ICONik Patient Centric Monitoring The ICON s risk-based monitoring approach

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1 ICONik Centric Monitoring The ICON s risk-based monitoring approach Journée d'information "Les évolutions des pratiques et des besoins dans les essais cliniques industriels" Nancy, 24 Juin 2014 Frédéris BLAIS, PhD Clinical Data Analyst

2 Risk-Based Monitoring: not a revolution an evolution. Trial s costs Number & Complexity of trials Clinical IT Solutions: ecrf, ecoa (epro, ClinRO..) Risk-Based Monitoring World economic s context Pharma s landscape: from Products to Health Outcomes

3 RBM: not a revolution an evolution Knowing GAP Doing The Knowing Doing Gap Jeffrey Pfeffer & Robert I. Sutton

4 RBM: not a revolution an evolution Knowing - Doing The Knowing Doing Gap Jeffrey Pfeffer & Robert I. Sutton

5 Risk-Based Monitoring: not a revolution an evolution. Clinical development is at a cross roads, requiring new approaches to deliver drugs to market faster with less cost while mitigating risk, and without compromising safety or quality.

6 Risk-Based Monitoring: not a revolution an evolution...the most important tool for ensuring human subject protection and high-quality data is a well designed and articulated protocol..sponsors should prospectively identify critical data and processes that if inaccurate, not performed, or performed incorrectly, would threaten the protection of human subjects or the integrity of the study results..no single approach to monitoring is appropriate or necessary for every clinical trial. FDA recommends that each sponsor design a monitoring plan that is tailored to the specific human subject protection and data integrity risks of the trial use of alternative monitoring approaches should be considered by all sponsors when developing risk-based monitoring strategies and plans..incorporation of centralized monitoring practices, where appropriate, should improve a sponsor s ability to ensure the quality of clinical trial data..fda believes that risk-based monitoring could improve sponsor oversight of clinical investigations risk-based approaches to monitoring, focused on risks to the most critical data elements and processes necessary to achieve study objectives, are more likely than routine visits to all clinical sites and 100% data verification to ensure subject protection and overall study quality

7 Traditional monitoring SIV Numerous travels on sites (up to 30% of the trial cost). FPI CRA visits each investigational site per predetermined schedule. 6-8 hours onsite with up to 100% SDV Manual review of data listings Limits of the traditional approach: - Not focused on critical data - Most sites are good enough - Reactive approach - Little opportunity for comparative analysis - Inefficient, expensive, uncertain quality

8 Risk-Based Monitoring Focus on the critical study data More efficient use of CRA time onsite Effective use and support of available technology Greater use of centralised monitoring Comparative analysis of site performance Early identification of issues, trends and outliers Cost reduction Inspection readiness

9 Overview 1. Why Centric Monitoring Opportunity to build on technology and big data Need improved paradigm for quality, cost and efficiency of clinical trials FDA guidance on Risk Based Monitoring, EMA Reflection paper on Quality Risk Management Engage with customers, investigators and employees: the individual Deploy human behavioral sciences to improve Decision-making at all levels with a data framework on what matters 2. What is Centric Monitoring Prevent, Detect, Mitigate error, and Learn from error Data for all

10 ICONIK -Centric Monitoring Clinical Trials Transformation Initiative Quality in Clinical Trials is the absence of errors that matter in decision-making. Overarching intent: Absence of errors that matter in decision-making for the patients. The patient is the research subject as well as the patient relying on the data once the product is on the market. Centric Monitoring

11 ICONik Centric Monitoring Process Oversight Planning Data entry Central Monitoring Site Monitoring ICON- Sponsor PM/CTM Investigator Compliance verification & Root Cause Analysis CRA Planning & Oversight: 1.Risk assessment (quality by design) 2.Centralised Monitoring Plan and Guidance for Additional Monitoring (the Risk Indicators) Risk Indicators ICONIK Data integration Risk Indicators Resolution Clinical Data Analyst Comparative Site Performance Analysis: Investigator Site Monitoring: Monitor sites through an Onsite visit Offsite visit Phone Call 1.Identify outliers, trends and risk 11 2.Monthly multidisciplinary review and decision if data are outside governance criteria

12 ICONik Centric Monitoring Process Oversight Planning Data entry Central Monitoring Site Monitoring ICON- Sponsor PM/CTM Investigator Compliance verification & Root Cause Analysis CRA Planning & Oversight: 1.Risk assessment (quality by design) 2.Centralised Monitoring Plan and Guidance for Additional Monitoring (the Risk Indicators) Risk Indicators ICONIK Data integration Risk Indicators Resolution Clinical Data Analyst Comparative Site Performance Analysis: Investigator Site Monitoring: Monitor sites through an Onsite visit Offsite visit Call 1.Identify outliers, trends and risk 12 2.Monthly multidisciplinary review and decision if data are outside governance criteria

13 Study A Study B Study C Study D ICONik: How it works? Visualize Recruitment Startup Metrics Quality Metrics Safety Metrics Risk Indicators Centralize Data Repository Study Data Mapper Standardize CTMS EDC IMI Labs IVR 13

14 The role of Clinical Data Analyst (CDA) To: compare the performance of all study sites using ICONIK identify site outliers, trends, signals and risk instigate increased monitoring activities at identified sites if necessary Using: Pre-specified risk indicators ICONIK reports and DM/EDC listings To communicate findings to the CRA using ICOTrial: Track CRA actions (on CDA findings) to successful resolution 14

15 Central Monitoring: example Clinical Data Analysts review aggregated data and compare Investigators ICONIK Aggregated data Investigator 1 CRA A Investigator 2 Clinical Data Analyst Investigator 3 CRA B Investigator 4 Investigator 5 Risk-Indicator: Number of Adverse Events: When comparing the data from Investigators 1, 2, 3, 4 and 5, the Clinical Data Analyst reports that investigator 4 is an outlier. Investigator 4 has no Adverse Events, the other investigators have multiple Adverse Events. 15

16 Unique BP Frequency CDAs can identify outliers - combine with CRAs knowledge Protocols XYZ states that Sitting Blood Pressure will be measured and recorded to the nearest mmhg BP Measurements: 99 Unique BP: 21 Site x Site x BP Measurements BP 16

17 Frequency Frequency CDA Findings: outlier vs non-outlier for BP variability Site x Site y BP BP Measurements: 99 Unique BP: 21 BP BP Measurements: 256 Unique BP: 241 Identified as outlier during CDA monthly analysis CDA Finding entered into ICOTrial Findings Module 17

18 The CDA process cycle CDA CDA data analysis CDA CDA reviews and closes findings CDA raises risk findings in CTMS CDA CDA PM Dashboard CRA logs feedback in CTMS to resolve CDA findings Risk Review Meeting CRA CRA Targeted monitoring interventions by CRA PM PI CRA

19 CRA: focused on the Root Cause Analysis "If I had only one hour to save the world, I would spend fifty-five minutes defining the problem, and only five minutes finding the solution." ~ Albert Einstein The root cause is THE cause which, if corrected, will prevent the error from happening again

20 Centric Monitoring Differentiated CRA monitoring practices with sites Telephone Contact Call Offsite Visit Onsite Visit «Informal» call to site, Focus on specific issues Motivational Drive Quality Telephone contact documented in CTMS. Formal call to site, Routine or scheduled, Direct with PI and SC, Review Protocol and Protocol amendments Site Process Assessment, Resolving issues and non-compliance, Reviewing Site performance, Specific trip report. Formal visit to site, SDV + SDR, Focus on CDA findings, Source Data Verification, % of, Site Process Verification : consistency of compliance in processes at site Includes all offsite monitoring visit activities, Specific trip report.

21 ICONIK Centric Monitoring Example of dynamic targeted monitoring of sites Example of baseline (minimum) monitoring, based on QbD Risk Assessment Onsite Visit Onsite Visit Onsite Visit Onsite Visit Offsite visit Offsite visit Offsite visit Offsite visit First X patients recruited Soft DBL Study duration CRA + Action based on triggers and Risk Indicator findings - Conduct Root Cause Analysis - Implement corrective and preventive measures ICONIk Triggered Monitoring Pool of additional site visits Offsite visit Onsite Visit Offsite visit Onsite Visit

22 Integrated Risk Based Monitoring Strategy Centralized Data Analysis CRA Monitoring Interactions with sites Baseline Monitoring Targeted Monitoring Source Data Verification Issue Investigation Source Document Review Issue Resolution Quality review Site support 22

23 What is expecting from the site? - Prompt Data Entry - Availability for new type of visits (off-site visit) - Awareness of centralized monitoring of the data - Support to clarify site trends - Availability of all source documents for adaptive SDV strategy - Rigorouness in data collection

24 ICONIK Centric Monitoring: Impact % SDV & On-Site Activity sites

25 ICONIK Centric Monitoring Strategy to detect and mitigate errors ICON- Sponsor PM/CTM Planning & Oversight: 1.Quality by Design: disease, IP, protocol 2.Design quality & risk management plan 3.Design and Implement oversight Monitoring plan Risk Indicators Oversight ICONIK Data integration & site data Risk Indicators Clinical Data Analyst Central Monitoring and analysis: Investigator 1. Identify outliers 2. Decision if data within governance criteria 3. Multidisciplinary review and decision if data are outside governance criteria CRA & Monitoring data Review Finding Compliance verification & Root cause analysis Resolution CRA Investigator Site Monitoring: 1. Urgent Action Required 2.Action Required at next Monitoring Visit Action recorded in Monitoring Visit Report Planning Central Monitoring Site Monitoring

26 Any questions? Chance favors the prepared mind. Louis Pasteur