Giuliano 4th SS 2016.ppt [modalit compatibilit...
Transcript of Giuliano 4th SS 2016.ppt [modalit compatibilit...
4th International Summer School on Rare Disease and Orphan Drug Registries
The PillarsDefining the scientific aims
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 2016
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 2016
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 2016
Joseph GiulianoGlobal Medical Affairs
Amicus Therapeutics
Princeton, NJ USA
Presentation agenda
1. What are the PILLARS?
2. Role of scientific observation and aims of a
registry (Huntington disease)
3. Clear aims have impact – the registry’s
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 2016
3. Clear aims have impact – the registry’s
purpose
4. Registry adaptability
2
Registries defined
• “a file of documents containing uniform information about individual persons, collected in a systematic and comprehensive way, in order to serve a predetermined purpose.” 1
• “an organized system for the collection, storage, retrieval, analysis, and dissemination of information on individual persons who have either a particular
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 20163
on individual persons who have either a particular disease, a condition (e.g., a risk factor) that predisposes [them] to the occurrence of a health-related event, or prior exposure to substances (or circumstances) known or suspected to cause adverse health effects.” 2
1 Brooke EM. The current and future use of registers in health information systems. Geneva: World Health Organization; 1974. Publication No. 82 National Committee on Vital and Health Statistics. Frequently Asked Questions About Medical and Public Health Registries. [August 14, 2012]
The Pillars of a successful registry
AimsPatients
Families, Carers
STAKEHOLDERS
Investigators/HCPsAcademia, Hospitals, Community
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Rome (Italy), September 26-28, 2016
Sustainability
Governance
4
Academia, Hospitals, Community
ResearchersBasic, Translational, Public Health
GovernmentPublic Health, Payers, Regulators
IndustryPharma/Biotech, CROs
Aims
The overall purpose of the registry,
clearly defined, aligned with
important questions and other
objectives stakeholders want to
achieve
Sustainability
The continuation of a registry’s
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 2016
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 20165
efforts to meet current needs and
deliver its desired outcomes to the
community of stakeholders.
Governance
The processes of governing:
Policies, monitoring progress,
scientific integrity, ethical oversight
Presentation agenda
1. What are the PILLARS?
2. Role of scientific observation and aims of a
registry (Huntington disease)
3. Clear aims have impact – the registry’s
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 2016
3. Clear aims have impact – the registry’s
purpose
4. Registry adaptability
6
Always begin with observation
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Rome (Italy), September 26-28, 20167
The original observations of George Huntington
The hereditary chorea, as I shallcall it, is confined to certain andfortunately a few families, and hasbeen transmitted to them… hardlyever manifesting itself until adultor middle life, and then coming ongradually but surely, increasing by
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Rome (Italy), September 26-28, 20168
gradually but surely, increasing bydegrees, and often occupying yearsin its development, until thehapless sufferer is but a quiveringwreck of his former self.
"On Chorea," by George Huntington, M.D., The
Medical and Surgical Reporter: A Weekly Journal,
(Philadelphia: S.W. Butler), vol. 26, no. 15 (April 13,
1872), pp. 317-321.
The original observations of George Huntington- 2
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 20169
"On Chorea," by George Huntington, M.D., The
Medical and Surgical Reporter: A Weekly Journal,
(Philadelphia: S.W. Butler), vol. 26, no. 15 (April 13,
1872), pp. 317-321.
There are three marked peculiarities in this disease:
1. Its hereditary nature.
2. A tendency to insanity and suicide.
3. Its manifesting itself as a grave disease only in adult life.
Scientific aims
• Understand the phenotype as it evolves over time
• Differences between prodromal and manifest disease
• Patterns of symptom onset: age, family history, gender
• Treatment effects on different symptoms
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• Treatment effects on different symptoms
• Prevalence and risk factors for suicide
The HD mutation
180 kb DNA
CAG CAG CAG CAG+n
> 40
> ~70
unaffected
adult onset HD
juvenile onset HD
36-39
6-35
incomplete penetrance
Short Arm of Chromosome 4
(4p16.3)
Htt
The Huntington's Disease
Collaborative Research Group
(1993) Cell 72, 971-83
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 2016
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 2016
180 kb DNA
66 67321
≤ 35 CAG - unaffected
≥ 40 CAG – causes disease within normal lifespan
≥ 70 CAG – causes childhood onset
36 - 39 CAG – increased likelihood of developing HD
A single mutation with an expanded tri-nucleotide repeat
40
60
80
Ag
e a
t N
eu
rolo
gic
On
se
t
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Rome (Italy), September 26-28, 2016
Normal alleles HD alleles
J. Gusella, Harvard/MGH
0 10 20 30 40 50 60 70 80 90 100 110 120
Number of CAG Repeat Units
0
20
Ag
e a
t N
eu
rolo
gic
On
se
t
HD Degeneration
NormalNormal HDHD
Cortical
Thinning
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Basal Ganglia
Degeneration
Ventricular
Enlargement
Scientific Aims
• Neuronal/structural correlates of disease
symptoms
• CAG-length relationship to structural
changes and neuronal dysfunction
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changes and neuronal dysfunction
• Genetic modifiers of disease onset –
GWAS
The three main aims for Enroll-HD
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Landwehrmeyer, B., et.al, (2016) Movement Disorders- Clinical Practice
Registry scope
• What data will be collected?
– Characterization of the phenotype
– Natural history, symptom progression
– Disease sub-types
• Sample collections?
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Rome (Italy), September 26-28, 2016
• Sample collections?
– DNA
– Plasma, lymphocytes
• Tissue donations?
– Biopsies
– Target organs
16
Presentation agenda
1. What are the PILLARS?
2. Role of scientific observation and aims of a
registry (Huntington disease)
3. Clear aims have impact – the registry’s
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 2016
3. Clear aims have impact – the registry’s
purpose
4. Registry adaptability
17
Clinical Observatio
n
Natural History
Etiology
Interventions
Public Health
New TxDevelopme
nt
Natural history Disease characteristics (S&S)
Disease progression
Outcomes
Etiology Environmental exposure
Genetics
Interventions Clinical effectiveness
Cost effectiveness
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Rome (Italy), September 26-28, 2016
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 201618
Cost effectiveness
Safety/harm
Public health Disease surveillance
Public policy
New treatment
development
Recruitment in CTs
Feasibility
Protocol design
Presentation agenda
1. What are the PILLARS?
2. Role of scientific observation and aims of a
registry (Huntington disease)
3. Clear aims have impact – the registry’s
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 2016
3. Clear aims have impact – the registry’s
purpose
4. Registry adaptability
19
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 2016
Organised by Istituto Superiore di Sanità
Rome (Italy), September 26-28, 201620
Why do registries need to be adaptable?
Adaptability – able to adjust the registry readily
to changing conditions
• Changes in science and medicine (new observations)Changes in science and medicine (new observations)Changes in science and medicine (new observations)Changes in science and medicine (new observations)
• Changes in personnel and leadershipChanges in personnel and leadershipChanges in personnel and leadershipChanges in personnel and leadership
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Rome (Italy), September 26-28, 201621
• Patient reported outcomes (PRO): testing, validating Patient reported outcomes (PRO): testing, validating Patient reported outcomes (PRO): testing, validating Patient reported outcomes (PRO): testing, validating and adoptingand adoptingand adoptingand adopting– Include new measures to replace oldInclude new measures to replace oldInclude new measures to replace oldInclude new measures to replace old
• Important for sustainabilityImportant for sustainabilityImportant for sustainabilityImportant for sustainability
• Align technology for adaptabilityAlign technology for adaptabilityAlign technology for adaptabilityAlign technology for adaptability
• Align governance for adaptabilityAlign governance for adaptabilityAlign governance for adaptabilityAlign governance for adaptability