Quality of life and health utility in
drug abuse comparative effectiveness
and cost-effectiveness research
Bruce R. Schackman, PhD
Department of Public Health
Weill Cornell Medical College
January 23, 2013
Center for Advancing Longitudinal Drug Abuse Research
UCLA Integrated Substance Abuse Programs
Funding and financial disclosures
• Funding
– National Institute on Drug Abuse: R01 DA027379;
R01 DA033424; R01 DA031059
– National Institute of Mental Health:
R01 MH087328
– National Institute of Allergy and Infectious Diseases:
R37 A1042006
– Robert Wood Johnson Foundation Substance Abuse
Policy Research Program Grant #63625
• Financial Disclosures: None
2
Health care costs are rising
Rettenmaier and Wang, 2009
3
Drug abuse treatment is becoming part of the
health care system
• Parity requirements in health insurance
coverage
• Impact of health reform on expanded access
to health insurance
• More medication-assisted treatment options
• Consolidation of mental health and substance
abuse treatment systems
4
Drug abuse treatment is becoming part of the
health care system: implications
• Investments in drug abuse treatment should
be valued on the same basis as treatment for
other chronic diseases
– Benefit to the patient
– Efficiency
– Cost-savings not required
5
Paying for value
•
•
•
•
•
•
Pay for performance
Value-based purchasing
Comparative effectiveness
Patient-centered outcomes
Cost-effectiveness
The “R” word
6
Agenda
• Comparative effectiveness and patientcentered outcomes definitions
• Quality-of-life measures
• Cost-effectiveness overview
• Cost-effectiveness of medication-assisted
treatment of opioid dependence
• Addressing methodological and data gaps:
planned studies
7
Comparative effectiveness research (CER)
“Comparative effectiveness research is the conduct
and synthesis of research comparing the benefits
and harms of different interventions and strategies
to prevent, diagnose, treat, and monitor health
conditions in “real world” settings. The purpose of
this research is to improve health outcomes by
developing and disseminating evidence-based
information to patients, clinicians and other
decision makers, responding to their expressed
needs, about which interventions are most effective
for which patients under specific circumstances.”
Coordinating Council for Comparative Effectiveness Research, 2009
http://www.hhs.gov/recovery/programs/cer/cerannualrpt.pdf
8
Categories of methods for CER
• Systematic reviews, including meta-analysis
• Decision modeling, with or without cost information
• Retrospective analysis of existing clinical or
administrative data, including “natural experiments”
• Prospective observational studies, including registries,
which observe patterns of care and outcomes but do
not assign patients to specific study groups
• Experimental studies, including randomized clinical
trials (RCTs), in which patients or groups of patients are
assigned to alternative treatments, practices, or
policies
Tunis SR, Benner J, McClellan M. Stat Med 2010;29:1963-76.
9
Estimated types of CER studies by federal
agency/department 2006-2009
Study Type
AHRQ
n = 144
NIH
DoD
VHA Total
n = 466 n = 25 N = 96
Randomized controlled trial
11%
79%
0%
77%
60%
Practical/pragmatic controlled trial
3%
1%
16%
1%
2%
Other non-randomized controlled trial
2%
2%
32%
0%
3%
Observational study (natural experiment)
1%
2%
0%
4%
3%
Observational study (prospective
registry)
4%
3%
16%
6%
4%
Observational study (retrospective)
9%
5%
6%
4%
6%
Systematic review
58%
0%
13%
0%
14%
Meta-analysis
3%
0%
0%
0%
1%
Mathematical model
4%
3%
3%
3%
3%
Federal Coordinating Council for Comparative Effectiveness Research, 2009
http://www.hhs.gov/recovery/programs/cer/cerannualrpt.pdf
10
Estimated types of interventions in CER studies
by federal agency/department 2006-2009
Study Type
AHRQ
n = 144
NIH
n = 466
DoD
n = 25
VHA
N = 96
Total
Pharmacologic treatment
35%
68%
24%
10%
34%
Biologic treatment
1%
1%
10%
4%
4%
Alternative medicine
2%
8%
1%
2%
Medical device/equipment
17%
0%
7%
11%
Surgical procedure
11%
3%
9%
9%
Behavioral intervention
11%
11%
24%
16%
Public health intervention
2%
17%
3%
3%
Delivery system
11%
19%
41%
20%
Other
10%
8%
1%
2%
6%
24%
Federal Coordinating Council for Comparative Effectiveness Research, 2009
http://www.hhs.gov/recovery/programs/cer/cerannualrpt.pdf
11
Patient-centeredness
“Patient-centeredness refers to the extent to
which the preferences, decision-making needs,
and characteristics of patients are addressed,
and is the key characteristic differentiating PCOR
from comparative effectiveness research.”
Methods Committee of PCORI. JAMA 2012;307:1636-40.
12
Patient-centered outcomes research
• Assesses the benefits and harms of preventive, diagnostic,
therapeutic, palliative, or health delivery system interventions to
inform decision making, highlighting comparisons and outcomes
that matter to people;
• Is inclusive of an individual’s preferences, autonomy and needs,
focusing on outcomes that people notice and care about such as
survival, function, symptoms, and health related quality of life;
• Incorporates a wide variety of settings and diversity of participants
to address individual differences and barriers to implementation
and dissemination; and
• Investigates (or may investigate) optimizing outcomes while
addressing burden to individuals, availability of services,
technology, and personnel, and other stakeholder perspectives.
Patient Centered Outcomes Research Institute (PCORI)
http://www.pcori.org/what-we-do/pcor/
13
Quality of life is not frequently measured in
drug abuse research
• Primary outcomes of treatment studies are
abstinence-based
• Economic studies focus on financial costs and
savings
• General health status quality-of-life measures (SF36, SF-12, WHOQOL-BRF) sometimes used for
patients entering treatment
• IDU-specific quality-of-life measure (IDUQOL) not
widely used
• Little data on quality of life among prescription
drug users
14
Health status versus health utility
• Health status measures emphasize rating
different domains, e.g.
–
–
–
–
Physical function
Psychological function
Social function
Impairment
• Preference-based utility measures require
uncertainty or tradeoff
– Societal preferences for cost-effectiveness analyses
15
Changes in health status after 12 months
in the NAOMI trial
Nosyk B, Guh DP, Sun H, et al. Drug Alcohol Depend 2011;118:259-64
16
Health utility measure: standard gamble
17
Drug abuse research studies using
directly-elicited health utilities
• Utilities for ASI-defined health states derived
from 143 local health planning board
members in Massachusetts1
• Utilities for pharmacy-dispensed methadone
and buprenorphine treatment health states
derived from internet survey of 22 members
of the general UK population2
1
2
Daley M, Shepard DS, Bury-Maynard D. Subst Use Misuse 2005;40:375-94.
Connock M, Juarez-Garcia A, Jowett S, Frew E, Liu Z, Taylor RJ, et al. Health Technology Assessment 2007;11:1-171, iii-iv.
18
Translating health status to health utility: EQ-5D
19
Health utility trajectories
in the NAOMI trial
Nosyk B, Guh DP, Sun H, et al. Drug Alcohol Depend 2011;118:259-64.
20
Drug abuse research studies in the US reporting
indirectly elicited utilities
• Utilities measured in a trial of substance use
treatment linkage and engagement strategies
in a Midwestern city1,2
• Cost-effectiveness of extended
buprenorphine-naloxone for opioiddependent youth from the CTN-0010 trial3
1
Pyne JM, French M, McCollister K, Tripathi S, Rapp R, Booth B.. Addiction 2008;103:1320-9.
2 Pyne JM, Tripathi S, French M, McCollister K, Rapp RC, Booth BM.. Addiction 2011;106:507-15.
3 Polsky D, Glick HA, Yang J, Subramaniam GA, Poole SA, Woody GE. Addiction 2010;105:1616-24.
21
Translating utilities into QALYs
CABG
1
MI
P
o
s
t
M
I
Utility
Perfect
Health
0.5
0
1
2
Post-CABG
A
n
g
i
n
a
3
4
5
6
7
8
9
10
Years
• Life expectancy: 10 years
• QALYs = (3.5)(1) + (1)(0.5) + (5)(0.9) +
(0.5)(0.2) = 8.6 QALYs
M. Roberts, University of Pittsburgh
22
Cost-effectiveness ratio
Additional Resources Used ($)
Additional Health Benefits Gained (QALYs)
23
Cost-effectiveness misconception #1
“Cost-Effective” = “Cheap”
“Cost-Effective” = “Saves Money”
24
Cost-effective ≠ Cost saving
25
Cost-effectiveness is about value for money
• Very, very few health interventions save more
money than they cost
• Cost-effectiveness analysis is about
comparative assessment of worth
• Investments in health can be compared to
evaluate competing claims on scarce
resources
26
Cost-effectiveness misconception #2
If an intervention is cost-effective,
payers should pay for it
27
Cost-effectiveness depends on the perspective
of the analysis
• Cost-effectiveness analyses attempt to
account for all costs and benefits, regardless
of payer or beneficiary
• “Cost-effective” from the societal perspective
doesn’t mean “budget-neutral” from the
payer perspective
• Budget impact analysis addresses the question
of where the money comes from
28
Cost-effectiveness misconception #3
Cost-effectiveness is the only consideration
when making resource allocation decisions
29
Only one of many measures of the
appropriateness of health interventions
•
•
•
•
•
Clinical duty
Ethical duty
Equity / justice
Patient preference
Economic efficiency
30
Cost-effectiveness vs. cost-benefit?
• Cost-benefit analysis (CBA) allows
consideration of benefits and costs outside
the health care system
• CBAs have shown methadone maintenance to
be cost-saving considering savings in crime
costs, welfare payments, and health care costs
and/or increases in earnings1
1
Simoens S, Ludbrook A, Matheson C, Bond C. Drug Alcohol Depend 2006;84:28-39.
31
Cost-benefit issues
• CBA is not commonly accepted for evaluating
medical treatments; cannot compare results
to other health care interventions
• Decision makers may not be interested in
savings outside the health care system
• Requires extrapolation from studies of
methadone treatment and heroin use; may
not be relevant to other patient populations
32
33
Opioid dependence treatment gap
• Estimated population with opioid dependence or
abuse in last year1:
– Pain relievers: 1,921,000
– Heroin: 359,000
• Many patients are unwilling or unable to attend
methadone maintenance clinics
– Lack of availability (only 1,521 sites nationwide)2
– Often requires daily visits and directly observed dosing
– Stigma
• Very limited use of office-base methadone
maintenance3
1
SAMHSA, National Survey on Drug Use and Health (NSDUH), 2010
SAMHSA, United States National Survey of Substance Abuse Treatment Services (N-SSATS), 2009
33Gunderson EW, Fiellin DA. CNS drugs 2008;22:99-111
2
34
Buprenorphine cost
• Cost has been considered a barrier to adoption
– Drug cost is at least 7x higher than methadone, but
methadone is very rarely used in the outpatient
setting1
• Brand-name buprenorphine lost patent
exclusivity in October 20091,2
– Brand-name buprenorphine/naloxone (Suboxone) has
no generic competitors
– Brand-name buprenorphine (Subutex) has one generic
competitor; cost was estimated to be 80% of Subutex
cost
1
2
Murray L (ed), Red Book Pharmacy’s Fundamental Reference, 2010
http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm
35
Study aims
• To evaluate the cost-effectiveness of long-term officebased buprenorphine treatment compared to no
treatment for clinically stable patients
– Assume patients are unwilling or unable to engage in
methadone maintenance treatment
– Health care perspective with patient benefits measured in
QALYs
• To evaluate the impact of uncertainty about model
inputs on cost-effectiveness results
– Price of buprenorphine
– Duration of treatment
– Quality of life on/off buprenorphine
36
All models are wrong,
some models are useful
37
Treatment cohort simulation model
Enter
In Treatment
Off Drugs
Off Treatment
Off Drugs
In Treatment
On Drugs
Off Treatment
On Drugs
Note: Separate models run for injection drug users (IDUs) and non-IDUs
38
Data from published cohort study
• Patients had been followed in an RCT of buprenorphine
management strategies and successfully completed 24
weeks on buprenorphine/naloxone (w/ at least 9 weeks
abstinence)1
• We used follow-up study data on retention in treatment up
to 24 months after completion of the RCT2
• For those not retained in treatment, assumed 89% to be
actively using drugs when out of treatment3
• Unit cost data from previous analysis of the same cohort4
• Average weekly cost for IDU and non-IDUs calculated based
on patient-level resource utilization
1
Fiellin DA, Pantalon MV, Chawarski MC, Moore BA, Sullivan LE, O'Connor PG, Schottenfeld RS. N Engl J Med 2006;355:365-74.
DA, Moore BA, Sullivan LE, Becker WC, Pantalon MV, Chawarski MC, Barry DT, O'Connor PG, Schottenfeld RS. Am J Addict 2008;17:116-20.
3 Connock M, Juarez-Garcia A, Jowett S, Frew E, Liu Z, Taylor RJ, et al. Health Technology Assessment 2007;11:1-171, iii-iv.
4 Jones ES, Moore BA, Sindelar JL, O'Connor PG, Schottenfeld RS, Fiellin DA. Drug Alcohol Depend 2009;99:132-40.
2 Fiellin
39
Monthly probability of retention in treatment
100%
90%
80%
70%
60%
Probability of 50%
Retention
40%
30%
20%
10%
0%
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Months in Treatment
40
Mean (SD) utility weights
Base Case1
Sensitivity Analysis2
In treatment, off drugs
0.867 (0.152)
0.856 (0.150)
In treatment, on drugs non-IDU
0.683 (0.204)
Health State
0.876 (0.100)
In treatment, on drugs IDU
0.633 (0.208)
Out of treatment, off drugs
0.867 (0.152)
Out of treatment, on drugs non-IDU
0.678 (0.207)
0.856 (0.150)
0.806 (0.194)
Out of treatment, on drugs IDU
1
2
0.588 (0.212)
Connock M, Juarez-Garcia A, Jowett S, Frew E, Liu Z, Taylor RJ, et al. Health Technology Assessment 2007;11:1-171, iii-iv.
CTN 0010 (NCT00078130), Buprenorphine/Naloxone-Facilitated Rehabilitation for Opioid Dependent Adolescents
41
Mean cost-effectiveness ratios
Base case
Current drug cost
20% drug cost
reduction
50% drug cost
reduction
$35,100/QALY
$30,300/QALY
$23,000/QALY
42
Mean cost-effectiveness ratios
Current drug cost
20% drug cost
reduction
50% drug cost
reduction
Base case
$35,100/QALY
$30,300/QALY
$23,000/QALY
60-month
treatment
duration
$35,200/QALY
$30,300/QALY
$23,100/QALY
43
Mean cost-effectiveness ratios
Current drug cost
20% drug cost
reduction
50% drug cost
reduction
Base case
$35,100/QALY
$30,300/QALY
$23,000/QALY
60-month
treatment
duration
$35,200/QALY
$30,300/QALY
$23,100/QALY
$138,000/QALY
$119,000/QALY
$90,600/QALY
Sensitivity
analysis QOL
44
Cost-effectiveness acceptability curve
45
Value of information
• Using the $100,000/QALY threshold
– Value of eliminating uncertainty about quality-oflife estimates is $6,400 per person eligible for this
office based buprenorphine/naloxone treatment
– Value of eliminating uncertainty about nonmedication cost items is <$5 per person eligible
for this office-based buprenorphine/naloxone
treatment
46
Limitations
• Cohort treated at a single site
• Drug use out of treatment was not observed,
we assume 89% return to drug use based on
available data
• Ignores 6-month “start-up” costs and benefits
• Ignores other costs and benefits
– Other medical costs saved or incurred
– Deaths avoided
47
Conclusions
• Office-based buprenorphine for clinically stable
patients is cost-effective compared to no
treatment using accepted thresholds for medical
treatment in the US
• Price reductions have a small effect on costeffectiveness findings
• Lack of certainty about quality-of-life weights
reduces robustness of findings
• Further research about quality of life on and off
buprenorphine is necessary
48
Quality of life in prescription and injection
opioid dependence: study team
• Weill Cornell
– Bruce Schackman, PhD (PI); Brandon Aden, MD, MPH; Ann
Beeder, MD; Jared Leff, MS; Ashley Eggman, MS
• Harvard School of Public Health
– Eve Wittenberg, PhD; Adrianna Saada, MPH
• UCLA/University of British Columbia
– Bohdan Nosyk, PhD; Yih-Ing Hser, PhD
• RTI International
– Jeremy Bray, PhD
• Consultants
– David Fiellin MD, Yale; Louise Haynes, MSW, MUSC; Todd
Korthuis, MD, MPH OHSU; Don Shepard, PhD, Brandeis
49
Quality of life in prescription and injection
opioid dependence: Aim #1
• To create an “off the shelf” list of utility
weights for opioid dependence health states
with and without social welfare considerations
– Develop descriptions of opioid use and treatment
and their effects on family members with and
without non-health descriptors (stigma, legal
involvement, etc.)
– Conduct a web-based survey of a representative
panel of US residents (community members) to
assign utility weights to these health states
50
Health states included in survey
Health-related
QOL
“Extended”
QOL
Family
spillover
Active IDU
X
X
X
Active Rx user
X
X
X
Early-stage treatment,
methadone
X
X
X
Early-stage treatment,
buprenorphine-naloxone
X
X
X
Maintenance treatment,
methadone
X
X
Maintenance treatment,
buprenorphine-naloxone
X
X
Health State
Post-treatment
X
51
Quality of life in prescription and injection
opioid dependence: Aim #2
• To estimate utility weights for patientreported opioid dependence health states
using self-reported data from two CTN
randomized trials
– Determine utility weights (SF-6D) for heroin IDU
and prescription opioid-dependent patients on
and off treatment with methadone or
buprenorphine/naloxone
– Determine the effect of non-health problems
described in ASI-Lite on these utility weights
52
Quality of life in prescription and injection
opioid dependence: Aim #3
• To assess the impact on opioid dependence utility
weights of poorly controlled HIV and chronic HCV
using self-reported data from the BHIVES cohort
– Determine utility weights for heroin IDU and
prescription opioid-dependent patients on and off
treatment with buprenorphine/naloxone by HIV and
HCV status
– Compare algorithms that combine off the shelf utility
weights from Aim 1 and the literature to BHIVES
results
53
Impact of illicit drug use and HCV status on
health utility by HIV status in the WIHS cohort
Aden B, Nosyk B, Schackman BR, Wittenberg E. 34th Annual Meeting of the Society for Medical Decision Making. October 19, 2012.
Phoenix, AZ.
54
CTN-0051 comparative effectiveness trial
• Extended-Release Naltrexone vs.
Buprenorphine for Opioid Treatment
– To assess the comparative effectiveness of
extended release injectable naltrexone (XR-NT)
versus buprenorphine-naloxone (BUP-NX)
– Duration of treatment: 6 months
• XR-NT requires complete detoxification, BUPNX requires sufficient withdrawal for induction
• XR-NT costs more than BUP-NX
55
Economic analysis design issues
• How collect quality-of-life information?
– Which questionnaire? How frequently?
– Consider non-health benefits?
• Which economic outcome?
– Cost/opioid-free day?
– Cost/QALY?
– Cost-benefit?
• Model treatment outcomes beyond 6
months?
56