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?