Advancing stated-preference
methods for measuring the
preferences of patients with type 2 diabetes
Second DAB Meeting
November 20, 2014
Baltimore, MD
Development of the
Preference Tasks
Section Outline
• 
• 
• 
• 
Stated-preference methods in diabetes
Research question/vignette
Attributes and levels
Preference elicitation
© 2014, Johns Hopkins University. All rights reserved.
– von Arx
– Janssen
– Janssen
– Bridges
Stated preference methods in
diabetes
Lill-Brith von Arx
University of Southern Denmark, COHERE
Novo Nordisk A/S, Dep. of Epidemiology
4
Date
Presentation title
Agenda
1
Background
2
Systematic Review
3
Project aim
4
Discrete Choice Experiment
The patient perspective in drug development
§  Patient-centred development – how is it realised?
Research
Development
Phase 1
Assessment of
patient unmet
medical needs
Research
project
approval
Phase 1 - 2
Development
candidate
selection
First
human
dose
PROs
Anthropological methods/Qualitative research
Stated preference methods
Commercialisation
Phase 3
Phase 3
Stop/go
decision
Clinical
proof of
concept
Phase 4
Pricing &
reimbursement
Product
launch
Marketing
authorisation
LCM
Presentation title
Date
Priorities in drug development
Diabetes self-­‐
management Health outcome Quality-­‐of-­‐life Efficacy A1c Safety Ease of use Cost Cost-­‐Effec.veness Clinical development Decision makers Pa.ents 7
Date
Project idea
Examine patient preference towards insulin treatment
§  defining patient-important outcomes in diabetes
research
§  In an era where diabetes research goes beyond lifesaving therapies (glucose lowering efficacy)
§  what patient segments benefit the most from innovative
products?
§  Is there a social gradient in benefit gained from innovation?
8
Date
Aim of the systematic review
§  To provide an overview of the current application of stated
preference methods in diabetes care
§  examine how stated preference methods are applied in
diabetes (pharmaceutical diabetes treatments)
§  evaluate the value of this information in developing the
patient perspective in clinical and policy decisions.
von Arx LB. Kjaer T. The Patient Perspective of Diabetes Care: A Systematic
Review of Stated Preference Research. Patient 2014;7(3):283-300
9
Date
Funding of DCE studies (n=11)
10
Date
Rationale provided in articles for study conduct
Key aspect
Rationale provided in the articles
Shared decision making (n=7)
To foster patient-caregiver concordance
To enhance treatment outcome
To improve adherence
To reduce health care costs
Product differentiation (n=9)
To inform a choice between distinct
treatment alternatives (e.g. oral versus.
injectable medication)
To differentiate between similar products
(e.g. insulin analogues)
11
Date
Attribute selection
§  Efficacy – Glycemic control
§  Adverse events
§  Hypoglycemia
§  Nausea
§  Weight control
§  CVD (treatment inherent risk)
§  Product ease of use
§  Mode and timing of administration
12
Date
Efficacy measure
7
6
5
4
3
2
1
0
HbA1c
PPG/FPG
Blood sugar/Glucose
control
•  HbA1c: % change
•  Post-prandial glucose/Fasting-plasma glucose: mmol/L or generic •  Blood sugar/glucose control: generic description (optimal, poor)
13
Date
Summary
§  Although the rationale for conducting a DCE is patient-centered the
attribute selection in most applications are based on clinical outcome
measures
§  Clear definition of the attribute levels describing the choice scenarios
(e.g. severity of hypoglycaemic events)
§  Supporting the choice task with relevant respondent health information
§  Paucity in SP research examining health outcomes beyond what is examined
during the development programme
§  Applications of current DCEs could be for pricing-and reimbursement
decisions
§  Therapeutic application
§  Glycemic control preferred over avoiding minor hypo glycemic events,
but not nighttime or severe hypos.
14
Date
Project aim
To examine patient preference towards the benefits and risks of
insulin treatment
§  To evaluate the effect benefit-risk tradeoffs of presenting benefit
is an actual health outcome rather than a surrogate measure
§  To examine individual predictors of preference
§  General- and diabetes specific health status
§  Socioeconomic status and labour market attachment
§  Health behaviour and risk aversion
15
Presentation title
Date
16
Survey design of the DCE
Risk
Benefit
Questionnaire
Surrogate
A1c %
A
A1c % + guidance
B
A1c % + cheap talk
Health
benefit
Reduced risk of
longterm complications
Weight
Heart attack
Minor Hypos
Major Hypos
C
D
Presentation title
DCE choice task
8.5 %
8.5 % (moderate)
8.5 % +
Date
17
Date
Source data
Self-administered questionnaire (postal)
§ 
§ 
§ 
§ 
DCE choice task
Health literacy (diabetes/HbA1c)
Health behaviour/Time preference/Risk aversion
Sociodemographics
Diabetes registry
§ 
§ 
§ 
§ 
3300 type 2 diabetes pts using insulin
Health and diabetes status
Long term complications
General health status (incl. CVD)
18
Date
Follow- up project
§  Qualitative study
§  Examining patient understanding of A1c and
long-term sequalae risk
Mathilde L.M. Eriksen, MSc stud, RN, SDU & NN
Helle Ploug Hansen, professor, SDU
Lill-Brith von Arx, MSc, PhD stud, SDU & NN
19
Date
Thank you!
20
Identification of the research
question, vignette, and attributes
Ellen Janssen, BA
PhD Student
Department of Health Policy and Management
Johns Hopkins Bloomberg School of Public Health
21 Presentation Outline
• 
• 
• 
• 
Background
Research Question
Vignette
Attributes and levels
© 2014, Johns Hopkins University. All rights reserved.
Background
Many different types of medications for type 2 diabetes
•  Oral medications
•  Subcutaneous medications
•  Insulin
Metformin generally first line treatment
•  Considered safe
•  5% of patients that initiate metformin treatment need
to switch medications due to severe gastro-intestinal
side effects
© 2014, Johns Hopkins University. All rights reserved.
Research Question
Objective: quantify the relative preferences of adults
with type 2 diabetes for diabetes medication related
attributes
Research question: What are the treatment
preferences for patients with type 2 diabetes who
have recently been diagnosed and need to switch
medications due to a metformin intolerance?
© 2014, Johns Hopkins University. All rights reserved.
Vignette
Imagine that you were recently diagnosed with type 2
diabetes. Your doctor prescribed you metformin. You have
been taking metformin for the past three months and are
experiencing severe side effects. These side effects include
continuous diarrhea, nausea, and abdominal bloating. You
are now talking to your doctor about switching medications.
Out of the two medications below, which one would you
prefer?
© 2014, Johns Hopkins University. All rights reserved.
Attributes
Eight attributes identified
1.  Glycemic control
2.  Hypoglycemia
3.  Weight Changes
4.  Heart Attack
5.  Gastrointestinal side effects
6.  Glucose monitoring
7.  Dosage and administration
8.  Cost
© 2014, Johns Hopkins University. All rights reserved.
Attributes – Detailed
Definition
Attribute
Level
HbA1C levels at 9% (poor)
Glycemic
HbA1C levels at 7.5%
HbA1c levels
control
(suboptimal)
HbA1C levels at 6.5% (optimal)
Symptoms of hypoglycemia: nausea, No events
Hypoglycemia rapid pulse, shakiness, blurred
4 events in a month
vision, hunger, fatigue, pallor
8 events in a month
20% of people gain weight
Weight
Weight loss in first six months since
10% of people gain weight
Changes
starting medication
10% of people lose weight
No additional person will have a
heart attack
1 additional person out of 1000
Additional medication related risk of
(0.1%) will have a heart attack
Heart Attack
a heart attack
10 additional patients out of
1000 (1.0%) will have a heart
attack
© 2014, Johns Hopkins University. All rights reserved.
Attributes – Detailed Cont’d
Attribute
Definition
Percent of people who will suffer
Gastrointestinal from medication related risk of
Side Effects
diarrhea, nausea, and abdominal
bloating
Glucose
Monitoring
Dosage
Cost
Level
0% – no risk of diarrhoea,
upset stomach and/or nausea
10%
20%
Three times a day
How often your doctor recommends
Once a day
that you monitor your blood glucose
Once a week
Injection once a day in
relation to meal
How often you will need to take the Oral medication once a day in
medication
relation to meal
Oral medication once a day
irrespective of meal
$25/month
Out of pocket costs
$50/month
$75/month
© 2014, Johns Hopkins University. All rights reserved.
Ques.ons •  Relevance of attributes
•  Number of attributes
•  Framing of attributes
–  Denominator
–  Severe side effect
29 The Preference Elicitation
Task
John F.P. Bridges, Ph.D
Principle Investigator
Associate Professor
Department of Health Policy and Management
Johns Hopkins Bloomberg School of Public Health
30 Presentation Outline
•  Randomized Experiments
•  Statistical efficient design vs Bayesian Optimal
Design
•  DCE vs. BWS
© 2014, Johns Hopkins University. All rights reserved.
Randomized Experiment
•  Design two different preference elicitation tasks
•  Randomly assign respondents to the different preference
elicitation tasks
Motivation:
•  Paucity of research comparing different preference
elicitation methods or different experimental designs
•  Use of a randomized trial will increase ability to draw
inferences from results
•  Fill in evidence gaps in stated-preference methods
•  Advance measurement of patients’ and
stakeholders’ values
•  Introduce stakeholders to innovative stated-preference
methods
© 2014, Johns Hopkins University. All rights reserved.
Comparisons
•  Original experiment: Statistically D-efficient design to
Bayesian optimal design
•  Proposed experiment: Compare Discrete Choice
Experiment (DCE) to Best-Worst Scaling Case 2
(BWS Case 2)
© 2014, Johns Hopkins University. All rights reserved.
Original Experiment: Statistically
Efficient vs. Bayesian Optimal Design
•  Traditional experimental designs for conjoint analysis
have focused on orthogonality and statistical
efficiency,
•  Prone to scale biases.
•  Modern experimental design techniques employ
Bayesian techniques to maximize respondent
efficiency.
•  No direct comparison of results from a statisticallyefficient experimental design and respondent-efficient
experimental design.
© 2014, Johns Hopkins University. All rights reserved.
DCE and BWS Case 2
•  DCE and BWS make use of treatment profiles that
consist of attributes at different levels
•  DCE: two distinct treatment profiles at a time
•  Select treatment profile that is preferred
•  BWS case 2: one treatment profile at a time.
•  Select “best” attribute and “worst” attribute
© 2014, Johns Hopkins University. All rights reserved.
DCE
Profile Medication
Feature
HbA1c change
AJribute Number of
hypoglycemic
events per month
Water retention
Weight gain in first
6 months
Mild stomach
upset
Medication A
Medication B
From 8.5 to 8.3* (poor
blood glucose control)
From 8.5 to 6.5* (optimal
blood glucose control)
1 to 2
More than 2
Yes
No
None
10 pounds
Mild nausea and vomiting
or diarrhea that continues
as long as you take the
medicine
No stomach problems
10 additional people out
Chance of a heart No additional person (0%)
of 1,000 (1.0%) will have
attack
will have a heart attack
a heart attack
Which medication
would you
choose?
I would choose
Medication A
☐ I would choose
Medication B
☐ ** Attributes cited from Hauber et al. (2009)6 with adjustment.
© 2014, Johns Hopkins University. All rights reserved.
Level Best-Worst Scaling (Case 2)
Best
Medication features
HbA1c changed from 8.5 to 8.3*
(poor blood glucose control)
1 to 2 hypoglycemic events per
month
Worst
Experience water retention
No weight gain in first 6 months
Profile Mild nausea and vomiting or diarrhea
that continues as long as you take
the medicine
No additional person (0%) will have
a heart attack
Imagine you were offered this oral diabetes medication.
Tick the medication feature that is the best and the
medication feature that is the worst.
** Attributes cited from Hauber et al. (2009)6 with adjustment.
© 2014, Johns Hopkins University. All rights reserved.
AJribute with level Proposed experiment: DCE vs.
BWS Case 2
•  DCE well established
•  One of the most popular stated-preference
methods
•  Technical, many requirements on study design
•  BWS not as well established
•  Requires less questions for same amount of
information
•  Less burdensome
Concordance/discordance of DCE and BWS case 2 still
needs to get established
© 2014, Johns Hopkins University. All rights reserved.
Reasons for Switching Experiments
•  Design experiment was highly technical
•  Not very relevant to patients and other
stakeholders
•  Comparison of DCE and BWS case 2 more relevant
to patient engagement
•  Easier to communicate and understand for
patient and stakeholder groups
•  Will provide more concrete advise/methods for
(patient) groups new to stated-preferences
© 2014, Johns Hopkins University. All rights reserved.
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