The document summarizes a presentation on managed entry agreements for high-cost innovative pharmaceuticals. It discusses the issues of assessing value for money given uncertainty around health effects and budget impact. It defines managed entry agreements and performance-based risk-sharing agreements as formal arrangements to address these issues. While these schemes aim to improve access to innovative treatments, the evidence on their effectiveness is limited and implementation has proven difficult, particularly for outcomes-based arrangements. Overall, more structured evaluation is still needed but these schemes may help address challenges posed by high-priced drugs when traditional reimbursement is not suitable.

1. The Potential for Using Managed Entry
Agreements
Adrian Towse
ISPOR 6th Asia-Pacific Conference
Beijing • 6-9 September 2014
Issue Panel: Managing High-Cost, Innovative Pharmaceuticals in Asia: Is
Something Lost When Translating Theory into Practice?

2. ISPOR Asia-Pacific • 6-9 September 2014
2
Agenda
• What are the issues with high-cost innovative
pharmaceuticals?
• Value for money
• What are ‘managed entry agreements’?
• The same as PBRSAs?
• Three or four types of schemes?
• ISPOR PBRSA Task Force Report
• What do we know about what works and what doesn’t
work?
• Summary

3. What are the issues with high-cost
innovative pharmaceuticals?
ISPOR Asia-Pacific • 6-9 September 2014
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• Value for money
• Given health effects and the price, is it a good use
of resources?
• Uncertainty. Is there a lot of uncertainty:
• About the expected health and related effects
• As to whether the drug will get to the right
subgroup of patients
• Budget Impact
• Given the price and potential size of the patient
population, budget impact is large

4. What are elements of value?*
ISPOR Asia-Pacific • 6-9 September 2014
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Usually recognized
• Health effects that are
well captured
• Cost offsets
• Uncertainty
*Towse and Barnsley (2013). IJTAHC. 29(4), 360-4.
Less frequently or
consistently recognized
• Health effects that are
captured less well
• Wider societal impacts
• Severity or unmet need
• Process issues
• Information
• Innovation

5. How aggregated and judged?
A ‘decision on value’
ISPOR Asia-Pacific • 6-9 September 2014
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• Two types of challenges for decision makers:
— Scientific uncertainty
— Value judgements
• They are weighting multiple criteria relevant to
the decision using:
— Deliberative processes?
— Algorithms?
• How structured could /should this become?

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Differential pricing*
• Price transparency plus reference pricing links
markets together
• This makes companies less willing to offer
discounts
• Local value assessment and reference pricing
are inconsistent tools
• Need for confidentiality to get discounts
reflecting local value
• e.g. UK Patient Access Schemes
*Danzon, P., Towse, A. and Mestre-Ferrandiz, J.(2013) Health Economics. Epub. doi: 10.1002/hec.3021.

7. Managed Entry Agreements*
ISPOR Asia-Pacific • 6-9 September 2014
7
• MEAs are used to give access to new technologies when
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.
*Klemp, Frønsdal and Facey on behalf of the HTAi Policy Forum (2011) IJTAHC 27: 77-83

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9. 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.

10. Performance based risk sharing
arrangements (PBRSA)
To manage utilization in the
real world
To provide evidence regarding
decision uncertainty
- Outcomes
guarantees
- Money back
guarantees
- Conditional
treatment
continuation
Cost sharing
arrangement
- Budget capping
- Utilization capping
- Discounts
- Price/volume
MEA: Payer-producer/
provider
arrangement
Coverage with evidence
development
Performance linked
reimbursement
Intermediate endpoint
Clinical endpoint
- Only with
research
- Only in
research
- Process
of care
Pre-specified agreement
No pre-specified agreement

11. US Medicare:
LVRS, PET,
PTAS
11
Performance based risk sharing
arrangements
To manage utilization in the
real world
To provide evidence regarding
decision uncertainty
- Outcomes
guarantees
- Money back
guarantees
- Conditional
treatment
continuation
- Budget capping
- Utilization capping
- Discounts
- Price/volume
Coverage with evidence
development
Performance linked
reimbursement
Intermediate endpoint
Clinical endpoint
- Only with
research
- Only in
research
- Process
of care
UK: MS RSS
Aus: Bosentan
UK: Votrient
France: DPP4;
risperidone
Pre-specified agreement
No pre-specified agreement
Italy: oncology schemes
UK: Velcade, Lucentis etc.

12. Possible Uncertainties that Might Be Addressed by Data
Collection Under PBRSA
1. Efficacy or effectiveness in the tested population as compared to current standard of care
2. The efficacy or effectiveness in a broader, more heterogeneous population than used in
ISPOR Asia-Pacific • 6-9 September 2014
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registration trials or in pre-licensing testing
3. The effects on long-term or more clinically-significant endpoints than those included in
registration trials (which—in the case of a drug—may have used surrogate markers) or in
pre-licensing studies (e.g., for procedures or devices)
4. Any adverse effects and adherence issues
5. Whether health care providers’ management of the patient will change the relative
benefits and harms under conditions of usual care
6. The size and value of cost-offsets, such as due to fewer hospital visits
7. The proportion of patients who will respond, i.e., achieve a pre-set (minimum) outcome
which may be an intermediate/surrogate endpoint
8. The numbers and types of patients likely in real-world practice to be treated with the new
therapy
9. Whether the patients treated are the ‘right’ ones, i.e., they have attributes matching those
patients which, on the basis of current evidence, the payer is willing to fund (which may
or may not include off-label use).
Source: ISPOR PBRSA Task Force

14.  Pueg-Peiro et al. (2011) conducted a systematic
literature review to identify existing knowledge about
the costs and benefits, assessed either quantitatively or
qualitatively, of PBRSAs. Found little quantitative
evidence.
 Neumann et al. (2011) reviewed five PBRSAs in the US
and UK and conclude that they are hard to implement in
practice. The results from Italy and other EU countries
are also unclear and the schemes are in evolution.
 Overall, the literature suggests there is an important
gap in structured ex post evaluation of PBRSAs.
Utilisation schemes appear to have been more
successful to date than CED schemes. However, the
evidence is limited, mixed, qualitative, and partial.

15. Summary
• High-cost innovative pharmaceuticals are one of
ISPOR Asia-Pacific • 6-9 September 2014
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the challenges facing health systems
• Assessing local value is key
• MEAs can be used to address issues of price,
uncertainty and budget impact
• Implementation is difficult, particularly for
PBRSAs
• The alternatives to using these schemes is not
an easy option, either!

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