rare disease
TRANSCRIPT
2014-06-04
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RARE DISEASE: TERMS & DEFINITIONS USED
IN OUTCOMES RESEARCH
Tuesday, June 3, 2014
FORUM
Moderator
FORUM
RARE DISEASES: TERMS & DEFINITIONS
USED IN OUTCOMES RESEARCH
Zeba M. Khan,
RPh, PhD Vice President, Strategic
Market Access & Policy,
Celgene Corporation,
Summit, NJ, USA
2014-06-04
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Trevor Richter PhD, MSc, BSc, Research Manager,
Health Economics, Canadian Agency for Drugs and
Technologies in Health (CADTH), Ottawa, ON, Canada
FORUM
SPEAKERS
Robert Babela, PhD, MSc, Head of Department of Health Economics/HM,
St. Elizabeth University, Bratislava, Slovakia
Zeba M. Khan, RPh, PhD Vice President,
Strategic Market Access & Policy,
Celgene Corporation, Summit, NJ, USA
Robert Babela, PhD, MSc, Head of Department of Health
Economics/HM, St. Elizabeth University, Bratislava, Slovakia
Sandra Nestler-Parr, PhD, MPhil, Director, Market Access &
Reimbursement, Advocate Consulting, London, UK
Trevor Richter PhD, MSc, BSc, Research Manager, Health
Economics, Canadian Agency for Drugs and Technologies in
Health (CADTH), Ottawa, ON, Canada
Dyfrig Hughes, PhD, MSc, Professor, Centre for Health
Economics and Medicines Evaluation, Bangor University, Wales,
UK
Zeba M. Khan, RPh, PhD, Vice President, Strategic Market
Access & Policy, Celgene Corporation, Summit, New Jersey,
USA
FORUM
Writing Group
2014-06-04
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FORUM
Ruzan Avetisyan, PhD, MD, Global Evidence and Value Development Department,
Genzyme / Sanofi, Belmont, MA, USA
Robert Babela, PhD, MSc, Head of Department of Public Health / HM
St. Elizabeth University, Bratislava, Slovakia
Bryan Bennett, PhD, BSc, Senior Outcomes Researcher, Oxford Outcomes, Oxford, UK
Jacqueline Bowman-Busato, Executive Director, EPPOSI, Brussels, Belgium
Annie Chicoye, PhD, Development Vice-President, Health Management Institute, ESSEC
Business School, Paris, France
Melike Deger, MSc, Health Economist, Cochlear AG, Basel, Switzerland
Meg Franklin, PharmD, PhD, Associate Professor of Pharmacy Administration,
Department of Pharmaceutical and Administrative Sciences, Presbyterian College School
of Pharmacy, Clinton, SC, USA
Vivian Herrera, Director, Global Evidence and Value Development, Rare Diseases & MS,
Sanofi US, Bridgewater, NJ, USA
Zoltán Kaló, PhD, MD, MSc, Director, Health Economics Research Centre, Faculty of
Social Sciences, Eötvös Loránd University (ELTE), Budapest, Hungary
LEADERSHIP GROUP
FORUM Katarzyna Kolasa, MSc, Market Access Associate Director, Biogen Idec, Zug,
Switzerland
Yasufumi Kuroda, PhD, Manager, Daiichi Sankyo Pharma Development, Edison, NJ,
USA
Zhimei (Jamae) Liu, PhD, Director, Oncology US Health Economics & Outcomes
Research, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
Sandra Milev, MSc, Health Economist, Canadian Agency for Drugs and Technologies in
Health (CADTH), Ottawa, Canada
Sandra Nestler-Parr, PhD, MPhil, Director, Market Access & Reimbursement, Advocate
Consulting, London, UK
Chris Pashos, PhD, Vice President, Global Outcomes and Epidemiology Research,
Takeda Pharmaceuticals International, Inc., Cambridge, MA, USA
Trevor Richter PhD, MSc, BSc, Research Manager, Health Economics, Canadian
Agency for Drugs and Technologies in Health (CADTH), Ottawa, ON, Canada
Phil Ruff PhD, BSc, Director, Global Market Access, Shire HGT, Lexington, MA, USA
Ruth Suter MBA, RD, Market Access - Pt S, BioMarin, Novato, CA, USA
Vlad Zah PhD, BSc, Health Economist, ZRx Outcomes Research Inc., Belgrade, Serbia
LEADERSHIP GROUP (continued)
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RARE DISEASE TERMINOLOGY & DEFINITIONS
USED IN OUTCOMES RESEARCH WORKING
GROUP
FORUM Co-Chairs
Dyfrig Hughes, PhD, MSc Professor,
Centre for Health Economics
and Medicines Evaluation,
Bangor University, Wales, UK
Zeba M. Khan, RPh, PhD Vice President,
Strategic Market Access &
Policy, Celgene Corporation,
Summit, New Jersey, USA
WHY DO WE HAVE A RARE DISEASE SIG?
FORUM
Attention on rare diseases is increasing as
policy incentives for R&D are working.
Rare disease treatment costs are increasingly
scrutinized.
Unmet needs, and therefore, opportunities for
advancements in care are great, with ~75% of
currently recognized rare diseases having no
effective treatment.
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FORUM
Many different concepts and terms are used
to describe rare diseases, their treatments,
and related health technologies.
Terms & definitions differ:
Nationally and internationally
Across geographic boundaries and jurisdictions
Across stakeholders and stakeholder types
WHY RARE DISEASE TERMINOLOGY
AND DEFINITIONS?
RARE DISEASE SPECIAL INTEREST GROUPS
FORUM
Currently 2 SIG Working Groups
Rare Disease Terminology & Definitions Used in
Outcomes Research
Rare Disease Challenges In Assessment and Appraisal
of Diagnostics & Treatments
Upcoming 2 More SIG Working Groups
HTA of Rare Disease Diagnostics & Treatments
Methodology - Measuring Use, Costs and Effectiveness
of Rare Disease Care
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There are approx. 7000 rare diseases affecting an
estimated 27- 36 million people in the European Union
and a further 25 million in the USA
On average, five new diseases are described every
week in the medical literature
The two most common ways of expressing rare
disease prevalence rates are either by:
number of affected individuals in total population within
a jurisdiction, or
proportion of an absolute number within a jurisdiction
ORHANET: About Rare Diseases. Available at: http://www.orpha.net/consor/cgi-
bin/Education_AboutRareDiseases.php?lng=EN [Accessed March 19, 2014]
EMA: Medicines for rare diseases. European Medicines Agency 2014, Available at:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general/general_content_000034.jsp&mid=W
C0b01ac058002d4eb [Accessed March 17, 2014]
The EMA and FDA have been encouraging applications
for orphan designation since 2008 (incl. Japan, 2012)
In 2013, the FDA approved 33 drugs for treating rare
diseases and funded 15 new orphan product grants for
about $14 million, all supporting clinical research in rare
diseases
EMA recommended for marketing authorization 11
orphan drugs for the treatment of rare diseases in 2013,
compared to 4 in 2011
FDA: FDA Speeds Innovation in Rare Disease Therapies. Food and Drug Administration 2014, Available at:
http://www.fda.gov/forconsumers/consumerupdates/ucm387513.htm [Accessed: March 17, 2014]
EMA: Rare Disease Day 2014 – twelve new orphan medicines available to patients over the past year. European Medicines Agency
2014, Available at:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/02/news_detail_002033.jsp&mid=WC0b01ac058004
d5c1 [Accessed March 17, 2014]
EMA: Orphan designation. European Medicines Agency 2014, Available at:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000029.jsp&mid=WC0b01ac05800240ce
[Accessed March 17, 2014]
FORUM
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Stakeholder groups other than regulators, including
payers and reimbursement bodies, patient groups, and
other organizations differ in how they define rare
disease terms
The use of diverse terminology, the absence of a clear
taxonomy, and the use of inconsistent definitions can
result in confusion, or the encouragement of
strategic manoeuvring that may not be in the best
interests of patients or wider society
Despite progress in a wide range of collaborative
regulatory and patient-related activities internationally,
no common definition of rare diseases and related
healthcare interventions has been adopted
FORUM
Our review presents definitions for rare disease
identified from a systematic search of 32 countries
from each of the six global regions
Our review provides a comprehensive overview of the
commonalities and differences that exist in
definitions used across all of the relevant types of
organization and multiple jurisdictions globally
FORUM
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FORUM
METHODOLOGY
Members of ISPOR were invited to join the leadership
working group
Members represent diverse range of stakeholders:
Regulatory
Academic
Pharmaceutical industry
Patient organizations
FORUM
METHODOLOGY
Identified 17 English-language terms used in defining
rare diseases and associated therapeutic interventions
Rare disease(s)
Rare disorder(s)
Rare condition(s)
Neglected disease(s)
Orphan disease(s)
Orphan subset
Syndrome(s) without a name
Rare and neglected disease(s)
Undiagnosed disease(s)
Ultra-orphan disease(s)
Ultra-rare disease(s)
Very rare disease
Highly specialized technologies
Orphan drug(s)
Orphan medicinal product(s)
Orphan product(s)
Ultra-orphan drug(s)
Other
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FORUM
Identify agencies / organizations where terms are used
METHODOLOGY
Organization Definition
HTA Agency Agencies with the a primary mandate to carry out health
technology assessments, including governmental, quasi-
governmental, and non-governmental organizations.
Private Payer Organizations such as private health insurance providers.
Public Payer Public health insurance providers.
Regulator Regional and national government agencies that regulate
pharmaceuticals and medical devices
Umbrella Patient
Organization
Includes advocacy (patient) groups, policy groups, and
organizations that provide resources for patients with rare
diseases.
Other
Any organization that could not be classified into one
category was categorized as ‘Other’, including
pharmaceutical trade organizations, research centers, and
non-regulatory government agencies.
FORUM
METHODOLOGY
COUNTRIES
NORTH AMERICA: Canada, Mexico, USA
SOUTH AMERICA: Argentina, Brazil, Chile, Columbia
EUROPE: Czech Republic, Denmark, EURORDIS,
European Union, France, Germany, Ireland,
Italy, the Netherlands, Poland, Slovakia,
Spain, Sweden, UK – England, Scotland,
Wales
ASIA: China, India, Japan, South Korea, Russia,
Taiwan, Turkey
AFRICA: South Africa
OCEANIA: Australia
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FORUM
DATA COLLECTION
Recruited local researchers who spoke the search country
native language.
Each researcher searched for all 17 terms (or equivalent
translations) for each agency online.
Definitions were recorded in the original language and in
English.
If a term was found, the full definition and source were
recorded.
Terms identified but not on the search term list were added to
the list and the definition and source were recorded.
FORUM
DATA COLLECTION
Collected data were submitted to the ISPOR Rare Diseases
SIG liaison.
Data were reviewed to ensure quality.
Incomplete or improperly recorded entries were returned to
researchers for proper completion through additional
searches.
In some cases, data were verified by additional volunteers
identified through the ISPOR Regional Chapters, the ISPOR
Regional Consortia, or the ISPOR member database.
Data from each country were combined into a single
consolidated database.
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FORUM
5,444 searches performed
296 definitions identified
Definitions in all 32 countries
RESULTS
FORUM
Jurisdiction Organization Definition of Rare Disease
United
States FDA
The term "rare disease or condition'' means
any disease or condition which (A) affects less
than 200,000 persons in the United States,
or (B) affects more than 200,000 in the United
States and for which there is no reasonable
expectation that the cost of developing and
making available in the United States a drug
for such disease or condition will recovered
from sales in the United States of such drug.
European
Union EMA
Rare diseases are defined as life-threatening
or chronically debilitating conditions that affect
no more than 5 in 10,000 people in EU.
Definitions from prominent regulatory agencies
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FORUM
TERMINOLOGY I
Words used most often:
‘Disease’
‘Rare’
‘Orphan’
RESULTS
FORUM
RESULTS
Frequency of words used in definitions
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FORUM
TERMINOLOGY II
Terms used most often:
‘Rare disease’
‘Orphan drug’
RESULTS
FORUM
TERMS USED IN DEFINITIONS
38%
27%
6%
5%
4%
3%
3%
3%
2%
1%
1%
1%
1%
1%
1%
1%
0%
0%
0%
0%
0%
0%
0%
Rare disease
Orphan drug
Orphan disease
Orphan medicinal product
Rare disorder
Ultra-rare disease
Highly specialised technologies
Rare condition
Neglected disease
Very rare disease
Orphan product
Ultra-orphan drug
Ultra-orphan disease
Rare disability
Orphan indication
Pharmacological therapies of high…
Rare medicinal technology
Orphan pharmaceutical product
Priority review drugs
Orphan subset
Extremely rare disease
Rare and neglected disease
Syndrome without a name
Relative frequency of use in definitions
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FORUM
ORGANIZATIONS
Patient organizations & regulators have the
most definitions
RESULTS
FORUM
Proportion of organizations with definitions
RESULTS
30%
26%
16%
14%
10%
3%
Umbrella PatientOrganization
Regulator
Public payer
HTA Agency
Other
Private Payer
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FORUM
PREVALENCE THRESHOLDS I
88% of countries included a prevalence
threshold in at least one definition of rare
disease
Umbrella patient groups & regulators have
the most liberal prevalence thresholds
RESULTS
FORUM
Prevalence thresholds by organization type
Patients per 10,000 people
5
4
4
3
3
3
4
Umbrella Patient…
Other
Regulator
Public payer
Private Payer
HTA Agency
Average
most liberal
least liberal
RESULTS
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FORUM
PREVALENCE THRESHOLDS II
Relatively small regional differences in
prevalence thresholds
Range: 3 to 5 patients per 10,000 people
Global average threshold:
4 patients per 10,000 people (0.00039)
RESULTS
FORUM
RESULTS
Patients per 10,000 people 8
6 6
5 5 5 5 5 5 5 5 5
5 4
4 4
4 4 4 4 4 4
3 3 3
3 3
2 2
1 1
1
ChinaUnited States
BrazilIndia
ArgentinaChile
ColombiaCzech Republic
FranceIrelandMexico
SlovakiaGermany
PolandItaly
SpainEuropean Union
JapanNetherlandsGrand Total
CanadaTurkey
ScotlandEngland
United KingdomWales
South AfricaSwedenRussia
DenmarkTaiwan
Australia
most liberal
least liberal
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FORUM
Australia
Canada Denmark
England Korea
Russia
Scotland
South Africa
Sweden
Taiwan
Turkey
Wales
Argentina
Brazil
Chile
China
Colombia
Czech Republic
France
Germany India
Ireland
Italy Japan Mexico
Netherlands
Poland Slovakia
Spain
United States
Lower than global averageHigher than global average
Prevalence Thresholds by Country
FORUM
Prevalence thresholds by region
RESULTS
Patients per 10,000 people
5
5
4
4
3
1
4
SA
NA
EU
AS
AF
OC
Average
most liberal
least liberal
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FORUM
There is a global trend towards defining ‘rare
disease’
Definitions are generally rigorous
With respect to prevalence, but other criteria also need to
be considered & defined
There is some consistency in prevalence thresholds
But variation within & among countries & organizations
Most definitions from most organizations in
most countries use a prevalence of 4 patients
per 10,000 people
CONCLUSIONS
FORUM Activity Date
Rare Disease Meeting in Berlin November 2012
Rare Disease SIG development January – April 2013
RD SIG meeting at 18th Annual ISPOR International Meeting May 21, 2013
RD Terms & Definitions WG developed June 2013
T & D Kick Off TC July 29, 2013
Gather sources, develop research methodology, select countries August – September 2013
RD T&D WG meeting 16th Annual European Congress in Dublin November 5, 2013
RD SIG Forum 16th Annual European Congress in Dublin November 5, 2013
Country research – assign authors, conduct research December 2013 – March 2014
Development of the draft manuscript Mid-January – April 2014
Circulation of draft to primary reviewers May 12 – 19, 2014
Forum presentation June 3, 2014
Writing team working meeting during Montreal June 4, 2014
Revisions based on comments from forum Due Friday, June 20, 2014
Revisions DUE Tuesday, July 15, 2014
Final review by RD SIG Review Group July 21 – August 4, 2014
Revisions DUE Wednesday, Sept. 3, 2014
Manuscript finalized by co-chairs September 3 – 17, 2014
Final paper submitted to Value in Health September 19, 2014
RARE DISEASE TERMINOLOGY & DEFINITIONS USED
IN OUTCOMES RESEARCH WORKING GROUP
2014-06-04
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If you would like to join the Rare Disease SIG
review group:
Please email Theresa ([email protected]), or
Go to www.ispor.org and click the green
Special Interest Group menu at the top of the
homepage, then select “JOIN” on the pull-
down menu.
FORUM
RARE DISEASE TERMINOLOGY & DEFINITIONS USED
IN OUTCOMES RESEARCH
Q & A
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FORUM
Is there an appetite for global harmonization
of definitions?
Does a universal definition of ‘rare disease’
make sense?
FUTURE CONSIDERATIONS