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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

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“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”

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FDA FDASIA and PDUFA legislation (2012)

• Committed the FDA to initiate the Patient-Focused 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)

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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?

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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)

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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

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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.

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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

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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)

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Example BWS choice taskChoose 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.

Best Treatment Worst

○ Slows the progression of weakness ○

○ 2 year gain inexpected lifespan ○

○1 year of post-approval drug

information available○

○ Causes loss of appetite ○

○Increased risk of

bleeding gums and increased bruising

○

○Increased risk of harmless heart

arrhythmia○

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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

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Worries and domainsDomain Attribute descriptionChild affect 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 familyFamily and social 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 familiesChild medical concerns 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 budgetParent well-being 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

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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 Least worried

○ My child having good friends ○

○ The wellbeing of my other children ○

○ 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 ○

○ My child feeling happy ○

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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

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Sample (119)Participant characteristics Mean (SD) Caregiver age in years 43.7 (SD=7.7)Relationship to child(ren) Biological mother 67.2% Biological father 28.6% Adoptive mother 3.4% Adoptive father 0.8%Marital status Married/long-term relationship 89.9% Divorced/Separated 9.2% Widowed 0.8%Race Caucasian 91.6%Education High school/GED 4.2% Some college 14.3% Technical school 5.0% Associated degree 7.6% Four-year college degree 42.9% Graduate/professional degree 25.2%Income <$25,000 5.9% $25,000-$50,000 8.4% $50,000-$75,000 18.5% $75,000-$100,000 18.5% >$100,000 47.1%

Child characteristics PercentChild age in years 21.1 (SD=6.4)Number of affected children One child 92.4% Two or more children 7.6%Living arrangements In caregiver's home 98.3% Independent 0.8% Other 0.8%Ambulation status Ambulatory 63.9% Non-ambulatory 36.0%Research participation Clinical research 58.0% Clinical trial 34.0%Had life-threatening emergency Yes 18.5% No 81.5%

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Stops Slows

None 5 yr 2 yr None 2 yr 1 yr None None Mild Mod None Mild Sev None Mild Sev

Levels 0.87675070028011

2

0.79971988795518

2

-0.07983193277310

92

NaN 0.46358543417366

9

0.40756302521008

4

-0.11344537815126

NaN 0.05602240896358

54

0.02240896358543

42

-0.02100840336134

45

NaN -0.00980392156862745

-0.13165266106442

6

-0.28011204481792

7

NaN -0.01120448179271

71

-0.26610644257703

1

-0.71988795518207

3

NaN -0.03781512605042

02

-0.16946778711484

6

-0.78571428571428

6

-0.9

-0.7

-0.5

-0.3

-0.1

0.1

0.3

0.5

0.7

0.9

Rela

tive

best

-wor

st sc

ore

Relative attribute importance

28.66% 17.29% 2.31% 8.10% 21.23% 22.41%

Effect on muscle function Lifespan Knowledge about drug Nausea Risk of bleeds Risk of heart arrhythmia

Figure 2. Relative best-worst scores for attribute levels and relative attribute importance

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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

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

-3.000 -2.000 -1.000 0.000 1.000 2.000 3.000

Worry Prioritization by Ambulation Status

Non-ambulatory

Ambulatory

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ConclusionsPreference 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.

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Some benefits of community-engaged 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 mutually-beneficial process

• Give the community a productive action

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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

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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).

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Results: Treatment preferencesTreatment benefits and risks Best Worst Utility SE T-testP-

ValueStops progression of weakness 628 2 0.877 0.01 69.4 <0.001Slows progression of weakness 571 0 0.800 0.02 53.4 <0.001Does not change progression of weakness 68 125 -0.080 0.02 -4.1 <0.0015 year gain in expected lifespan 348 17 0.464 0.02 22.7 <0.0012 year gain in expected lifespan 299 8 0.408 0.02 21.2 <0.001No extra gain in expected lifespan 12 93 -0.113 0.01 -8.3 <0.0012 years of post-approval drug info available 109 69 0.056 0.02 3.0 0.0011 years of post-approval drug info available 20 4 0.022 0.01 3.3 0.001No post-approval drug info available 41 56 -0.021 0.01 -1.5 0.064No increased chance of nausea 19 26 -0.010 0.01 -1.0 0.148Causes loss of appetite 1 95 -0.132 0.01 -10.3 <0.001Causes loss of appetite with occasional vomiting 17 217 -0.280 0.02 -15.0 <0.001No increased risk of bleeds 3 11 -0.011 0.01 -2.1 0.016Increased risk of bleeding gums and increased bruising 0 190 -0.266 0.02 -16.1 <0.001Increased risk of hemorrhagic stroke and lifelong disability 0 514 -0.720 0.02 -42.8 <0.001No increased risk of heart arrhythmia 5 32 -0.038 0.01 -4.5 <0.001Increased risk of harmless heart arrhythmia 1 122 -0.169 0.01 -11.9 <0.001Increased risk of dangerous heart arrhythmia and sudden death 0 561 -0.786 0.02 -51.1 <0.001

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Results: Worry prioritization

Worry Domain Estimate Std Error Z score P-valueChild missing new treatments MC 0.93 0.073 12.73 p<0.001Child getting weaker MC 2.30 0.074 31.09 p<0.001Getting the right care over time MC 1.00 0.073 13.64 p<0.001Child feeling happy CA 0.67 0.076 8.84 p<0.001

Child having good friends CA 0.10 0.076 1.34 0.18Child feeling like burden CA -0.67 0.073 -9.22 p<0.001Child becoming independent FS -0.85 0.071 -11.92 p<0.001Child unable to express worries CA 0.09 0.075 1.27 0.21Good enough parent PWB -0.05 0.083 -0.61 0.54Handling emotional demands PWB -0.20 0.076 -2.65 0.01Managing my uncertainty PWB 0.49 0.076 6.43 p<0.001Having time for myself PWB -1.97 0.071 -27.59 p<0.001Isolated from other families FS -1.10 0.071 -15.5 p<0.001Affording care my child MC 0.27 0.074 3.67 p<0.001Effect on closest relationships FS -0.85 0.072 -11.77 p<0.001Wellbeing of other children FS -0.16 0.078 -2.12 0.03