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The Role of RWE in Drug Development
Billy Franks, PhDDirector Biostatistics
Astellas Pharma Global Development4 June 2015
Disclaimer
The presenter is a paid employee of Astellas. The opinions and positions presented today are my own and do not necessarily reflect those of Astellas or any of its affiliate companies or entities.
Questions to Consider
– Clinical Development should not stop with regulatory approval – how can we also meet the needs of payers and patients?
– Using RWE to improve study design and conduct• Do we still need Advisory Boards and KOL meetings?• What matters to patients – do we capture this?
– Should we include RWE in the Clinical Development process?
– Can we better communicate clinical study results to convey patient experience in real-world terms?
“Traditional” Target for Clinical Development
Targeting Research and Estimating Market Size
Clinical Development
Additional Targets for Clinical Development
Targeting Research and Estimating Market Size
Clinical Development
Payers HCPs
Patients Advocacy Groups
• Prescribed popn. vs. Research popn.• Broader usage, off-label usage• “How do I feel?”, “How long do they
persist?”, “Is this the cure?”• “How do I choose amongst
alternatives?”• Frequently long-term/lifetime horizons• “How does this impact my budget?”
“Traditional” Model for use of RWE by Pharma
Targeting Research and
Estimating Market Size
Phase 1 Phase 2 (POC)
Phase 3Post-
market research
and HEOR
Filing
Commercial Needs Driven
Clinical R&D Driven
• HEOR Concept• PRO
Research/Development• Literature review on unmet
medical need, prevalence, incidence, burden of illness, epidemiology
• PRO Validation/Use• RWE studies to fill in gaps
o Burden of Illnesso Epidemiology
Digesting existing RWE
Generating RWE to support regulatory interactions and commercialization
Broadcasting New RWE to support differentiation
• Identify new targets• Registries• Claims/EHR Studies
1-2yr Gap
Revamped Model for use of RWE by Pharma
Targeting Research and
Estimating Market Size
Phase 1 Phase 2 (POC)
Phase 3Post-
market research
and HEOR
Filing
Commercial Needs Driven
Clinical R&D Driven
• HEOR Concept• PRO
Research/Development• Literature review on unmet
medical need, prevalence, incidence, burden of illness, epidemiology
• PRO Validation/Use• RWE studies to fill in gaps
o Burden of Illnesso Epidemiology
Digesting existing RWE
Generating RWE to support regulatory interactions and commercialization
Broadcasting RWE to support differentiation
• Identify new targets• Registries• Claims/EHR Studies
1-2yr Gap
Targeting and Messaging with RWE• Identify key real-world data sources:
• Identify global-strategy in the current environment of local data assets
• Identify and assess benchmarks for existing therapies
• Partner with academic centers focused on target population
• Use RWD assets earlier to:• Inform target product profile with focus on
“non-clinical” areas for differentiation• Message on unmet medical needs
Rich Environment – Lots of Options!Insurance Claims
Electronic Health Records
Physician/Patient Notes
Genomic
Sales Channel
Primary Care
Secondary Care
Licensable
Lab or Survey Data
Private or National Healthcare
http://www.ispor.org/digestofintdb/countrylist.aspx
Revamped Model for use of RWE by Pharma
Targeting Research and
Estimating Market Size
Phase 1 Phase 2 (POC)
Phase 3Post-
market research
and HEOR
Filing
Commercial Needs Driven
Clinical R&D Driven
• HEOR Concept• PRO
Research/Development• Literature review on unmet
medical need, prevalence, incidence, burden of illness, epidemiology
• PRO Validation/Use• RWE studies to fill in gaps
o Burden of Illnesso Epidemiology
Digesting existing RWE
Generating RWE to support regulatory interactions and commercialization
Broadcasting RWE to support differentiation
• Identify new targets• Registries• Claims/EHR Studies
1-2yr Gap
Targeting and Messaging with RWE• Identify key real-world data sources:
• Identify global-strategy in the current environment of local data assets
• Identify and assess benchmarks for existing therapies
• Partner with academic centers focused on target population
• Use RWD assets earlier to:• Inform target product profile with focus on
“non-clinical” areas for differentiation• Message on unmet medical needs
Sample FDA Labeled Indications for Diabetes Products
• Metformin – “as monotherapy are indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes… …Metformin may be used concomitantly with a sulfonylurea to improve glycemic control in adults”
• Glipizide (sulfonylurea class) – “as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus”
• Repaglinide (Meglitinide class)– “as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus”
• Rosiglitazone Maleate (Thiazolidinediones class) – “as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus… …monotherapy… …combination with sulfonylurea, metformin, or insulin [due to failure on maximum dose monotherapy with sulfonylurea or metformin]… …combination with a sulfonylurea plus metformin”
• Pioglitazone Hydrochloride (Thiazolidinediones class) – “as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings”
10
Clinical Benchmarks used for drug development did not lead to labels which clearly differentiated products!
What kind of benchmarks would help payers/patients select? • Reduced visits to the GP/Endocrinologist?• Reduced visits to the ER?• Reduced number of “sick days” from work?• Less likely to switch to an alternate therapy?• …
Shouldn’t drug development be informed by the current state of medical care as the development plan and target product profile is formed?
Reduction in use of healthcare services with combination sulfonylurea and rosiglitazone: findings from the Rosiglitazone Early vs SULfonylurea Titration (RESULT) study.
Revamped Model for use of RWE by Pharma
Targeting Research and
Estimating Market Size
Phase 1 Phase 2 (POC)
Phase 3Post-
market research
and HEOR
Filing
Commercial Needs Driven
Clinical R&D Driven
• HEOR Concept• PRO
Research/Development• Literature review on unmet
medical need, prevalence, incidence, burden of illness, epidemiology
• PRO Validation/Use• RWE studies to fill in gaps
o Burden of Illnesso Epidemiology
Digesting existing RWE
Generating RWE to support regulatory interactions and commercialization
Broadcasting RWE to support differentiation
• Identify new targets• Registries• Claims/EHR Studies
1-2yr Gap
Targeting and Messaging with RWE• Identify key real-world data sources:
• Identify global-strategy in the current environment of local data assets
• Identify and assess benchmarks for existing therapies
• Partner with academic centers focused on target population
• Use RWD assets earlier to:• Inform target product profile with focus on
“non-clinical” areas for differentiation• Message on unmet medical needs
Revamped Model for use of RWE by Pharma
Targeting Research and
Estimating Market Size
Phase 1 Phase 2 (POC)
Phase 3Post-
market research
and HEOR
Commercial Needs Driven
Clinical R&D Driven
• PRO Validation/Use• RWE studies to fill in gaps
o Burden of Illnesso Epidemiology
Generating RWE to support regulatory interactions and commercialization
Decision Making and Efficiency with RWE• Use identified RWD sources:
• Measure agreed benchmarks for existing therapies and assess the performance of the investigational therapy
• Inform “Go/No-Go” and B/R discussions with latest evidence
• Assess novel metrics at academic centers on existing therapies
• “Stress-test” enrollment projections accounting for I/E criteria (proxies as needed)
• Referral Recruitment Strategy• Continue messaging on unmet medical
needs
“Stress-testing” & ReferralsKaiser Permanente Locations
Intermountain HealthCare
CPRD - UK
10+ Million Lives60+ Million Lives
500k+ LivesUnited HealthCare (10+ million lives across the US)
Nordic Registries (5+ million lives)
“Stress-testing” & Referrals
• HEOR utilizes these databases (and ones like them) to:– Identify patients with a particular treatment
history or ongoing therapies– Identify patients with a particular disease state or
mix of diseases– Identify patients with certain lab values– Identify patients with certain demographics
This sounds quite similar to list of items considered when creating the Inclusion/Exclusion Criteria for a clinical trial!
• This set of entry criteria are typically created after careful consultation with KEEs and potential sites for future recruitment.
• Does industry do enough due diligence in checking that the criteria do not cause:• A non-representative subject mix compared to the target patient population• A difficult to recruit study
When the criteria are non-negotiable AND the study faces recruitment challenges, has industry recognized the potential for accelerating recruitment through the use of RWD which overlaps the geography of participating centers?
Geisinger Example
http://www.clinmedres.org/content/8/3-4/185.3
101/148 = 68% screening success rate. How did that compare to overall study performance?
Revamped Model for use of RWE by Pharma
Post-market
research and
HEOR
Commercial Needs Driven
Clinical R&D Driven
• Identify new targets• Registries• Claims/EHR Studies
Broadcasting New RWE to support differentiation
Real World Experimentation• Establish Key Partner
Payer/Provider Networks for research:• Move beyond the observational
research paradigm• Conduct cluster-randomized
research to address key concerns not addressed by label:
• Optimum line of therapy• Cost impacts (true
payer/provider scope data)• Persistence and adherence• Survey/PRO
• Efforts by organizations like PCORI are already engaging in this CER
In conclusion, I think there is a large space for innovation
in the use of RWE earlier and more broadly in
Clinical Development!
Thanks for your attention!Any questions?