Rare Disease Centres of Excellence Webinar May 5, 2022 CORD Rare Disease Strategy Update/Overview NORD Centres of Excellence: Marybeth McAfee

1. RARE ONE
CANADA:
Canada’s Smart Rare Disease
and Rare Drug Strategy

2. WHERE ARE WE NOW
AND WHERE DO WE
NEED TO GO?
It is mid-2022. As we move closer to the launch of Canada’s Rare Drug Strategy, CORD is
stepping up consultations with five to six webinars in April and May and a two-day “in person”
conference on June 8-9 in Ottawa. Our intended outcome is NOT a plan to allocate the $1
billion start-up funding nor the $500 million annual commitment. We are NOT proposing
minor tweaks to address gaps in the system nor even incremental improvements. We are
calling on all stakeholders to arrive at “as near a consensus as possible” on a complete re-
imagining of a system from the bottom up and top down that is “fit for purpose” of assuring
all Canadians have access to the best therapies as soon as they are available anywhere in the
world.
This means reimaginig and executing a patient-centred rare disease system that assures
every person, in as short a time as possible, gets an accurate diagnosis, sees a specialist, forms
an individualized care, treatment, and support plan, is enrolled in a patient registry and
referred to a patient support group, gets timely monitored access to the best treatment and,
most important, has the knowledge and right to participate as a full partner in all health-
related decisions. This is available for all Canadians, regardless of where they live, their
insurance coverage or their ability to pay.

3. WHY IS RARE DISEASE
A PUBLIC HEALTH
ISSUE?
There are more Canadians with a rare disease than with all cancers,
cardiovascular disease, diagnosed diabetes. Altogether, 3 million
Canadians, about 1 in 12, have a rare disease. Moreover, while 80% of rare
diseases are genetic, 50% have no known family history. So everyone is
potentially at risk. Two-thirds of those affected are children, 30% of whom
will not live to their fifth birthday. Sadly, in Canada, a child dies of a rare
disease every 18 minutes.
In terms of economic impact, rare disease costs the Canadian economy
about $111 billion per year in direct medical costs, nonmedical cost, and
productivity costs.

4. WHY IS NOW THE TIME
FOR CANADA’S SMART
RARE DRUG STRATEGY?
Rare disease drugs are saving lives, preventing and reducing disability, allowing patients and families to live more “normal”
productive lives, and, for some conditions, providing a long-lasting treatment or “cure.” Rare disease research is leveraging
genomic breakthroughs, advanced medical technologies, application of data science and artificial intelligence to big data, patient
registries, and real-world data, multiple disease cell-and-gene therapy platforms, and remote patient engagement. So rare disease
therapies are at the forefront of innovative research, providing solutions with impacts beyond rare diseases, including viruses,
cancers, and cardiovascular diseases.
Thanks to the US and EU Orphan Drug Acts, about 600 new therapies have been approved in the past 40 years but these cover
only about 5% of up to 7,000 rare diseases. To date, Canada has contributed to only a small handful of rare disease drug discoveries.
However, that scenario can and should change. Canada’s burgeoning life sciences strategy has the scientific, clinical, and patient
capacity to contribute significantly to discovery, manufacture, and management of rare disease diagnosis and treatment.
Consider two axioms here: “Your very success is what is going to destroy you” and the “tragedy of the commons” whereby pursuit
of individual good can result in disaster for the common good. In other words, early reimbursement solutions for rare disease drugs
therapies cannot be repeated infinitely when the number of new therapies expand exponentially. Most would agree that our drug
assessment procedures were never designed to accommodate innovative therapies for small patient populations but we have
continued to put them through the process and have mostly “cobbled” “on-off” reimbursement agreements with ostensibly
minimal impact on the overall drug budgets. The solutions were rarely evidence-based, equitable, or sustainable. The question is
not whether we have reached the breaking point with the “old” access pathways but “how can we do better?”

5. WHAT ARE THE HALLMARKS
OF A SMART RARE DRUG
STRATEGY?
The opportunity to introduce a new Rare Disease Drug
System is to build it with SMART principles. SMART
systems share three attributes.
• engaged patients;
• digital capture, linkage and timely sharing of relevant data;
• timely production of research evidence;
• appropriate decision supports;
• aligned governance, financial and delivery arrangements;
• a culture of rapid learning and improvement; and
• competencies for rapid learning and improvement.
1. SMART HEALTH SYSTEMS ARE
DESIGNED TO BE RAPID LEARNING
SYSTEMS, AS INDICATED BY:

6. • Specific: Well defined, clear, and unambiguous
• Measurable: With specific criteria that measure your
progress toward the accomplishment of the goal
• Achievable: Attainable and not impossible to achieve
• Realistic: Within reach, realistic, and relevant to your life
• Timely: With a clearly defined timeline, including a starting
date and a target date. The purpose is to create urgency.
2. SMART HEALTH SYSTEMS
ENGAGE IN AGILE PLANNING
WHICH MEANS CONTINUOUSLY
UPDATING SMART GOALS, WHICH
ARE DEFINED AS:

7. 3. SMART HEALTH SYSTEMS INTEGRATE
SMART TECHNOLOGY, REFERRING TO
SELF-MONITORING ANALYSIS AND
REPORTING TECHNOLOGY
Two trends driving healthcare are, on the demand side, growing recognition of health services
as a basic human right and an investment for a healthy society and, on the supply side,
increasingly complex and impactful solutions that are highly specialized and costly. The
conundrum is compounded by increasing competition for resources both within healthcare
and with other sectors as economies recover from the pandemic and beleaguered healthcare
providers exit their professions.
The way forward is the digital transformation of healthcare, and technology companies are
being called up to develop solutions that improve healthcare performance and outcomes.
Examples span individual devices to system management including:
• digitally connected remote healthcare services to expert centres and even more remote
patients;
• sharing of patient health data across a variety of systems for multiple purposes;
• employing AI to rollout vaccines, conduct virtual screening, simulate drug adverse effects,
and speed up diagnosis using algorithms
• Proactive healthcare wearables that can collect signals in real time
• Smart hospital management: workloads and patient flow

8. Initial Response to: Canadian Government’s
Discussion Guide for National Strategy on Drugs
for Rare Diseases
CORD High-Level Critique
Our reactions to What We Heard: We feel dismayed, bewildered, and betrayed.
• Know you heard us because your recapitulation of your WWH summary was mostly what we said back then
• Potential Draft Framework: sets up the slippery slope toward no meaningful action
• Language throughout is highly speculative, theoretical, and deliberately vague with no commitment to actions, goals
or outcomes, and timelines
1. Potential common vision is underwhelming, not worthy of the boldacious 2019 government commitment backed with $1
billion initial funding. We cannot galvanize the Canadian rare disease community to collective action with a vision of
“improved access” and “better health outcomes.”
2. These eight principles are meaningless. Principles are “fundamental truths” that underlie actions, whereas these are
presented as a list of words with no explanation as to how these will be fundamental to the design, implementation and
evaluation of the Rare Disease Drug Framework.
3. Invest in 4 Strategic Pillars
• These are not strategic nor pillars nor even “four” different sects of activities but necessarily highly related toward one
(unstated) goal
• Many of the activities are couched in the form of “advisory” activities, such as “explore feasibility”, “engage with”,
“create a plan for future”, “support”, “invest in”, “build relationships with” with no reference as to “the entity” that is
doing the advising (government, advisory committee, new drug agency) and to whom the advice is provide for
execution (designated or accountable body or coalitions).
• There are no linkages of activities to the guiding principles or the desired outcomes of these activities.

9. Initial Response to: Canadian Government’s
Discussion Guide for National Strategy on Drugs
for Rare Diseases cont…
Pillar 1: Improve access to rare disease treatments and make it consistent across Canada
• Improved and consistent access could be a “death spiral” unless there is a clear commitment to an overarching
principle: All rare disease patients shall get the fasted access possible to the best drug for their specific condition and
personal profile in the shortest time possible (through clinical trials, special access, and other early access paths)
comparable to the best countries). Otherwise:
• Improved access without requirement of best could mean any therapy that is better than nothing or access for all rare
disease patients to the lowest common denominator of willingness to fund
• Without commitment to rapid access, coordination across decision makers could lead to intolerable delays anchored
by the least willing funder
Pillar 2: Optimize, collect and use data along drug system continuum and across lifecycle must be
based on:
• Principle of “adaptive learning”, that is, recognize the realities of our non-existent national data platform and system
(have we learned nothing from InfoWay)?
• Learn from discrete programs (existing and new) which rely on existing data systems and platforms that are already
collecting health data and using them to monitor treatment and outcomes, in specialty clinical networks, in cancer
networks, in private services using and service public systems.

10. Initial Response to: Canadian Government’s
Discussion Guide for National Strategy on Drugs
for Rare Diseases cont…
Pillar 3: Support optimal patient outcomes and sustainability of health system by spending on
drugs that bring “value for money.”
• This pillar is just big giveaway or back door to health technology assessment (HTA), that is, cost-effectiveness and cost-
utility assessments (cost per Quality-Adjusted Life Year calculations) with comparative and competitive ICERS
(incremental cost-effectiveness ratios). The premise of “value for money” can ONLY work in achieving the best
outcomes for patients and society are the driving principles and IF the failure of tradition HTA methodologies (timing,
evidence requirements, and benchmark ICERs) to achieve optimal and even reasonable assessments for rare disease
therapies.
• Additional concern for Pillars 1, 2, and 3: these are all the same domain and all directed toward shared or consensual
HTA for DRDs and providing access to those that meet whatever criteria or threshold would be deemed “value for
money.” These do not represent an innovative step forward.
Pillar 4: Strengthen alignment of research and innovative systems with DRD access objectives
• This in and of itself is not very illuminating. However, the proposal to build rare disease research capacity to create data
collection and sharing systems that can contribute to clinical trials (and other goals) is worthwhile, even if vague as to
implementation.

11. Initial Response to: Canadian Government’s
Discussion Guide for National Strategy on Drugs
for Rare Diseases cont…
Iterative Implementation
Drug Coverage
Why as first phase federal support, with partners and payers, of coverage for “select drugs of common concern.” Not most
pressing concern from patients.
Duplicates what already exists. More reasonable to gaps: provide mandatory coverage to all families, similar to the Quebec
model.
Greatest obstacle to consensus is which drugs are to selected by whom and serving whose common concern? By
definition, rare disease drugs are not common concerns.
Top priority is access to those (often new and advanced) therapies that have the greatest impact on saving lives,
improving disease outcomes, or transforming lives.
Need accelerated pathways that would provide access at the very earliest possibility, during clinical trials, pre-NOC,
immediately upon NOC through managed access programs that would provide patient access with provisions for
monitoring and real-world data collection, with reimbursement potentially conditional on outcomes.
An initial “common concerns” drug list does not address the patient needs, the system gaps and definitely not long-term
“value for money” and sustainability of the Rare Drug program and the health system.

12. Initial Response to: Canadian Government’s
Discussion Guide for National Strategy on Drugs
for Rare Diseases cont…
Governance
Committees for specific therapies include experts from affected rare disease community, including patients and families,
clinicians, and other care providers.
Independent Rare Disease Drug Program = all stakeholders at all levels in multiple roles, including patients, not only on advisory
committees but also assessment, monitoring, and decision-making bodies at every level, including the top governing board.
All stakeholders should receive the necessary training and support to share expertise in a collaborative environment.
Transparency should include open access to all materials and to the assessment, deliberation,
and decision-making processes.
Optimal patient outcomes
“Value for money” is just another way of describing HTA; traditional methodologies not working for rare disease drugs in Canada
or elsewhere)
Streamlining process and efforts for DRD will NOT resolve the fact that the traditional model is not “fit for purpose”, which is true
worldwide.
Risk-sharing and equitable sharing of costs need a single platform for assessment and development of “managed access”
agreements including CT evidence, extension to non-trial patients, and collecting outcomes in real-world to monitor safety and
efficacy.
Risk-sharing of the costs and innovative payment models are on-going processes where the costs paid (over time) may vary as
evidence on outcomes and number of patients evolve over time in real-world usage.
Establish Canadian Network of Rare Disease Centres of Excellence with specialty networks embedded across the Centres. These
Centres of Excellence are also the vehicles for data collection and analysis, which will allow for aligning research and therapy
management.

13. SPRING 2022
WEBINAR
SERIES
Planning SMART

14. SPRING 2022
WEBINARS
MAY 3
12 - 1 pm
Rare Disease
Patient Registries:
Key to Drug
Development and
Access
MAY 5
12 - 2 pm
Rare Disease Centres
of Excellence:
Linchpin to patients,
community care,
and collaboration
MAY 19
12 - 1 pm
Leave No One
Behind
MAY 26 *POSTPONED
Economic Case for
Rare and Innovative
Research
* Now will be held as a
session during the June 8-9
conference
APRIL 19
12 - 1 pm
Application of
RWE in Drug
Access Decision
Making
APRIL 26
12 - 1 pm
Lessons for a SMART
Rare Drug System

15. MAY 5
12 - 2 PM
The government of Canada has committed $1 billion to set up Canada’s Rare Disease Drug
Strategy. The rare disease community, under the leadership of the Canadian Organization
for Rare Disorders, has called for the implementation of a SMART Rare Drug Strategy as
part of Canada’s SMART Rare Disease System that will address the challenges of access
today and carry us into the future to provide FAST access to medicines that will also
stimulate investment in innovation that will deliver best health outcomes, research and
development, and sustainable public health, economic growth, and societal benefits.
As continuation to two years of public consultation, CORD has launched a six-session
consultation on a SMART Rare Disease Drug Strategy and System. CORD in collaboration
with Institute of Genetics, CIHR, and MICYRN (Maternal, Infant, Child, Youth Research
Network) are hosting Webinar 4 on Rare Disease Centres of Excellence to learn about COEs
in other jurisdictions, rare disease research and treatment networks across Canada, and
rare disease specialty network. An expert multi-stakeholder panel will consider how
learnings from other countries can be applied in Canada (or not) and deliberate on a plan
of action to implement toward establishment of a Canadian Network for Rare Disease
Centres of Excellence, especially as a foundation for the Rare Drug Strategy.
Rare Disease Centres of Excellence:
Linchpin to patients, community care,
and collaboration

16. AGENDA
• Learning from Ex-Canada
⚬ European Reference Networks (Sara Talarico/Domenica Taruscio)
⚬ WHO-RDI Global Rare Disease Network (Matt Bolz-Johnson)
⚬ NORD Centres of Excellence (Marybeth McAfee)
• Canada’s Rare Research Networks
⚬ Institute of Genetics, CIHR (Christopher McMaster/Étienne Richer)
⚬ Maternal, Infant, Child, Youth Research Network (Thierry Lacaze-Masmonteil)
⚬ Genome Canada (Ivana Cecic)
• Excellence in Canada
⚬ All for One/Genomics 4RD, CHEO (Kym Boycott)
⚬ Metabolic Disorders Research/Clinical Program, Manitoba (Cheryl Rockman-Greenberg)
⚬ Ottawa Pediatric Bone Health Group and Canadian Working Group (Leanne Ward)
⚬ Pediatric Neurology Research Program, Western University (Craig Campbell)
• Faculty Discussion
• Visioning, SMART Thinking, Next Steps

17. PRESENTERS
An opening panel will present exemplars of existing, emerging, and proposed models and best
practices in coordinated rare disease network from across the globe.
• Sara Talarico/Domenica Taruscio, European Reference Networks
• Matt Bolz-Johnson, WHO-RDI Global Rare Disease Network
• Marybeth McAfee, NORD Centres of Excellence
• Christopher McMaster/Étienne Richer, CIHR Institute of Genetics
• Thierry Lacaze-Masmonteil, Maternal, Infant, Child, Youth Research Network
• Ivana Cecic, Genome Canada
• Kym Boycott, Children’s Hospital of Eastern Ontario
• Cheryl Rockman-Greenberg, Max Rady College of Medicine, University of Manitoba
• Leanne Ward, Children’s Hospital of Eastern Ontario
• Craig Campbell, Department of Pediatrics, Western University

18. DISTINGUISHED
FACULTY
·A panel of distinguished faculty from across Canada are invited to respond to presenters and
consider the implementation of Canada’s Rare Disease Network
• Stuart Turvey, BC Children's Hospital
• Peter Kannu, Stollery Children Hospital, Edmonton
• Francois Bernier, Alberta Children's Hospital
• Micheil Innes, Alberta Children's Hospital
• Beth Potter, CHEO
• Jason Berman, CHEO
• Ronald Cohn, The Hospital for Sick Children, Toronto
• James Dowling, The Hospital for Sick Children, Toronto
• Jacques Michaud, Sainte Justine
• Hugh McMillan, McGill - Montreal Children's Hospital
• Nicolas Chrestian, CHU Laval - Quebec
Moderators
• Bill Dempster, 3Sixty Public Affairs
• Durhane Wong-Rieger, CORD

19. CONFERENCE
JUNE 8 - 9, 2022
Ottawa Marriott Hotel
Building Canada’s SMART Rare
Disease and Rare Drug System

20. National Organization for Rare Disorders | rarediseases.org
NORD RARE DISEASE CENTERS
OF EXCELLENCE PROGRAM
Marybeth McAfee, MA, GC
Associate Director, NORD RD CoE Program

21. NORD, a 501(c)(3) organization, is a patient
advocacy organization dedicated to individuals
with rare diseases and the organizations that
serve them. NORD, along with its more than
330 patient organization members, is committed
to the identification, treatment, and cure of rare
disorders through programs of education,
advocacy, research, and patient services.
NORD® MISSION STATEMENT
rarediseases.org 2

22. 3
rarediseases.org
NORD Rare Disease Centers of Excellence
On Nov 4th 2021, NORD announced its designation of 31 medical institutions across
the United States with exceptional programs for patients with rare diseases as NORD
Rare Disease Centers of Excellence (NORD RD CoE’s).

23. 4
rarediseases.org
Vision of the NORD RD CoE Program
All persons living with a rare disease, regardless of disease, socioeconomic level, or
demographics, have access to timely diagnosis, quality, compassionate clinical care, research
opportunities, and supportive resources. ​
• Policy
• Professional Education
• Research
• Care

24. 5
rarediseases.org
Building the Application
• A framework for the application was developed
• Committee refined the application
• Scoring rubric developed

25. 6
rarediseases.org
Application Overview – Multiple Choice Questions
• Slightly over 100 Multiple Choice
Questions
• Qualitatively assessing each site’s
“Onsite” or “Local” access to specific
staffing, facilities, or services
• Quantitative collection of “clinical
fulltime equivalents” (cFTE’s) in key
specialties very often involved in
rare disease diagnosis and care.
• Examples:
• Liver transplant service
• Pediatric heart surgery
• Disease patient “navigators” and/or
case managers
• Specialty laboratories for esoteric
rare disease diagnostic or
monitoring tests, etc.
• # of Genetic Counselors, Clinical
Geneticists, Biochemical or
Molecular Geneticists, Pediatric
Neurologists

26. 7
rarediseases.org
Application Overview – Essay Questions & LOS
10 Essay Questions
• 750-word limit
• Answers to focus on rare disease
• Rubric for scoring was included
Letters of Support
• Ranged from 1-4
• Examples:
• Multidisciplinary clinics
• Types of rare disease certified
clinical training programs
• Rare disease patient resources
• Programs to reach underserved
• Pediatric to adult transition
• Patient satisfaction scores

27. 8
rarediseases.org
Applications Process
Invitations
• Invitations were sent to the 40 plus
Institutions
• Directed to head of clinical genetics
programs
• Had ACGME certified clinical training
programs
Technical Assessment Call
• Program information – more than a
sticker
• Application information
• Explanation of rubrics
• Q&A

28. 9
rarediseases.org
Analyzing the Applications
Multiple choice questions:
• Pulled from application system
• Did little to differentiate between applicants
Essay questions:
• Scored using rubric by 3 different NORD staff
• Each staff had 8 or so applicants essay answers to review
• Letters of Support were read but were not scored or included in scoring rubric

29. 10
rarediseases.org
31 NORD RD CoE
• University of Alabama at Birmingham Medicine/Children’s of Alabama
• Children’s Hospital of Orange County / UC Irvine
• University of California, San Francisco & UCSF Benioff Children's Hospitals
• University of Colorado Anschutz Medical Campus/Children’s Hospital Colorado
• University of Miami Miller School of Medicine
• Emory Division of Medical Genetics
• Indiana University School of Medicine
• University of Iowa Health Care
• Johns Hopkins Medicine/Kennedy Krieger Institute
• Mass General Hospital/Mass General Hospital for Children/Brigham and Women’s
Hospital/Boston Children’s Hospital
• Mayo Clinic
• M Health Fairview-University of Minnesota Masonic Children's Hospital
• Washington University/BJC Healthcare
• UNMC Munroe-Meyer Institute, Omaha Children's Hospital and Nebraska Medicine
• Columbia University Irving Medical Center
• Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount
Sinai
• Duke University Medical Center
• UNC Children's - North Carolina Children's Hospital
• Cincinnati Children's Hospital Medical Center
• Nationwide Children's Hospital/Ohio State University
• OU Health/University of Oklahoma Health Sciences Center
• Penn Medicine/Children’s Hospital of Philadelphia
• UPMC Center for Rare Disease Therapy
• Vanderbilt University Medical Center
• Baylor College of Medicine/Baylor St. Luke’s Medical Center/Texas Children’s Hospital
• McGovern Medical School/UTHeath
• UT Southwestern Medical Center
• University of Utah Medical Genetics
• Rare Disease Institute at Children’s National Hospital
• Children's Wisconsin/Medical College of Wisconsin
• University of Wisconsin Center for Rare Diseases

30. 11
rarediseases.org
Geographic Distribution vs. Population Density

31. 12
rarediseases.org
Revising the Application
Multiple Choice Questions
• Retain most of the questions
• Consolidate some of specialist questions
• Remove redundancies
• Increase clearness of questions
Essay Question
• Analyzing reviewers’ comments (2021 cycle)
• Reconsider 750-word limit
• Refine rubric
• Modify weighting

32. 13
rarediseases.org
A Few Thoughts to Consider
• Try to envision situations where worthy
applicants will apply that won’t meet the
designation criteria
• Independent children’s hospital
• Independent specialty hospitals
• Come up with strategies to mitigate loss of
quality applicants
• Support working with a hospital that treats
adults to put in a joint application
• Support with larger university hospital to put
in a joint application
• Know ahead of time what you
want to analyze to distinguish
your vision of a rare disease
center of excellence
• Be cautious making
announcements that may commit
you to a challenging timeline
• Consider supporting co-director
structure rather than single
director at each Center

33. 14
rarediseases.org
Marybeth McAfee, MA, GC
mmcafee@raredisease.org
Thank you.