Measuring the priorities and
treatment preferences of
caregivers of a child with
Duchenne Muscular Dystrophy
using best-worst scaling
Holly Peay, M.S.
Parent Project Muscular Dystrophy
ParentProjectMD.org
“I understand the need for caution and
care, but I also know that our children are
dying. Parents should be able to decide the
risk/benefit of a drug that has gone through
and passed preliminary testing. I would
rather my son die trying and fighting than
waiting and wondering and wishing….I am
one parent willing to take an educated
risk!”
PPMD “Share Your BRAVE Story”
ParentProjectMD.org
FDA FDASIA and PDUFA
legislation (2012)
• Committed the FDA to initiate the PatientFocused Drug Development Program
• Aims to inform the FDA’s benefit/risk
assessments and includes goals of
systematically obtaining the patient’s
perspective on disease impact and
treatment benefits
(http://www.fda.gov/forindustry/userfees/prescriptiondruguserfee
/ucm326192.htm)
ParentProjectMD.org
A time of unique opportunity
• How do we influence regulatory bodies?
– Who represents patient/family preferences?
• What do regulators want?
– Less “emotion”?
– More “patient stories”?
– Quantifiable, generalized data?
• What does the community want?
– What is a “good enough” benefit?
– Is any risk too high for approval?
– What information needed for decision making?
ParentProjectMD.org
Engagement models
• Direct engagement via representation,
consultation and/or testimony
• Formal study of the preferences and
views of patients and the public
• “When asking the public to assist in
determining health priorities, we should
use techniques that allow people to reveal
their true preferences. If not, why bother
asking them at all?” (Gafni,1995)
ParentProjectMD.org
PPMD’s benefit/risk study
Advocacy-led, community-engaged study to:
1. Quantify treatment preferences of
caregivers for benefits and risk of potential
treatments (BWS case 2)
2. Prioritize Duchenne-related worries of
caregivers to describe impact (BWS case 1)
– Compare worry priorities of parents of
ambulatory and non-ambulatory children
ParentProjectMD.org
A BWS benefit:
• Offers alternative to complex algorithms:
score a level given the times a level was
rated as best or worst.
– Level receives +1 if rated as best
– Level received -1 if rated as worst
– Level receives 0 otherwise
• An approximation to the utility of the level
is given by averaging the score, or as
– Score = (B – W)/N
– where N is the number of times a level appears
across all choice sets.
ParentProjectMD.org
Treatment preferences
• Hypothetical treatment features (attributes)
identified and refined in consultation with
parents, clinicians, researchers and
industry
• In-depth pilot testing with 7 parents
• Parents/guardians identify what parts of
each treatment were best and worst
• Experimental design identified 18 potential
treatments that systematically varied
across the six chosen attributes
ParentProjectMD.org
Attributes and levels
•
•
•
•
Effect on muscle function (none, slows, stops)
Gain in expected lifespan (none, 2, 5 years)
Post-approval information (none, 1, 2 years)
Nausea (none, loss of appetite, loss of appetite
and occasional vomiting)
• Risk of bleeds (none, risk of bleeding gums and
increased bruising, risk of hemorrhagic stroke)
• Risk of heart arrhythmia (none, risk of
harmless heart arrhythmia, risk of dangerous
heart arrhythmia and sudden death)
ParentProjectMD.org
Example BWS choice task
Best
Treatment
Worst
○
Slows the progression
of weakness
○
○
2 year gain in
expected lifespan
○
○
1 year of postapproval drug
information available
○
○
Causes loss
of appetite
○
○
Increased risk of
bleeding gums and
increased bruising
○
Increased risk of
○
harmless heart
arrhythmia
ParentProjectMD.org
○
Choose the best thing in this
treatment by clicking the
circle under “best” and
choose the worst thing by
clicking the circle under
“worst”. You have to choose
a best thing and worst thing
to move on. Remember that
a computer chose the
combinations to make the
experiment work, and some
of them seem bad. Even so,
please pick the best and
worst thing.
DMD worries: BWS case 1
• Responsive to the FDA’s request to
understand disease impact
• Aim: prioritize “qualitative” DMD-related
worries using quantitative methods
• 5 parents contributed worries, ultimately
resulting in list of 16 DMD-related worry
statements after stakeholder
engagement, categorized under 4
domains
• Pilot study conducted with 7 parents
ParentProjectMD.org
Worries and domains
Domain
Child affect
Family and social
Child medical concerns
Parent well-being
ParentProjectMD.org
Attribute description
My child feeling happy
My child having good friends
My child not being able to express deep worries
My child feeling like a burden on the family
The wellbeing of my other children
Effect of Duchenne on my closest relationships
My child becoming independent from me over time
Feeling isolated from other families
My child getting weaker
Getting the right care for my child over time
My child missing out on new treatments
Affording care my child needs within the family budget
Managing my uncertainty about my child's future
Being a good enough parent for my child
Me handling the emotional demands of Duchenne
Having time for myself
BWS worry choice task
In the past 7 days, choose which of the following concerns you have been most
worried about and which you have been least worried about.
Most worried
○
○
Concerns
My child having good friends
The wellbeing of my other children
Least worried
○
○
○
My child not being able to express deep
worries
○
○
Being a good enough parent for my child
○
○
My child feeling like a burden on the family
○
○
ParentProjectMD.org
My child feeling happy
○
Recruitment
• Recruitment:
– Using PPMD, DuchenneConnect Registry, and
snowball recruiting
• Inclusion/exclusion:
– At least one living child with DMD, living in the
US, over 18 years of age, and able to
complete an online survey in English
• Ethics:
– Study determined to be exempt by the
Western Institutional Review Board
ParentProjectMD.org
Participant characteristics
Caregiver age in years
Relationship to child(ren)
Biological mother
Biological father
Adoptive mother
Adoptive father
Marital status
Married/long-term relationship
Divorced/Separated
Widowed
Race
Caucasian
Education
High school/GED
Some college
Technical school
Associated degree
Four-year college degree
Graduate/professional degree
Income
<$25,000
$25,000-$50,000
$50,000-$75,000
$75,000-$100,000
>$100,000
ParentProjectMD.org
Mean (SD)
43.7 (SD=7.7)
67.2%
28.6%
3.4%
0.8%
89.9%
9.2%
0.8%
91.6%
4.2%
14.3%
5.0%
7.6%
42.9%
25.2%
5.9%
8.4%
18.5%
18.5%
47.1%
Sample (119)
Child characteristics
Child age in years
Number of affected children
One child
Two or more children
Living arrangements
In caregiver's home
Independent
Other
Ambulation status
Ambulatory
Non-ambulatory
Research participation
Clinical research
Clinical trial
Had life-threatening
emergency
Yes
No
Percent
21.1 (SD=6.4)
92.4%
7.6%
98.3%
0.8%
0.8%
63.9%
36.0%
58.0%
34.0%
18.5%
81.5%
Figure 2. Relative best-worst scores for attribute levels and relative attribute importance
1.0
Effect on muscle function
Lifespan
Knowledge about drug
Nausea
Risk of bleeds
Risk of heart arrhythmia
Relative best-worst score
0.8
0.6
0.4
0.2
0.0
-0.2
-0.4
-0.6
-0.8
-1.0
Stops Slows None
Levels 0.877 0.800 -0.08
Relative attribute
importance
28.66%
ParentProjectMD.org
5 yr
2 yr None
2 yr
1 yr None
None Mild Mod
None Mild Sev
None Mild Sev
0.464 0.408 -0.11
0.056 0.022 -0.02
-0.01 -0.13 -0.28
-0.01 -0.26 -0.72
-0.03 -0.16 -0.78
17.29%
2.31%
8.10%
21.23%
22.41%
Worry Prioritization by Ambulation Status
-2.500
-2.000
-1.500
-1.000
-0.500
0.000
0.500
1.000
1.500
2.000
2.500
B. Child getting weaker
C. Getting the right care
A. Miss out new treatments
D. Child feeling happy
L. Managing my uncertainty
P. Affording care
E. Child having friends
H. Not able to express worries
Ambulatory
Non-ambulatory
J. Good enough parent
R. Wellbeing other children
K. Handling emotional demands
F. Child feeling like burden
Q. Effect on closest relationships
G. Child becoming independent
N. Isolated from other families
M. Time for myself
ParentProjectMD.org
3.000
Conclusions
Preference experiment:
– Stopping/slowing the progression of muscle
weakness accounted for the largest proportion of the
variation.
– The presence of side effects/risks could be
compensated for by a treatment that stops/slows
progression to muscle function.
Worries experiment:
– Child’s disease management was ranked as of
greatest concern, followed by child’s affect.
– Impacts of DMD on the family and parents’
wellbeing were less prioritized.
ParentProjectMD.org
Some benefits of communityengaged approach
• Identify the “right” attributes and levels
– Meaningful to patients/families
– Acceptable to other stakeholders
• Set up the experiment “properly” for the
community
• Bring together stakeholders in a mutuallybeneficial process
• Give the community a productive action
ParentProjectMD.org
Engaging the FDA
• On July 9, 2013, PPMD met with Dr. Janet
Woodcock and senior staff from FDA; one
objective: review BR results
• On December 12, 2013 PPMD held an
FDA/community engagement meeting that
also covered the BR study
• Anecdotally, FDA senior staff have
encouraged other advocacy organizations
to use it as a model
ParentProjectMD.org
Acknowledgements
• Co-authors:
– John Bridges, JHSPH
– Ilene Hollin, JHSPH
– Hadar Sheffer, PPMD
– Ryan Fischer, PPMD
This research was supported through funding
from Parent Project Muscular Dystrophy
(PPMD).
ParentProjectMD.org
Results: Treatment preferences
Best Worst Utility SE
Treatment benefits and risks
Stops progression of weakness
Slows progression of weakness
Does not change progression of weakness
5 year gain in expected lifespan
2 year gain in expected lifespan
No extra gain in expected lifespan
2 years of post-approval drug info available
1 years of post-approval drug info available
No post-approval drug info available
No increased chance of nausea
Causes loss of appetite
Causes loss of appetite with occasional vomiting
No increased risk of bleeds
Increased risk of bleeding gums and increased bruising
Increased risk of hemorrhagic stroke and lifelong disability
No increased risk of heart arrhythmia
Increased risk of harmless heart arrhythmia
Increased risk of dangerous heart arrhythmia and sudden
death
ParentProjectMD.org
628
571
68
348
299
12
109
20
41
19
1
17
3
0
0
5
1
0
2
0
125
17
8
93
69
4
56
26
95
217
11
190
514
32
122
0.877
0.800
-0.080
0.464
0.408
-0.113
0.056
0.022
-0.021
-0.010
-0.132
-0.280
-0.011
-0.266
-0.720
-0.038
-0.169
0.01
0.02
0.02
0.02
0.02
0.01
0.02
0.01
0.01
0.01
0.01
0.02
0.01
0.02
0.02
0.01
0.01
PT-test Value
69.4 <0.001
53.4 <0.001
-4.1 <0.001
22.7 <0.001
21.2 <0.001
-8.3 <0.001
3.0 0.001
3.3 0.001
-1.5 0.064
-1.0 0.148
-10.3 <0.001
-15.0 <0.001
-2.1 0.016
-16.1 <0.001
-42.8 <0.001
-4.5 <0.001
-11.9 <0.001
561 -0.786 0.02 -51.1 <0.001
Results: Worry prioritization
Worry
Domain
MC
MC
MC
CA
Estimate
0.93
2.30
1.00
0.67
Std Error
0.073
0.074
0.073
0.076
Z score
12.73
31.09
13.64
8.84
P-value
p<0.001
p<0.001
p<0.001
p<0.001
Child missing new treatments
Child getting weaker
Getting the right care over time
Child feeling happy
Child having good friends
Child feeling like burden
Child becoming independent
Child unable to express worries
Good enough parent
Handling emotional demands
Managing my uncertainty
Having time for myself
Isolated from other families
Affording care my child
Effect on closest relationships
ParentProjectMD.org
Wellbeing
of other children
CA
CA
FS
CA
PWB
PWB
PWB
PWB
FS
MC
FS
FS
0.10
-0.67
-0.85
0.09
-0.05
-0.20
0.49
-1.97
-1.10
0.27
-0.85
-0.16
0.076
0.073
0.071
0.075
0.083
0.076
0.076
0.071
0.071
0.074
0.072
0.078
1.34
-9.22
-11.92
1.27
-0.61
-2.65
6.43
-27.59
-15.5
3.67
-11.77
-2.12
0.18
p<0.001
p<0.001
0.21
0.54
0.01
p<0.001
p<0.001
p<0.001
p<0.001
p<0.001
0.03