Transcript Slide 1

C-Path Multiple Sclerosis Outcome
Assessments Consortium
ASENT
February 20, 2014
Richard Rudick, M.D. (Co-Director, MSOAC)
Mellen Center for Multiple Sclerosis
Cleveland Clinic
Multiple Sclerosis Outcome Assessments Consortium (MSOAC)
MSOAC Engages Many Stakeholders
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43 member international organization
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10 pharmaceutical companies
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27 academic medical centers
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6 MS patient advocacy organizations
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Created and managed by C-Path with
funding and input from the National MS
Society (NMSS).
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FDA Liaison, Dr. Marc Walton
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EMA Advisor, Dr. Maria Isaac
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MSOAC Co-Directors:
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Richard Rudick, M.D., Cleveland Clinic
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Nicholas G. LaRocca, Ph.D., NMSS
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Lynn Hudson, Ph.D., C-Path
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
Confidential
2
Mission of MSOAC
MSOAC will develop and support adoption
throughout the MS community (patients,
clinical investigators, pharmaceutical
industry, regulatory agencies, and advocacy
groups) of a clinical outcome assessment
tool (COA) for future MS clinical trials.
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
Confidential
3
Purpose of the planned COA
The purpose of this COA will be to reflect the
impact of an intervention on the disability due
to MS. MSOAC will obtain regulatory
qualification of the COA for registration trials.
Therefore, the COA must be useful for
demonstrating clinical, and clinically
meaningful, change due to MS.
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
Confidential
4
MSOAC Project Focus
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Primary outcome measure for interventions
targeting the disease process (not symptom Rx)
Selected quantitative neuroperformance
measures related to functions directly affected
by MS and important to patients
Certain symptoms (pain, fatigue, sexual
dysfunction, depression, etc) contribute to
overall burden of MS, but these are not
objectively measurable by observers, so are not
intrinsic to the planned COA
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
Confidential
5
Guidelines for COA Components
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Multidimensional (reflect key aspects of MS)
Objectively measurable by trained observers
Have high reliability (precision), and high
validity, including importance to the patient
Change over time to permit demonstration of
a therapeutic effect
Be acceptable to patients, practical, and
cost-effective
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
Confidential
6
Why Do We Need This?
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Traditional measures – relapse and EDSS –
are imprecise, subjective, and have
uncertain relationships to the underlying
disease process and concept of interest
Quantitative neurological and
neuropsychological performance testing
have favorable psychometric properties and
offer an alternative to clinician rating scales
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
Confidential
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Framework For Performance Measure
for MS Clinical Trials
People with
Multiple Sclerosis
1. Target Population
A
2. Concept of interest
3. Examples of Activities of
Daily Living Limited by
Disability in MS
4. Bodily Functions Involved in
Activities of Daily Living
Walking quickly
to make an
appointment
Speed
6. Method of measurement
(examine options)
T25FW
8. “Validation” and
Interpretation
C
Keeping up with
conversations
“Disability”
Remembering
to take
medications
Higher Level
Cognitive
functions
Walking
5. Sub-components of
Bodily Functions
7. Generation of
measurements
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Pace of
Thought
SDMT
Memory
CVLT
Attention
BVRT
7/24
SRT
E
F
Reading a
newspaper
Using a knife and
fork, writing, using a
computer keyboard
Seeing
functions
Muscle
Power
functions
Acuity
Fine
Hand
Use
LCVA
Control of
Voluntary
Movement
Eye-Hand
Coordination
9-HPT
Disability measurement (score)
Meaning of scores, changes, and differences
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
Confidential
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Multiple Sclerosis Functional Composite
Rudick, Antel, Confavreux, et al. Annals of Neurology, 1997
• An International NMSS Task Force recommended
the quantitative neuroperformance assessment as
an alternative to clinician rated outcomes
• Recommended a 3-part “Multiple Sclerosis
Functional Composite”
 Walking: Timed 25-Foot Walk (T25FW)
 Manual Dexterity: 9-Hole Peg Test (9HPT)
 Cognitive Function: Paced Auditory Serial Addition Test (PASAT)
• Recommended these and other
neuroperformance measures be included in
clinical trials
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
Confidential
9
Response to this Recommendation
More than 30 clinical trials and
countless clinical studies incorporated
the MSFC or its components, providing
>15 years worth of prospectively
collected data on the MSFC
A large collection of datasets containing MSFC, and
other outcomes (EDSS, QoL, MRI, relapses, etc.).
This data has not been fully analyzed
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
Confidential
10
Data Acquisition Status
Study
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Dose Comparison 802
ACT
313
DEFINE
1237
CONFIRM
1232
MSCRG
301
AFFIRM
942
SENTINEL
1171
CHOICE
230
CombiRx
1008
FREEDOMS
1272
FREEDOMS 2
1083
TRANSFORMS
1153
CARE-MS 1
581
CARE-MS 2
840
TEMSO
1088
IMPACT
436
MAESTRO
596
Olympus
439
PROMISE
943
MS Study Group 547
CUPID
493
Fampridine-SR
240
Total = 22
16947
Drug
MS Type EDSS FSS
IFNß-1a
RRMS
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IFNß-1a + MP + MTX
RRMS
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BG-12
RRMS
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BG-12
RRMS
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IFNß-1a
RRMS
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Natalizumab
RRMS
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Natalizumab
RRMS
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Daclizumab + IFNb-1a RRMS
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IFN+GA
RRMS
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Fingolimod
RRMS
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Fingolimod
RRMS
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Fingolimod
RRMS
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Alemtuzumab
RRMS
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Alemtuzumab
RRMS
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Teriflunomide
RRMS
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IFNß-1a
SPMS
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Dirucotide (MBP8298) SPMS
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Rituximab
PPMS
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GA
PPMS
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Cyclosporine
PP/SP
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No
Dronabinol
PP/SP
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Fampridine-SR
All
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subjects
25FW 9HPT PASAT LCVA SDMT Imaging
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PRO
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FAMS, SF-36
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MSQLI
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EQ5D,MFIS,Primus
EQ5D,MFIS,Primus
EQ5D,MFIS,Primus
FAMS, SF-36
FAMS, SF-36
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QENF MRD, AI
Received
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MSIS-29-Phys
In-process
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Contacted
PRO Instruments: MSIS-29-PHYS: MS Impact Scale - 29 items, FAMS, SF-36A, MSQLI: MS Quality of Life Inventory- 10 individual scales
MFIS - Modifed Fatigue Impact Scale, EQ5D - Euro-QOL, PRIMUS - Patient Reported Indices in MS
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
Confidential
11
MSOAC Project
1. Create CDISC Standard for MS, based initially on
elements from the NINDS MS CDE project
2. Create a pooled data set from completed clinical trials
containing traditional clinical outcomes (relapses and
EDSS), neurological performance measures (e.g.
MSFC), and patient reported outcomes
3. Analyze pooled data set to determine components of a
neuroperformance based composite outcome measure,
and recommended approach to using the composite
outcome
4. Seek regulatory approval of a new MS outcome
measure
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
Confidential
12
Current Status
1. MS CDISC standard V1.0 completed, being
reviewed internally
2. Completing data sharing agreements with
pharma and academic investigators
3. Mapping data sets to the CDISC standard to
create a pooled data set for analysis
4. Preparing a comprehensive literature review
5. Formulating statistical analysis plan
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
Confidential
13
MSOAC “Deliverables” and implications
1. CDISC data standard for MS: Will improve ability to compare
data across studies, to interpret findings, and to analyze
pooled datasets.
2. A database of pooled, de-identified clinical trial data mapped
to the CDISC standard: Will allow studies of clinical
outcomes assessment tools, disease modeling, and
potentially imaging or biomarker studies.
3. A new methodology to measure performance: Could provide
approved disability endpoint in future MS clinical trials.
4. Use of the EMA and FDA outcome measure qualification
pathways: Will provide an example for other groups
interested in pursuing better outcome measures through
regulatory sciences
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
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MSOAC Publications and Press
Multiple Sclerosis Outcome Assessments Consortium: Genesis and
initial project plan
Richard A. Rudick, Nicholas LaRocca, Lynn D. Hudson and MSOAC
Mult Scler Journal, published online 20 September 2013
The Multiple Sclerosis Outcome Assessments Consortium: Bringing
the Community Together to Shape the Future of Multiple Sclerosis
Drug Development
Janet Woodcock and Anne M. Rowzee
Therapeutic Innovation & Regulatory Science, published online
12 September 2013
An Expanded Role for Patients in Clinical Trial Design
Anne M. Rowzee and Stephen Spielberg
http://dij.sagepub.com/site//misc/index/podcasts.xhtml
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
MSOAC Collaborators
Industry Members
Partners
MSOAC Coordinating Committee Members
Jane Haley
Matthew Sidovar
Craig Sherburne
Jacob Elkins
Gilmore O'Neill
Sanjay Keswani
Tanuja Chitnis
Jeff Cohen
Deborah Miller
Richard Rudick
Lynn Hudson
Krystal Elms
Ann Robbins
Bess LeRoy
Gary Lundstrom
Jon Neville
Maria Isaac
Geoffrey Dunbar
Kathy Smith
Marc Walton
Irina Antonijevic
Jennifer Panagoulias
Michael Panzara
Paul Thompson
AbbVie
Acorda
Alberta MS Research Foundation
Biogen Idec
Biogen Idec
BMS
Brigham and Women’s Hospital
Cleveland Clinic & ECTRIMS
Cleveland Clinic Foundation
Cleveland Clinic Foundation
C-Path
C-Path
C-Path
C-Path
C-Path
C-Path
EMA
EMD Serono
Fast Forward (NMSS)
FDA
Genzyme/Sanofi
Genzyme/Sanofi
Genzyme/Sanofi
GSK
Paul Matthews
Ellen Mowry
Fred Lublin
Timothy Coetzee
Nicholas LaRocca
Weyman Johnson
Ursula Utz
Frank Dahlke
Gordon Francis
Laura Balcer
Jeremy Hobart
Donna Masterman
Bruno Musch
Giancarlo Comi
Joshua Steinerman
Volker Knappertz
Elizabeth Morrison
Raj Kapoor
Gary Cutter
Ralph Benedict
Maria Pia Sormani
Rob Motl
Brenda Banwell
Bernard Uitdehaag
Imperial College London
Johns Hopkins
Mt Sinai
National MS Society
National MS Society
National MS Society
NINDS
Novartis
Novartis
NYU
Plymouth Hospital
Roche/Genentech
Roche/Genentech
Scientific Institute H.S. Raffaele, Italy
Teva
Teva
UC Irvine
UCL Institute of Neurology
University of Alabama
University of Buffalo
University of Genoa
University of Illinois
University of Pennsylvania
VU University Medical Center
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)
Confidential
17
DISCUSSION OR QUESTIONS
Multiple Sclerosis Outcome Assessments Consortium
(MSOAC)