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PRIORITY MEDICINES FOR EUROPE AND THE WORLD

Warren KaplanRichard Laing

Other WHO Participants:

Saloni Tanna Marjolein WillemenEduardo Sabaté Monique RenevierJoyce Wilson Lisa GreenoughAnn Wilberforce Kathy Hurst

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Objectives/Deliverables

• Provide a methodology for identifying priority diseases with 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, which includes research into barriers to pharmaceutical innovation and ways of overcoming such barriers.

• Provide a Report for 18 November

“Good public policy aims to prioritise spending of public funds on areas of greatest public needs”

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Priority Medicines Project

1. Background/Introduction

2. Priority Setting

3. Methods

4. Results/Conclusions

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"Priority Medicines"

• Medicines which are needed to meet the priority health care needs of the population (“essential medicines”) but which have not yet been developed.

– For the purposes of this Report, a "priority" medicine for a priority disease is by definition also a significant improvement over already-marketed products

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Pharmaceutical "Gaps"

pharmaceutical treatments for a disease/condition which:

• does not yet exist OR

• are likely to become ineffective in the future OR

• are available but the delivery mechanism or

formulation is not appropriate for the target

patient group.

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Context/Background

• Pammoli, G-10 and EU Commission Reports– Europe was “lagging behind in its ability to generate, organize,

and sustain innovation processes that are increasingly expensive and organizationally complex.”

• The Lisbon and Barcelona European Councils: the “3% solution”

• Responses by EMEA : "Roadmap to 2010…"• US FDA "Innovation or Stagnation…?"• Framework Programmes• European and Developing Countries Clinical Trials

Partnership (EDCTP)

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Identifying gaps (unmet therapeutic needs):a public health perspective

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Few treatments

available, better

formulations and

delivery mechanisms

needed

2

Treatable with

existing interventions

but obstacles to

access exist

1

Treatable with current

mix of interventions

Untreatable with existing interventions including incurable chronic conditions

4

0%

0%

100%

100%

Maximum achievable

coverage

Population coverage

with current mix

of interventions

Combined

efficacy

of a mix

of all

available

interventions

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What this Report does not address

• Health system issues such as access or quality of care, or logistical or sociological barriers.

• Obesity as an underlying risk factor which can be considered a major cause of morbidity or mortality.

• Availability of diagnostics or medical devices • Relationship between trade, pricing, intellectual

property, as this is the subject of the WHO Commission on Intellectual Property Rights, Innovation and Public Health.

(See http://www.who.int/intellectualproperty/en/)

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Priority Medicines Project

1. Background/Introduction

2. Priority Setting

3. Methods

4. Results/Conclusions

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International organizations and less formal groups have developed

methods for prioritizing health research

• The Commission on Health Research for Development (1990)

• The World Development Report (1993 )

• The Ad Hoc Committee on Health Research (1996)

• The Global Forum for Health Research (2000)

• WHO-IFPMA Round Table (2000-2001)

• The UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR)

• The US National Institutes of Health (NIH) (1998)

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Prioritization must be multifactorial

INTUITION

ANALYSIS

Quality ofAnalysis

Quality ofIntuition

Least precise/explicit Most precise/explicit

MODE: 7 6 5 4 3 2 1

Knowledge Generation

Decision/Policy Making

non-cognitivejudgment

clinicaljudgment

expertconsensusjudgment

descriptivemodels

casecontrolstudy

randomizedcontrolled

trial

laboratoryexperiment

non-cognitivejudgment

clinicaljudgment

expertconsensusjudgment

decisionmodels

A Cognitive Continuum Framework

Source: Adapted from Dr. Kenneth Hammond, Univ. Colorado, USA

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Priority Medicines Project

1. Background/Introduction

2. Priority Setting

3. Methods

4. Results/Conclusions

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Generating a Preliminary List of Diseases and Gaps

Burden of disease rankingEU10, EU25

The world (including EU25)

Cochrane database of systematic reviews

Clinical efficacy

FINAL REPORT

Projectionsand trends

Socialsolidarity

PRELIMINARY LISTOF PRIORITY DISEASES AND

GAPS

IN DEPTH REVIEWS OF PRELIMINARY LIST OF DISEASES AND GAPS

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No Pharmaceutical "Gap"

Secondary Prevention of "Occlusive Event (Stroke/MI") with Antiplatelet Therapy

0

0.5

1

1.5

2

2.5

. . . . . . . . . . . .

Re

lati

ve R

isk

(<1

fa

vors

pla

ceb

o)

Prior MI

Prior MI

Prior Stroke All trials Aspirin any doseDipyridamole

Sulfinpyrazole

Ticlopidine

Suloctidil

Picotamide

Secondary Prevention of "Occlusive Event (Stroke/MI") with Antiplatelet Therapy

0

0.5

1

1.5

2

2.5

. . . . . . . . . . . .

Re

lati

ve R

isk

(<1

fa

vors

pla

ceb

o)

Prior MI

Prior MI

Prior Stroke All trials Aspirin any doseDipyridamole

Sulfinpyrazole

Ticlopidine

Suloctidil

Picotamide

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Pharmaceutical "Gap"Treatment of ACUTE Stroke (Outcome: Survival at end of treatment or follow-up, unless noted otherwise)

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

Rel

ativ

e R

isk

(<1

favo

rs p

lace

bo)

Various excitatory nerve amino acid antagonists

Ion channel,modulators

NMDAantagonists

Fibrinogendepleting agents

Gangliosides

Antiplatelettherapies

Streptokinaseurokinase( 7 days)Glycerol

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Generating a Preliminary List of Diseases and Gaps

Burden of disease rankingEU10, EU25

The world (including EU25)

Cochrane database of systematic reviews

Clinical efficacy

FINAL REPORT

Projectionsand trends

Socialsolidarity

PRELIMINARY LISTOF PRIORITY DISEASES AND

GAPS

IN DEPTH REVIEWS OF PRELIMINARY LIST OF DISEASES AND GAPS

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In-depth Reviews

• What is the size and nature of the disease burden?

• What is the control strategy?

• Why does the disease burden persist?

• What can be learnt from past/current research into pharmaceutical interventions for this condition?

• What is the current “pipeline” of products that are to be used for this particular condition?

• What are the opportunities for research into new pharmaceutical interventions?

• What are the gaps between current research and potential research issues which could make a difference, are affordable and could be carried out in a) five years or b) in the longer term?

• For which of these gaps are there opportunities for pharmaceutical research?

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Priority Medicines Project

1. Background/Introduction

2. Priority Setting

3. Methods

4. Results/Conclusions

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"Commonality of interest"

Results (1)

EUROPE THE WORLD

?? ??

?? ??

* Includes bladder, breast, cervical,colon, uterine, lungliver, mouth, oesophageal, ovarian, pancreatic,prostate, stomach cancer and leukemias, melanomas,lymphatic cancers and myelomas

** "Cerebrovascular disease"

*** Chagas disease, Dengue, Leishmaniasis, lymphaticfilariasis, Onchocerciasis, Schistosomiasis, Trypanosomiasis

10% 8% 6% 4% 2% 0 2% 4% 6% 8% 10%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

Unipolar depression

Maternal hemorrhage

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Global Public Health Threats

Antibiotic Resistance:

• For acute diseases, particularly infectious diseases, the burden in Europe is low.

• Healthcare systems are only slowly "rationalizing" antibiotic use

• Most antibiotics are inexpensive- less robust market incentives to create new antibiotics

• Less research on antibiotics could have profound consequences for future generations in view of the global increase in the spread of drug-resistant bacteria.

Pandemic Influenza:

• Overdue for a new pandemic

• Uptake of existing vaccines is poor

• Current capacity to produce either vaccines or antiviral medicines is not sufficient

Results (2)

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High burden, preventable diseases with pharmaceutical gaps

Smoking-related conditions:

• Public health, anti-smoking policies are the key interventions

• Pharmaceutical interventions to stop smoking may be useful adjuncts and better products are needed.

• For COPD, translational research to convert basic science advances into products that can be used in clinical trials.

Secondary prevention of cardiovascular disease:

• The "polypill" concept using fixed dose combinations deserves further study.

Treatment of acute stroke:

• A major basic and clinical research effort is required as the current treatment of acute stroke is unsatisfactory.

• Most agents are not effective and they are associated with an increased risk of adverse events.

Results (3)

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High burden, preventable diseases with pharmaceutical gaps

HIV/AIDS:

• There are particular "gaps" with regard to pediatric HIV formulations

Alcoholic liver disease:

• The overriding imperative should be to reduce the prevalence and

incidence of drinking. • Need for translational research to convert basic science advances

on fibrosis into products that can be used in clinical trials.

Results (3 continued)

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High burden diseases without cure

Results (4)

Osteoarthritis: • New diagnostics, biomarkers and imaging technology will help the medical

community to determine who is likely to get arthritis, the severity and progression of disease, and the response to medicines.

Alzheimer disease: • More sensitive, reliable and valid tools for detecting changes in normal ageing

and the onset of early Alzheimer disease.

• Lack of surrogate markers as therapeutic endpoints remains a major barrier in the clinical development of efficacious AD drugs

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High burden diseases where existing therapies could be improved

Results (5)

Cancer : • More capacity (infrastructure and human resources) and coordination to

conduct comparative Phase II/III clinical trials • Continue to invest in basic research into cancer biology

Type 2 Diabetes: • Heat stable insulin would be a major advance in public health• Increased infrastructure to facilitate diabetes clinical trials, in particular

comparative clinical “head-to-head” trials

Type 1 diabetes: • Gaps in basic biology, stem cell research, transplantation research

Depression in children/elderly: • Gaps in understanding biology of depression and its treatments in these

groups

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"Neglected" diseases

Malaria: • Lack of cost efficient experimental models for medicines discovery and development. • Weak EU creation and funding of new partnerships toward translational research

Tuberculosis: • More FDCs for second-line treatment of multidrug-resistant TB • Weak EU creation and funding of new partnerships toward translational research

Leishmaniasis, trypanosomiasis, Buruli ulcer: • Most of the medicines being used are "old" and often dangerous• Weak EU creation and funding of new partnerships toward translational research

Post-partum haemorrhage: • A significant cause of maternal mortality in developing countries, heat stable oxytocin

would be a major advance in public health

Results (6)

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Conclusions: Preliminary List of Priority Diseases for which "priority medicines"

are needed

• Infections due to antibacterial resistance

• Pandemic Influenza• Smoking-related

diseases/interventions for smoking cessation

• Cardiovascular disease• Diabetes • Cancer• Acute stroke• HIV and AIDS• Tuberculosis• Neglected diseases

• Malaria• Alzheimer disease • Osteoarthritis• Chronic obstructive

pulmonary disease• Alcohol dependency,

alcohol liver disease• Depression in Children

and the Elderly• Postpartum hemorrhage

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Priority Medicines Project

For further questions, please do not hesitate to contact us at:

Laingr@who.int

wak22@comcast.net

+41-22-791-4533

http://mednet3.who.int/prioritymeds/interimReport_04_2004/index.htm