Transcript AFL Cost-Effectiveness Study Poster

Cost-effectiveness of Improving Adherence to
Antiretroviral Therapy Using Electronic Drug Monitor
Feedback among HIV-Positive Patients in China:
The Adherence for Life (AFL) Study
Lora
1,2
Sabin, Mary
1,2
DeSilva, Xu
3
Keyi,
Bachman
Davidson H
6
1,2
Kee Chan, and Christopher J. Gill
1,2,4,5
Hamer,
1Center
for Global Health and Development, Boston University, Boston, MA, U.S.A.; 2Department of International Health, Boston University School of Public Health, Boston, MA, U.S.A.;
3WHO Collaborating Center for Comprehensive Management of HIV Treatment and Care, Ditan Hospital, Beijing, China; 4Zambia Centre for Applied Health Research and Development, Lusaka, Zambia;
5Infectious Diseases Section, Department of Medicine, Boston University School of Medicine, Boston, MA, U.S.A.; 6Department of Health Sciences, Sargent College of Health and Rehabilitation,
Boston University, Boston, MA, U.S.A.
Introduction
Methods
AFL Intervention Design
 Identifying effective and cost-effective ways to
improve adherence to antiretroviral therapy (ART)
is critical to maximize the benefits of therapy and
use scarce resources most efficiently
 Few rigorous ART adherence interventions have
been evaluated in low-resource settings; even
when effective, few include a cost-effectiveness
analysis
 Reviews indicate that previous cost-effectiveness
analyses of adherence-enhancing interventions are
too few in number, use weak methods and poor
cost data, and fail to provide complete, clear
results1,2
 We aimed to analyze the costs and costeffectiveness of a highly effective ART adherence
intervention conducted in a low-resource setting
 80 ART patients were enrolled, given eCAPs
 Subjects stratified into high vs. low adherence groups
(based on mean adherence ≥95% in Months 1-5), and
randomized in each stratum to intervention or control
 Intervention subjects: received EDM adherence data at
6 monthly visits; if adherence was ‘sub-optimal’
(<95%) in previous month, counseled by a clinician
using EDM report; otherwise, counseling was optional
 Controls: continued standard of care, received
counseling if self-reported adherence in previous
month was <95%
 Adherence measure: incorporated +/- 1 hour dose
window, found to be best predictor of CD4 and
undetectable VL4
AFL Intervention Effect
 At month 12, mean adherence was 96.5% in
intervention subjects vs. 84.5% in controls (P-value
= 0.003)
 Intervention effect largely due to a sharp increase in
adherence in previously low adherers (Figure 1)
 EDM feedback associated with mean CD4 change
(+90 cells/ul in intervention subjects vs. -9 cells/ul in
controls (P-value = 0.020))
Background and Objectives
 China has one of Asia’s most serious HIV epidemics,
with ≈ 740,000 people living with HIV and tens of
thousands of new infections occurring annually
 Few rigorous ART adherence intervention studies
have been assessed in China
 In the “Adherence for Life” (AFL) study, we
assessed an intervention that involved integrating
electronic drug monitor (EDM, via eCAPs) data into
HIV clinical care—a process we term ‘EDM
feedback’—on ART adherence
 The results showed a significant improvement in
mean ART adherence in intervention patients3
Figure 1: Monthly mean adherence in AFL
subjects, stratified by mean adherence in preintervention period: high (≥95%) vs. low (<95%)
Adherence
100%
95%
90%
85%
AFL Study Site
80%
 Dali 2nd People’s Hospital HIV Clinic, in Dali Old
City, Yunnan Province, China
 Semi urban area, population mainly from Bai
minority
 Most HIV infections contracted via injection drug
use (IDU)
75%
70%
65%
Low adherers, intervention group
60%
Low adherers, control group
High adherers, intervention group
55%
High adherers, control group
50%
1
2
3
4
5
6
7
8
9
10
11
12
Study Month
China
Dali
Analytic Methods
 Calculated AFL’s financial and economic costs, forecasted
economic cost of a 1-year intervention in 2012 among 500
patients, typical size of an ART clinic in China
Financial analysis: included all project expenditures: 1)
equipment & supplies (EDM scanner, eCAPs, user guide);
2) training in eCAP use; 3) shipping; 4) price cuts provided
by eCAP supplier
 Excluded: 1) all research-related costs; 2) control group costs;
3) clinicians’ time (counseling fit into regular workday)
 China-based costs were converted to US$ (2007 exchange
rate), then added to nominal US$ costs
Economic analyses: to capture societal costs, included:
1) project coordinator/clinicians’ time; 2) opportunity cost
of patients’ time for orientation and counseling, valued at
mean patient income; 3) full costs (no price cuts)
Economic analysis of forecasted 1-year program:
1) no US personnel; 2) addition of local project manager;
3) addition of counselors to orient and counsel patients
 All costs adjusted to 2012 prices
Cost effectiveness analysis (CEA):
 Estimated incremental cost per change from sub-optimal to
optimal adherent patient during 6-month program using
standard formula: ICEA=(CI–CC)/(AI–AC), (C=total costs;
A=change in optimal adherent patients (≥95%); and I/C
=intervention/control
 Change in adherence based on AFL’s effect size (difference
between intervention and control groups in net change in
patients with optimal adherence, capturing both increase in
intervention arm and avoided loss in control arm
 Uncertainty assessed using sensitivity analysis
Results
Costs
Sensitivity Analysis
 Estimated financial and economic costs of AFL were $7,943 and $9,065 (2007 US$),
respectively, or $732 and $836 per patient
 Fixed costs accounted for 75% of total costs
 For 2012 scaled-up 1-year program, total and per patient costs were $42,222 and $84 (2012
US$) (Table 1)
 Cost-effectiveness most sensitive to variation in effect size, number of patients participating,
and cost of eCAPs
 If intervention effect increased to 45%, cost per adherent patient falls by 25%
 If unit price of eCAPs increased by 1/3, to $80, cost per adherent patient rises 25%.
 Other cost variables, such as cost of EDM scanner, and assumptions such as time spent on
counseling, do not greatly affect cost-effectiveness
Table 1: Costs and cost-effectiveness of AFL intervention
1
Cost item
1
Table 2: Results of one-way sensitivity analysis on the
2
Financial
2007
Cost % total
Economic
2007
Cost % total
Scale-up
2012
Cost % total
6060
426
4404
1704
2200
500
695
500
35
1710
-
6974
454
4705
1704
301
2200
500
695
920
200
2091
196
160
36
1895
9065
5663
33
3185
485
2200
500
1695
250
500
36560
2939
2094
845
33621
Table 2. Results of one-way sensitivity analysis on the incremental cost of moving an
incremental
cost of moving an ART patient from subART patient from sub-optimal adherence to optimal adherence (=95%)
optimal adherence to optimal adherence (≥95%)
Costs
Total Fixed Costs
Program set-up
Training activities
US personnel3
China personnel4
Travel5
EDM training fee
Equipment & supplies6
Technical support/management
Miscellaneous (shipping)
Total variable costs
Intervention delivery personnel time
Clinic personnel7
Patient time8
Equipment and supplies9
TOTAL ($2007 US$)
TOTAL ($2012 US$)
Cost per subject2
Variable cost per subject2
1710
7943
76.3
5.4
55.4
21.5
27.7
6.3
8.7
6.3
0.4
23.7
0
23.7
100.0
76.9
5.0
51.9
18.8
3.3
24.3
5.5
7.7
10.1
2.2
23.1
2.2
1.8
0.4
20.9
100.0
Base case
$247
Intervention effect varied from 45%-25% (base case = 24%)
$188-338
Number of patients participating in intervention varied from 1,000 to
200 (base case = 500)
$126-606
Time spent on counseling varied from 10 minutes to 30 minutes per
patient per clinic visit
$246-248
Proportion of patients participating in intervention that require
counseling sessions varied from 20% to 80%
$246-248
Cost of EDM data scanner varied from $500 to $2,500 (base case =
$1,595)
$241-252
1
Values expressed in 2007 US$, except where otherwise indicated.
Values expressed in 2012 US$.
3
Training in EDM use with manufacturer (based in Canada) and training of
clinicians in China.
4
Economic costs include time of clinicians in training; Scale-up model includes
time of training by local trainer.
5
Training activities in Canada and China.
6
Includes EDM scanner and eCAP in Mandarin Chinese.
7
For Economic costs, refers to 3 doctors and 6 nurses; for scale-up model, refers
to 2 nurses who are employed to deliver intervention.
8
Patient time spent on one-time enrollment, and in monthly clinic visits, on
waiting for scanning of EDM and counseling sessions.
9
Includes eCAPs and medication vials (one per patient plus 10% contingency).
2
259
61
295
68
42222
84
73
12
732
12
836
171
247
Cost-effectiveness
Optimal adherent patients (change) (#)
Cost per optimal adherent patient
(2012 US$)
Estimated incremental
cost-effectiveness ratio
Variation tested
13.4
0.1
7.5
0
1.1
5.2
1.2
4.0
0.6
1.2
86.6
7.0
5.0
2.0
79.6
100.0
Cost-effectiveness (see Table 1)
 Cost per newly optimally adherent patient in AFL trial:
$732 (financial analysis) and $836 (economic
analysis)
 Cost per newly optimally adherent patient in projected
10–year program: $249
Acknowledgements
Thanks to: Mary Jordan, Billy Pick, David Stanton, Neal Brandes, Connie
Osborne, Ray Yip, Ira Wilson, and staff at Med-ic, and our deep appreciation
to the medical staff at the Dali Second People’s Hospital and the Dali-based
HIV/AIDS patients who participated in the AFL study.
Cost of eCAPs varied from $30 to $80 apiece (base case = $59)
Note: all values expressed in 2012 US$
$154-314
Conclusions
 We found that an intervention using EDM feedback to inform counseling can improve ART
adherence to optimal levels in Chinese patients at a low incremental cost ($247/patient)
 Compared to average annual cost of providing ART to a patient in China (estimated at over
$2,000), and the social costs of poor adherence, this intervention may be considered a good
use of scarce resources
 We recommend further analysis of ART adherence interventions and scale-up of those
found to be cost-effective in order to treat rising numbers of ART patients most efficiently
Citations
1. Elliott RA, Barber N, Horne R. Cost-effectiveness of adherence-enhancing interventions: a quality assessment of the
evidence. Ann Pharmacother 2005;39(3):508-15.
2. Rosen AB, Spaulding AB, Greenberg D, Palmer JA, Neumann PJ. Patient adherence: a blind spot in cost-effectiveness
analyses? Am J Manag Care 2009;15(9):626-32.
3. Sabin LL, Desilva MB, Hamer DH, et al. Using Electronic Drug Monitor Feedback to Improve Adherence to
Antiretroviral Therapy Among HIV-Positive Patients in China. AIDS Behav 2009.
4. Gill CJ, Sabin LL, Hamer DH, et al. Importance of dose timing to achieving undetectable viral loads. AIDS Behav 2009;
Published online: April 8, 2009.