This document summarizes discussions around improving early patient access to innovative new drugs in Europe. It discusses the perspectives and needs of various stakeholders in health care systems, including patients, regulators, payers, providers, and drug companies. It also evaluates different approaches that have been tried or proposed, such as adaptive licensing pathways, managed entry agreements between drug companies and health systems, and performance-based risk-sharing arrangements. Finally, it outlines areas where more progress could still be made, such as increased coordination between regulatory agencies and health technology assessment bodies, better use of disease registries and electronic health records to generate real-world evidence, and public-private partnerships to support these efforts.

1. Adrian Towse
Director of the Office of Health Economics
New Challenges for Improving European Health Care: EARLIER ACCESS TO INNOVATION – IS IT WORTH IT?

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What do we need? Trusheim, October 2014*
•Patients: Early, appropriate access refined over time and accounting for their preferences
•Regulators: Staged benefit / risk improving over time
•Payers: Deliver better health while stewarding resources
•Providers: More therapeutic options with improving knowledge of which are best for whom
•Sponsors: Sustainable innovation chain from science to patient to investor
*Presentation http://vitaltransformation.com/wp- content/uploads/2014/10/Trusheim-Stakeholder-Metrics-Overview-FINAL-PRINT.pdf
Success Requires Increased Collaboration Supported by Prospectively Planned Evidence & Decisions to Build Trust and Viability

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Can it deliver? Baird et al. 2013. Comparison of stakeholder metrics*
Drug
Scenario
eNPV US$
AdaptivenessScore
Change in Patient Access years
Inappropriately treated patients
Comments
Zelboraf
1:Traditional
$23m
NA
NA
-
(skin cancer)
2: Actual
$34m
5
9100
-
3: Adaptive
$30m
10
9100
-
As per fast track but with continuous planned data collection
Gilenya
1: Actual
$127M
NA
NA
-
(relapsing MS)
2: Staged
$169M
12
41,000
-
Smaller quicker trials for narrower authorisation. Later expansion of label
Acomplia
(anti- obesity)
1:Actual
($73M)
NA
NA
0.9M
Withdrawn in EU after 2 years, never approved in the US
3: Post Market Surveillance
($43M)
13
11.5M
1.7M
Controlled for off label, adherence, maintained over life cycle
5:Staged
($16M)
16
10.1M
None
Smaller quicker trials for narrower authorisation. Later expansion of label. Controlled for off label, adherence, maintained over life cycle
*Baird et al. 2013. Therapeutic Innovation & Regulatory Science 47(4):474-483.

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Where are we now? Boon et al. 2014 Escher Report*
•CMA is granted on the base of less comprehensive data, but assessment timelines were longer. CMA is perceived as a ‘rescue option’ by regulators and companies, rather than as a prospectively planned pathway to provide early access.
•Of the cohort of 47 NASs approved in 2007, at least one PASS was requested at market entry for 22. Yet Post Authorisation Safety Studies (PASS) are not the main source of new safety information listed in the SmPC, but the costs of conducting these studies appear substantial.
•‘Adaptive licensing has been discussed for a long time with very little action ..new regulatory pathways will only be useful if they are considered in a holistic approach including health technology assessment (HTA) and payers’. Furthermore, the importance of ‘understanding the business needs for new pathways’ is stressed.
*Improving the EU system for the marketing authorisation of medicines.
Learning from regulatory practice. Escher Foundation

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•MEAs are used to give access to new technologies where traditional reimbursement is deemed inappropriate.
•Three different forms of MEAs have been identified:
•management of uncertainty relating to clinical and/or cost- effectiveness;
•management of utilization to optimize performance.
•management of budget impact;
•The rationale for using these approaches and their advantages and disadvantages differ.
•All forms of MEA should take the form of a formal written agreement among stakeholders, clearly identifying the rationale for the agreement, aspects to be assessed, methods of data collection and review, and the criteria for ending the agreement.
Role for Managed Entry Agreements?*
*Klemp, Frønsdal and Facey on behalf of the HTAi Policy Forum (2011) IJTAHC 27: 77-83

6. Performance-Based Risk-Sharing Arrangements—
Good Practices for
Design, Implementation, and Evaluation
Garrison, L.P., Towse, A., Briggs, A., de Pouvourville, G., Grueger, J., Mohr, P.E., Severens, J.L., Siviero, P. and Sleeper, M. (2013 Report of the ISPOR Good Practices for Performance-based Risk-sharing Task Force. Value in Health. 16(5), 703-719.

7. WHERE COULD WE BE? MOVEMENT TOWARD BETTER EVIDENCE GENERATION IN EUROPE
Post-authorisation efficacy studies (PAES) implemented
Greater HTA body and EMA coordination pre-launch
Disease registries in some countries , and progress in EHRs
Coordination across HTA bodies in demand for post-launch studies, often linked to CED, P4P schemes
Collaborations across large registries
Full use of EHRs
Good progress in methods
Public-private partnerships
have a major role
Adaptive licensing applied to a variety of drugs
Joint HTA and EMA coordination for pre-and post- launch
Most Likely Scenario
Scenario Most Conducive To Evidence Generation
Anticipating the future for CER and RE in the pharmaceutical industry. Research conducted by CMTP and OHE, sponsored by Amgen, GSK, Lilly, Novartis, Sanofi. Publications in progress.

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