Dharssi et al. Orphanet Journal of Rare Diseases (2017) 12:63
DOI 10.1186/s13023-017-0618-0

REVIEW

Open Access

Review of 11 national policies for rarediseases in the context of key patientneeds
Safiyya Dharssi1* , Durhane Wong-Rieger2, Matthew Harold1 and Sharon Terry3

Abstract
Rare diseases collectively exert a global public health burden in the severity of their manifestations and the total
number of people they afflict. For many patients, considerable barriers exist in terms of access to appropriate care,delayed diagnosis and limited or non-existing treatment options. Motivated by these challenges, the rare disease
patient community has played a critical role, elevating the patient voice and mobilizing legislation to support thedevelopment of programs that address the needs of patients with rare diseases.
The US Orphan Drug Act of 1983 served as a key milestone in this journey, providing a roadmap for other countries
to introduce and implement similar orphan drug legislation; more recently, the European Union (EU) has gone
further to encourage the widespread adoption and implementation of rare disease plans or strategies designed tomore adequately address the comprehensive needs of patients with rare diseases. Despite these legislative efforts
and the growing contributions of patient advocacy groups in moving forward implementation and adoption ofrare disease programs, gaps still exist across the policy landscape for several countries. To gain deeper insights into
the challenges and opportunities to address key needs of rare disease patients, it is critical to define the current
status of rare disease legislation and policy across a geographically and economically diverse selection of countries.
We analyzed the rare disease policy landscape across 11 countries: Germany, France, the United Kingdom, Canada,
Bulgaria, Turkey, Argentina, Mexico, Brazil, China, and Taiwan. The status and implementation of policy wasevaluated for each country in the context of key patient needs across 5 dimensions: improving coordination ofcare, diagnostic resources, access to treatments, patient awareness and support, and promoting innovative research.
Our findings highlight the continuing role of the patient community in driving the establishment and adoption oflegislation and programs to improve rare disease care. Further, we found that while national rare disease plansprovide important guidance for improving care, implementation of plans is uneven across countries. More researchis needed to demonstrate the effect of specific elements of rare disease plans on patient outcomes.
Keywords: National rare disease plan, Policy, Legislation, Patient advocacy, Europe, Asia, North America, South America

Background
Rare disease is a global public health issue

Individual rare diseases by definition affect few people,
but cumulatively have a major impact on public health.
While the definition of rare disease varies by country,
prevalence-based definitions range from 1 in 500,000 to
1 in 2000 [1, 2]. In the United States, the Orphan DrugAct of 1983 defined a rare disease by the number of affected people; by this definition, the actual prevalence of* Correspondence: Safiyya.Dharssi@pfizer.com
1
Pfizer Inc., 235 E 42nd St, New York, NY 10017, USA
Full list of author information is available at the end of the article

rare diseases varies with population numbers [3]. A disease is considered rare if it affects fewer than 200,000 individuals, whereas other countries define a rare disease
based on prevalence rates [1, 3–6]. For example, in Europe, diseases are considered rare when they affect fewer
than 5 individuals in 10,000 [7]. In Brazil, the definitionis similar to the World Health Organization definition,
as those affecting less than 65 out of 100,000 individuals[8]. In Taiwan, a rare disease is defined as a disease thatis prevalent in fewer than 1 in 10,000 individuals [9].
An estimated 5000 to 8000 rare diseases have been
identified worldwide, affecting approximately 6 to 8% of© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Dharssi et al. Orphanet Journal of Rare Diseases (2017) 12:63

the population [10]. While rare diseases exhibit considerable diversity in etiology and clinical presentation,
most are severely disabling with serious effects on life
expectancy and physical and mental abilities [11]. Further, rare diseases constitute a major economic burden
independent of a country’s size and demographics; thesecosts arise from increased healthcare spending and lost
productivity [1, 12–14].
Many rare disease patients experience barriers in access to care, and fewer than 10% receive disease-specifictreatment [15]. Delayed diagnoses, limited access to resources, and absence of specific therapies often preclude
patients from receiving proper, timely care. Even briefdelays in diagnosis may have profound effects on outcomes; for over 40% of rare disease patients, treatment
delays are precipitated by misdiagnoses [11, 16]. Whenpatients are diagnosed, many are unable to access resources such as centers of expertise, coordinated care,patient support systems, and effective treatment. For
many rare diseases, there are no effective treatments andinformation on disease progression is limited. Therefore,
research into the natural history and underlying pathophysiological mechanisms of rare diseases is necessary todevelop a foundation for discovering targeted medicines.
The patient community plays a critical role toward addressing these challenges, by elevating the patient voice
and partnering in the development of programs to address the needs of patients with rare diseases. Approximately three and a half decades ago, the patient
movement to create awareness and support for rare diseases took shape in the United States under the bannerof the National Organization for Rare Disorders. Joint
efforts under the leadership of a mother (Abby Myers), a
congressman (Henry Waxman), and an actor (Jack Klugman) garnered the national stage in a series of headline
events that captured the public imagination and mobilized Congress to pass the world’s first orphan drug legislation in 1983. This was a seminal event in thedevelopment of national rare disease policy and transformed the landscape for rare disease drug development;from 10 new drugs in the decade preceding the Orphan
Drug Act to over 500 new drugs in the succeeding three
decades [3, 17]. The success of the Orphan Drug Act informed efforts to introduce orphan drug legislation inother countries [18] such as Japan, Singapore, South
Korea, Australia, and the European Union.
While these legislative efforts were more focused on
the development of innovative treatments for rare disease patients, the European Union went one step further,broadly ensuring that comprehensive policy programs
addressed all needs of rare disease patients. In 2009, theEuropean Council adopted the “Recommendation on an
Action in the Feld of Rare Diseases,” which supports the
adoption of national plans and strategies for responding

Page 2 of 13

to rare diseases. The council recommended the development of national plans or strategies to address comprehensive needs, including diagnosis, treatment, care, andsupport of citizens with rare diseases [10]. Countries
were encouraged to consider in these plans aspects suchas the improvement in the awareness of rare diseases,
the support for research into rare diseases, the development of centers of expertise, the empowerment of patient organizations, and the implementation of a robust
healthcare infrastructure.
A number of countries preceded the European Recommendation and France was already ahead of other member states, adopting the First National Plan for Rare
Diseases in 2004 [19]. The plan created centers of expertise that were responsible for coordinating diagnosis
and provision of health and social care, writing national
protocols for diagnosis and care, collecting data, andconducting clinical trials. France’s National Plan served
as the impetus and model for all European Union countries, which have developed or are in the process of developing National Plans or Strategies for rare diseases[19]. In the Asia Pacific region, Taiwan had a set of
established programs, where rare diseases are includedin the National Disability Registry and government social
services programs for patients with rare diseases that include health-related subsidies and tax deductions, school
fee reductions, employment supports, and transportation
discounts. Similarly, Japan had enacted special legislationin 1972 to address “nanbyo,” or rare and intractable diseases, with about 130 “tokutei shikkan” or special designated rare diseases receiving public subsidized care [20].
As national plans for rare diseases evolve, patients andpatient advocates continue to play an integral role inmoving forward the implementation and adoption of the
programs outlined in the plan. The European Project for
Rare Diseases National Plans Development (EUROPLAN) was a project co-funded by the EU Commission
to promote and implement National Plans or Strategies
to tackle rare diseases, to share relevant experiences
within countries, linking national efforts with a common
strategy at a European level [21]. Importantly, EUROPLAN formally included organized patient input and has
played a key role within the European Union in guiding
the establishment and implementation of National Plans
or Strategies for rare diseases [21]. To this end, EUROPLAN included a specific role for the European
Organization for Rare Diseases a European umbrellagroup of non-governmental associations of patients withrare diseases. The European Organization for Rare Diseases ensured that EUROPLAN processes were reflectiveof patient viewpoints, in part by organizing a series ofconferences to discuss coordination of the European
Union and national policy [16]. A committee of rare disease experts, the European Union Committee of Experts

Dharssi et al. Orphanet Journal of Rare Diseases (2017) 12:63

on Rare Diseases (EUCERD) Joint Action, was set up by
the European Commission to formulate and implement
policy to combat rare diseases [22, 23]. The mandate of
EUCERD Joint Action ended in July 2013 and been replaced by the EC Expert Group on Rare Diseases in2013 [24]. The EC Expert Group continues to have astrong presence of patients’ organizations in the field of
rare diseases. The elaboration of policies in the field of
rare diseases and improvement of the codification ofrare diseases has been continued through the scope of
RD-Action, a Joint Action co-funded via the 3rd EU
Health Programme for the years 2015–2018. The European Organization for Rare Diseases (EURORDIS) continues to play an integral role representing the voice of
patients and driving forward the adoption of important
rare disease and orphan medicine legislations at theEuropean level. In addition, similar organizations at anational level, such as the Canadian Organization for
Rare Disorders (CORD), actively play an instrumentalrole in driving forward policy development. Both organizations have developed key position statements that outline top priorities that public decision makers should
consider when addressing the needs of rare disease patients. While each countries policies and programs reflect the priorities of their health care system and needsof rare disease patients, the EURODIS and CORD position statements provide a general, but comprehensive
framework that could be applicable to a majority ofcountries. As such, in this paper, we analyzed the raredisease legislation and associated policies, regulations,and programs across a diverse sample of 11 countries
according to the goals outlined in the European
Organization for Rare Diseases and Canadian
Organization for Rare Disorders position statements.
The objective of the review is to understand where there
are opportunities for further policy development by
examining how these policies and programs might alignwith key needs of the rare disease community, which aresummarized in five dimensions: 1. improving coordination of care, 2. diagnostic resources, 3. access to treatments, 4. patient awareness and support, and 5.
promoting innovative research. We also considered thecontributions of patient advocacy groups and included
some external measures of healthcare provision as an
initial consideration for how current rare disease policy
might align with the healthcare climate. The findings
from this study will inform future studies evaluating
how specific elements for National Plans or Strategies
for rare diseases translate to provision of care for raredisease patients.

Methods
Information for this study was collected and analyzed
from 11 countries: Germany, France, the United

Page 3 of 13

Kingdom (UK), Canada, Bulgaria, Turkey, Argentina,
Mexico, Brazil, China, and Taiwan. Countries includedin the analysis were selected to be geographically and socioeconomically diverse, and represent a wide range ofrare disease policy development. The US was excluded
since it lacks a formal National Rare Disease Plan andpolicy variation across states confounds comparisonswith other countries. The term National Rare Disease
Plan (NRDP) was used to refer to strategies and plansthat have been developed to support a comprehensive
and integrated approach to the delivery of health and social care for rare disease patients.
NRDPs were assessed using publically available official
documents and secondary research. Based on guidance
published [25] for rare disease policy, the following elements of NRDPs were evaluated for each country:







National policy
Access to treatment
Diagnosis programs
Coordination of care
Research
Patient engagement

The data were then assessed on the basis of our fivekeys needs of the rare disease community: coordinationof care, diagnosis, access to treatments, patient awareness and support, and research.

Results
The status of National Rare Disease Plan (NRDP) policy
elements for each of the 11 countries is presented inTable 1. Countries were arranged in the table according
to overall healthcare/economic status, defined by grossnational income (GNI) per capita and healthcare spending (relative to gross domestic product [GDP]), and thelevel of NRDP development. France and Germany havewell-developed NRDPs that are being implemented at
the national level. With the highest healthcare spending
and average wealth healthcare ranks of the 11 countries
surveyed, France and Germany have centralized national
funding, good access to treatments, robust research initiatives, coordinated networks, and cross-border collaborations in place for rare diseases. The UK and Canada
have similar healthcare structures and NRDPs that areboth in the implementation stage with a number of robust programs in place. Bulgaria and Turkey have draft
or full plans approved and comparable levels of healthcare spending, but their plans have had limited implementation. Argentina, Mexico, and Brazil have similar
healthcare spending relative to gross domestic product(GDP) but NRDPs are awaiting development or are very
early in implementation. Finally, the NRDPs of China

Two plans
implemented;
Launch ofthird planunderway

Central EU
authorization
COMP OD
Designation

Processes inplace for ODs
with andwithout
marketauthorization

Marketauthorization
requiredODs can only
be prescribedin RD
competence
centers (+500
in France)
No ODspecificfunding

Neonatal
screening
available for 4
pathologies (2RDs)
Inequality inaccess to tests

131 centers ofreference and501 centers ofcompetence
are in place

300+ fundedclinicalNational
PolicyAuthorization
Process

Early Access
Programs

Current
Access toTreatment

Diagnosis
Programs

Coordinationof CareResearch

France28 RD organizations
supported by

RD expert centers
and networks forcross-border researchin place

Newborn screening
available for 14
conditions
Screening andgenetic testingmandatory, but nospecific RD policies

Several initiatives
exist to improveaccess to ODs
No OD-specificfunding

Granted during thethird phase of theclinical trial andwhen the product’s
safety and efficacy
are guaranteed.

Central EU
authorization
COMP OD
Designation

Adopted;implementation
underway

Germany

Canadian Institutesfor HealthCenters ofExpertise in
specific rarediseases; somelinked to researchacross sites withadult clinics
No national
coordinating bodyfor all RD Centersof Expertise

UK Strategy for
Rare Diseases
Calls for specialist
centres to deliver
coordinated care,
150 providers ofhighlyspecialized
services

Collaborative
initiatives with

Provincial
newbornscreening
programs vary innumber andconditions
Health Ministers to
implement
screening
programs for 22
conditions

ODs assessed
through same HTA
process as otherdrugs
Provincial Drug
Plans-special provisions for ODs

No plan for early
access;Patients may apply
to the Special
Access Program in
specialcircumstances

Accelerated review
available

TurkeyGrowingawareness but few

Not in place
RD committee notyet operational

National programfor early diagnosis
expected to be
fully funded/
operational by2016

No initiatives,
networks, or

Few centerswith specialized
services; mostly
university
hospitals andresearch centers

Few publicdiagnosis
centers
Neonatal
screening for 3
RDs throughMinistry of
HealthGenetic testingat universities;
testing abroad
possible

Pathways foraccess aredefinedNo OD-specificfunding

Programavailable forpatients withunmet medical
needs meeting
defined criteria

No legal provision
for early access

Access to ODs
improvedmarkedly over last
4 years
Specialconsiderations for
HTAs of ODs
10% of annual
NHIF budget
allocated to ODs

No defined OD
designation

Draft guideline
passed;implementation
delayedCentral EU
authorization
COMP OD
Designation

Bulgaria
Approved; limited
implementation

CanadaAdopted;implementation
underway

The UK Rare
Disease Strategy
does notspecificallycontain early
diagnosis
programs
Expansion of RD
testing in
newborns as of
2015

NICE HST review
process for ultraorphan drugs
Scotland’s New
Medicine Fund
allocated £80 M
for ODs

Early Access to
Medicines
schemeapproved, but
not specific toRD

Central EU
authorization
COMP OD
Designation

Plan adopted forall 4 UK nations;
implementation
underway

UK

Table 1 Summary of rare disease policy and regulatory frameworks across 11 countries
Argentina

No national
initiatives in place

Planned: Act 26.689
Cibersaludlaunched tostrengthen
specialist networks“Hiptour” patientlead initiative provides medical guidance to HCPs

Legislation passed,
but no programs in
place

Comprehensive RD
patient care: Act
26.689 not yet
implemented
Refund systemprovides financial
support to Social
Health Service forselect drugs

Program for freeaccess to drugs
from othercountries in place

ANMAT regulatesconditions for drug
approval
Streamlined
authorization
available for US or
EU-approved drugs
OD registration
process in place

Approved; awaiting
implementation

MexicoNo fundedresearch

No developed
centers, butfunctionallyactive networkof 12 civilorganizations
Lysosomal
Storage
Disease
Network:
diagnosis,
treatment,
supportNo early
diagnosis
initiatives
Limitednewbornscreening
Early Diagnosis
Clinic underdevelopment

Limitedinformation
available
No OD-specificfunding

No programsin place

Accelerated
review
available
Process inplace for OD
classification

No uniform
plan

Brazil

Few incentives; no long-standing initiatives;
Initiative in 2014 by the National Council of

National policy initiated with accreditation of
specialized health centers in progress;

Newborn screening available for 6 RDs
Main rare diseases research centers is locatedin the Federal University of Rio Grande do
Sul,for diagnosis

Limited access through public health system
No OD-specific funding

No legislation or programs in place
Unregistered medicines can be imported
upon request

Accelerated review available; timelines vary
No special registration process for ODs

In early implementation stageNo
comprehensive
specialist centers
Centers for
specific RDs
located in Beijing
and Shanghai
Most mature
treatments forhematologic RDs

No national
screening and/or
diagnostic
programs
available

No special accessconsiderations
No OD-specificfunding

ODs yet to beauthorized may
be available
through donation
programs

Delays in OD
drug approvaldespite fast-trackprogram
No distinction
between ODs
and regular drugs

None

China

No RD-specificnational registryNocomprehensive
specialist
centers
10+ RD genetic
counselingcenters
approved
Some NPs
implemented
but coordinatedcare not fully
developed

Improved
screening anddiagnosis indevelopment
Nation-wide
newbornscreening
program for 26+
diseasesSpecial accessconsiderations
Several drugs
approved
recently
Separate budget
not covered by
NHI

No formal NP inplace, but
policies
implemented
Unregistered
medicines canbe imported
upon request

Accelerated
review available
Process in place
for OD
classification

Adopted;implementation
underway

TaiwanDharssi et al. Orphanet Journal of Rare Diseases (2017) 12:63
Page 4 of 13

40,580

11.5

1.8

Gross
National
Income per
Capita (2015)

Healthcare
Spending (%GDP)

Average
WealthHealthcare
Rank

2.3

11.3

45,790Established patientorganizations areengaged and play arole in RD policy

Ministry of Education
and Research
BMBF funding 12
research projects;€23 million allocatedfor 3 years
Cross-borderresearch projects
No central
coordinated RD
registry

2.3

9.1

43,340Establishedpatient
organizations
play active role
Stakeholder
engagement byRare Disease UK
and Specialized
Healthcare
Alliance

pharmaceuticalcompanies forpatient-centeredresearch exist
UK10K project on
RD genetics
Public Health
England intends
to build national
RD registry

2.8

10.4

47,500Patient groupsupport andadvocacy
facilitated by
CORD
National Strategy
launched withRare Alliance
CanadaResearch funds
basic andtranslational
research
Proposed formal
inclusion of RD
research in CIHR,
Genome Canada,
and IRDiRC

7.8

8.4

7220

Patient
organizations
actively engaged
Implemented
support andeducation
programs andplayed a role in
the launch of 13
RD registries

research initiatives
in place
Centralized patientregistry approved
but not yet
operational

6.5

5.4

9950

Littleinformation
available

cross-bordercollaborations
No national
registries, but
Turkeyparticipates in
Europeanregistries
Comprehensive
national
epidemiologicalsurveyunderway

7.0

4.8

13,640Patient
organizations play
active role
Collaborations withgovernment aided
implementation of
RD legislation andprograms

Some research
conducted withsupport frompatient
organizations,research grants, or
private initiatives
Legislation passed,
but registries still
under development

7.3

6.3

9710

Patient
organizations
play animportant,active role

projects or
initiatives
Developmentof RD patient
database inprogress

6.5

8.3

9850

Patient organizations play an important role

Scientific and Technological Development(CNPq), which screened and funded 15 research projects devoted to rare diseases (diagnosis and treatment)
Bill to secure RD research funding underreview
No national registries
Patient groups collect data
DORA program and FEMEXER RD database indevelopment

5.0

5.5

7820

Patient advocacy
groups limited
but localized RDgroups raiseawareness/promotelegislation
ChineseOrganization for
Rare Disorders
active in RDICARDPT national
research program
initiated in 2013
Cross-border
initiatives gaining
momentumNo national
centralized
patient database/registry
Registry launchedat local level in2013
Patient groupdeveloped database in progress

8.8

6.6

22,723

Strong patient
support/advocacygroups active
in RD policy
TFRD helped
pass 2000 Rare
Disease Control
and ODA

National
disability registryin place andhemophilia
registry indevelopment

Abbreviations Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; BMBF Bundesministerium für Bildung und Forschung, Federal Ministry of Education and Research; CARDPT China Alliance for Rare Disease Prevention and Treatment;
CIHR Canadian Institutes of Health Research; CORD Canadian Organization for Rare Disorders; EU European Union; DORA Doenças Raras, rare diseases; FEMEXER Federación Mexicana de Enfermedades Raras, Mexican Federation for Rare Disorders; HTA
Health technology assessment; IRDiRC International Rare Diseases Research Consortium; NHI National Health Insurance; NHIF National Health Insurance Fund; NICE National Institute for Health and Care Excellence; NP national plan; OD orphan drug; RDrare disease; RDI Rare Diseases International; TFRD Taiwan Foundation for Rare Disorders

Establishedpatient
organizations
are engaged
and play arole in RD
policyPatient
Engagement

research
projects
Funding
allocated forbasic andclinicalresearch
BanqueNationale deDonnées
Maladies Rares
national
databaselaunched
European/international
collaborations
developed

Table 1 Summary of rare disease policy and regulatory frameworks across 11 countries (Continued)

Dharssi et al. Orphanet Journal of Rare Diseases (2017) 12:63
Page 5 of 13

Dharssi et al. Orphanet Journal of Rare Diseases (2017) 12:63

and Taiwan are not proposed or are proposed but not
fully implemented.
The patient organization actions for each country arepresented within each of the five dimensions representing key needs of the rare disease community, summarized below.
Dimension 1: Coordination of care

The term “coordination of care” was used to describe resources designed to improve the provision of timely,
equitable, and evidence-informed care. Programs andterminology vary by country but include Centers of Expertise (COEs) on rare diseases, integrated healthcare
administrative databases, and national registries for rarediseases. While some countries attempt to coordinate
their approach to rare disease management using centersof expertise, many countries do not, either because they
have not yet adopted this approach or are employing different strategies.
The concept of dedicated and comprehensive centers
for rare diseases was originally developed by France for
its first National Rare Disease Plan (NRDP), and thenadopted by the EU upon the request for national plansnearly a decade ago. France has over 600 centers thatcoordinate research, train healthcare professionals(HCPs), and facilitate diagnoses (Table 1) [26]. Although
centers of expertise do not exist, per se, in the United
Kingdom (UK), the UK Strategy for Rare Diseases recommended the creation of specialist centers to deliver
coordinated and expert care required to support theneeds of rare disease patients [27]. The Birmingham
Centre for Rare Diseases is an example of the way one
hospital has created a specialist center for treating patients with rare diseases. In addition, the English National Health Service lists about 150 providers of highly
specialized services, some of which are directed at rarediseases, such as liver transplant services, enzyme replacement therapy, and proton beam therapy for specificcancer treatments [28]. Further, the European Union recently issued criteria for designating European Reference
Networks (ERNs) across the European Union for treating rare medical conditions and in December 2016 approved the first wave of 23 European Reference
Networks (ERN)s [27, 29].
In the Asian countries surveyed, no formal NRDPs forCenters of Expertise are in place. The Taiwanese Bureau
of Health Promotion has approved medical institutions
to serve as centers for diagnosing and treating rare diseases, and Taiwan has at least 10 approved genetic counseling centers [30]. However, the coordinated care acrosscenters is not fully developed. Given the relatively small
geographic size of Taiwan, patients may not have totravel far to access treatment, but, in larger countries,
dispersal of uncoordinated resources is a challenge. To

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this point, barriers in the coordination of care in Latin
American countries are due to large population sizes
spread across vast landscapes, with many patients located far from urban centers where centralized expertise
tends to be located. However, to support access to expertise in rural areas, many countries are employing
technology to address this issue. In Argentina, theHealth Ministry recently launched Cibersalud, an innovative tool to strengthen the network of specialists inthe country and facilitate referrals, diagnosis, and monitoring. Cibersalud seeks to promote consultations
among healthcare professionals from different establishments in the country and to assist teaching activities,
through the provision of technological equipment andthe development of applications that allow videoconferencing between establishments. More recently, theMinistry of Health launched an interactive course on
Rare Diseases aimed at strengthening the diagnosis ofrare diseases. The course is intended for healthcare
professionals, including pediatrics, family medicine
and general practitioner residents of public hospitals
and training is conducted through on online discussion on clinical cases and biweekly telemedicine meetings (i.e. Cibersalud) [31, 32].
In countries without formal centers for rare diseases,
patient groups are playing an active role in supporting
coordinated care. For example, in Argentina, the Pituitary Diseases Association implemented “Hiptour” to provide medical guidance to professionals for the diagnosisof pituitary diseases in new patients. In Mexico, theLysosomal Storage Disease Patient network has helped
to create a model of comprehensive care starting withdiagnosis and including treatment and support thathas garnered high-level political attention and endorsement. However, it is centrally located and also
limited in outreach resources. Overall, identifying andcreating Centers of Expertise or comparable programs
represent an important step toward consolidating
existing rare disease expertise.
Dimension 2: Diagnosis

An accurate and timely diagnosis is predicated on availability of universal or highly accessible screening anddiagnostic programs and services. Across the surveyedcountries, policies and practices varied significantly.
Neonatal screening has the potential to contribute to an
early diagnosis and management of a fraction of rare diseases when there is an effective intervention which can
avoid or mitigate severe consequences and/or death ifprovided early enough Multiple conditions can be identified from a single bloodspot collected at birth. However
it is important to note that the composition of a newborn screening panel can vary between regions, depending on local prevalence. A number of newborn screeningDharssi et al. Orphanet Journal of Rare Diseases (2017) 12:63

programs commonly utilize criteria established by JMG
Wilson and F. Jungner in 1968 to decide whether a particular condition is a suitable candidate for screening [33].
A recent report on the practices of newborn screening implemented in EU member states noted that most jurisdictions also take guidelines of scientific societies inconsideration [34]. However, many aspects are subjective
and there is not always agreement about which disorders
should be part of the panel. With the advent of new diagnostic technologies, debates have currently arisen as tohow screening programs should adapt.
Many countries have implemented core programs of
neonatal screening (eg, Taiwan, Brazil, UK, Germany).
Taiwan has implemented a nation-wide newborn screening program that covers at least 26 diseases [30]. Similarly, Germany tests for 14 conditions nationwide [35].
While this number is far removed from the total numberof identified rare diseases, only a limited number of neonatal screening assays are currently available. In 2016,
Canada announced that the Health Ministers had agreed
to a list of 22 core conditions for newborn screening
programs across all provincial and territorial jurisdictions, although some provinces were already routinely
testing for 30+ diseases [36]. These requisites are allconsiderably lower than the number of rare diseases that
could be tested with a single bloodspot, and this is trueof most countries globally (except for the United States,
where some states test for 50 or more diseases). In mostof the countries surveyed, there was a distinct lack offormal programs for newborn screening and/or infrastructure/resources to support implementation, and thiswas apparent across geographic regions, with Argentina,
Brazil, China, and Taiwan as leading examples whereother rare disease initiatives are in place or in planning
but limited attention has been given to core newborn
screening as an essential component of the rare diseaseprogram. For example, in Brazil despite the progressive
translation of genetic research into a clinical field and efforts by the Ministry of Health to establish the National
Newborn Screening Program (Programa Nacional de
Triagem Neonatal – PNTN) in 2001, progress still remains to take place. Currently, only six diseases are included in the formal newborn screening program [8, 37].
The panel still is modest when compared with thescreening programs of other countries, including Taiwan
with 26 diseases and Germany with 15 diseases.
Beyond the neonatal stage, diagnosis of rare diseases
can be even more difficult, resulting in long delays indiagnosis and many misdiagnoses. Geographical challenges exacerbate this problem since long journeys tovisit specialists in different regions can impair accurate
diagnosis. In Mexico, some patients describe “medical
pilgrimages” to different doctors so as to reach a diagnosis, which can take 5 years or longer to achieve. A 2012

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European Organization for Rare Diseases survey of eightrare diseases representing 12,000 patients found that 25%
of patients had to wait between 5 and 30 years for a diagnosis, 40% received an initial erroneous diagnosis (leading
to wrong medical interventions), and 25% had to travel toa different region to obtain a diagnosis [38]. Similarly, asurvey conducted by the Canadian Organization for Rare
Disorders found that about 20% of patients waited between 6 and 14 years to get a diagnosis and 60% consulted
3 to 20+ specialists on the way to a diagnosis. Importantly,
the availability of robust diagnosis and neonatal screening
programs can significantly reduce the patient diagnostic
odyssey and bridge the gap between disease onset anddiagnosis that, for many countries, represents a major barrier in access to care.
Beyond awareness, an important strategy that is being
promoted in many countries is education for health carepractitioners to develop and expand expertise in rare diseases. For example, the Argentinian Health Ministry
launched a tool to promote collaboration between professionals from different institutions across the country withthe goal of improving diagnosis. In many emerging healthcare systems, patient groups have taken an active role inpromoting professional education and collaboration. The
mobilization of a cystic fibrosis patient group was important in shaping decisions on what diseases are screened in
Brazil, while, in Mexico, patient groups have spurred thedevelopment of early diagnosis funding, patient registries,and efforts to raising rare disease awareness. Progress inthese directions has also occurred in the Asia-Pacific region, as the Taiwan Foundation for Rare Disorders (TFRD)
coordinates efforts with the Bureau of Health Promotion
to send specimens for testing in both foreign and domestic labs for improving diagnosis and subsidizing costs forrare disease testing at local hospitals.
Dimension 3: Access to treatments

The availability of rare disease treatments is addressed in a
number of national regulatory and legislative policies designed to facilitate orphan drug designation, authorization,and early access programs. The European Union passed
regulation (EC) No 141/2000, on orphan medicinal products in 2000, which covers all of the countries in the EU, including the UK, Germany, Bulgaria and France represented
in this survey [39]. Further, the Committee for Orphan Medicinal Products (COMP) was established with the responsibility to recommend orphan designation of medicines forrare diseases to the European Commission for final decision[40]. In the European Union under the Regulation on Orphan Medicinal Products, medicines designated as orphan
medicinal products are provided incentives, including
protocol assistance. More recently, under the new Priority
Medicines (PRIME) scheme, the European Medicines
Agency (EMA) will offer early and enhanced scientific andDharssi et al. Orphanet Journal of Rare Diseases (2017) 12:63

regulatory support and enable accelerated assessment fortherapies that address significant unmet medical need andoffer the potential to bring a major therapeutic advantage
to patients [41]. Several other countries have expedited review processes for orphan medicines, namely, Turkey,
Mexico, Brazil, China [42], Taiwan, and Canada [43], but
the criteria and process vary across the countries [44, 45].
In Brazil, the Agência Nacional de Vigilância Sanitária(ANVISA), enacted a regulation (Resolution RDC 28) in2007 that was further clarified in 2008 (RDC 16), statingthat orphan drugs should receive priority review and a decision on approval within 75 days [8]. In practice, the approval can take much longer and regulatory developments
are underway to improve review timelines. In Mexico,
despite no specific regulation for expedited approval, orphan medicinal products that have been approved byother Agencies, such as the US Food and Drug Administration or the European Medicines Agency, can be expedited via a letter of recognition, and this mechanism has
shortened the authorization timeline to approximately
6 months [45]. Argentina has had similar success with aprogram administered by the Argentinian National Administration of Medicines, Food, and Medical Technologythat streamlines authorization requirements for orphan
drugs approved in the United States or the EU [45]. In
Canada, drugs for unmet needs or urgent situations are
eligible for expedited review.
For approved drugs, several countries have policies inplace to ensure timely patient access to treatment following regulatory approval. The UK’s National Institutesfor Health and Clinical Excellence (NICE) have established a separate review process for “Highly Specialised
Therapies” which address ultra-orphan diseases (population of less than 1 in 10,000) [46]. Elsewhere, within the
UK, The Scottish Medicines Consortium has also developed a new approach for reviewing rare disease medicines designed to increase the influence of patients andclinicians in the appraisal process. This “Patient andClinician Engagement group” can be convened to address additional benefits that may not be represented in
the conventional clinical and economic assessment
process. Scotland also has a New Medicine Fund thatwas recently expanded to £80 million a year allocated toorphan drugs to ensure patient access to the most advanced therapies for diseases with unmet needs [47].
Similarly, in Bulgaria, special considerations are madefor health technology assessments for rare disease treatments [48]. Further, Argentina employs a unique systemof refund that administers financial support to the Social
Health Service for certain drugs.
Dimension 4: Patient awareness and support

To what degree do patients and families get the education and support for their rare disease? For each country,

Page 8 of 13

we looked at three key indicators: public awareness directed toward better identification and support, patient
education toward, among other things, engagement, advocacy and access to resources, and healthcare professional development to enhance diagnosis, treatment, andcare. The countries within our sample varied considerably regarding who was involved, what was done, andhow much was achieved. Public awareness ranged fromcomprehensive campaigns organized by dedicated national or international organizations to local awarenessinitiatives implemented by stand-alone groups. In all
types of activities at all levels, patient organizations wereactively engaged. In the United Kingdom, France, andGermany, established patient advocacy organizations,both disease-specific and cross-disease, organized anddelivered a range of programs including education andawareness conferences, patient guides to rare disease research [49], and advocacy that spanned from support forlegislative acts to receptions with government leaders[50]. In other countries where few other stakeholders
were active, strong national rare disease patient networks had the strongest influence on awareness, policy,
and health system response. Examples come from disparate regions in our sample. For instance, in Bulgaria,
patient organizations implemented award-winning programs and support for rare diseases and, as importantly,
educated and motivated the rare disease patient community not only to better access and navigate the healthcare
system but also to advocate for their cause, including acall for legislative action to support their needs and playing an integral role in the launch of 13 epidemiologicalregistries for rare diseases [51]. Similarly, national raredisease collaborations in Argentina and Canada [52]have prompted governments to implement legislation
and rare disease programs.
In the Asia-Pacific region where our sample consistsof China and Taiwan, rare disease patient support andadvocacy groups have been active but the scope and impact of their involvement have varied, reflecting differences in political, economic, geographic, and healthcare
contexts. In Taiwan, the non-governmental organization
Taiwan Foundation for Rare Disorders (TFRD) deliberately focused on obtaining government support for patients and families with rare diseases. To that end,
Taiwan Foundation for Rare Disorders has had a key rolein shaping rare disease policy and advocating for raredisease patients. Established nearly two decades ago, theorganization leads education, awareness, and advocacy
efforts. Through coordinated efforts with governmentalorganizations, Taiwan Foundation for Rare Disorders
helped pass the Rare Disease Control and Orphan DrugAct of 2000. In China, where patient advocacy groups
are limited in number, localized and disease-specific,
medical rare disease groups have focused their efforts

Dharssi et al. Orphanet Journal of Rare Diseases (2017) 12:63

primarily on implementing educational initiatives. Recent efforts have been made to bring together different
members of the stakeholder community. In 2011, Chinese medical professionals issued a call to support healthcare, research, drug development, and epidemiologicalstudies for rare diseases [53]. Patient groups, charitableorganizations, and pharmaceutical companies have cohosted patient assistance programs and academic meetings on International Rare Disease Day (February 29)
and China Birth Defects Prevention Day (September 12)
each year to raise public awareness and promote legislation for rare diseases. More recently, the Chinese
Organization for Rare Disorders, formed from an amalgamation of several groups and now representing approximately 40 rare diseases, has conducted several
highly innovative and impactful awareness and education
programs.
The Chinese and Taiwanese national networks are distinct in their focus and advocacy. Taiwan has more generally focused on within-country awareness raising andlobbying, eschewing most international activities, while
the Chinese Organization for Rare Disorders has participated extensively in international arenas and also invited
many foreign patient advocates and other experts to
support their efforts in China. The differences are due tocontext. Taiwan is geographically and population-wise asmall country, with a relatively strong economy and ahigh-quality and well-resourced healthcare system that isreasonably accessible to most patients. China, by contrast, is huge in both land mass and population with an
emerging economy and evolving healthcare system. The
Chinese Organization for Rare Disorders has sought toattract international attention, best practices, and advocacy support. To that end, the Chinese Organization for
Rare Disorders is a founding member of the Asia-Pacific
Alliance of Rare Disease Organizations and in 2014 washost to the founding meeting of Rare Disease International (RDI), a global alliance of rare disease patientsand advocates, to raise awareness, exchange information,and increase the support of the rare disease cause. Participation in the Rare Disease International meetingbreaks new ground in that it is an international, patientled advocacy group and the Chinese Organization for
Rare Disorders has the opportunity to host the International Conference on Rare Diseases along with theRare Disease International meeting in 2017.
Some countries had plans that specifically included
health care professional education and training as a key
area of focus (Argentina, Germany), while other countries did not emphasize health care professional development (Mexico, China), and this difference reflects, tosome degree, the differential involvement of HCPs in therespective patient organizations. The Treatment and Research Centre for Rare Diseases in Germany provides

Page 9 of 13

continuing medical education through the German
Academy for Further Medical Training on Rare Diseases
program, which facilitates interactions and communications between physicians and relevant experts as well as
patient organizations [54]. In Brazil, a new National Policy of Integral Attention to People with Rare Diseases includes health care professional training to create
specialized teams of professionals to treat patients withrare diseases.
Dimension 5: Research

Research for rare diseases is commensurate with overall
GDP as well as investment in innovation, science, andhealthcare; it has been relatively well funded with government investment in some countries (France,
Germany, UK, Canada) and not officially supported inother countries (Turkey, Mexico). At a regional level,
the European Union has demonstrated a strong commitment to rare disease research through the EU Framework Programme for Research and Innovation. Under
the Seventh Framework Programmes for research(2007–2013), over €620 million in support was granted
to over 120 collaborative research projects on rare diseases. The funding facilitated the formation of multidisciplinary teams from universities, research organizations,industry, and patient organizations from across Europe
and beyond [55]. More recently, Horizon 2020, whichruns from 2014 to 2020 continues the European Union’s
strong commitment to funding rare disease research[56]. At a country specific level, France, which currently
funds over 300 clinical research projects with collaborations across national and international institutions, isseen as a leader in the research space [26]. In Germany,
the Federal Ministry of Education and Research (BMBF)
is currently funding 12 research consortia since 2012,
with more than €23 million for three years and has supported additional funding through initiatives such as the
National Genome Research Network [54, 57]. In China,
the China Alliance for Rare Disease Prevention andTreatment (CARDPT) has established the first ever national research program of prevention and treatment forrare diseases, which intends to compile basic data onrare disease pathophysiology and natural history, develop
and apply medical guidelines, and promote molecular
testing for rare diseases [58]. In Canada, the government
has committed funding through the Canadian Institutesfor Health Research for emerging teams and consortia ofresearchers, as well as funding to maintain rare diseasemodels and funding for translational research (geneidentification, disease registries, and pilot clinics).
In several countries (Bulgaria, Turkey, Argentina,
Mexico, Brazil), there appear to be few or no national
initiatives to promote research and/or innovation in thetreatment of rare diseases. Research projects inDharssi et al. Orphanet Journal of Rare Diseases (2017) 12:63

Argentina are often conducted and funded through private initiatives, research grants, or support from patientorganizations. Similarly, there is no long-standing initiative to promote research on rare diseases at the national
level in Brazil; however, a bill intending to secure funding for rare and neglected disease-related research iscurrently being reviewed by Congress.
Registries are important means of collecting disease,demographic, and treatment data. France is a model fornational coordination of registries with their BanqueNationale de Données Maladies Rares, a nationalorganization collecting and organizing data from centersof expertise [59]. French patients enter the registry via thecenter at which they receive care. In contrast, the UK,
Bulgaria, and Argentina, have national patient registries invarious stages of planning, but not implemented as of yet.
To help support the standardization and sharing of information across rare disease registries, the European Commission, within the EU Program of Community Action in
the field of Public Health, has initiated the establishmentof a European Platform for Rare Disease Registries to address the challenge of standardizing and sharing information across rare disease registries. [60]. This platform isstill in development. Orphanet tracks rare disease registries, databases, and biobanks so as to provide access tothis information to all stakeholders
Overall, a movement toward international registries is
evolving; for example, national rare disease registries are
not well developed in Turkey, but the country has participated in European registries such as TREAT-NMD (forneuromuscular disease) and EUROCARE CF for cystic fibrosis. In Bulgaria, patient groups are working to modify
legislation addressing patient registries. In Brazil, no national registries exist for rare diseases, but patient associations have been able to collect information in diseasespecific areas. Some countries such as Mexico and China
have registries that are geographically dispersed and locally based, but lack standard structures to facilitate
patient-specific or whole-population analyses. While a national disability registry exists in Taiwan, registries specific
to rare disease are lacking; however, the Taiwan Society ofThrombosis and Hemostasis is currently implementing apatient registry specific to hemophilia.

Discussion
This study assesses the status of rare diseases in a sample of countries varying across economic, political,
healthcare factors and, at the same time, examines therole of patient organizations in shaping national policy
and programs, including rare disease legislation, nationalrare disease plans, and coordinated comprehensive services directed to rare diseases. Most of the countries
represented in our sample (France, Germany, the UK,
Canada, Bulgaria, Argentina, Brazil, Mexico, andPage 10 of 13

Taiwan) have developed or announced intentions to develop a National Rare Disease Plan, some of which are
officially recognized by the government but none, except
for France, are experiencing coordinated strategies andpolicies toward comprehensive implementation. Indeed,
the scope and capacity vary considerably. In general,countries that had higher healthcare spending and GNI
per capita, as well as national healthcare delivery systems(France and Germany), also had well-developed national
plans that encompass early access to treatments, fundingfor orphan drug access, diagnosis programs, coordinatedcare, and strong research initiatives. In contrast, the UK
and Canada are similar in their financial metrics as well
as regionalized healthcare delivery structures, whichhave challenged the development of national centers ofexpertise, national guidelines for screening and diagnosis, and national criteria for access to therapy. Scotland,
Northern Ireland, and the United Kingdom have uniquedrug assessment agencies. In the United Kingdom, theNational Institute for Healthcare Excellence (NICE) has
developed a separate body to assess “highly specialized
drugs” primarily for ultra-orphan indications [61], while
Scotland introduced a dedicated Rare Conditions Medicines Fund [62] and Northern Ireland considers someform of “ring fenced fund” for orphan drugs [63].
Turkey, Mexico, and China do not have orphan drug
legislation; analysis of external financial metrics revealed
that these countries also had the lowest GNI per capita
and healthcare spending. Countries that were lesser developed and/or had low healthcare spending and GNI
per capita were more likely to have National Rare Disease Plans (NRDP) that were not endorsed or implemented. Still, some countries lacking formal NRDPs had
legislation/policies/regulations in place to improve access to orphan drug treatment (eg, orphan drug classification and accelerated review policies exist in Mexico).
Clearly, gaps exist between policy and practice. While anumber of countries have regulations specific to orphan
drugs that are designed to accelerate the authorization
process, streamlined processes do not necessarily expedite
or guarantee drug approval. In Brazil, the established timeframe for responding to authorization requests is 75 days,
but authorization times have varied from 13 to 30 months.
Bulgaria and Scotland were the only countries acrossthose surveyed to have specific funding allocated to orphan drugs. However, orphan drug licensing in Bulgaria isoften delayed from 1 to 6 years.
Despite the lack of formal NRDPs in place, several
countries have been able to make great progress in improving processes in the rare disease landscape. Though
Canada did not have a national plan in place until September 2015, it has a very strong newborn screening
policy and well-established diagnostic centers that exceed what is available in many other countries [36]. InDharssi et al. Orphanet Journal of Rare Diseases (2017) 12:63

the Asia-Pacific region, Taiwan provides a model for good
programs that exist in the absence of specific policy; improved screening and diagnosis programs are in development, led by advocacy groups and funded by the
Taiwanese government. Further, Turkey has defined pathways for early treatment, designated specialized centers
for coordinated care, and provides screening and diagnosis
programs despite delayed implementation of its NRDP.
Several countries, inspired by the progress in Europe,
have adapted the consultation process and the core indicators developed by the EUROPLAN project to support
the development and implementation of rare diseaseplans and strategies [64]. In Canada, the Canadian
Organization for Rare Disorders played an instrumentalrole in the strategic development and implementation of
the Canadian NRDP, which was distilled from 30+ other
NRDPs and asserts goals that are closely aligned withthose of the UK Strategy for Rare Diseases [65, 66]. Consistent with the position of the European Organization
for Rare Diseases (EURODIS) on rare disease research
infrastructure, development, and governance, the inclusion of patients as full and equal partners is a central
recommendation set forth by the Canadian Organization
for Rare Disorders (CORD) [65, 67].
In other countries, including Mexico, the patient advocacy community is playing a large role in shaping discussions, educating policy makers and driving the political
agenda to support national rare disease strategies by actively participating in small working groups with theirnational Health Commissions. In several countries without formal NRDPs, coordinated and influential diseasespecific advocacy groups have provided leadership in addressing gaps and implementing programs to support
key needs within the community. One such example of
the active role patient groups are playing in supporting
coordinated care in the absence of formal centers of expertise is seen in Argentina, where advocates from thePituitary Diseases Association in Argentina travel
around the country and provide medical updates on pituitary diseases to professionals to help identify anddiagnose patients. Similarly, patient groups in Bulgaria
have been working to modify legislation addressing patient registries to create a centralized registry that ismore compatible with international databases. In China,
the China Alliance for Rare Disease Prevention andTreatment has established the first ever national research program of prevention and treatment for rare diseases. This demonstrates that despite national
prioritization, patient advocacy organizations can drive
successful implementation of programs that can help
support the key needs of rare disease patients. However,despite the successful adoption of these programs, integrated and coordinated strategies are necessary to ensure
holistic access to care and treatment for patients.

Page 11 of 13

To further garner support, patients can further policy
development by creating alliances between/among organizations. The Iberoamérican Alliance for Rare Diseases(ALIBER) has established a system across IberoAmerican countries to collaborate and share ideas surrounding rare diseases. The recently formed Asia-Pacific
Alliance of Rare Disease Organizations (APARDO) represents a collaborative unification of national rare disease groups aimed at improving access to care andtreatment of rare diseases in China, Japan, India,
Australia, and Singapore. Importantly, many countries
analyzed in this study are members of Rare Disease
International (RDI), which provides a clear framework
for establishing and improving advocacy, awareness, information sharing and networking, research, and partnerships. As the landscape of rare disease policy
continues to evolve, the unification of rare disease patient organizations will be essential to driving innovative
research with shared resources and best practices, andamplifying the role of the patient voice in the development of programs to address the needs of the rare disease community.

Conclusion
According to the goals outlined in the EURORDIS and
CORD position papers, our study explored the rare disease legislation, associated policies, regulations, and programs across a diverse sample of countries through theperspective of the key needs of the rare disease community. Consistent with previous reports [25, 68, 69], ouranalysis revealed substantial differences in rare disease
infrastructure across countries; however, it was limitedin the scope of the countries considered and was not designed to assess the effect of specific policies and structures on patient outcomes. Subsequent analyses should
be conducted to correlate policy with the presence of actual programs and, ultimately, their effects on patientcare. Importantly, this information will provide a strategic framework that can structure ongoing dialogues
within and between countries so as to define best practices in rare disease management and harmonize efforts
across the globe in improving patient care.
Abbreviations
ALIBER: Alianza Iberoamericana de Enfermedades Raras, Iberoamérican Alliancefor Rare Diseases; ANVISA: Agência Nacional de Vigilância Sanitária, National
Health Surveillance Agency; APARDO: Asia-Pacific Alliance of Rare Disease
Organizations; BMBF: Bundesministerium für Bildung und Forschung, Federal
Ministry of Education and Research; CARDPT: China Alliance for Rare Disease
Prevention and Treatment; COE: Centers of Expertise; COMP: Committee forOrphan Medicinal Products; CORD: Canadian Organization for Rare Disorders;
EMA: European Medicines Agency; ERN: European Reference Networks;
EU: European Union; EUROPLAN: European Project for Rare Diseases National
Plans Development; EURORDIS: European Organization for Rare Diseases;
GDP: Gross domestic product; GNI: Gross national income; HTA: Healthtechnology assessment; NICE: National Institute for Health and Care
Excellence; NORD: National Organization for Rare Disorders (NORD);
NRDP: National rare disease plans; ODA: Orphan Drug Act; PRIME: Priority

Dharssi et al. Orphanet Journal of Rare Diseases (2017) 12:63

Medicines; RDI: Rare Diseases International; TFRD: Taiwan Foundation for Rare
Disorders; UK: United Kingdom
Acknowledgements
InVentiv Medical Communications provided medical writing and editorial
supportKyra Faircloth provided support in the initial research
Funding
This project was funded by Pfizer Inc.
Availability of data and material
The datasets used and/or analyzed during the current study available fromthe corresponding author on reasonable request.
Authors’ contributions
Conceived and designed the review: SBD, DWR, ST, MH. Compiled andanalyzed the reviewed material: SBD, DWR, MH. Wrote the paper: SBD, DWR,
ST, MH. All authors read and approved the final manuscript.
Competing interests
SBD & MH are employees of Pfizer Inc.
Consent for publication
Not applicable
Ethics approval and consent to participate
Not applicablePublisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.
Author details
1
Pfizer Inc., 235 E 42nd St, New York, NY 10017, USA. 2Canadian Organization
for Rare Disorders, 151 Bloor Street West, Suite 600, Toronto, ON M5S 1S4,
Canada. 3Genetic Alliance, 4301 Connecticut Ave., NW, Suite 404,
Washington, DC 20008-2369, USA.
Received: 18 January 2017 Accepted: 21 March 2017

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