risk and holistic review of data

RBM recommendations and guidelines have been developed by various bodies, including:

▶ U.S. Food and Drug Administration (FDA)

▶ European Medical Agency (EMA)

▶ Medicines and Healthcare Products Regulatory Agency (MHRA)

▶ TransCelerate Biopharma Inc., a consortium of pharmaceutical and biotechnology companies

▶ International Congress on Harmonization

THREE FOUNDATIONS OF XCELLERATE® MONITORING A framework to help address risk and improve outcomesSetting up risk-based monitoring starts with early, proactive planning. Critical processes and data are identified in a baseline risk assessment to anticipate future needs and determine the amount of monitoring required.

Once a study is underway, data gathered from risk-based monitoring will trigger issues so that sponsors can deploy mitigating actions, redirect resources to where they make the most impact and iteratively adjust the monitoring plan.

At Covance, we designed our robust Xcellerate Monitoring solution to encompass three pillars based on TransCelerate principles:

1. Quality by Design Help build quality in and design risk out of studies during the planning phase to proactively reduce complexity—from the start.

2. Adaptive and Triggered Monitoring Identify issues and focus on critical data and processes through SDV/SDR and remote monitoring and risk-triggered on-site monitoring.

3. Central Monitoring Reviews a wide spectrum of data with specialized central reviewers, spanning global patterns to atypical sites across multiple clinical data sources.

Xcellerate® Monitoring: 3 Foundations

Quality by Design Adaptive and Triggered Monitoring

Central Monitoring

▶ Protocol review

▶ Risk assessment

▶ Critical data & process definition

▶ Central review of risk

▶ Source document review

▶ Reduced source data verification

▶ Reduced on-site monitoring

▶ Increased remote monitoring

▶ Central Medical Review

▶ Central Statistical Monitoring

▶ Central Data Review

▶ Issue & Risk Management

An Xcellerate Monitoring Plan defines the frequency of SDV, SDR, on-site and centrally-monitored visits while allowing for specific monitoring interventions to dynamically address risks in real time.

PROFILING RISKS AT THE STUDY, SITE AND OPERATIONAL LEVELS TO IMPROVE EFFICIENCIESThe innovative Xcellerate® Monitoring approach

Risks can emerge in many different areas and times in a clinical trial, creating the need for a flexible method that examines risks from multiple angles. Xcellerate Monitoring was designed to recognize and evaluate these risks across multiple time points.

Study Risk Assessment: Before starting, new studies can be evaluated and ranked with a risk profile, from very low to very high. This risk assessment sets the level of monitoring intervention required to mitigate potential risks if they arise.

Site Risk Assessment: Each planned site in the study is reviewed to set a baseline risk level and a strategy for intervention when significant challenges are observed.

Operational Risk Assessment: Once a study is underway, ongoing reviews examine emergent risks from the sites and patient data and assesses measurable operational risks through performance across sites, regions and countries.

IMPROVING DECISIONS WITH ADVANCED TECHNOLOGY: XCELLERATE® MONITORING

As clinical research and trial data are becoming increasingly digitized—and stem from multiple electronic data sources—Xcellerate Monitoring can standardize data and present it in a user-friendly format to drive faster decision making.

As an integrated data visualization solution, Xcellerate Monitoring encompasses medical review, data review, statistical monitoring and operational risk monitoring. Here, users can see where risk is occurring across the study and site level to quickly highlight issues and enable mitigating actions.

Key areas of risk identified by operational risk monitoring

▶ Protocol compliance

▶ Site performance & compliance

▶ Monitor performance & compliance

▶ Data collection & quality

▶ Subject enrollment and retention

▶ Safety

OBSERVED RESULTS WITH XCELLERATE® MONITORINGFollowing a fluid set of guidelines, Xcellerate Monitoring is very adaptive to its specific study. In our observations over a period of two-and-a-half years, we have been able to compare trials employing Xcellerate Monitoring to traditional trials and have determined the following:

LET’S DISCUSS SOLUTIONS TO TRANSFORM YOUR RISKS INTO RETURNS.

QUALITY▶ 20% less Critical/Major findings per clinical quality control (CQC) visit

EFFICIENCY▶ Higher levels of monitoring oversight (on-site/remote) per dollar spent on clinical monitoring activities

▶ Up to 36% lower site management spending

▶ Up to 18% lower travel spending

Efforts are in place to expand the use of these technological advances, further integrating disparate data sources and evaluating the success of risk-based monitoring methods. An ongoing iterative approach will deliver greater improvements to both the monitoring process itself as well as data quality, patient safety and cost efficiencies in clinical trials.

TIMELINESS▶ Up to 66% fewer missing eCRF Pages

▶ Up to 50% less SDV backlog sites

ABOUT THE AUTHORS

Adam BaumgartSenior Director, Monitoring & Data Flow Optimization, Covance

Adam has spent 26 years in clinical research and has been with Covance for over eight years. With job roles in pharma and with an EDC vendor and several major CROs, he is experienced in RBM, process excellence, project management, clinical data management and clinical monitoring. Adam leads the Covance full-service RBM and central monitoring team, which implements RBM tools and processes on client studies. Until October 2015, Adam led the cross-functional transformational project team responsible for the implementation of RBM at Covance. Most recently, the transformational team launched Xcellerate® Monitoring version 2.1, which includes expanded RBM services and capabilities such as medical review, protocol deviation reporting, study data warehouse and client access.

Chris McConachySenior Manager, Monitoring & Data Flow Optimization, Covance

Chris has been with Covance five years, after starting in the clinical research industry with Quintiles in 2006. With broad experience in clinical operations and line management in the Asia Pacific region, Chris is now applying RBM into clinical monitoring and other functions. Chris is the Process Lead for RBM at Covance, and a Senior Manager within the Monitoring & Data Flow Optimization team (the Covance RBM function). In this role, Chris coordinates the design of RBM tools and processes across interdependent functional groups and supports the implementation of new components as part of the Covance full-service RBM and central monitoring offerings.

ABOUT COVANCE

Covance, the drug development business of Laboratory Corporation of America® Holdings (LabCorp®), is the world’s most comprehensive drug development company, dedicated to advancing healthcare and delivering Solutions Made Real®. We have helped pharmaceutical and biotech companies develop each of the top 50 prescription drugs in the marketplace today.

Because of our broad experience and specialized expertise, we’re in a unique position to supply insights that go above and beyond testing. Together with our clients, we create solutions that transform potential into reality.

1. Study Risk

2. Site Risk

3. Operational Risk

Learn more about our drug development solutions at www.covance.comCovance Inc., headquartered in Princeton, NJ, USA is the drug development business of Laboratory Corporation of America Holdings (LabCorp). COVANCE is a registered trademark and the marketing name for Covance Inc. and its subsidiaries around the world.

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