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High costs of new drugs
Carin A. Uyl-de Groot, PhD
Professor of health technology assessment
iBMG/iMTA, Erasmus University Rotterdam
Thanks to Maureen Rutten and Marc Koopmanschap
Content• Introduction
• Chronology of drug innovation
• The life cycle of a drug
• Pricing of new drugs
• Challenges facing several stakeholders
• Reimbursement
2
Examples prices of new drugs
Pompe disease: Myozyme:
- Cost: Euro 500,000
- Outcome: difficult to assess
- ICER: around 1 mln
Melanoma: Vemurafenib:
- Progression free survival: 5.3 vs 1.6 months mnt months
- Cost: 8.471 euro per monthMelanoma: Ipilimumab:
- 10-20% patients benefit
- Cost: € 84.000,- per patient
- Budget impact: €20-40 mln
5
6
System objectivesSystem objectives
Quality of care
Quality of care
Sustainability
Sustainability
EquityEquity
Policy goals in health care Policy goals in health care
Goal: Ensuring affordable and equitable access for (all) patients to effective medicinces in a sustainable manner
Policy goals, criteria and HTA aligned?
Goal Policy criterion in HTA?
Quality of care Health gain Cure Yes (QALYs)Care ???
Sustainability Budget impact Yes (cost/BI)
Equity “disease severity”(“need indicator”)
Yes, good enough?
Trade off Q vs S Cost-effectiveness Yes (ICER)
Cost-effectiveness vs drug reimbursement
• many EU countries: CE a formal reimbursement criterium,
BUT: no country (except UK) has strict & transparant threshold
(range) for acceptable cost per QALY
NL 2005-11: only 30% (=19/63) of drugs with positive 1B decisions
had pharmacoeconomic evidence!! (Franken et al 2012)
• Many exemptions: 24 orphan drugs, 7 HIV drugs
(Scotland stricter on PE evidence)
• 4 “insufficiently founded” evaluations got a positive decision
Question: Why are the prices of new drugs high?
• Development process
• Succes rate
• Uptake of innovation
• Reimbursement
11
Discovery
Exploratory Development
Full Development
Registration
Large Amounts ofCandidate Medicine
Synthesized
Project Teamand Plans
Synthesisof Compounds
EarlySafety
Studies
CandidateFormulations
Developed
ExtensiveSafety
Studies
Screening
Studies in HealthyVolunteers Phase I
Candidate Medicine Tested in3-10,000 Patients (Phase III)
Studies in 100-300Patients (Phase II)
Clinical DataAnalysis
Pfizer -- http://www.pfizer.co.uk/pfizer_uk/navigation/research_frame.htm
and Medical Devices and Technologies
Development phase: a long and winding road to registration
12
Development phaseFrom discovery to patient
Patent a
pplicati
on
1 medicinal product
Acute
toxicity
Pharmac
ology
Chronic
toxicity
Phase I
clinica
l trial
s
Phase I
IPhas
e III
Regist
ration an
d tran
spare
ncy
Price
Reimburse
ment
Pharmac
ovigila
nce
0 5 years 10 years 15 years 20 years Patent expiry
10 years of research
2 to 3 years of administrative
proceduresSource: “Recherche & Vie”, LIM (AGIM)
13
Life cycle of a drug
Time →
↑Sales
development introduction growth maturity decline
14
Ellery and Hansen, Pharmaceutical Lifecycle management, Wiley 2012
Development phaseDiscovery and development of a successful drug
1514131211109876543210
YEARS
INTRODUCTION/REGISTRATION
DEVELOPMENT
BASICRESEARCH
POST-MARKETING SURVEILLANCE Phase IV
CLINICAL TEST (HUMANS) Phase I to III
PRECLINICAL TEST (ANIMALS)
SYNTHESIS, EXAMINATION &
SCREENING
1
2
2 - 5
5 - 10
3,000 – 10,000
QUANTITY OF SUBSTANCES
16
Costs of development new molecular entity (NME)
• Estimation: 1 billion euros
Cost factor:
• R&D (including failures): 17%
• Manufacturing
• Marketing and promotion: 23%
• More is spent on marketing than on R&D
17
Costs per clinical phase in percentage of total R&D, period 2000-2007
Phase Percentage of total R&D
Pre-clinical (incl. Basic research) 8%
Phase I 12%
Phase II 20%
Phase III 60%
18
Growth phase
• Slower rate of growth than typical industrial product
– Switching patients to other drugs may be risky
– Me-too’s or established drug classes are doing well
– Promotion limited
– Health authorities cautious about letting new drug be introduced initially to a broad population because of safety issues
– More and more biologics that target multiple smaller indications, which are introduced successively over the life of a drug
– Cost containment policies affecting supply, demand, price
21
Growth phase: International Reference Pricing (IRP) is used in some form in most European countries
IMS HEALTH Pharmaquery Sept 2012
22
OECD (2011), “Pharmaceutical expenditure”, in Health at a Glance2011: OECD Indicators, OECD Publishing.
Growth in real per capita pharmaceutical expenditure, 2000-09 (or nearest year)
23
Challenges
1. Pipeline NME drying
2. Cancer: need for more therapeutic value (not only end of life drugs)
3. Higher development costs
4. Increased regulatory requirements because of safety concerns
5. Tougher environment for pricing, reimbursement, listing
6. Increased competition
7. Earlier generic drugs
8. Poor image
24
Tougher environment for pricing, reimbursement, listing
Regulatory
QualityEfficacySafety
Pricing, Reimbursement
Comparative effectiveness in real worldCost-effectiveness (trial-based and model-based)
Purchase, listing
Budget impact analyses
25
What is our “Product”? - Product Positioning
• A molecule is not a product…..for price estimation purposes we must define its “positioning”
• “Positioning” (here) = place in the treatment regimen
Line of therapy?
Target Patients?
Prevention or treatment?
Monotherapy or combination?
Positioning variables …different implications for…..
Reference Price
Positive Differentiatio
n Value
Negative Differentiatio
n Value
Perceived Value
VR
D
Price Optimization across countries
US
France
Germany
1. Assess individual market price/demand dynamics
UK
Canada
etc
3. Implement and maintain a Global Pricing Strategy
Global floor or corridor
Launch sequence
Price targets
Cohesive Global
Strategy
2. Overlay global context and optimize
Individual Demand curves
Optimization Modeling
Cross Market Interactions
Recent turbulence, turning point in NL?
“CvZ to delist 2 expensive ultra-orphan drugs” (Pompe/Fabry, after 5 yrs conditional reimbursement)
Fueled discussion (“finally….”) =>• Ethical to stop treatment?• Ethical to value health monetarily?• Ethical to deny the scarcity of resources?• Better options to limit cost explosion?• Why are these orphan drugs so expensive?• Negotiate on prices with industry?
9/2012 CvZ, struggle-> advise “reimburse”,
but not in regular benefit package…………
Recent turbulence ultra orphans in NL
Argument contra reimbursement:
•Cost per QALY too high (up to 1 mln € per QALY)
Argument pro:
•For subgroup that benefits it is established treatment for several years (“acquired right on care”)
Lesson: maybe conditional reimbursement of these orphan drugs 5 years ago was unwise?
A proposal for ultra orphans in NL
Say: WTP/QALY for normal drugs up to 80,000 € per QALY,
Say: for ultra orphan drugs WTP 300,000 € per QALY
For sub group that really benefits say a gain of 0.75 QALY per year
Given max WTP/QALY -> max drug costs per year:
= 225,000 € (as 225,000/0.75= 300,000).
Message of reimbursement authorities to producers:
“Don’t develop drugs with annual treatment costs of more than 225,000 €, we will not even allow conditional reimbursement”.
Reimbursement (1)
Coverage with evidence NL: final reimbursement decision after 4 years, based on cost-effectiveness in daily practice and appropriate drug use (extended in 2013);
• Quite comfortable arrangement for producers: 4 years a high price (t=0-4, risk for payer);
Reimbursement (2)• Volume-price agreements (France ea)• sales < Y price P1; sales > Y lower price P2
Advantages:• less uncertainty on budget impact• industry can cover R & D costs (Price1*Volume1)
Disadvantages: • does not address value for money• negotiations not transparant
Reimbursement (3)
• Contract : reimbursement depend on treatment success (outcomes based risk sharing,
Pay for performance) • August 2012 CVZ omalizumab (severe asthma)
• Advantages:– “no cure, no pay” => value for money– application on best patient sub groups – after contract new decision possible
• Disadvantages:– transaction costs contract– clear outcome indicator crucial– cost of monitoring/registration
Equal access: dynamics in treatments multiple myeloma (IEqual access: dynamics in treatments multiple myeloma (I) )
Equal access: non small cell lung cancer patients receiving 1st line Iressa or Tarceva (II)
25% - 50%
<25%
50% - 75%
>75%