PRIORITY
MEDICINES FOR
EUROPE AND THE
WORLD
A report prepared by WHO for the
Netherlands Government
by
Warren Kaplan
Richard Laing
and
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Saloni Tanna
Eduardo Sabaté
Joyce Wilson
Ann Wilberforce
Marjolein Willemen
Monique Renevier
Lisa Greenough
Kathy Hurst
Objectives of Priority
Medicines Project
• Provide a methodology for identifying
pharmaceutical “gaps” from a public health
perspective, for Europe and the World .
• Provide a public-health based pharmaceutical
R&D agenda for use by the EU in the 7th
Framework Programme,
“Good public policy should spend public funds
on areas of greatest public needs”
2
Generating a Preliminary List of
Diseases and Gaps
Cochrane database of
systematic revie ws
Clinical efficacy
Burden of disease ranking
EU10, EU25
The world (including EU25)
Projections
and trends
PRELIMINARY LIST
OF PRIORITY DISEASES AND
GAPS
IN DEPTH REVIEWS OF PRELIMINARY LIST OF DISEASES AND GAPS
FINAL REPORT
3
Social
solidarity
Pharmaceutical "Gap"
Treatment of ACUTE Stroke (Outcome: Survival at end of treatment or follow-up, unless noted otherwise)
1.8
Various excitatory nerve
amino acid antagonists
1.6
Ion channel
,modulators
Antiplatelet
therapies
Fibrinogen
depleting agents
Glycerol
Relative Risk (<1 favors placebo)
1.4
1.2
1
0.8
0.6
0.4
0.2
0
4
NMDA
antagonists
Gangliosides
Streptokinase
urokinase
( 7 days)
Example of an absent
pharmaceutical gap
Secondary prevention of occlusive event (Stroke/MI) with antiplatelet therapy
2.5
Picotamide
Relative risk (<1 favours placebo)
2
Suloctidil
Ticlopidine
Prior MI
1.5
Prior
MI
Prior stroke
Aspirin any
dose
Dipyridamole
All trials
1
Sulfinpyrazole
0.5
0
5
.
.
.
.
.
.
.
.
.
.
.
.
"Commonality of
interest"
EUROPE
10%
??
??
8%
6%
4%
THE WORLD
2%
0
2%
4%
6%
Antimicrobial Resistance
Pandemic Influenza
Ischaemic Heart Disease
Diabetes Mellitus
Cancer*
Acute Stroke**
HIV/AIDS
Tuberculosis
Neglected Diseases***
Malaria
Alzheimer and other dementias
Osteoarthritis
COPD
Alcohol use disorders
6
Unipolar depression
Maternal hemorrhage
8%
10%
??
??
Special Needs for Women,
Children, and the Elderly
• All groups neglected in drug development
• Complicated by different physiology &
metabolism
• Recent improvements in situation of women and
children
• Considerable gaps remain for the elderly who
use the most medicines
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Promoting Innovation and
Removing Barriers
• Public Private Partnerships may be a vehicle
to address market failure
• Pricing issues are critical to the future of the
European pharmaceutical industry. Propose
investigating differential pricing based on GNI
per capita and efficacy measures. Reseach
prospective price setting.
• EMEA, FDA, Rawlins and Industry have all
proposed similar measures to remove barriers
• Comparative trials provide critical information
on head to head comparisons. Use of European
databases may facilitate such studies
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Differential Pricing: Indicative prices in
US$/annum of highly active antiretrovira
(HAART) and a new hypothetical regime
in countries of variable wealth
30000
United Kingdom
France
Italy
25000
15000
Slovenia
Czech Republic
10000
Latvia
5000
Indicative price existing treatment
26076
23225
15000 20000 25000
Per capita GNI $US
9
22783
19831
15627
12620
5000
10881
6199
4921
3744
3477
2500
2566
2557
2000
2401
2125
1959
1000
1637
1214
993
500
855
607
441
200
763
Russian Fed.
Kazakhstan
Philippines
Georgia
India
294
267
Mali
0
487
Indicative price $US
Spain
20000
Indicative price new drug
Barriers to Innovation:
Background
• Cost and duration of medicines development have
increased
– Many projects in early development stages, but not enough of
this potential innovation is being translated into market
approvals.
• For some diseases, there remains an inadequate
understanding of basic science, and potential
targets for medicines development have not been
identified.
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Recent Publications
• Four papers published almost simultaneously,
plus commentary on Priority Medicines website
– EMEA: Discussion Paper: The European Medicines
Agency Road Map to 2010: Preparing the Ground for the
Future
– FDA: " Challenge and Opportunity on the Critical Path to
New Medical Products"
– Perspectives – "Cutting the Cost of Drug Development?"
M.D. Rawlins
– Sue Middleton: GSK Commentary on "Barriers to
Innovation"
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Barriers to Innovation:
Suggested Solutions
• All authors agreed that every aspect of the regulatory process
should be re-examined and that the evidence base for
regulatory practices should be critically analysed using modern
methodologies.
• Preclinical studies
– Many old tests and methods
– New analytic tools needed
– Validation of old methods required
• Clinical Studies
– Regulatory authorities are risk averse so the RCT has become the
gold standard
– Other approaches even using historical controls may be possible
and desirable
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Neglected Areas:
Post marketing Surveillance and
Patients
• All papers neglect Phase IV studies as a part of
the innovation process. Great opportunities for
Europe from use of electronic data bases for
Phase IV studies on both efficacy and safety
• Apart from the industry paper, none of the three
other papers mention any role for patients in this
review. They are referred to as beneficiaries of
the process but never as contributors to the
decision-making.
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Role of Patients remains
unclear
• Patients have speeded innovation e.g.
AIDS and Orphan diseases
• Valuable role in treatment guideline
development emerging e.g. NICE
• Patients play important role in ethical &
hospital committees e.g. IRB & DTCs
• Will now be part of CSM in UK
• Future role likely to be important and
growing
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A "barriers to innovation"
Research Agenda
• Bottlenecks and barriers in the current medicines development
process are to be identified and solutions elaborated to
overcome them.
– Range of stakeholders required: academia, clinicians, patient
organizations, large and small industry, regulatory and ethics
specialists
– Every requirement within the medicines development process
whether clinical or preclinical should be questioned for its
regulatory relevance, costing, and predictive value.
– The involvement of the EMEA and the various European national
regulatory agencies and their scientists is critical to this initiative.
– 6th Framework already has issued a call closing November 16th
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PRIORITY MEDICINES FOR
EUROPE AND THE WORLD
Comparative Clinical Trials
Chapter 8.4
Warren Kaplan
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Comparative Trials: Background
•
For most medications at launch, we know little about whether or not a
given medication is better value for the money than alternatives.
– This knowledge gap exists because most drug regulatory authorities do not
examine "value for money"
•
For most medications at launch, clinical trials are not designed to look
at whether or not a given medication is better than another drug.
•
Typically, efficacy is measured versus a control which is often, but not
invariably, a placebo lacking any active ingredient.
– Many registration authorities do require comparative benefit studies
•
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To estimate comparative benefit between two medicines, large (time
consuming and expensive) trials are needed since there are often
small differences between treatment outcomes when comparing the
interventions.
Comparative Trials:
Who should pay for them and who
conducts them?
• Industry? Government? Or…
• Private insurers and the government could set aside some
fraction of their annual medicines spending to endow an
organization to provide an independent source of reputable
research into comparative effectiveness and cost.
– Electronic prescription and medical databases to conduct Phase IV
and/or pharmacoepidemiologic studies in place of controlled,
comparative clinical trials.
– EU has a great comparative advantage over the USA as this kind of
electronic linkage of prescribers and medical records is still fragmented
in the USA
– Phase IV studies could add a randomization step ("randomized
epidemiology")
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Comparative Trials/
Comparative Effectiveness
• Europe 2005: "An information society for all",
available at
http://europa.eu.int/information_society/eeurope/2002/news_lib
rary/documents/eeurope2005/eeurope2005_en.pdf.
• This Action plan on "electronic health" should be
used as a way of creating post-marketing
studies to better understand comparative
effectiveness and cost-effectiveness.
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General Conclusions
• Commonality of interest exists for chronic diseases
between Europe and the World
• Priorities can be set based on evidence, trends and
projections and social solidarity
• Pharmaceutical gaps exist as a result of biological
challenges and market failure
• Highest priorities are antibacterial resistance, influenza,
smoking and neglected diseases
• Pricing issues and barriers to innovation strongly affect
the European industry
• The EU needs to find a way to support translational
research for market failure pharmaceutical gaps
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Regulatory Conclusions
• Common view as to how regulatory obstacles
serve as a barrier to innovation
• Different solutions proposed by different
stakeholders. All should be considered
• Striking lack of attention to Phase 4 activities.
Vioxx and FDA hearings may change everything
• Strong interest in routine use of large (even
complete) patient data bases
• A researchable topic!
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Priority Medicines
Project
For further questions, please contact:
laingr@who.int
wak22@comcast.net
+41-22-791-4533
http://mednet3.who.int/prioritymeds/report/index.htm
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