Download Patient Benefit-Risk Preferences for Advanced Renal Cell

Patient Benefit-Risk Preferences for Advanced Renal Cell Carcinoma Treatments:
Results From a Conjoint Analysis Study
Ateesha F Mohamed,1 Jui-Chen Yang,1 A Brett Hauber,1 Zhimei Liu,2 Michael K Wong,3 Jaqueline Rogerio,2 Carlos Garay2
RTI Health Solutions, Research Triangle Park, NC, United States; 2 Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States; 3 University of Southern California, Los Angeles, CA, United States
ABSTRACT
BACKGROUND
OBJECTIVE: To quantify patients’ benefit-risk preferences
for benefits, toxicities, and serious adverse events of
advanced renal cell carcinoma (RCC) treatments.
• In recent years, multiple new systemic therapies for advanced RCC
have demonstrated significant benefit on patient median PFS
METHODS: United States (US) adult residents with a
self-reported diagnosis of RCC completed a Web-enabled
choice-format conjoint survey consisting of a series of
10 treatment-choice questions and a pair of hypothetical
RCC medication profiles. Each profile had different
attributes: efficacy (progression-free survival [PFS]),
tolerability (fatigue, stomach problems, mouth sores,
hand-foot syndrome [HFS]), serious adverse events
(lung damage and liver failure), and mode of
administration. Treatment-choice questions were based
on a predetermined experimental design with known
statistical properties. Random-parameters logit was used
to estimate relative preference weights for each attribute
level and mean relative importance weights, and to
calculate risk tolerance for each adverse event for
different improvements in PFS.
RESULTS: 272 respondents completed the survey.
A 7-month improvement in PFS was the most important
attribute. Remaining attributes were ranked in
decreasing order of importance: eliminating severe
fatigue (7.0; 95% confidence interval [CI]: 4.6-9.4),
eliminating severe stomach problems (7.0; 95% CI: 4.79.3), eliminating a 2% liver-failure risk (6.1; 95% CI: 4.08.2), eliminating severe mouth sores (5.7; 95% CI: 3.77.7), eliminating severe HFS (4.5; 95% CI: 2.7-6.4),
eliminating a 2% lung-damage risk (4.1; 95% CI: 2.5-5.8),
and switching from infusion once a week to one pill once
a day (2.5; 95% CI: 1.4-3.6). To increase PFS by 1 month
(baseline: 3-4 months), patients accepted a maximum
level of lung-damage risk of 1.0% (95% CI: 0.8%-1.4%)
and liver-failure risk of 0.7% (95% CI: 0.4%-1.0%). A
7-month improvement in PFS was two times as
important as eliminating severe HFS and a 2.0% risk of
lung damage (P < 0.05).
CONCLUSIONS: PFS was the most important outcome
for RCC patients, while severe fatigue and severe
stomach problems were rated as the most troublesome
toxicities.
• Because these treatments are not curative, life-long sequential
therapy may become necessary, increasingly resulting in tradeoffs
between survival benefit and drug toxicities and serious adverse
events
• The available treatment guidelines often give multiple possible
choices for a given clinical scenario, often with drugs that possess
distinct toxicity profiles
• There are few studies that quantifiy and rank patient preferences in
this regard, and none of the treatment guidelines incorporate this
information into the decision algorithims
OBJECTIVE
• To quantify patients’ benefit-risk preferences for benefits, toxicities,
and serious adverse events of advanced RCC treatments
METHODS
Respondents
• Inclusion criteria:
– Aged 18 years or older
CONCLUSIONS
– Three survey versions with different combinations of 10 treatment-choice
questions (30 treatment-choice questions in total), randomly assigned to
respondents
• Demographic information (e.g., age, sex, race, marital status, and education)
and items about the patients’ experiences with RCC (e.g., time since diagnosis,
kidney surgery status, metastatic disease status, and current treatment status)
also were collected
Table 1. Attributes and Levels for the Choice Questions
Attribute
How long the medicine will keep the cancer from
getting worse (PFS)
Feeling weak or tired
(fatigue)
Stomach problems
Sores in your mouth or throat
(mucositis or stomatitis)
Redness or sores on your hands and feet
(HFS)
Chance of lung damage
(pneumonitis)
– Resident of the US
– Self-reported physician diagnosis of RCC
• Patient recruitment occurred through the Kidney Cancer Association
• All participants provided online informed consent
Survey Instrument
• A Web-enabled survey instrument was specifically developed for the
purpose of this study
• The survey applied a discrete-choice experiment (choice-format
conjoint survey method) which:
Chance of liver failure
(hepatic impairment)
How you take the medicine
(mode of administration)
Figure 1. Example Choice Question
Medicine Feature
(Click on a link below to view feature information)
How long the medicine will keep the
cancer from getting worse
– Is recognized in the field to be one of the most valid, reliable, and
robust techniques available for quantifying patient preferences1-3
Feeling weak or tired
– Test the clarity of the survey instrument and the appropriateness of
the descriptive information
– Confirm that the eight attributes included in the survey (based on a
review of product label inserts: sorafenib, sunitinib, pazopanib,
everolimus, temsirolimus) were of concern to patients
– Assess patients’ willingness to accept tradeoffs among attributes in
evaluating hypothetical medications
• Relative preference estimates using a random-parameters logit
Stomach problems
Sores in your mouth or throat
Redness or sores on your hands and feet
• The experimental design included:
– Combinations of attribute levels in each treatment-choice question
– Main-effects D-efficient criteria using SAS Version 9.25-6
– Eliminating a 2% liver-failure risk (6.1; 95% CI: 4.0-8.2)
– Eliminating severe mouth sores (5.7; 95% CI: 3.7-7.7)
– Eliminating severe HFS (4.5; 95% CI: 2.7-6.4)
– To facilitate the interpretation of the results, we assigned an
importance weight of 10 to the most important attribute and
calculated the importance weight for each of the other attributes
relative to the most important attribute
– Eliminating a 2% lung-damage risk (4.1; 95% CI: 2.5-5.8)
– Switching from infusion once a week to one pill once a day
(2.5; 95% CI: 1.4-3.6)
• A 7-month improvement in PFS was two times as important as
eliminating severe HFS and a 2.0% risk of lung damage (P < 0.05)
• Risk tolerance estimate that patients require to compensate for
each toxicity for different improvements in PFS
Medicine A
Medicine B
10 months
5 months
Severe
Mild-to-moderate
None
Severe
Mild-to-moderate
Severe
None
Severe
Chance of lung damage
• To increase PFS by 1 month (baseline: 3-4 months), patients
accepted a maximum level of:
RESULTS
Patient Sample
– Lung-damage risk of 1.0% (95% CI: 0.8%-1.4%)
• Final patient sample (n = 272)
– Liver-failure risk of 0.7% (95% CI: 0.4%-1.0%)
– Female: 53%
– Married: 74%
– White: 92%
• Respondents were asked to evaluate hypothetical medications
– Associate’s degree or higher: 66%
• Cost and resource use were not factored into the decision
– Employed: 56%
– These simulated clinical decisions may not have the same clinical,
financial, and emotional consequences of actual decisions
– Mean age (standard deviation): 57 years (10)
– Diagnosed with RCC at least 2 years ago: 65%
• We provided numeric and graphical representations of treatment
outcomes and adverse-event risks. However:
– Had metastatic disease: 43%
– Currently taking prescription medication: 27%
– Numeracy skills in the general population are poorly developed
Which medicine would you choose if
these were your only options?
– Respondents may have applied simplifying heuristics in comparing
probabilities that are inconsistent with actual numeric magnitudes
• A 7-month improvement in PFS was the most important attribute
(10.0; 95% CI: 7.0-13.0)
Figure 2. Relative Importance Weights, Relative to PFSa,b
Funding for this study was obtained from Novartis
Pharmaceuticals Corporation, East Hanover, New
Jersey.
8
7
6
5
4
3
2
1
Two pills twice a day
without food
10.0
7.0
7.0
5.7
4.5
4.1
6.1
2.5
PFS
Fatigue
Stomach
problems
Mucositis
or stomatitis
HFS
Chance of
lung damage
Chance of
liver failure
Mode of
administration
The vertical bars surrounding each mean importance weight denote the 95% CI about the point estimate.
Each importance weight for each attribute is estimated as an improvement from the worst level to the best level. For example, for HFS it is an improvement from severe to none
and for chance of lung damage it is an improvement from 2% to 0%.
a
b
1. Bridges JFP, Kinter ET, Kidane L, Heinzen RR, McCormick C.
Patient. 2008 Dec 1;1(4):273-82.
2. Hauber AB, Mohamed AF, Watson ME, Johnson FR,
Hernandez JE. AIDS Patient Care STDs. 2009 Jan;23(1):29-34.
4. National Cancer Institute. The Common Terminology Criteria
for Adverse Events (CTCAE) Version 4.02. 2009.
5. Kuhfeld W. Marketing research methods in SAS:
experimental design, choice, conjoint, and graphical
techniques. Cary, NC: SAS Institute Inc.; 2010.
6. Kuhfeld W, Tobias F, Garratt M. J Mark Res. 1994;31:545-57.
CONTACT INFORMATION
Ateesha F. Mohamed
Senior Research Economist
Health Preference Assessment
RTI Health Solutions
200 Park Offices Drive
Research Triangle Park, NC 27709
Presented at: ISPOR 17th Annual International Meeting
June 2-6, 2012
Washington, DC, United States
9
No chance
REFERENCES
Phone: +1.919.541.6916
E-mail: [email protected]
10
0
How you take the medicine
DISCLOSURE
– Differences can arise between stated and actual choices
– Had kidney surgery to treat RCC: 98%
10 out of 1,000 (1.0%)
One pill once a day
with or without food
• Despite PFS’s position as the most important
outcome, patients with the diagnosis of RCC were
willing to trade off toxicities for a given level of PFS.
3. Johnson FR, Ozdemir S, Mansfield C, Hass S, Miller DW,
Siegel CA, et al. Gastroenterology. 2007 Sep;133(3):769-79.
LIMITATIONS
No chance
Chance of liver failure
• PFS was the most important outcome for RCC
patients, while severe fatigue and severe stomach
problems were rated as the most troublesome
toxicities
Risk Tolerance
– Each medication profile was described by eight attributes (Table 1)
• Patients were asked to choose the option they would prefer if these
were the only two medications available (Figure 1)
– Eliminating severe stomach problems (7.0; 95% CI: 4.7-9.3)
– The distance between the preference weights for the best and worst
levels of an attribute can be interpreted as the overall mean relative
importance of the attribute over the specific ranges presented in the
survey
5 out of 1,000 (0.5%)
• Respondents answered 10 treatment-choice questions, each including
a pair of hypothetical RCC medication profiles:
– Attributes were described in patient-friendly terms using clinical
definitions4
– Eliminating severe fatigue (7.0; 95% CI: 4.6-9.4)
• Overall mean relative importance weights
Relative Importance Weights (Figure 2)
– Elicits respondent tradeoffs among alternatives with varying levels of
different attributes
• Prestudy survey validation included open-ended interviews (n = 15)
with patients diagnosed with RCC in order to:
Levels
10 months
5 months
3 months
None
Mild-to-moderate
Severe
None
Mild-to-moderate
Severe
None
Mild-to-moderate
Severe
None
Mild-to-moderate
Severe
No chance
5 out of 1,000 (0.5%)
10 out of 1,000 (1.0%)
20 out of 1,000 (2.0%)
No chance
5 out of 1,000 (0.5%)
10 out of 1,000 (1.0%)
20 out of 1,000 (2.0%)
One pill once a day with or without food
Two pills twice a day without food
Infusion once a week
• Remaining attributes were ranked in decreasing order of
importance:
Analyses Performed
Mean Relative Importance
1