Transcript Taiwan is a small HIV market and its pricing is referenced

Cost-Effectiveness Analysis of
Raltegravir in TreatmentExperienced HIV Patients in Spain
Mohammad A. Chaudhary, Santiago Moreno,
Ritesh N. Kumar, Gonzalo Nocea & Elamin Elbasha
International AIDS Economics Network Symposium
Cuernavava, Mexico, August 1-2, 2008
Background
Raltegravir (ISENTRESS®), the first approved
integrase inhibitor for managing treatmentexperienced HIV patients
Superior efficacy observed at 16, 24, and 48 weeks
in combination with optimized background therapy
(OBT) versus OBT alone*
Safety profile comparable to placebo*
* N Engl J Med 2008;359:339-54.
2
Objective
In light of proven efficacy and safety, the current
study evaluates the economic benefits of raltegravir
through a cost-effectiveness model
Cost-effectiveness is determined by dividing the
incremental costs with the drug by the qualityadjusted life years (QALYs) gained by using the
drug.
3
Model Overview
Continuous-time state-transition cohort model developed
in Mathematica version 6
– Markov process with limited history
Two treatment strategies
A. Placebo + OBT
B. Raltegravir + OBT
Three sets of differential equations corresponding to
opportunistic infection (OI) status:
– No OI
– History of OI
– Current OI
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Model Overview
Each of the three broad health states further
stratified by
– 8 OI types, 7 HIV RNA levels & 6 CD4 levels
Number of health states
(1 Without + 8 Past + 8 Current) * 7 RNA * 6 CD4 = 714
Opportunistic Infections
Patients progress through each health state
depending on the transition rates, treatment
group and other factors
Followed up until death.
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HIV Diseases Progression Model
6
BENCHMRK population
Characteristics
Raltegravir + OBT Placebo + OBT
Number of patients
462
237
Mean Age, years (SD)
45.7 (8.6)
45.1 (8.1)
Male, %
87.7
88.6
Caucasian, %
65.2
73.0
Mean CD4 Count, cells/mL (SD)
151.4 (141.2)
158.0 (150.4)
GM, HIV RNA, copies/mL
44,252
39,034
Mean HIV RNA, log10 copies/mL (SD)
4.6 (0.8)
4.6 (0.8)
History of AIDS, %
92.5
91.1
Median years of prior ART use
10.1
10.2
Median number of prior ARTs used
12.0
12.0
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Clinical Inputs: HIV RNA
Transition intensity matrices for HIV RNA states
estimated from BENCHMRK data
(Kalbfleisch & Lawless, 1985)
Two temporal phases
– 0 to 4 weeks
– 4 weeks to 48 weeks
Annual changes in CD4 are determined as a function of
HIV RNA and CD4 levels following EuroSIDA
Model assumes treatment effect would remain stable in
first 5 years and diminish at a rate of 8% per year
thereafter
(Phillips et al 2004)
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Clinical Inputs: Mortality data
OIs could have a significant impact on mortality.
Three broad categories of mortality rates
depending on OI status
–Without OI: Spanish male life table data
–History of OI: Excess deaths according to CD4 using
EuroSIDA data, Olsen et al (2005), The PLATO
Collaboration (2004)
–Current OI: Moore & Chaisson (1996) and Chaisson
et al (1998)
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Cost Inputs
Drug Costs
– OBT Cost: Average drug cost in Spain weighted by
the OBT drug frequencies in BENCHMRK (€ 54.90
per day)
– Raltegravir cost € 27 per day
Resource Use Cost
– Resource use by HIV patients stratified by CD4 and
VL levels was obtained from BC Center of
Excellence in HIV (Canada)
– Unit prices from Spain
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Quality of Life Inputs
Simpson KN et al (2004)
[Base case]
Weights by CD4 and VL strata
EQ-5D, 21000 patients, recent
Stavem K et al (2005)
[Sensitivity analysis]
Small sample, recent, weights by CD4 only
Schackman et al. (2002) and Freedberg (1998)).
Large sample, weights CD4 strata and by OI, history of OI,
and no OI history
[Sensitivity analysis]
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Cost Effectiveness
Strategy
Placebo+OBT
Raltegravir+OBT
Life
Expectancy
(years)
Dis. QALYs
(years)
Dis. Cost
(€)
24.65
10.18
275,509
29.17
11.90
329,490
*Assumes 5-year treatment duration, raltegravir daily cost of €27; QALY = qualityadjusted life year; ICER = incremental cost effectiveness ratio
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ICER
(€/QALY)
31,431
Sensitivity Analysis – I
(Assuming 5-Year Raltegravir Treatment Duration)
Parameter
13
Assumption
ICER
(€/QALY)
---------------- Base case --------------Treatment duration
3 years
Treatment duration
Lifetime
Analytic time horizon
10 years
31,431
22,908
74,468
59,753
Analytic time horizon
Analytic time horizon
Cost of OBT per month
20 years
30 years
50% higher
36,456
32,495
39,316
Cost of OBT per month
50% lower
23,546
Sensitivity Analysis - II
(Assuming 5-Year Raltegravir Treatment Duration)
Parameter
Assumption
ICER
(€/QALY)
Cost of raltegravir per month
20% higher
36,183
Cost of raltegravir per month
20% lower
26,678
Discount rate/ year: costs & benefits
None
21,325
Discount rate/ year: costs & benefits
3%
23,414
Incidence of OI per month
None
30,938
Incidence of OI per month
Pre cART
32,522
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*Base case used pre cCRT OI rates adjusted by data from
CASCADE collaboration
Sensitivity Analysis – III
(Assuming 5-Year Raltegravir Treatment Duration)
Parameter
15
Assumption
Decrement in quality of life
Decrement in quality of life
25% higher
25% lower
ICER
(€/QALY)
29,919
33,103
Decrement in quality of life
Estimates of quality of life
Estimates of quality of life
Failure rate after treatment
Failure rate after treatment
None
Stavem
Schackman
1%
16%
39,389
28,047
42,399
31,462
31,396
Summary
Long-term outcomes of raltegravir therapy projected
using a cohort state-transition model
Model suggests raltegravir provides substantial clinical
benefits (e.g., longer life expectancy)
Based on model, raltegravir is cost-effective when added
to OBT
Results are however sensitive to
– Treatment duration
– Quality of life weights
– Analytical time horizon
ICER also sensitive to cost of OBT and raltegravir still
raltegravir cost effective
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Limitations
A model is an abstraction of reality
Did not model explicitly
–Regimen changes over time
–Patient compliance
–Productivity losses
Long-term efficacy not known
Data limitations - multiple sources
–Incidence, duration, and mortality by CD4
–HIV-related mortality by CD4 and VL
–Quality of life weights
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