ISPOR 19th Annual European Congress
Vienna, 31st Oct 2016
IP#6: FROM TESTIMONIALS TO QUALITATIVE
RESEARCH EMBEDDED IN CLINICAL TRIALS: HOW
DO HEALTH TECHNOLOGY ASSESSMENT BODIES
CONSIDER THE VOICE OF RARE DISEASE
PATIENT'S WHEN GRANTING ACCESS TO ORPHAN
DRUGS?
© Mapi 2016, All Rights Reserved
PRO Claims in orphan drugs
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The frequency of PRO claims in orphan medicines is comparable or
inferior to the frequency of PRO claims in all products approved by
the FDA and EMA Acquadro et al, ECRD Berlin 2014. Vernon, Ruff et al, ISPOR Montreal 2014

This is remarkably small, considering the profound effect of rare
diseases on patients’ lives due to their severe symptomatic
expression

HTA bodies are presented dossiers that frequently lack essential
information concerning clinical outcomes

More efforts are needed to systematically include the patient’s
perspective (i.e., PRO / OBSRO assessment) in the evaluation of
orphan drugs
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© Mapi 2016, All rights reserved
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Challenges for patient-centered outcomes research in rare
diseases
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Generic measures inappropriate
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Functional limitations to Self-Reporting
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Too costly
Take too much time
Competition for patient involvement
Conceptual model too rich and complex
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Age / cognitive impairment / physical limitations
Disease/condition-specific measures face practical barriers
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Lack of validity
Lack of responsiveness
Symptom scales
Function scales
Quality of life
Family impact
Caregiver burden
By age group/disease stage
Issues for testing quantitative scores
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Endpoint hierarchy
Power
Comparator
Timepoint / trial duration
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© Mapi 2016, All rights reserved
What is Mixed Methods Research?

Mixed Methods Research, a developing research paradigm in health
sciences, and outcome research

Mixed Methods Research defined as:
 "Research in which the investigator collects and analyses data, integrates
qualitative and
quantitative approaches or methods in a single study or program of
the findings, and draws inferences using both
inquiry"
(Tashakkori & Creswell, Journal of Mixed Methods research 2007)

Mixed Methods Research is a promising approach to have the patient
perspective integrated into clinical research
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Unique potential of mixed methods research

Well-designed mixed methods research combines advantages of
qualitative and quantitative research methodologies:

Qualitative research (e.g. patient interviews and thematic analysis)
is good for exploration
 affordable, flexible, rich, powerful, and conveys accessible messages

Quantitative research (e.g. drug efficacy in clinical trial) is good for
hypothesis testing and evidence generation
 reliable, well accepted to support decision making
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Applications of Mixed Methods Research in clinical
development

Strategy
 Needs and priorities (Burden Of Illness)
 Treatment Benefit (Concept Of Interest)
 Signal detection

Methodology
 Test content validity of a specific PRO
 Develop conceptual model
 Set foundation for instrument adaptation or development
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Evidence generation
 Inform endpoint selection and choice of measures
 Individual Risk/Benefit Assessment
 Goal definition and attainment
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© Mapi 2016, All rights reserved
3
The Issue(s)
 To what extent do patient testimonials
impact health technology assessment
(HTA) decisions?
 Is this sufficient to ensure reliable
decision making?
 Would qualitative research fill a gap?
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© Mapi 2016, All rights reserved
The panelists
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Moderator
Benoit Arnould PhD,
Senior Director, Global
Patient-Centered Outcomes
Mapi Group
Tel.: +33 (0)4 72 13 69 53
Mobile: +33 (0)6 80 45 55 28
[email protected]
www.mapigroup.com
Benoit leads the Global Patient-Centered Outcomes research
team. He has been conducting studies to develop and validate
Patient-Reported Outcome and other Clinical Outcomes
Assessment instruments for more than 15 years, measuring a
large variety of concepts including Adherence, Acceptance,
Satisfaction, Health-Related Quality of Life, Function and
Symptoms. In recent years, he has increasingly been asked by
Industry clients to assist in their Endpoint strategy definition. His
current primary interest is Mixed Methods Research.
Benoit is a Health Economics graduate with a specialty in
statistics, and has completed his PhD on tools for clinical decision
making, a subject on which he publishes regularly.
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© Mapi 2016, All rights reserved
Sheela Upadhyaya
Associate Director – Highly Specialised Technologies, NICE
Sheela Upadhyaya is currently the Associate Director of the Highly
Specialised Technology program at NICE and is responsible for running
the program to evaluate medicines and technologies for rare and ultrarare conditions for commissioning in the NHS.
Tel: +44 7045 2243
[email protected]
https://www.nice.org.uk/
Prior to joining NICE, she was responsible for commissioning rare and
ultra-orphan disease services in NHS England, where she delivered many
improvements to these services by collaborating with industry, clinicians
and patient groups.
As commissioner for the National Specialised Commissioning team, she
held responsibility for the genetics and metabolic portfolio leading
nationally for lysosomal storage disorders. In this role she delivered more
efficient drug and homecare prices by running national tender exercises
with the Department of Health, Commercial Medicines Unit. As a result of
this, she was selected to sit on the Department of Health’s National
Homecare Medicines Committee developing the national homecare
standards. Sheela has a passion for partnership working believes that
collaboration across the sector is the key to delivering high quality results.
She strives to ensure services for patients with rare conditions provide
excellent quality and good outcomes in an efficient effective environment
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5
Panelist: Charlotte Roberts
Charlotte Roberts
Business Development Manager,
MPS Commercial
Charlotte has been with the Society for
Mucopolysaccharide Diseases since 2014.
Having led the successful 18 month campaign for
access to Vimizim for those with MPS IVA Morquio,
Charlotte now manages MPS Commercial, a not for
profit subsidiary of the MPS Society supporting
patients on clinical trials.
Tel: +44(0) 345 389 9901
[email protected]
www.mpssociety.org.uk
In the last two years the MPS Society has been
involved in 3 NICE HST appraisals and provided
guidance to another patient organisation going
through the process.
Panelist: Samantha Parker
Samantha Parker MBA,
SVP, Chief Patient Access Officer
Lysogene
Tel.: +33 (0)1 41 03 03 93
Mobile: +33 (0)6 08 17 18 85
[email protected]
om
www.lysogene.com
Samantha Parker is Head of Lysogene’s Patient and Policy Affairs.
Ms. Parker has specialised in rare disease research and public
health since 2000. She has focused on expanding the expert
disease community of healthcare professionals, patients, industry
and regulators; building disease registries and natural history
studies; developing consensus care guidelines; and developing
strategies to improve the quality of diagnosis and patient care.
Ms. Parker contributed, for several years, to the area of
independent professional education in rare diseases. She is a
member of the European Group of Experts on Rare Diseases
(EGRD) and the International Rare Diseases Research Consortium
(IRDiRC).
Ms. Parker graduated from Edinburgh University and obtained a
M.B.A in Life Sciences
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The HTA Body perspective: Questions to Sheela
Upadhyaya

How do testimonials from patients or their representatives impact
HTA decisions?

Is this reliable enough to support decisions from a public health
perspective?
Patient Participation in the
Highly Specialised Technology
(HST) Evaluation process
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7
Disclaimer
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Decision-making in HST
Nature of
condition
Delivery of
specialised
services
Impact of
Technology
Value
Indirect
and nonhealth
benefits
Cost to
NHS and
PSS
Value for
money
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8
Patient Involvement in NICE
HST Process
Scoping : clarity on patient numbers,
current treatment and details of the
condition and outcomes to be
considered
Evaluation: patient testimonies, further
details on patient numbers, patient
experience on condition
Guidance Development : Clarity that
information submitted has been
accurately represented in guidance
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Patient Involvement in NICE
HST Process
Scoping
Evaluation
Guidance
Development
• Comment on scope
• Attend scoping meetings
• Submit testimonies
• Participate in committee meetings
• Comment on guidance
• Ensure accurate reflection of information.
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How information is Presented
• HST Committee lay team :
– Template and guidance issued by NICE
– Summarise submitted testimonies into slides
– Presented at committee meeting
– Committee then check understanding with
attendees
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The role of patient experts
Patient Experts
– Provide statements which will help the
Committee consider key criteria such as the
nature of the condition
– Attend Committee meetings as individuals
They will have
– experience of the broader patient population
relevant to the evaluation and/or
– relevant personal experience
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Value Delivered by Patient Input
• Defining the patient population
– Patient numbers
– Burden of disease
– A better understanding of what is important to
patients
– Clarity on the patient population that will most
benefit
– Impact of treatment
– Likely uptake – adherence issues
Bringing the condition to life for committee
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Challenges
• Is it evidence or
testimony ?
• No need to
quantify
• Information needs
to have some
quality assurance
Evidence
Testimony
HTA Evaluation
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The patient’s perspective: Questions to Charlotte Roberts

How do patient representatives communicate toward HTA bodies?

To which extent do HTA bodies listen to the voice of the patients,
their families and their representatives?
Patient Organisation Involvement in HST
Evaluations
• Attend NICE Scoping Meeting
• Identify expert patient(s) to write submission and
attend NICE Committee meetings
• Support and Counsel Patient Experts
• Encourage whole patient community to respond
12
The Impact of Patient Involvement
• Patients are invited to be part of the HST
process
• QoL Data not easily captured but often the
biggest impact on patients
• Development of first Managed Access
Agreement (MAA)
MAA Criteria
The MAA is available to individuals
who:
•
Have a confirmed diagnosis of MPS
IVA
•
Must have a confirmed enzymatic
test, elevated urinary keratan
sulfate and mutation analysis
•
Will sign up to the Managed
Access Patient Agreement
The MAA isn’t available to
individuals who:
• Are diagnosed with an additional
progressive life-limiting condition
where treatment would not
provide long-term benefit, e.g.
Cancer or Multiple Sclerosis
or
• Have a lung capacity (FVC) of less
than 0.3 litres and require
ventilator assistance
or
• Are unwilling to comply with the
associated monitoring criteria
FVC: forced vital capacity
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Managed Access Agreement QoL Overview
QoL ASSESSMENT
BASELINE
MONTH 4
MONTH 8
MONTH 12
MPS-HAQ
X
X
EQ-5D-5L
X
X
Brief Pain Inventory
(BPI)
or
Adolescent Paediatric
Pain Tool (APPT)
X
Beck Depression
Inventory
X
X
X
X
X
Key Patient Reported Benefits Not Captured By
the QoL Tools Used In the MAA Were:
•
•
•
•
•
Less tiredness
Clearer speech
More strength
Increased independence
Reduced number of
illnesses/infections
• Growth or weight in
children
•
•
•
•
•
•
Increased energy levels
Improved stamina
Better sleep
Hearing improvement
Eyesight improvement
Less breathlessness
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4 Month Testimonial Data
PATIENT ID
ANECDOTAL BENEFITS
6540209436
Increased mobility – able to climb stairs and into bed
Fantastic energy levels - Able to go out on family trips
6535323116
Increased concentration – wanting to learn
Increased vocabulary
Improved hand-eye co-ordination
41166695
Stronger arms and hands – better grip
Less tired – able to do more during the day
Reduced amount of pain
6439458361
More energy – for school and also able to go out with friends at the weekend
Sleeping better
Able to reduce pain medication
Fewer instances of headaches and nausea
6480190696
Grown 1cm
Increased appetite
The Industry perspective: Questions to Samantha Parker
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How do Pharmaceutical Companies capture the patient perspective
when developing therapeutic innovation?
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How do they align their endpoint strategy to patient needs and
priorities?
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Clinical evolution of
MPS IIIA
MPS IIIA is an autosomal recessive lysosomal storage disease, with first clinical symptoms occurring early in
life, neurological symptoms manifesting at around 1-4 years

Patients present with severe behavioural, sleep and cognitive deficiencies and progressively lose functions
such as talking, eating, walking
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Extremely deteriorating quality of life, devastating for
patients and families
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There are no approved or effective treatments
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Less than 15% patients survive beyond their teens
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The incidence of MPS IIIA ranges from 0.5-1.5 per
100,000 live births
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No biomarkers
Cognitive Age Equivalent (years)
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Normal development
6 Developmen
5
tal delay
Frequent falls
Impaired swallowing
Spasticity
4
3
Seizures
2
MPS IIIA
1
0
Death
0 1
2
3
4
5
6
7
8
9 10 11 12 13 14 15
Chronological Age
(years)
Graph adapted from UMN natural history study (Shapiro et al)
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Questions from audience
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Thank You!
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