Copyright © 2017 IQVIA. All rights reserved.
Saturday 15 June 2019, 13:00-16:30
Maritim Hotel Cologne
Massoud Toussi, MD, PhD, MBA
Senior Principal, Pharmacoepidemiology and Drug Safety Lead, IQVIA
Chair, Regulatory Interactions and Conditional Coverage IG, HTAi
HTAi Workshop
A Primer on RICC:
How to Generate Real
World Evidence? A
Modern Approach
1HTAi RICC IG Workshop - Massoud Toussi - 2019
A paradigm change is under way!
Diseaseorientedcare
EBMClinical trials
Patient oriented care
• RWE
• Observationalstudies
2
Increasing focus on RWE is associated with the greater supply of electronic patient-level data.
HTAi RICC IG Workshop - Massoud Toussi - 2019
Cumulative publications; some of the research output is not related to medicines
Source: PubMed
0
500
1 000
1 500
04012000 02 03 0605 07 2010 20121108 09
UK Germany USACanadaFrance
3
The volume of « unused » data is massively growing.
HTAi RICC IG Workshop - Massoud Toussi - 2019
Source: IDC Digitila Universe 2020 Study
RWD supply push causes a seismic shift in our approach.
Few evaluators at launch, mostly
regulators and large payers
Many groups over time
including clinical and
small payers
THE PASTTHE PRESENT
RCT
Few
Many
Efficacy and Safety Almost everything
Initial view of
benefit-risk
Insights on environment,
outcomes, costs, comparative
effectiveness
Controlled trials,
manufacturer led
Shift to secondary patient-level
data across sources
RCT and RWE
HTAi RICC IG Workshop - Massoud Toussi - 2019
5
Social media
Test results,
lab values,
pathology results
Consumer
data
Claims
databases
Meaningful
questions
Fit for purpose
data
REAL-WORLD EVIDENCE (RWE)
Data sources
Primary data collection
(excluding RCTs)
Mortality,
other registries
Hospital visits, service
details
Pharmacy
data
Electronic medical and health
records
Generating evidence from real world data (RWD)
Appropriate
Analyses
HTAi RICC IG Workshop - Massoud Toussi - 2019
6
Step 1: Asking the right questions
Regulatory HTA
Exposure
Epidemiology of the indication(s)
Prescribing conditions
Characteristics of patients who actually receive the drug
New safety concerns, known ones, risk factors
Efficacy in real life / in specific populations
Effectiveness of risk minimization measures
Signal detection
Burden of target disease (mortality, morbidity
prevalence, incidence, DALYs, QALYs)
Conditions of use
Expected benefit of the technology
- On burden of disease
- On management of disease
- Economical
- Organisational
- Social
Confirmation of the expected benefit versus risk
Potential to cover unmet medical needs or to improve
covered needs
HTAi RICC IG Workshop - Massoud Toussi - 2019
7
Step 2: Finding fit-for-purpose data
Fit-for-purpose
Relevance (appropriate data)
Accuracy (lesserrors)
Timeliness (data stillusefull)
Linkability(identifying fields)
Completeness (lessmissing records /
variables)
Accessibility(available easily)
Representativeness
HTAi RICC IG Workshop - Massoud Toussi - 2019
8
Cost effective approach to data collection
The data shall be collected entirely (primary)
The data shall be collected partially (enriched, mosaic)
The data resides in a database (secondary)
We don’t know if the data is available in a database (landscaping)
Begin with the research question.
Rele
vance
Co
st
Tim
e
Desig
n fre
edom
HTAi RICC IG Workshop - Massoud Toussi - 2019
9
Claims data
Initial purpose
• Economic management
• Reimbursement
Content
• Demographics
• Diagnoses
• Diagnostic related groups
• Procedures
• Reimbursed drugs/devices
Settings
• Mainly Hospitals
• Increasingly linked to outpatient claims
Good for
• Economic and resource utilization
• Epidemiology
• Healthcare system
0
0,5
1
1,5
2
2,5
3
3,5
4
Accuracy
Timeliness
Linkability
Completeness
Accessibility
Representativeness
0
0,5
1
1,5
2
2,5
3
3,5
Accuracy
Timeliness
Linkability
Completeness
Accessibility
Representativeness
Claims
HTAi RICC IG Workshop - Massoud Toussi - 2019
10
EMR data
0
0,5
1
1,5
2
2,5
3
3,5
4
Accuracy
Timeliness
Linkability
Completeness
Accessibility
Representativeness
Initial purpose
• Clinical management
• Patient follow up
Content
• Demographics
• Diagnoses
• Signs and symptoms, allergies, smoking
• Lab values
• Drugs and to a less extent procedures
Settings
• Mainly primary care
• Increasingly secondary care and hospitals
Good for
• Exposure evaluation
• Drug utilization
• Disease epidemiology
• Benefit-risk assessment
• Unmet needs, burden, adherence
0
0,5
1
1,5
2
2,5
3
3,5
4
Accuracy
Timeliness
Linkability
Completeness
Accessibility
Representativeness
Claims EMR
HTAi RICC IG Workshop - Massoud Toussi - 2019
11
Pharmacy records / sales data
Initial purpose
• Sales management
• Benchmarking
Content
• Demographics
• Drugs (packages sold)
Settings
• Retail pharmacies
• Wholesales
• Company outputs
Good for
• Exposure
• Treatment dynamics (switch, discontinuation…)
• Population movements
• Linkage
0
0,5
1
1,5
2
2,5
3
3,5
4
Accuracy
Timeliness
Linkability
Completeness
Accessibility
Representativeness
0
0,5
1
1,5
2
2,5
3
3,5
4
Accuracy
Timeliness
Linkability
Completeness
Accessibility
Representativeness
Claims EMR Pharmacy/sales
HTAi RICC IG Workshop - Massoud Toussi - 2019
12
Registries
Initial purpose
• Research
Content
• Demographics
• Clinical details
• Procedures
• Drugs
• Lab values
• Relevant markers, genetic data, tests, etc
Settings
• Disease or drug oriented
• Mostly secondary care
• Mostly research intensive areas (oncology, ...)
Good for
• Disease epidemiology
• Benefit-risk assessment
• Treatment pathways
0
0,5
1
1,5
2
2,5
3
3,5
4
Accuracy
Timeliness
Linkability
Completeness
Accessibility
Representativeness
0
0,5
1
1,5
2
2,5
3
3,5
4
Accuracy
Timeliness
Linkability
Completeness
Accessibility
Representativeness
Claims EMR Pharmacy/sales Registries
HTAi RICC IG Workshop - Massoud Toussi - 2019
13
Social media, wearables, connected devices, etc
Initial purpose
• Networking
• Follow up
• Experimental
Content
• Demographics
• Narrow and specific data
Settings
• Everyday life
• Smoothly entering the healthcare system
• Telemedicine programs
Good for
• Hypothesis generation
• Signal detection / monitoring
• Population behavior
• Public health intervention evaluation
0
0,5
1
1,5
2
2,5
3
3,5
4
Accuracy
Timeliness
Linkability
Completeness
Accessibility
Representativeness
0
0,5
1
1,5
2
2,5
3
3,5
4
Accuracy
Timeliness
Linkability
Completeness
Accessibility
Representativeness
Claims EMR Pharmacy/sales Registries Social media
HTAi RICC IG Workshop - Massoud Toussi - 2019
14
Syndicated surveys
Initial purpose
• Market Research
Content
• Demographics
• Clinical data
• Procedures
• Labs & specialized tests
• Drugs
• Outcome measures
Settings
• Inpatient & outpatient
• Focused on pathologies with high demand for data
Good for
• Disease epidemiology
• Treatment dynamics (split per indication, off label use,…)
• Clinician behavior and understanding
0
0,5
1
1,5
2
2,5
3
3,5
4
Accuracy
Timeliness
Linkability
Completeness
Accessibility
Representativeness
0
0,5
1
1,5
2
2,5
3
3,5
4
Accuracy
Timeliness
Linkability
Completeness
Accessibility
Representativeness
Claims EMR Pharmacy/sales Registries Social media Syndicated survey
HTAi RICC IG Workshop - Massoud Toussi - 2019
15
Linking different types of secondary data may be needed.
Deep, flexible
therapy area specific data including
primary data collection
Broad
Deep
Population coverage
Ra
ng
e o
f d
ata
typ
es
National claims, dispensing data
Electronic Medical Records
Labs, registries, biobanks
T-Shaped model for
better efficiency in
database studies
HTAi RICC IG Workshop - Massoud Toussi - 2019
16
Step 3: Conducting the appropriate analyses
BETTER TRADITIONAL
STUDIES
Collect data from clinicians
and/or directly from patients;
combine with existing data for
broader stakeholder value
Reusable, scalable approaches
to evidence generation
Improved execution of
traditional studies, more precise
selection of sites, reduced
timelines and errors
INNOVATIVE STUDY DESIGN SMARTER EVIDENCE
GENERATION
HTAi RICC IG Workshop - Massoud Toussi - 2019
17
Data and technology make innovative designs possible
Primary data
collection
Secondary data
collection
Copyright © 2017 IQVIA. All rights reserved.
Pragmatic
clinical trialsProspective
research (registries,
RCTs)
Mosaic
studies &
Enriched
studies
Site less
studies
Database
studiesExtension
studies with
direct to
patient
follow-up
Evidence
platformsAugmentation
studies
Tra
dit
ion
al
New
HTAi RICC IG Workshop - Massoud Toussi - 2019
18
What are Mosaic studies?
Database analysis
Prospective study
Enriched EMR based panel
driven approach
Enriched claims based
approach
Case Study: A Global PASS
Challenge:
• Client wanted a cost effective and innovative solution for
a PASS in US and EU (~5000 patients globally over 10
year time-frame)
Enriched opportunity:
• Bring together a segmented solution for the best-fit
design for the US and each EU market, identified by the
use of secondary data for feasibility and planning
• Use data from claims + primary site network to identify
optimal US sites for recruitment & data collection
• Utilize network of registries to collect, analyse and pool
relevant safety information
Enriched value points:
• Huge cost efficiencies (~$25M) through avoidance of
unnecessary data collection in certain markets
• Early indication of improved site and patient recruitment
timelines using IQVIA data–driven approach
Mosaic studies identify the best-fit data in each country
• Due to the differences in secondary data availability across
countries, one method for data collection cannot be always
used in all countries
• Mosaic studies use multiple data collection approaches within
a single study - countries are grouped according to the method
for data collection – to provide an optimised study design to
the client.
HTAi RICC IG Workshop - Massoud Toussi - 2019
19
Enriched studies combine primary and secondary data
STUDY PLANNING RECRUITMENT STUDY EXECUTION STUDY
DATABASE
• Linkage and de-ID patient
information
• Final study database
linking all data sources
EMR “backbone”• Aids patient
recruitment
• Provides core
patient informationEMR data Other datasets
(e.g. claims)
E-CRF and
PRO provide
supplementary data
on variables not in
EMR, including QoL Data collected directly
from MD (e-CRF)
Patient reported
outcomes (PRO)
HTAi RICC IG Workshop - Massoud Toussi - 2019
20
• Evidence platforms are built on a foundation of real world data that supports clinical and commercial needs.
• It embeds a layer of technology to extract and analyze the data in a consistent way across the organization, with
appropriate governance and privacy protections.
• Applications designed to help teams use those insights appropriately for their needs.
Evidence platforms: the future of evidence generation
R&D
Predictive
Analytics Tools
Platform
Core
Regulatory
Studies /
Publications
HTA / HEOR
Forecasting & KOL
Engagement
Commercial
Patient Analytics
Software Application
(e.g., E360™, SAS, R, Tableau
• Data integration
• Data Hosting
• Business Rules & Analytical Methods
• Ongoing Data Governance
Broad, Nationally Relevant Databases (e.g., IMS RWD Claims Data)
Augmented Datasets (e.g., Oncology EMR)
Deep
Clinical Data
(e.g., Genomics
Data)
Enriched Data
(e.g., NLP,
Linkage, Local
Registry)
T-Shaped portfolio
of Data Sources
Services &
Engagement
Technology-
Enabled
Analytics
Real-World
Data
HTAi RICC IG Workshop - Massoud Toussi - 2019
21
Trends in real-world data, evidence, and insights
Expanding
application of
RWD in
clinical
development
Increasing use
and acceptance
of innovative
study designs to
generate RWE
Scalable
approaches to
generate real
world insights
(RWI)
HTAi RICC IG Workshop - Massoud Toussi - 2019
Thank you!
Massoud Toussi, MD, PhD, MBA
Senior principal, Pharmacoepidemiology and
Drug Safety Lead, IQVIA
