changing the future of primary ciliary dyskinesia (pcd): pcd clinical centers kickoff
DESCRIPTION
The PCD Foundation hosted a meeting for top pulmonologists in North America to share an exciting initiative to create a network of PCD Clinical Care Centers. This initiative is part of the PCD Foundation \'Path to Clinical Trials\' program, which is a way to accelerate our understanding of PCD, develop standards for diagnosis and treatment and ensure access to better therapies through clinical trials. The Path to Clinical Trials consists of creating PCD Clinical Care Centers for diagnosis and treatment and developing a national clinical registry in conjunction with these centers. See www.pcdfoundation.org for more.TRANSCRIPT
1 © Copyright 2011 | PCD Foundation | Confidential
Primary Ciliary DyskinesiaKartagener Syndrome
Immotile Cilia Syndrome
Changing the Future of PCD:A New Path
© Copyright 2011 | PCD Foundation | Confidential2
Welcome & Introductions
• Welcome to the PCD Clinical Centers Kickoff– The Path Starts Here
• Introductions– Michele Manion, Founder & Executive Director, PCD Foundation– Carey Kauffman, President, PCD Foundation– Mike Knowles, MD, Professor of Medicine, University of North Carolina,
Chapel Hill– Margaret Leigh, MD, Director, Cystic Fibrosis Center, North Carolina
Children’s Hospital– Stephanie Davis, MD, Chief, Division of Pediatric Pulmonology, North
Carolina Children’s Hospital
• Special Thanks– Bob Beall, CEO CF Foundation– CF Foundation– Dedicated PCD researchers and clinicians
© Copyright 2011 | PCD Foundation | Confidential3
Agenda
• WHAT Do Patients Need?– PCD Past, Present & Future
• WHY Now? A New Path for the Future– Rationale for the Path to Clinical Trials (PTCT) Program
• WHO Has PCD?– Defining PCD: Overview of Data from GDMCC Studies– Definition of PCD Clinical Phenotype
• WHEN to Look for PCD/Initiate Therapies?– Illustrative Cases – Data from Longitudinal Studies
© Copyright 2011 | PCD Foundation | Confidential4
Agenda
• HOW to Confirm the Diagnosis of PCD– Addressing the Challenge of Diagnosis– Ciliary Biopsy and Motility Studies—Are There Better Options?– Update on PCD Gene Identification
• NOW is the Time– Getting Clinical Centers Up & Running– Open Discussion
• WHERE We Go From Here– Wrap Up– Action Items/Next Steps
© Copyright 2011 | PCD Foundation | Confidential5
What Do Patients Need?
PCD Past: Where We Were
1991: Diagnosed
– Probably have a ‘normal’ life expectancy
– Large spectrum of disease severity
– No other families to connect with
– What was published did not necessarily match what we weredealing with
– There would never be any research on PCD
© Copyright 2011 | PCD Foundation | Confidential6
What Do Patients Need?
PCD Past: Where We Were
2000: UNC PCD Research Group
2001: Requested seed money to start PCDF in 2001
2002: ATS debut of ‘PCD Foundation’
2003: Creation of the GDMCC
‘The PCD (Primary Ciliary Dyskinesia) Foundation seeks to promote research, increase public awareness, and provide information and support services for individuals with inherited ciliary motility disorders and their caregivers’
© Copyright 2011 | PCD Foundation | Confidential7
2002: PCDF Founded
2007: Kennedy, et al publish paper on PCD heterotaxy and congenital heart defects
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
1999-2000: UNC PCD Research Site Initiates Early Studies
2007: First genetic test for PCD becomes available
2002: First PCD Family Day
2002: Co-Sponsored First Mtg:Cilia, Mucus & MC Interactions
2003: ORDR AnnouncesRDCRN Grants
2004: GDMCC Formedw/RDCRN Grant
Knowles predicts 1st
PCD Gene test in 5 yrs
2006: Omran, et al publish DNAH5 gene
2008: Ciliopathies & PCD Workshop at ATS
2008: DNAH11 published.
2011: First International PCD Medical Mtg (Germany)
2010: First ‘PCD & Related Conditions’ Mtgin St. Louis
2011: PCD Clinical Centers Initiative
What Do Patients Need?
PCD Past & Present: Where We’ve Been To Date
© Copyright 2011 | PCD Foundation | Confidential8
PCD Future: Where We Need To BeWhere We Were:
Battling the 3 ‘A’s’Where We Are:
Still Battling, Yet Poised for Major Growth
Where We Need to BeGreatly Impacting QOL & Means
to Find a Cure
Awareness:Lack of awareness leads to delayed/missed diagnosis & can have fatal consequences.
Better awareness has led to phenomenal patient group growth‘Unmasking the Faces of PCD’ campaign & others like it will move PCD into mainstream.Still too many go undiagnosed or have delayed diagnosis.
PCD included early in differential diagnosis when suspicious phenotype present.Simpler and more accurate diagnostic process
Availability:Availability of care, expertise & support—no published standards of care, insurance denials for ‘lack of evidence.’
7 centers for research & diagnosis funded through GDMCC in North AmericaNeed to support & expand the existing network as that funding will end soonNo published standards of care.
PCD clinical centers in each state & all major citiesEvolving standards of care based on evidenceAccess to clinical trialsLess need for ‘off label’ therapies
Access:Access to clinical research:1) Funding2) Logistically: Little natural
history data; Dx was a mess; No research support infrastructure
GDMCC studies very successful, but PCDF funding not sufficient for other endeavorsLimited industry interest for clinical trials due to current patient population size/difficulty identifying endpoints.
Fully funded research plan for clinical & basic science initiativesContinue natural history studiesSolid infrastructure to support future work
What Do Patients Need?
© Copyright 2011 | PCD Foundation | Confidential9
Obstacles to Overcome: Misconceptions
What Do Patients Need?
Misconceptions• PCD is a mild, non-progressive
disorder• Consequences of PCD only affect
older patients• It is impossible to confirm the
diagnosis of PCD• Treatments already exist: They are
the same as for cystic fibrosis (CF)• PCD is incredibly rare and only
affects a few thousand people• Situs inversus is a benign condition• ‘Normal’ life expectancy
Reality• Progressive disorder that can result
in serious lung disease• Infants can have severe lung
disease; Neonatal mortality• It can be accurately diagnosed
(current = 30% misdiagnosed)• PCD and CF are different genetic
disorders. No PCD EBM to date. • PCD is poorly understood and
under-reported (Est. 400K WW) • Not necessarily; Myth leads to
delayed diagnosis• Wrong on two counts
© Copyright 2011 | PCD Foundation | Confidential10
Obstacles to Overcome: “Normal” Life Expectancy
Age Gender Situs0 M SI0 F SA0 F SA0 M SA24 F SA24 M SS30 F SS39 F SI42 M SS45 F SI47 M SS50 F SI55 F SS64 M SA66 F SS73 F SI
What Do Patients Need?
Average Age at Death:
46.6 years old (excluding infants)
34.9 years old (including infants)
© Copyright 2011 | PCD Foundation | Confidential11
The Role of the PCDF
• Improved– Diagnosis– Quality of Life– Prognosis
• Education & Support– Patients, Families &
Caregivers– Scientific & Medical
Communities
• Awareness & Advocacy– Legislators, Policy
Makers– Medical Communities– General Public
What Do Patients Need?
© Copyright 2011 | PCD Foundation | Confidential12
The Role of the PCDF
To support these goals, our primary focus is to:• Support research efforts that will benefit the PCD patient
community• Sponsor research directly
We will measure success based on the impact of efforts to:• Diagnose more PCD patients overall and earlier in life• Enhance quality of life and prognosis for people with inherited
disorders of motile cilia (and related ciliopathies)• Improve access to affordable, effective therapeutics and
appropriate medical care• Expand visibility of PCD with key public/private institutions,
medical professionals and the general public
What Do Patients Need?
© Copyright 2011 | PCD Foundation | Confidential13
Research Holds the Key
Research
Evidence-Based Care
Education & Support
PTCT
What Do Patients Need?
© Copyright 2011 | PCD Foundation | Confidential14
PCD Future Opportunities
Ware, S., et al. Clinical Spectrum of Ciliopathies; PATS. Vol. 8: Sept, 2011
What Do Patients Need?
© Copyright 2011 | PCD Foundation | Confidential15
PCD Future Opportunities: Newborn Screening
What Do Patients Need?
• Recommendation from HHS that all infants be screened for CCHD via pulse oximetry
• Positive screens will have cardiology follow up
• Opportunity to educate neonatologists, cardiologists & families about the CHD/cilia connection
• Could result in much earlier diagnosis of PCD
© Copyright 2011 | PCD Foundation | Confidential16
PCD Future Opportunities: Newborn Screening
What Do Patients Need?
• In the past decade, the role of sensory monocilia in a vast array of human diseases has been established
• Tremendous interest in disease pathophysiology & potential therapeutic targets related to cilia
• Initially, ‘primary’ (sensory) ciliarydisorders & motile ciliarydisorders were thought to be distinct, but there is growing evidence of overlap
Explosion of interest in
cilia & ciliopathies in the research community
© Copyright 2011 | PCD Foundation | Confidential17
PCD Future Opportunities: Ciliopathies
PCDNephronophthisis
Leber Congenital AmaurosisARPKDADPKD
JeunechondrodysplasiaAlstrom Syndrome (COPD)
Oral Facial Digital Syndrome Ellis van Creveld Syndrome
HeterotaxyJoubert syndrome
PCDBardet-Biedl
Leber Congenital AmaurosisAlstrom syndrome
Retinitis Pigmentosa Jeunechondrodysplasia
PCDMeckel Gruber Syndrome Bardet-Biedl Syndrome
McKusick-Kaufman SyndromeEllis van Creveld Syndrome
HeterotaxyAlstrom Syndrome
CiliopathiesAssociated with
Pulmonary Disease
Ciliopathies Associated with Heart Defects
CiliopathiesAssociated Eye
Disease
Ware, S., et al. Clinical Spectrum of Ciliopathies; PATS. Vol. 8: Sept, 2011
What Do Patients Need?
© Copyright 2011 | PCD Foundation | Confidential18
Patients Need A Path to Clinical Trials
Now is the Time!
What Do Patients Need?
© Copyright 2011 | PCD Foundation | Confidential19
A New Path: Why Now?
What is the PCDF Path to Clinical Trials (PTCT)?
A strategy designed to establish credible, evidenced-based knowledge of PCD, the most important factor in fulfilling our mission to provide education, support & better therapeutic options to affected individuals.
© Copyright 2011 | PCD Foundation | Confidential20
Why Is the PTCT The Right Strategy?
A New Path: Why Now?
Better treatment options/cures require (1) Research & (2) Access to clinical trials
• The PTCT provides a scalable framework to accelerate research efforts & patient access to clinical trials
• The PTCT is a proven, successful model based in insight from:– Clinical advisors & research partners at NIH– Non-profit colleagues
• Bob Beall, CF Foundation (CFF)• Sue Byrnes, LAM Foundation
© Copyright 2011 | PCD Foundation | Confidential21
How Does It Work? Two Critical Building Blocks
A New Path: Why Now?
• Network of PCD Clinical Care Centers• Patient Registry
– 2-tiered approach to improve patient numbers
Contact(Patient-Reported)
Clinical(Physician-Reported)
© Copyright 2011 | PCD Foundation | Confidential22
Overcoming Obstacles: Geography, Numbers & Mis(sed)diagnosis
Need for clinical centers and a patient registry were identified
back when the PCDF was founded, but we were faced with monumental obstacles,
including:
• Geographically dispersed & small patient population
• Misdiagnosis was a big problem—became clear to us as patient group started communicating and interacting:• ‘Selective’ PCD• Highly suspect inheritance patterns • Clinical centers claiming to have large #’s of
PCD pts.
A New Path: Why Now?
© Copyright 2011 | PCD Foundation | Confidential23
Overcoming Obstacles: GDMCC Paved the Way
The Genetic Disorders of Mucociliary Clearance Consortium (GDMCC) Paved the Way to the PTCT
A New Path: Why Now?
• University of North Carolina at Chapel Hill - Chapel Hill, NC• Children's Hospital Colorado - Denver, CO• Children's Hospital & Regional Medical Center - Seattle, WA• The Hospital for Sick Children, Toronto, Ontario, Canada• National Institute of Allergy and Infectious Diseases• Stanford University Medical Center, Palo Alto, CA• Washington University in St. Louis, MO
© Copyright 2011 | PCD Foundation | Confidential24
Overcoming Obstacles: Lessons from the GDMCC
A New Path: Why Now?
Refined the definition of the clinical phenotype in ‘classic’ PCD & identified variants
Verified that PCD mutations do not always result in defects that are visible on biopsy
Created 1st genetic test for PCD (2 genes)
Validated the center model for PCD
Accelerated gene identification providing basis for more comprehensive genetic test (14 verified genes -more on the way)
Expanded PCD research network to include international collaborators & basic science researchers working on other cilia-related projects
© Copyright 2011 | PCD Foundation | Confidential25
PCD Clinical Centers: Overview
A New Path: Why Now?• The PCDF will work with key
constituents in North America to define, recruit, launch & support PCD expert/satellite centers
• Clinical Care Centers will provide expert care for people living with PCD
• Clinical Care Centers will be based on the model established by the Cystic Fibrosis Care Center Network• Identified by the NIH as a
model of effective & efficient health care delivery for chronic disease
Goals Reliable diagnosis Consistent, high-quality,
appropriate care Comprehensive data
collection through the NorthAmerican PCD Registry (NAPCDR)
© Copyright 2011 | PCD Foundation | Confidential26
PCD Clinical Centers: Support & Accreditation
A New Path: Why Now?Centers Will Support:• A ’Certification’ process for ensuring expertise in diagnosis
& treatment• Local patient registry entry• Contributions to evolving PCD Standards of Care including ongoing
education & training
Accreditation Standards• Multidisciplinary team: Board-certified Pulmonologists (pediatric &
adult), ENT Specialists• Defined number of patients with PCD• Age-appropriate care: Outpatient (clinic), Inpatient (hospital) care• Specialist availability: Cardiology, Nephrology, Fertility • Applies guidelines for diagnosis and care• Teaching: Medical, Allied health students• Research: Basic &/or Clinical
© Copyright 2011 | PCD Foundation | Confidential27
PCD Clinical Centers: Projecting Future Growth
A New Path: Why Now?
Expansion of centers based on:• The ability to identify centers who meet agreed up on criteria• The ability of the PCDF to fund centers coming online
A starting point: Launch . . . • 7 current GDMCC sites to form basic core• X additional sites Year 1• X additional sites Year 5• X additional sites Year 10 . . .
© Copyright 2011 | PCD Foundation | Confidential28
A New Path: Why Now?
What Do Patients Need?
A Path to Clinical Trials
Summary
• Better diagnostics = Rapid PCD patient population growth– Can support clinical trials
• Unprecedented interest & collaboration– Window of opportunity
• Infrastructure to support growth
Together, we can change the future of PCD . . . and more.
© Copyright 2011 | PCD Foundation | Confidential29
Who Has PCD?
Topics Covered*• Defining PCD: Overview of Data from GDMCC Studies• Definition of PCD Clinical Phenotype
* Slides for this section are not included in this presentation
© Copyright 2011 | PCD Foundation | Confidential30
When to Look For PCD/Initiate Therapies?
Topics Covered*• Illustrative Cases • Data from Longitudinal StudiesDefining PCD: Overview of Data
from GDMCC Studies
* Slides for this section are not included in this presentation
© Copyright 2011 | PCD Foundation | Confidential31
How to Confirm PCD
Topics Covered*• Addressing the Challenge of Diagnosis• Ciliary Biopsy and Motility Studies—Are There Better Options?• Update on PCD Gene Identification
* Slides for this section are not included in this presentation
© Copyright 2011 | PCD Foundation | Confidential32
Now is the Time
Topics Covered*• Getting Clinical Centers Up & Running• Open Discussion: Sample topics
– Demographics• How many pts to justify effort?• Okay to start small with expectation of growth? • How small is too small?
– Diagnosis • Do we need designated centers for EM?
– Logistics• Access to specialists (card, etc)? • Access to dx? • IRB concerns (registry)?
– Budgeting• CF per capita model sufficient? • Additional staffing needs?
* Information for this section is not included in this presentation
© Copyright 2011 | PCD Foundation | Confidential33
Where We Go From Here
• Wrap Up• Action Items/Next Steps
Together, we can change the future of PCD . . . and more.