This talk was presented at the Advances in Precision and Personalized Medicine Workshop.

1. 1
Patient Preference Studies:
How they Contribute to Personalized
Medicine
SAMSI Workshop
Advancements in Industry
March 15, 2019
Rachael DiSantostefano
Senior Director, Epidemiology
Janssen R&D, LLC

2. 2
Funding and Disclosures
 Financial Disclosures
None
 Relationship Disclosures
R. DiSantostefano is an employee of Janssen R&D, LLC
and shareholder of Johnson & Johnson
R. DiSantostefano is a participants in PREFER, an IMI
project on patient preferences
 Statements made in this presentation are those of
the author and not necessarily those of her employer

3. 3
Objectives
 Patient preferences in medical decision making
What
When
How
 Connection to personalized medicine
Shoulder Dislocation Surgery
Whole Genome Sequencing

4. 4
What is Patient Preference Information?
Type What it Measures
Attributes What Matters
Relative
Importance
How much it matters
Tradeoffs
What tradeoffs patients are willing
to make between benefits, harms,
and other aspects
Adapted from RTI-HS and MDIC

5. 5
Some Decisions Are More Complex
Which Medication is Best?
B
E
C
D
A
Reduction in days hospitalized (benefit)
Probabilityofinfection(risk)
Ideal
Preference information is
needed to choose
between A and C
“Preference-Sensitive” Decision
Medical Device Innovation Consortium Patient-centered Benefit-risk Framework,
http://mdic.org/wp-content/uploads/2015/05/MDIC_PCBR_Framework_Web.pdf

6. 6
When might you conduct a preference study?
 When treatment decisions are more complicated
Examples
 Preference-sensitive
Benefits and risks are relatively uncertain
Different patients may make different decisions based on how they
value benefit-risk tradeoffs
 Novel or new treatment or technology

7. 7
How: Many Methods for Assessing Preferences
Medical Device Innovation Consortium Patient-centered Benefit-risk Framework, http://mdic.org/wp-
content/uploads/2015/05/MDIC_PCBR_Framework_Web.pdf
Group Method
Structured-weighting
• Simple direct weighting
• Ranking exercises
• Swing weighting
• Point allocation
• Analytic hierarchy process
• Outranking methods
Health-state utility
• Time tradeoff
• Standard gamble
Stated-preference
• Direct-assessment questions
• Threshold technique
• Conjoint analysis and discrete-choice experiments
• Best-worst scaling exercises
Revealed-preference
• Patient-preference trials
• Direct questions in clinical trials

8. 8
Explosive Growth of Regulatory Expectations, Guidance and
Initiatives in Patient-Focused Drug Development, Benefit-Risk,
Patient Preferences
Regulatory/Govt
Trade /
Academic Orgs Pub Private/Prof Patient Groups
21st
Century
Cures Act
MDUFA IV

9. 9
Preference Studies
Applications in Personalized Medicine

10. 10
Towards Preferences of the Individual
 Population vs. Individual Decisions
Regulatory decisions – population level
Treatment decisions – individual level
 Nearly all preference studies assess population level
preferences
 Movement towards individual-level preferences
Subgroup analyses / covariates / heterogeneity
Shared or individual decision making tools

11. 11
Shared Decision Making
 Dislocated shoulder – surgery or non-operative treatment?
Courtesy of Shelby Reed
Streufert, B., et al. (2017), Orthop J Sports Med 5(3)

12. 12
Tradeoffs in Treatments for First-Time Anterior Shoulder
Dislocation – Typical Values
Streufert, B., et al. (2017), Orthop J Sports Med 5(3)
Attribute Surgery Non-Surgical
Limited ability to
move your arm
Arm in a sling for
1 month
No limit on moving arm
Avoid contact
sports and
lifting overhead
Discontinue all
high-risk
activities for 6 months
Discontinue all high-risk
activities for
1 month
Duration of
physical therapy
12 weeks 4 weeks
Chance of another
Shoulder dislocation in 2
years
5%
15% - 80%
(age- and sex-dependent)
Out-of-pocket cost,
US$
1000 0

13. 13
Example Adaptive Conjoint Task
No Surgery vs. Surgery
Streufert, B., et al. (2017), Orthop J Sports Med 5(3)

14. 14
Conjoint Analysis: Mean Importance Weights
(n=347)
0 5 10 15 20 25 30 35
LIMITS ON SHOULDER MOTION
AVOID HIGH-RISK ACTIVITIES
DURATION OF PT
CHANCE OF RECURRENCE
OUT-OF-POCKET COST
Relative Importance
Importance of Attributes in
Shoulder Dislocation
Streufert, B., et al. (2017), Orthop J Sports Med 5(3)

15. 15
Streufert, B., et al. (2017), Orthop J Sports Med 5(3)
Variations in Preferences Between Individuals
10
12
10
32
36
0 20 40
LIMITATIONS ON
SHOULDER MOTION
RETURN TO HIGH-
RISK ACTIVITIES
DURATION OF
PHYSICAL THERAPY
CHANCE OF A
REPEAT INJURY IN
THE NEXT 2 YEARS
TOTAL OUT-OF-
POCKET COST
Relative Importance
14
15
11
41
18
0 20 40
LIMITATIONS ON
SHOULDER MOTION
RETURN TO HIGH-
RISK ACTIVITIES
DURATION OF
PHYSICAL THERAPY
CHANCE OF A
REPEAT INJURY IN
THE NEXT 2 YEARS
TOTAL OUT-OF-
POCKET COST
Relative Importance

16. 16
Results
 Subject’s treatment choice was dependent on their
concern about recurrent dislocation
 Decision tool to assess preferences was valued
87% - measured preferences match what they expect
89% - would share preferences with their healthcare provider
 Step towards objectively measuring individual
patient preferences and how they might be used in
shared decision making
Streufert, B., et al. (2017), Orthop J Sports Med 5(3)

17. 17
Marshall DA, Gonzalez JM, MacDonald KV, Johnson FR. Value Health. 2017 Jan;20(1):32-39.
 Would you be interested in WGS to identify risk
of diseases?
Whole Genome Sequencing (WGS) for Disease
Risk Identification

18. 18
Preferences for Whole Genome Sequencing (WGS)
 38% of people were not interested in WGS, even if free
 Among those interested in WGS, they valued:
actionable results
being able to choose which results were provided
 Positive and negative utility associated with testing
Many layers of complexity: uncertainty and down stream consequences
Produces information that could lead to outcomes, no outcomes per se
 Are people willing to act on genomic results?
Treatment vs. watchful waiting vignettes were evaluated based on
1) risk of disease diagnosis
2) benefits and risks associated with preventive treatments
Marshall DA, Gonzalez JM, MacDonald KV, Johnson FR. Value Health. 2017 Jan;20(1):32-39.

19. 19
Conclusions
 Personalized medicine can be complicated, requiring
patients to be engaged in decisions guided by their
risk group
healthcare provider
preferences
 Decision tools and/or counseling may be needed in some
areas of personalized medicine
 Not everyone wants to know about or act upon
personalized medicine
 Account for preference heterogeneity when developing
policies or procedures that integrate patient preferences
with personalized medicine

20. 20
Questions
This Photo by Unknown Author is licensed under CC BY-SA
Rachael DiSantostefano (rdisanto@its.jnj.com)

21. 21
References: MDIC Framework and FDA CDRH
Patient Preference Guidance
www.mdic.org/PCBR
http://www.fda.gov/downloads/medicaldevices/de
viceregulationandguidance/guidancedocuments/
ucm446680.pdf

22. 22
BACK UPS

23. 23
21st Century Cures Act

24. 24
PREFER Project
 5-year public, private partnership (2016-2021)
32 partners, 100+ participants
Representation from patient groups, academia, industry,
government
 Goals
To look at how and when it is best to perform and include patient-
preference in decision making during the drug life cycle
To make recommendations that support development of guidelines
for Industry, Regulatory Authorities and HTA bodies
 https://www.imi-prefer.eu/
Funding is from the Innovative Medicines Initiative 2 Joint Undertaking, grant agreement No 115966. This Joint Undertaking receives support
from the European Union's Horizon 2020 research and innovation programme and EFPIA.

25. • Suppose your doctor tells you that you have a gene variant
that may lead to health problems
• [20% or 60%] of people with the gene variant will
development a health problem involving no difficulty in usual
activities, some pain and discomfort, some anxiety, and a 5%
chance of death in the next 10 years.
• If these were the only alternatives available, which would you
choose?

26. 26
How to Conduct a Preference Study
Adapted from Mühlbacher, 2011
Treatment Attributes
EfficacyBenefits
Endpoint B1
Endpoint B2
Adverse
Events
Risks
Endpoint R1
Endpoint R2
Choice Questions
Treatment X Treatment Y
 Prefer X
Endpoint B1
Endpoint B2
Endpoint R1
Endpoint R2
 Prefer Y
Endpoint B1
Endpoint B2
Endpoint R1
Endpoint R2
Choice-Model
Analysis
22R11R
22B11B
RwRw
BwBwU


MAR
MAB NEB
NSB
Risk-Tolerance
Measures
Efficacy
Safety
Dose
Cost
Duration
Attribute Importance

27. 27Adapted from Mühlbacher, 2011
Treatment Attributes
EfficacyBenefits
Endpoint B1
Endpoint B2
Adverse
Events
Risks
Endpoint R1
Endpoint R2
Choice Questions
Treatment X Treatment Y
 Prefer X
Endpoint B1
Endpoint B2
Endpoint R1
Endpoint R2
 Prefer Y
Endpoint B1
Endpoint B2
Endpoint R1
Endpoint R2
Choice-Model
Analysis
22R11R
22B11B
RwRw
BwBwU


MAR
MAB NEB
NSB
Risk-Tolerance
Measures
Efficacy
Safety
Dose
Cost
Duration
Attribute Importance
How to Conduct a Preference Study

28. 28Adapted from Mühlbacher, 2011
Treatment Attributes
EfficacyBenefits
Endpoint B1
Endpoint B2
Adverse
Events
Risks
Endpoint R1
Endpoint R2
Choice Questions
Treatment X Treatment Y
 Prefer X
Endpoint B1
Endpoint B2
Endpoint R1
Endpoint R2
 Prefer Y
Endpoint B1
Endpoint B2
Endpoint R1
Endpoint R2
Choice-Model
Analysis
22R11R
22B11B
RwRw
BwBwU


MAR
MAB NEB
NSB
Risk-Tolerance
Measures
Efficacy
Safety
Dose
Cost
Duration
Attribute Importance
How to Conduct a Preference Study
• Random Parameters
Logit Model
• Latent Class Analysis

29. 29Adapted from Mühlbacher, 2011
Treatment Attributes
EfficacyBenefits
Endpoint B1
Endpoint B2
Adverse
Events
Risks
Endpoint R1
Endpoint R2
Choice Questions
Treatment X Treatment Y
 Prefer X
Endpoint B1
Endpoint B2
Endpoint R1
Endpoint R2
 Prefer Y
Endpoint B1
Endpoint B2
Endpoint R1
Endpoint R2
Choice-Model
Analysis
22R11R
22B11B
RwRw
BwBwU


MAR
MAB NEB
NSB
Risk-Tolerance
Measures
Efficacy
Safety
Dose
Cost
Duration
Attribute Importance
How to Conduct a Preference Study

30. 30Adapted from Mühlbacher, 2011
Treatment Attributes
EfficacyBenefits
Endpoint B1
Endpoint B2
Adverse
Events
Risks
Endpoint R1
Endpoint R2
Choice Questions
Treatment X Treatment Y
 Prefer X
Endpoint B1
Endpoint B2
Endpoint R1
Endpoint R2
 Prefer Y
Endpoint B1
Endpoint B2
Endpoint R1
Endpoint R2
Choice-Model
Analysis
22R11R
22B11B
RwRw
BwBwU


MAR
MAB NEB
NSB
Risk-Tolerance
Measures
Efficacy
Safety
Dose
Cost
Duration
Attribute Importance
How to Conduct a Preference Study
Maximum acceptable risk
(MAR) for a given benefit

31. 31
Some Decisions May be Relatively Easy
Which Device is Best?
C
B
E
A
Reduction in days hospitalized (benefit)
Probabilityofinfection(risk)
Ideal
D
Preference information
is not needed to
determine the best
device
Device C is
superior on
both
benefit and
risk
Medical Device Innovation Consortium Patient-centered Benefit-risk Framework,
http://mdic.org/wp-content/uploads/2015/05/MDIC_PCBR_Framework_Web.pdf

32. 32
Does it Make a Difference?
Recent Preference Studies in Regulatory Settings
 FDA CDRH obesity device
 Conducted by FDA, supported approval
 EMA Multiple Myeloma and Melanoma
 EMA pilots on patient preferences
 NxStage home hemodialysis
 Preference survey informed expanded indication for use without a partner
 Dexcom G5 Continuous Glucose Monitoring
 Informed risk mitigation strategy to prevent unintended boluses by children
 Genentech SQ versus IV B-cell blood cancer crossover trial
 Mini preference survey as primary endpoint in crossover pivotal trial
 Janssen preference study to support esketamine for treatment resistant
depression
 Informed FDA and advisory committee (Ad Com) about patient’s preferences, cited as influential
in Ad Com decision
 Sponsors are starting to include preference studies in their submissions
FDA
“We invite companies to start a
conversation with FDA about using
patient preference information to
support your submission”
Ho, M. P., et al. (2015). Surg Endosc
Postmus, D., et. al. (2017). Oncologist
Rummel, M. (2017). Ann Oncol
https://web.archive.org/web/20180925225311/https://blogs.fda.gov/fdavoice/index.php/tag/continuous-glucose-
monitoring/