presentation - the economics of the market for medicines, jorge mestre-ferrandiz 17 march 2016
TRANSCRIPT
Economics of the market for medicines
Dr Jorge Mestre-Ferrandiz
City University17th March 2016
2
Agenda
1. The supply side – R&D
2. Demand for medicines
3. NICE – the cost-effectiveness ‘4th hurdle’
4. Regulating medicine prices
3
Structure
Time
£
Supply Issues
• R&D process
• Cost of an NME
• Public/private
collaborations
• R&D incentives
• Capital market
Nature of competition
• Follow-on compounds
(dynamic)
Competition in the
off-patent segment
Demand / Regulation
• Role of HTA
• Uptake drivers
• Prescribing Incentives
• Demand vs. Supply
controls
t0t1
t2 t3
LaunchPatent
expiry
4
Five global challenges
•Challenge 1: Increasing importance of specialised and stratified medicines
•Challenge 2: Rising drug development costs
•Challenge 3: Closer benefit-risk monitoring by regulators over a medicines’ life cycle
•Challenge 4: Increase in demand for real world evidence of relative effectiveness by HTA, payers and regulators
•Challenge 5: Disconnect between regulators and payers/HTA bodies evidence needs
Key variables: Price * Volume * Time (and VALUE!)
5
Characteristics of Medicines Markets
•Supply is R&D intensive, which implies:
• Intellectual property rights (patents)
• Long lead times
• High risk
• Dynamic competition is as important as static
• Generic competition after patent expiry
•Demand is regulated – governments and social insurers are major buyers of medicines
•Prices are regulated
6
Supply Side – Main Characteristics (1)
•Patents are an incentive for dynamic efficiency –by promising temporary monopoly if successful
•Patents last 20 years; first 9-11 of which are spent getting the medicine to market, i.e. research & development (R&D)
•Commercial success in R&D-based companies has depended on finding ‘blockbusters’
7
Supply Side – Main Characteristics (2)
•Average R&D cost of a new medicine up to launch c£1.2bn
•Includes costs of failures
•Out of pocket costs ≈ 50%
•Opportunity cost of capital ≈ 50%
•Only ≈ 30% of launched medicines earn revenues that exceed their lifetime costs
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REGULATION
TIME (YEARS)
PHASES OF DRUG
DEVELOPMENT
Phase III
Development research
Final patent application
Marketing application
Post-mktg research*
Phase IV
2002-7
Discovery research
Investigational new drug application (US)
1999
Phase I Phase IISynthesisBiological testing &
pharmacologic screening
2008
Marketing approval/
product launch
2010
Regulatory review
Basic research
Short-term animal testing
Long-term animal testing
Toxicology and pharmacokinetic studies
Chemical development
Pharmaceutical development
Discovery & Development of a New Medicine
*Phase IV is not part of the R&D process, although data collected during that time may affect how the drug is used.
Source: Mestre-Ferrandiz, J., Sussex, J. and Towse, A. (2012) The R&D Cost of a New Medicine. London: Office of Health Economics
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The Cost of an NME is Rising
10
Understanding the R&D process: basic concepts
Most new medicines are developed simultaneously
The innovation race stimulates competition
Being the first in class does not imply being the best in class
The market (clinical practice) determines the ‘winners’
There exists spillovers in the R&D process
Alliances have an important role to play
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Cash Flow for a Successful Medicine
Launch
Patent
expiry
£ p.a. +
_
0
12
Supply Side – Main Characteristics (3)
•R&D costs are sunk (global) joint costs
•R&D costs ≈ 17% of pharmaceutical sales p.a.
But ≈ 31% of costs on net present value basis
•=> (even long-run) marginal cost << average cost
•=> Price discrimination (based on Ramsey rule?) if non-linear pricing is impractical
• Parallel trade
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% of ‘World’ Pharmaceutical Industry R&D Spend
Source: ABPI R&D Sourcebook (2015). http://www.abpi.org.uk/our-work/library/industry/Pages/131115.aspx
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Agenda
1.The supply side – R&D
2.Demand for medicines
3.NICE – the cost-effectiveness ‘4th hurdle’
4.Regulating medicine prices
15
Types of Prescription Medicines
•In 2011 generics accounted for c64% of the total number of prescriptions dispensed by pharmacies in England, compared with fewer than one in six as recently as 1982
•Proportion of prescriptions written generically (c90% in 2011 vs. 35% in 1985)
•Source: OHE Compendium (2013)
[OTCs = over the counter medicines]
Original brand Branded Unbranded OTCs
On-patent Off-patent generics generics
NHS
Private
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Expenditure on medicines per head of population is low in the UK relative to OECD comparators
Expenditure on medicines per person £ for selected OECD countries
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UK spending on medicines as a percentage of GDP is already amongst the lowest in developed countries
(1) IMS Health World Review Analyst 2012. OECD Health Database. All data accessed March 2012
0.9
1.2
1.2
1.2
1.3
1.3
1.4
1.5
1.5
1.8
2.1
1.0
1.0
1.4
1.4
0.9
1.4
1.4
1.4
1.7
2.0
2.1
UK
Sweden
Denmark
Austria
Ireland
Germany
Italy
Spain
Belgium
France
US
2008
2011
Spending on medicines as a percentage of GDP in various countries in 2011(1)
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The UK has among the highest penetration of and use generics across European countries, c. 65%
Generics market share in Europe by volume
%
51%
34% 35% 35% 36% 37%
47% 48% 51% 53% 55% 55% 57% 58% 60% 61% 64% 65% 66%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
GR
34%
BE
35%
AT
36%
CH
39%
IT
40%
IE
42%
NO
43%
ES
45%
PT
45%
FR
47%
FI
49%
TK
52%
SE
53%
NE
63%
DK
64%
CA
65%
DE
65%
UK
66%
MEAN
49%
% GENERIC PRODUCTS
% NON GENERIC PRODUCTS
Source: IMS 2012 (2011 data)
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Source: EFPIA
Source: EGA
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Demand Side Characteristics
Chooses Pays Consumes
Normal market
Consumer Consumer Consumer
Prescription medicines market
Prescriber Government / insurer
Patient
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Measures Affecting Prescriber Price Sensitivity
•Primary Care Trust budgets
•Practice budgets and prescribing incentive schemes
•Provision of information (PRODIGY, PACT, NICE guidance, pharmaceutical advisers, etc.)
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Agenda
1. The supply side – R&D
2. Demand for medicines
3. NICE – the cost-effectiveness ‘4th hurdle’
4. Regulating medicine prices
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National Institute for Health and Care Excellence
•NICE established in 1999
• Faster access to medicines
• Address the ‘postcode lottery’
• Provide evidence-based guidance to the health system on new technologies
•Independent special health authority
•Expanded remit to cover public health in 2005
•Covers England and Wales
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NICE
•NICE’s guidance falls into three main areas
Clinicalguidelines
Health technology evaluation
Public health guidance
• Recommendations on the use of new and existing technologies within NHS
• Medicines
• Medical devices
• Diagnostic techniques
• Surgical procedures
• Therapeutic technologies other than medicinal products
• Systems of Care
• Interventional procedures
• Screening tools
• Recommendations on the appropriate NHS treatment and care of people with specific diseases and conditions
• Recommendations for NHS and local government professionals on promoting a healthy lifestyle and reducing the risk of developing a disease
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Technology Appraisal Criteria - April 2013
•The Institute and Appraisal Committee take into account:
• the broad clinical priorities of the Secretary of State for Health and the Welsh Assembly Government
• the degree of clinical need of the patients with the condition under consideration
• the broad balance of benefits and costs
• any guidance from the Secretary of State for Health and the Welsh Assembly Government on the resources likely to be available and on such other matters as they think fit
• the effective use of available resources
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NICE’s Guide to Methods of Technology Appraisal, April 2013
•Below a most plausible ICER of £20,000 per QALY gained, the decision to recommend the use of a technology is normally based on the cost-effectiveness estimate and the acceptability of a technology as an effective use of NHS resources
•Above a most plausible ICER of £20,000 per QALY gained, judgements about the acceptability of the technology as an effective use of NHS resources will specifically take account of the following factors
• The degree of certainty around the ICER
• Whether there are strong reasons to indicate that the assessment of the change in health-related quality of life has been inadequately captured, and may therefore misrepresent the health utility gained
• The innovative nature of the technology, specifically if the innovation adds demonstrable and distinctive benefits of a substantial nature which may not have been adequately captured in the reference case QALY measure
• The technology meets the criteria for special consideration as a 'life-extending treatment at the end of life'
• Aspects that relate to non-health objectives of the NHS
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NICE’s Guide to Methods of Technology Appraisal, April 2013
•As the ICER of an intervention increases in the range of £20,000 to £30,000 per QALY gained, the Committee's judgement about the acceptability of the technology as an effective use of NHS resources will make explicit reference to the relevant factors listed before
•Above a most plausible ICER of £30,000 per QALY gained, the Committee will need to identify an increasingly stronger case for supporting the technology as an effective use of NHS resources, with regard to the factors listed
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Use of Thresholds?
Source: Rawlins and Culyer, 2004
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Effect of Thresholds
•Source: Dakin et al., 2013 (available at www.ohe.org)
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Not all QALYs are equal to NICE even now: “special weighting”*
•“Life extending treatment at the end of life” = less than 2 years’ life expectancy, extends life by ≥ 3 months for patient population ≤ 7,000 in England
•Severity of underlying condition
•Stakeholder persuasion
•Significant innovation not captured by QALYs
•Disadvantaged populations
•Children
* Rawlins M et al (2009) “Pharmacoeconomics: NICE’s approach to decision-making” British Journal of
Clinical Pharmacology
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There was a big (?) change in prospect…
Implementation of Value Based Pricing (VBP) replacing the PPRS in 2014 (when 2009 PPRS
expired) – but now called Value Based Assessment
July 2010 December2010 January 2014
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NICE’s Current Approach
£20,000 per QALY
£30,000 per QALY
£50,000 per QALY
Source: NICE Consultation Paper – Value Based Assessment of Health Technologies
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Proposed “Modifiers”
£20,000 per QALY
£50,000 per QALY
Source: NICE Consultation Paper – Value Based Assessment of Health Technologies
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NICE’s Response
•“Following a consultation, the Institute has decided to undertake further work before making changes to the way it appraises new medicines and other technologies for use by the NHS. It argues that any changes to NICE’s methods need to be made as part of a wider review of the innovation, evaluation and adoption of new treatments (including those for cancers) involving patients, people working in or with the NHS, the life sciences industries and health researchers” (18 September 2014)
•https://www.nice.org.uk/news/press-and-media/nice-calls-for-a-new-approach-to-managing-the-entry-of-drugs-into-the-nhs
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Economic Evaluation Elsewhere
•Focused on pharmaceuticals
•Fourth hurdle i.e. reimbursement decisions:
• Public reimbursement: Australia, Baltic countries, Belgium, Canada (British Columbia, Ontario), Czech Republic, Denmark, Finland, France, Hungary, Netherlands, New Zealand, Norway, Portugal, Russia, Slovenia, Sweden
• US managed care formularies
•Pricing negotiations
• Australia, France, Italy, New Zealand
•Advice to health service
• England and Wales (NICE), Scotland (SMC)
•Risk sharing arrangements
• Australia, New Zealand, UK (few cases)
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HTAs – Some Issues
What products to evaluate?
When to evaluate? How to evaluate?
For what purpose?
All vs. limited
• Clinical effectiveness &/or cost effectiveness • Additional modelling• Independence of agency• Information sources: RCT vs. other• Mandatory vs. advisory…
P&R vs. prescribing guidelines/use
Pre-launch (i.e. pre-requisite to launch) vs. post-launch
38
Agenda
1. The supply side – R&D
2. Demand for medicines
3. NICE – the cost-effectiveness ‘4th hurdle’
4. Regulating medicine prices
39
Why Regulate? - Market Failure
•Public goods and the free-rider problem (e.g. research)
•Externalities
• E.g. your vaccination reduces my risk of catching an infection
• E.g. the caring externality: I’m happy if you’re cared for
•Incomplete or asymmetric information
• Moral hazard (= ‘hidden action’)
• Selection problem (= ‘hidden information’)
• Principal/agent problems
•Government procurement
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Monopoly Power
•Economies of scale and/or scope
•Natural (local) monopoly
•Input constraints
•Patents: dynamic efficiency vs static monopoly
41
Options: Types of Regulation
•‘No regulation’ = 1998 Competition Act only
•Profit, i.e. rate of return, control:
• Unbanded
• Banded
•Price control:
• Baskets of products, as with ‘RPI-X’ control of utilities’ prices
• Individual products, e.g. via reference prices, or ‘cost-plus’, or related to therapeutic benefit
42
1998 Competition Act
•Came into force March 2000
•Based on EU Treaty - Articles 81 & 82
•Prohibitions:
• Chapter 1 – Agreements preventing, restricting or distorting competition
• Chapter 2 – Abuse of a dominant market position
•Fines up to 10% of turnover; 3rd parties may sue for damages
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Banded Rate of Return Regulation
Outturn RoR > threshold => repay excess
Outturn RoR < threshold => may increase prices
%RoR
£ capital employed
0
▲
▲
▲
▲
▲
▲
44
RPI-X Regulation of a Basket of ‘n’ Products
w1p11 + w2p
12 + w3p
13 + …….. + wnp
1n
--------------------------------------------------- -1 x 100 ≤ ΔRPI - X
w1p01 + w2p
02 + w3p
03 + …….. + wnp
0n
Where:
wi = weight for product ‘i’ (e.g. quantity sold in period 0)
pti = price of product ‘i’ in period t = 0,1
ΔRPI = % change in retail price index between period 0 and period 1
X = efficiency factor
{
{
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Regulation Criteria
•Static efficiency:
• Productive efficiency: making the right choice between different ways of achieving the same outcome
• Allocative efficiency: doing the things that people want and ensuring that the right people get them
•Dynamic efficiency
•Benefit to UK plc – economic rent
•Regulatory (administrative) burden
•Equity/other social policy objectives
46
(How) Should Pharmaceuticals be Regulated in the UK?• What, if anything, to regulate?
• On- and/or off-patent?
• Branded and/or unbranded?
• Prescribed and/or over-the-counter?
• Sales to NHS only, or all UK sales?
• If so, how?
• Rate of return control, unbanded
• Rate of return control, banded
• Price control – basket, RPI-X
• Price control – individual products, reference prices
• From 3 perspectives:
• General public: patients and taxpayers
• Government
• Industry
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Key Questions
1. How price-sensitive are the people making the consumption choices?
2. How much competition is there between one medicine and another, or between medicines and alternative treatments?
3. Do producers have incentives to keep costs down?
4. Will production and consumption choices become increasingly distorted over time?
5. Do producers have incentives to invest in the UK, especially in R&D?
6. Would the regulatory system be costly for the regulator to administer and the companies to comply with?
48
2 Forms of Price Regulation in UK
•Pharmaceutical Price Regulation Scheme (PPRS) regulates manufacturers’ profits earned on sales to the National Health Service of branded medicines (on- and off-patent)
•Schemes M ands W control the reimbursed price of generic medicines paid to dispensing pharmacists and doctors
49
The PPRS (2014)
•Have been variants of PPRS since 1960s
•Department of Health acts as regulator for whole UK
•Objectives of 2014 PPRS:
• Provide stability and predictability to Government and industry
• Support the NHS by ensuring that the branded medicines bill stays within affordable limits
• Improve access to innovative medicines commensurate to outcomes they offer patients by ensuring that medicines approved by NICE are available widely in the NHS
• Reduce bureaucracy and duplication
• Support the Government’s growth and innovation agenda for life sciences
•Voluntary – but statutory alternative scheme for firms that opt out
50
The PPRS (2014)
•Covers branded pharmaceuticals sold to the NHS
•Negotiated every 5 years or so between the ABPI and the Department of Health
•Current scheme commenced 1/1/14
•Scheme applies to all companies supplying BRANDED medicines to the NHS ≈ 80% by value of pharma sales to NHS
•Indirectly controls price by regulating profits earned by these firms
•Freedom of pricing at launch
51
PPRS (2014)
For the first time, it sets limits to the growth of sales of branded medicines to the NHS
52
PPRS (2014)
Innovation and access to medicines
•NICE will not negotiate, publicly set or publicly indicate prices
•The basic cost-effectiveness threshold will be retained at a level consistent with the current range and not changed for the duration of the agreement
53
The PPRS 2009 – still applies
•Flexible Pricing Schemes: where a company can increase
or decrease its original list price in light of new evidence or a
different indication being developed
•Patient Access Schemes: which will facilitate earlier patient
access for medicines that are not in the first instance found to
be cost and clinically effective by NICE within a framework
that preserves the independence of NICE
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Patient Access Schemes (1)
•Patient Access Schemes are schemes proposed by a
pharmaceutical company and agreed between the Department
(with input from NICE) and a pharmaceutical company in order to
improve the cost-effectiveness of a drug and enable patients to
receive access to cost-effective innovative medicines
•Note: only relates to England and Wales, as different HTA
arrangements are in place in Scotland and Northern Ireland
55
Patient Access Schemes (2)
(Some) Key principles:
•Arrangements must respect the role of NICE
•Schemes are to be discussed first and agreed in principle by the Department and the company
•Schemes should be clinically robust, clinically plausible, appropriate and monitorable
•Any scheme should be operationally manageable for the NHS without unduly complex monitoring, disproportionate additional costs and bureaucracy
•Schemes should be consistent with existing financial flows in the NHS and with local commissioning
•The more systematic use of such Schemes will need to be reviewed in light of experience. The timing of such a review will be jointly agreed but will be initiated not later than two years after the commencement of this Agreement
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Patient Access Schemes
2014 PPRS:
•Simple discount schemes; and
•Complex schemes
•Simple discount schemes must meet the simple discount criteria which ensure that a PAS imposes no significant ongoing additional burden on the NHS, as set out in the PASLU process guide and the relevant PAS proposal template. The other option for a scheme member would be to change the list price of the product.
•Complex schemes include all other types of PAS. This could potentially incorporate a wide range of models. To date, components of PAS have included:
• Rebates;
• Stock supplied at zero cost;
• Dose capping;
• Outcome-based schemes.
57
UK PAS’ by type/therapeutic area (July 2015)
Originally schemes were more complex and varied in nature; now,
there is a trend towards simple discounts due to confidentiality
agreements
Source: OHE analysis
Two thirds of schemes are for cancer and one
quarter for immuomodulating
biologics (mainly TNF’s)
58
Cancer Drugs Fund (1)
• For oncology medicines specifically, a “Cancer Drugs Fund” (CDF) was introduced in England in 2010
• Originally announced to run until 2014, it has now been given extra money and extended until 2016
• The CDF provides a means of improving patient access to cancer drugs, and is used to fund drug treatments, including radiopharmaceuticals, for patients who have been unable to access a drug recommended by their oncologist
• This includes drugs that are either not routinely available on the NHS or have not been approved or appraised by NICE. It also provides fast track access to cancer drugs that are awaiting NICE guidance as well as access to drugs for less common cancers
59
Distribution of NICE decisions for cancer drugs: before and after introduction of Cancer Drugs Fund (2006 – July 2015)
Cancer Drugs Fund associated with increase in NICE rejections and fall in restricted recommendations for cancer medicines
Source: OHE analysis
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Future of CDF
61
New CDF process
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New CDF process
63
New CDF process
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CDF - Consultation
https://www.england.nhs.uk/wp-content/uploads/2016/03/item-4-250216-updated.pdf
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Generics: M and W Schemes (2005)
•The reimbursed price (the Drug Tariff price) is the volume-weighted average price charged by manufacturers
•Manufacturers and wholesalers are required to submit quarterly data to the Department of Health on, among other things, net sales values and net acquisition costs, on a product by product basis i.e. including discounts
•Greater reliance on competition to control prices, but the generics market is more closely monitored than ever before
66
UK Prices
66
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But International Price Comparisons are Sensitive to ….
•Manufacturers’ prices or final selling price to the payer?
•Brands or generics or molecules?
•Sample size and selection (value versus volume, degree of market coverage)
•Bilateral versus multilateral
•Match single pack, match product form or price per unit (tablet, DDD, IMS SUs, Kg)?
•Volume weights: unweighted, own country (Paasche) or foreign weights (Laspeyres)?
•Choice of exchange rate
•What exactly is the question you are trying to answer?
68
Useful Reading
•Cockburn. I. and Henderson, R., “Racing to Invest? The Dynamics of Competition in Ethical Drug Discovery”, Journal of Economics and Management Strategy, Volume 3, No. 3, Fall 1994, pp. 481-519, 1994
•Danzon, P. and Chao. L., “Prices, Competition and Regulation in Pharmaceuticals: A Cross National Perspective”, Office of Health Economics, London, 2000a.
•Danzon, P. and Chao. L., “Cross-National Price Differences for Pharmaceuticals: How Large and Why?” Journal of Health Economics, 2000b.
•Danzon, P. and Chao. L., “Does Regulation Drive out Competition in Markets for Pharmaceuticals?” Journal of Law and Economics, 2000c.
•Danzon, P. and Kim, J., “The Life Cycle of Pharmaceuticals: A Cross-National Perspective” Office of Health Economics, London, 2002
•Di Masi, J., Hansen, R. and Grabowski, H., “The Price of Innovation: New Estimates of Drug Development Costs”, Journal of Health Economics 22, pp. 151-185, 2003
•Garau and Sussex, 2007, “Estimating pharmaceutical companies’ value to the UK economy. Case study of the BPG”, Office of Health Economics, London
•Grabowski, H., Vernon, J. and DiMasi, J., “Returns on Research and Development for 1990s New Drug Introductions”, Pharmacoeconomics, Supplement 3, 2002.
•Henderson, R. and Cockburn, I., “Scale, Scope and Spillovers: The Determinants of Research Productivity in Drug Discovery”, RAND Journal of Economics, Vol. 27, No. 1, pp. 32-59, Spring 1996.
•Kettler, H., “Updating the Cost of a New Chemical Entity”, Office of Health Economics, London, 1999.
•Mason. A., Towse, A., Drummond, M. and Cooke, J., “Influencing Prescribing in a Primary Care Led NHS”, Office of Health Economics, London, 2002
•Mestre-Ferrandiz, 2006, “The Faces of Regulation. Profit and price regulation of the UK pharmaceutical industry after the 1998 Competition Act”, Office of Health Economics, London
•Office of Health Economics, 2006, The Many Faces of Innovation
•Pharmaceutical Industry Competitiveness Task Force (PICTF), 2005, available at http://www.advisorybodies.doh.gov.uk/pictf/publications.htm
•PPRS: Documents available at: http://www.dh.gov.uk/en/Healthcare/Medicinespharmacyandindustry/Pharmaceuticalpriceregulationscheme/DH_494
•Sussex, J. and Marchant, N., (eds.), Risk and Return in the Pharmaceutical Industry, Office of Health Economics, 1999.
•Towse, A., Pritchard, C. and Devlin, N., (eds.), 2002, Cost-Effectiveness Thresholds: Economic and Social Issues, Office of Health Economics and King’s Fund
•Towse, A. and Danzon, P., 2003, “Differential Pricing for Pharmaceuticals: Reconciling Access, R&D and Patents”, Working Paper 03-7, AEI-Brookings Joint Centre for Regulatory Studies
•Wertheimer, A. Levy, R. and O’Connor, T. 200, “Too many drugs? The clinical and economic value of incremental innovations” in Investing in Health: The social and economic benefits of health care innovations, Volume 14, pp. 77-118, Elsevier Science Ltd.
