evolving risk indicators
TRANSCRIPT
Evolving Risk Indicators
Duncan Hall, CEO Triumph Research
Intelligence
The Risk-basedmonitoring company
Founded in 2013 Sister company to Triumph Consultancy Entirely Quality Oversight and RBM focused Creators of OPRA RBM platform One complete solution
Implementation services Study specific services Technology Hosting
Presentation Synopsis
EVOLVING RISK INDICATORSIdentifying Relevant Risk Indicators for Each Stage of the Trial to Optimize Quality Oversight by Mitigating Risk Early and Cost Effectively
Study Design Feasibility Country selection
Site Selection
Site Initiation
Patient Recruitment
Treatment / Monitoring
Why Should RBM Evolve During A Trial?
Internal process External process
Patients not involved Patients involved
Historic data Performance data
Clinical data
What Are The Key Variables?
Data SourcesKRI / KPIsData subsetFrequencyApproach
Study Design
Study Design
Feasibility
Country selection
Site Selection
Site Initiation
Patient Recruitment
Treatment / Monitoring
Evolution of Study Design
Robust Synopsis Final Protocol
Simplify where possible to reduce risk For the risks we have to accept:
What KRIs will help detect that risk? What KRIs are needed for endpoints / safety? What KRIs / KPIs will drive operational oversight?
Audience Poll #1
Question: What best describes your approach to Protocol risk assessment?
Answer:A. We perform risk assessment early
and revise the protocol accordinglyB. We perform risk assessment but
don’t revise protocolC. We don’t perform risk assessment
Study Design
Study Design
Feasibility
Country selection
Site Selection
Site Initiation
Patient Recruitment
Treatment / Monitoring
Are all indicators equal? Do you plan to roll up indicators
to give a site score? Are safety indicators more
important than performance?
Indicator ClassificationCommon across all protocols•Safety•Compliance•Data quality
Common across a therapy area/indication•Endoscopy•Mayo scoring system
Specific to the study•Subject response to treatment
Audience Poll #2
Question: What is your approach to different indicator types?
Answer:A. We use different indicators for each
studyB. We re-use some indicators but also
use study specific indicatorsC. We use the same indicators for all
studies
Feasibility
Study Design
Feasibility
Country selection
Site Selection
Site Initiation
Patient Recruitment
Treatment / Monitoring
Focus is on historic data What indicators have we used previously? How effective were they? What did we learn? Did we see any regional trends or bias? Do we need to adjust monitoring plans accordingly?
Use of Heat Maps Study profiling Overall historic risk bias Specific indicators
Country SelectionStudy
Design
Feasibility
Country selection
Site
Selection
Site
Initiation
Patient
Recruitment
Treatment
/ MonitoringRecommend Country Risk Assessments
Country specific standard of care practice Focused on risk factors, not recruitment /
performance factors May want to consider sub-setting the
country data
Countries in Region 1
Adverse Events Region 1 Adverse Events Region 2
Countries in Region 2
Data Sub-setting
Site SelectionStudy
Design
Feasibility
Country selection
Site
Selection
Site
Initiation
Patient
Recruitment
Treatment
/ Monitoring
Site Risk Assessments Focused on risk factors, not recruitment / performance
factors Have we used the site before? What were the findings and how do we learn and manage
this time? May want to adjust monitoring plans prior to recruitment
Adverse Events Region 2
Studies for site X
Absolute risk score
Relative ranking to other study
sites
How do we quickly assess historic / current use of a site?
Cross Study Site Assessment
Site InitiationStudy Design
Feasibility
Country selectio
n
Site
Selection
Site Initiatio
n
Patient Recruit
ment
Treatment / Monitoring First look at current data
KPIs - doc turnaround times Quality assessments
Multiple data sources Looking for correlation between initiation metrics
and subsequent quality issues May want to adjust monitoring plans prior to
recruitment
Patient RecruitmentStudy Design
Feasibility
Country selectio
n
Site
Selection
Site Initiatio
n
Patient Recruit
ment
Treatment / Monitoring
Focus on the process of recruitment and screening
Performance and quality considerations Ratios can be good indicators:
Enrolment / screen failure Screen failure / withdrawal
Patient RecruitmentStudy Design
Feasibility
Country selectio
n
Site
Selection
Site Initiatio
n
Patient Recruit
ment
Treatment / Monitoring
KRI • Does the KRI show risk?Companion
•Review companion metrics
Data
Deeper dives should be
possible at to refine the risk
signal and determine
actions
Adverse Events Region 2
What are the main reasons for
patient discontinuation?
What is the distribution of reasons across all
sites?
What is the distribution for
this site?
Companion Metrics
Drill down to the KRI data
set
What is the distribution for
this site?
Sort, group and export multiple
data sets for comparison
Treatment / MonitoringStudy Design
Feasibility
Country selectio
n
Site
Selection
Site Initiatio
n
Patient Recruit
ment
Treatment / Monitoring
Focus of most RBM and oversight activity KRI and data sources all now fully utilised Let’s consider the concept of data sub
setting from a time based perspective…
Treatment / MonitoringStudy Design
Feasibility
Country selectio
n
Site
Selection
Site Initiatio
n
Patient Recruit
ment
Treatment / Monitoring
This study made use of endoscopy images taken by sites
Looked at % images either missing or reported more than 10 days after procedure
Treatment / MonitoringStudy Design
Feasibility
Country selectio
n
Site
Selection
Site Initiatio
n
Patient Recruit
ment
Treatment / Monitoring
Sites with poor late endoscopy scores tended to score poorly in other areas
Monitoring corroborated that there were the sites with more issues
Treatment / MonitoringStudy Design
Feasibility
Country selectio
n
Site
Selection
Site Initiatio
n
Patient Recruit
ment
Treatment / Monitoring
Sites highlighted for more monitoring support improved, continued to be flagged as outliers
Looking at data in rolling six month subsets allowed a more current view on what is happening ‘now’
The results were significant:
Treatment / MonitoringStudy Design
Feasibility
Country selectio
n
Site
Selection
Site Initiatio
n
Patient Recruit
ment
Treatment / Monitoring
Dec 2014
Apr 2015
This showed both the efficacy of the monitoring interventions as well as the sub setting of the data
Summary
Clinical trials are by nature dynamic, as should our approach to quality oversight and RBM
RBM starts with Protocol design Different indicators, data sources, data subsets, frequencies and weightings can all
be used to evolve your approach throughout the trial Historic information can help inform selection and oversight of countries and sites Sub-setting of data can help deal with regional skew Companion metrics can help with root cause analysis and fine tuning of KRIs Should be continually evaluating the efficacy of KRIs and adjusting approach as we
learn All decisions and changes to approach need to be documented and justified
Questions / Contact Details
Duncan HallCEO and Founder
By website:www.tritrials.com
By email:[email protected]