Risk-Based Monitoring - Prospective from CRO

Transcription

1 Risk-Based Monitoring - Prospective from CRO New Trends in Clinical Trials Taipei 2016 Tong Guo, PhD Head of Biostatistics, Africa & Asia QuintilesIMS Copyright 2015 Quintiles

2 Disclaimer The views and opinions expressed in the following PowerPoint slides are those of the individual presenters and should not be attributed to the companies or organizations with which the presenters are employed or affiliated. 2

3 Agenda Rational of Risk-Based Monitoring (RBM) What is RBM? How to RBM? Benefit & Results of RBM Future Trend & Summary 3

4 Challenges facing Biopharma It takes too long and costs too much to develop a new drug It can take 10 years & cost $2.6B to develop a new drug 80% of total drug development time & cost is associated with clinical trials (CTs) 30% of total budget of CTs in the labor-intensive activities as extensive on-site visits and 100% source data verification (SDV) with limited contribution to data quality 4

5 The New Trend in Clinical Trials 5

6 The Next Wave of Centralized Monitoring Martin Giblin & Rajneesh Patil Webinar Nov. 10,

7 Rational of RBM Improve cost-effectiveness without compromising quality and integrity $ Regulatory requirement Reducing cost & shortening timeline Improving data quality 7

8 Regulatory Requirement FDA/EMA/ICH E6 Guidance U.S. Department of Health and Human Services Food and Drug Administration August 2013 Procedural New Requirement in ICH E6 Addendum- Sponsor Responsibility 8

9 FDA Guidance FDA Guidance Guidance for Industry - Oversight of Clinical Investigations A Risk-Based Approach to Monitoring Key Words flexibility; innovative; effectiveness; centralized access; statistical assessments 9

10 ICH E6 Addendum New Requirement in ICH E6 Addendum- Sponsor Responsibility Extent and Nature of Monitoring ADDENDUM The sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The flexibility in the extent and nature of monitoring described in this section is intended to permit varied approaches that improve the effectiveness and efficiency of monitoring. A combination of on-site and centralized monitoring activities may be appropriate. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan). On-site monitoring is performed at the sites at which the clinical trial is being conducted. Centralized monitoring is a remote evaluation of ongoing and/or cumulative data collected from trial sites, in a timely manner. Centralized monitoring processes provide additional monitoring capabilities that can complement and reduce the extent and/or frequency of on-site monitoring by such methods as: 10

11 What is RBM? Definitions Industry Definition Risk-based Monitoring is the concept of monitoring trials electronically from a central location and sending monitors to sites only when necessary rather than every four to six weeks (CenterWatch, 2012). 11

12 What is RBM? Key Words Central(-ized) monitoring Remote monitoring Risk-based Monitoring Targeted Monitoring Statistical or triggered Monitoring Adaptive or intelligent Monitoring Dynamic Monitoring Classical monitoring Traditional monitoring On-site monitoring 100% SDV Uniform oversight Resource intensive Reactive approach Robust study planning Effective study execution Increased efficiency 12

13 RBM - Risk Assessment is the Key What is Risk? * Courtesy from Dr. James Pusey 13

14 Dynamic Monitoring Model Balanced relationship between on-site, remote and centralized monitoring improves delivery & quality, leading to better trial performance On-site Monitoring Informed Consent & IP On-Site Relationship Source Document Centralized & Remote Monitoring Protocol Medical & Data Monitoring Virtual Relationship Site Progression Mngt Three Visit Types On-site Monitoring Visits Remote Monitoring Visits Site Risk High Medium Low Site Contacts Responsive Action Based on Level of Site Risk 14

15 RBM - Monitoring is Cross-Functional Data Management Review: Targeted cleaning focused on right subjects / data at right time. Centralized Data Review: Holistic subject data review (clinical & operational) improving quality of data for Medical Monitors and wider study team Data Analytics: Data-driven triggers and insights for optimal Site Monitoring and Study Project Management. Study Medical Monitoring CDOS DM Review Engine Sites (Clinical Monitoring) Study Project Management 15

16 How to RBM Quintiles Solution Data driven Trial Execution (DTE) Data-driven Trial Execution begins with an in-depth risk assessment where our team of experts evaluates the scientific and operational risk of each protocol. P o w e r e d b y T e c h n o l o g y & D a t a I n s i g h t s Data surveillance allows us to optimize and adapt monitoring throughout the trial, re-assessing risk and applying the right action at the right time. We use the right type of monitoring at the right time (on-site, remote, centralized), monitoring sites, data, patients and events that require more attention and focus. 16

17 DTE: Move swiftly from data to actionable insights Optimized resource allocation to improve efficiencies & data review Combination of award-winning Quintiles Infosario and centralized data surveillance Risk Identification and mitigation Ongoing risk assessment Fast identification of trends for rapid, proactive issue resolution Expert analysis turns data into insights Insights lead to timely actions to improve patient safety * Courtesy from Xiaoqiang Xue Using Predictive and Advanced Analytics to Enhance Risk-based Monitoring Integrates multi-sourced data in real-time for safe, efficient, high quality trial management Balances dynamic, on-going site, remote, centralized monitoring Puts focus on sites, data, patients, events where needed most Tracks global performance Facilitates early trend, soft signal recognition Fosters rapid initiation of triggers, alerts for proactive issue resolution Promotes timely site communication & compliance Enables more informed decision-making 17

18 Operational DTE Proven integrated model drives efficiencies Early Upfront Risk Assessment (CPM, Medical, DM, Bios, Customer) Medical / Medical Surveillance Project Management (Ongoing Risk Assessment and Iterative Operational Strategy) Project Triggers & Alerts Centralized Monitoring Issue escalation of any non triggered concerns picked up by talking to sites Data Management Subject-Level Review Triggers/ Analytics Site Data Queries Individual Subject Data Across Subject Data Operational Site & Trial Data Site Support Centralized Operations Document Management Monitoring Support Via On-site and Remote Monitoring Visits Site Relationship Patient / Site Triggers & Alerts Site Monitoring Site Visits 18

19 Benefits and results from DTE approach 19

20 Benefits and Results from RBM approach 4x lower error rate in critical data in a head to head comparison of RBM to traditional 100% SDV 45% reduction in the number of missing pages in RBM studies vs. traditional studies 47% higher Action Item closure on RBM vs. non-rbm Investigators report 6% higher overall satisfaction rate and 8% more effective site communication with RBM vs. traditional study approaches 4x as many RBM study sites enter data within 7 days vs. traditional study sites (53% vs 12%) 52% fewer aged queries in RBM studies vs. traditional studies (queries > 10 days) 30% reduction in SDV backlog on RBM studies Up to 25% savings Data from active studies as of June

21 Customer challenges Barriers to RBM Adoption Challenging change management environment Unrealistic concerns on data quality without 100% SDV Operational complex and siloed execution Lack of real-time data access in Greater China region Disparate and disconnected technologies Site compliance & CRA facing time 21

22 Future Trend Predictive & advance analytics Evolution from traditional 100% SDV to predictive analytics Traditional Monitoring Reduced Monitoring Only Risk-based Monitoring leveraging triggers Data-driven Trial Execution Enhanced by predictive & advanced analytics Standard RBM approach Upfront risk assessment Reduced SDV Monitoring approach combining on-site & remote monitoring Reduced on-site visits Reduced costs Follow FDA & TransCelerate guidance Expanded RBM approach Technology integrates data and connects insights Centralized monitoring for near real-time data review via Centralized Clinical Operations & Centralized Data & Operational Surveillance Data analysis performed by medically-trained staff Enhanced site monitoring & communications Predictive & Advanced Analytics for preemptive identification & issue resolution at site & patient level 22

23 Moving RBM Forward Advancing new analytics: simple and predictive Evolving Analytics Capabilities RBM Triggers and Alerts Outliers identification Trend analysis Hierarchical view Study > Geography > Site > Subject RBM Advanced & Predictive Analytics Signal detection Univariate analysis Multivariate analysis Compound distribution Descriptive statistics Predictive analytics Reactive triggers Proactive alerts Corrective actions Preventive measures * Courtesy from Xiaoqiang Xue Using Predictive and Advanced Analytics to Enhance Risk-based Monitoring 23

24 Summary Connecting insights with superior delivery for better outcomes B E N E F I T: Improved Quality Results Increased Patient Safety Faster, More Informed Decisions Enhanced Site Effectiveness Improved Operational Efficiency Reduced Costs while Reducing Risk VA L U E : New insights & knowledge drive quality, patient safety and regulatory compliance to new levels. Analytics & Early Signal Detection delivers actionable & timely response to issues. Innovative technology improves cross-study visibility & transparency. Technology usage & data interpretation enhances Site communication & drives patient focus. Operational execution with analytics and combined roles for enhanced quality & results. Up-front risk assessment allows more efficient allocation of resources 24

25 Video QuintilesIMS Data-Driven Trial Execution The Next Wave of Centralized Monitoring Martin Giblin & Rajneesh Patil Webinar Nov. 10,

26 DTE Overview for Biogen Idec 12Dec

27 Contact Information Tong Guo, PhD Head of Biostatistics, Africa & Asia Data Sciences, Safety, and Regulatory