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PGI1 |
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THE ADDITIVE CLINICAL VALUE
OF LAMIVUDINE IN ANTVIRAL THERAPY FOR PATIENTS
WITH CHRONIC HEPATITIS B
Sun X1, Wang X2, Liu X2, Li Y3, Guyatt G4,
1The Chinese Cochrane Centre, West China Hospital,
Sichuan University, Chengdu, China, 2Sichuan
University, Chengdu, Sichuan, China, 3Chinese
Evidence-Based Medicine Center, West China
Hospital, Chengdu, Sichuan, China, 4Department of
Clinical Epidemiology and Biostatistics, McMaster
University, Hamilton, Ontario, Canada
OBJECTIVE:
To investigate whether addition of lamivudine to other antivirals was superior to
single use of antivirals for patients with chronic
hepatitis B. METHODS:
Systematic review and
meta-analysis of randomized trials were conducted.
Medline, Cochrane Trial Register, Current
Contents, SCI-E and CBMdisc were searched.
References of included studies was also conducted.
Randomized trials that compared lamivudine plus
antiviral with single use of antiviral for
patients with chronic hepatitis B were eligible.
Studies that included patients with co-infection
of HCV and HIV, and with decompensate liver
diseases were excluded. Egger’s regression was
used to identify publication bias. Meta-regression
and subgroup analysis were used to investigate
heterogeneity. Type of comparison, duration,
doses, and ethnicity were considered for
heterogeneity. RESULTS:
Fourteen trials were
included, 78.6% of which were moderate to high
quality. Ten trials studied addictive effect of lamivudine in interferon therapy, two in thymocin
therapy, and two in other therapies. No
publication bias was identified (coefficient=2.73,
95%CI=-0.96-6.42). Duration was a prognostic
factor addressing heterogeneity in loss of HBeAg
across trials. Shortterm effect (<26 wks) of
lamivudine plus antiviral was superior to antivral
alone (OR=4.01, 95%CI: 1.83-15.8, P=0.000), but
this effect disappeared in pronged duration (>26
wks, OR=0.61, 95%CI: 0.78-1.54). Ethnicity
projected clinical difference in loss of HBV-DNA
across trials. The combination of lamiuvdine with
antiviral in Chinese patients produced significant
loss of HBV-DNA (OR=3.58, 95%CI: 2.48-5.16).
However, combination of lamivudine with interferon
was not better than interferon alone. The combined
therapy was superior to antiviral montherapy alone
in normalization of ALT (OR=1.49, 95%CI=1.12-
1.98). Loss of HBsAg was better in combined
therapy (OR=1.72, 95%CI=1.05-2.81). Seroconversion
were also better in combination therapy (OR=1.55,
95%CI=1.10-2.18), but this was not seen
specifically in lamivudine plus interferon against
interferon alone. CONLUSIONS:
Lamivudine
is clinically useful to improve the antiviral
effects in chronic hepatitis B patients.
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PGI33 |
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COST-EFFECTIVENESS OF THE
INTRAVENOUS PROTON PUMP INHIBITORS COMPARED WITH
HISTAMINE-2 RECEPTOR ANTAGONISTS IN THE TREATMENT
OF NON-VARICEAL UGIB
Chen Y, Chang Gung Memorial Hospital,
Kaohsiung, Taiwan Non-variceal
upper gastrointestinal bleeding (NVUGIB) is a
common cause of hospitalization all over the world
including in Taiwan. Patients with NVUGIB in
general practice are often treated empirically
with a standard dose of IV proton pump inhibitors
(PPIs) or histamine- 2 receptor antagonists
(H2RAs). Despite clinical evidence in favour of IV
PPIs, FDA has not yet been proved PPIs in this
indication. OBJECTIVE:
To compare the cost
effectiveness of IV PPIs and H2RAs in the
treatment of NVUGIB, we assessed the rebleeding
rate of initial medication choice (IV PPIs or
H2RAs) and direct medical cost using healthcare
claims data in Taiwan . METHODS:
We designed a
two-year retrospective longitudinal analysis
between January 1, 2002, and January 31, 2004 to
compare the 60-days rebleeding rate from the
healthcare claims in southern Taiwan, with about
three million members. We constructed a decision
tree model comparing two strategies: IV PPIs and
IV H2RAs started in the NVUGIB patients following
endoscopic therapy. The model was evaluated the
rebleeding to initial therapy and the rebleeding
prevented by competing different strategies.
Sensitivity analysis was used in the decision to
evaluate the strategies. Charlson comorbidity
score was used to adjust for severity. RESULTS:
After endoscopic therapy, severely rebleeding is
still common in Taiwan need for further endoscopic
haemostasis or surgery. Analysis showed that the
cost-effectiveness ratios for IV PPIs and H2RAs
groups were NT46761.18 and NT45107.88,
respectively, in averting one episode of recurrent
bleeding in one patient after initial hemostasis
was achieved. CONLUSIONS:
It is common in Taiwan
to administer IV H2RAs to patients with UGIB. The
analysis suggest that the use of IV PPIs in
conjunction with endoscopy haemostasis in a
standard dose was not superior effectiveness based
on the probability determination used in the
sensitivity analysis.
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PGI4 |
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ECONOMICS EVALUATION OF
LAMIVUDINE IN THE TREATMENT OF CHRONIC HEPATITIS B
Lu XZ1, Chen W2, Tan-Mulligan A1,
1GlaxoSmithKline (China) Investment Co Ltd,
Shanghai, China, 2Fudan University (former
Shanghai Medical University), Shanghai, China
Chronic hepatitis B (CHB) is one of the most
common infectious diseases in the world with
approximately 350 million carriers of the
hepatitis B virus (HBV). In China, it was reported
that the rate of HBV infection was as high as
57.63%, i.e., there were at least 600 million
people who were infected with HBV. Approximately
120 million carriers, with the prevalence rate of
HBV carriers 9.75%, accounted for one third of
that in the world. OBJECTIVE:
This study aims to
measure the cost-effectiveness of Lamivudine, a
once-daily oral antiviral treatment, of different
treatment durations compared with placebo in the
treatment of CHB from a long-term perspective.
METHODS:
A life-time Markov model was used to
estimate the cost and clinical effectiveness of
Lamivudine compared to placebo in treating CHB
patients. Transition probabilities and relevant
costs for each state in Markov model were from
China clinical trials, literature and expert
consultation method. Long-term costs and outcomes
were discounted by 5% per annum to represent
future consequences in present-value terms.
RESULTS:
In a long term perspective, the
incremental cost per life year gained from
Lamivudine of different treatment durations
compared to placebo was less than 23,800 yuan
(US$2,850), varying from 2,814 yuan (US$340) to
23,790 yuan (US$2,850), which is cost-effective.
CONCLULSIONS: The incremental cost per life year
gained from longer Lamivudine treatment is cost
effective especially when compared to the GDP per
capita of Shanghai (2002) which was often regarded
as the benchmark for the health care resource
allocation in China. In particular, the 4-year
Lamivudine treatment for CHB patients could bring
about the prolongation of life years at the
relative expense of less than 25,000 yuan per year
(US$3012). It can be concluded that longer term
Lamivudine treatment is a more cost-effective
treatment for CHB patients.
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PGI5 |
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AUSTRALIAN ECONOMIC
EVALUATION OF PEGASYS (PEGINTERFERON ALFA-2A)
VERSUS LAMIVUDINE FOR THE TREATMENT OF CHRONIC
HEPATITIS B
Todd CJ1, Patel KK2, Adena M3, Veenstra
DL4, 1Roche Products Pty Limited, Sydney, New
South Wales, Australia, 2Hoffmann-La Roche,
Nutley, NJ, USA, 3Covance Pty Ltd, Canberra, ACT,
Australia, 4University of Washington, Seattle, WA,
USA
OBJECTIVE:
To estimate the cost-effectiveness of peginterferon alfa-2a (PEG-IFN alfa-2a) 180mcg
once-weekly for 48 weeks versus long-term
lamivudine (LAM) 100mg once-daily for chronic
hepatitis B (CHB) from the Australian health care
system perspective. METHODS:
The efficacy and
safety of PEG-IFN alfa-2a versus LAM for 48 weeks
were assessed in two randomised phase III studies
in HBeAg-positive and HBeAg-negative CHB. Modelled
evaluations linked the clinical outcomes measured
in the studies (HBeAg seroconversion in HBeAg-positive
CHB and combined virological and biochemical
response in HBeAg-negative CHB) to life-years and
quality-adjusted life-years (QALYs) gained. The
models comprised the disease states: CHB;
response/HBeAg seroconversion; cirrhosis;
decompensated cirrhosis; hepatocellular carcinoma;
liver transplantation; post-liver transplantation;
and death. In clinical practice, LAM is not
discontinued at week 48; therefore,
end-of-treatment response rates from the studies
were included in the models and published
long-term data used to extrapolate response beyond
week 48. End-of-follow-up response rates were used
for PEG-IFN alfa-2a. In Australia, LAM is
continued for 6-12 months post-seroconversion in
HBeAg-positive CHB, otherwise indefinitely until
resistance develops. According to clinicians, the
majority of PEG-IFN alfa-2a failures would receive
LAM, and LAM failures adefovir dipivoxal. Resource
use was based on Australian clinical practice.
Transition rates, costs, and utilities for CHB-related
disease states were identified from the literature
and validated using expert opinion. RESULTS:
In
the HBeAg-positive model, PEG-IFN alfa-2a was
associated with additional lifetime costs (study
drug, salvage therapy and medical care costs) of
$A5,434 per patient and an increase of 0.39 QALYs,
resulting in an incremental cost-effectiveness
ratio of $A13,985 per QALY gained. In the HBeAg-negative
model, PEG-IFN alfa-2a was associated with
lifetime cost savings of $A1,617 per patient and
an increase of 0.52 QALYs. Results remained
favourable to variation in multiple parameters in
sensitivity analyses. CONLUSIONS:
Compared with
LAM, PEG-IFN alfa-2a is cost-effective in HBeAg-positive
and HBeAg-negative CHB.
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PGI6 |
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PHARMACOECONOMICS OF CHRONIC
HEPATITIS C IN SLOVAKIA.
Bielik J1, Huzicka I2, 1Trencín University,
Trencín, Slovak Republic, 2Schering-Plough,
Bratislava, Slovak Republic
OBJECTIVE:
There was no evidence about pharmacoeconomical outcomes of chronic hepatitis C
(CHC) in Slovakia or in other central and est
European countries.. This study offers results
obtained from the first Slovak cost of illnes
study in patients suffering from CHC. METHODS:
Pharmacoeconomics of CHC was studied in a group of
70 patients with CHC using our own “CHC
pharmacoeconomical Questionnaire”. RESULTS:
There
were 46 men and 24 women. The average age of
patients was 48 years. The direct costs were
established for following forms of CHC: a, HCV
negative patient after treatment- 283 USD, b, mild
CHC – 295 USD, c, moderate CHC – 880 USD, d,
cirrhosis without ascites – 970 USD, e, non
refractory ascites – 1165 USD, f, refractory
ascites – 13973 USD, g, hepatic encephalopathy
(first year) – 5247 USD, h, hepatic encephalopathy
(second year) – 3869 USD, i, variceal hemorrhage
(first year) – 8201 USD, j, variceal hemorrhage
(second year) – 4461 USD, k, hepatocellular
carcinoma – 3159 USD, l, liver tranplantation –
10565 USD. The indirects cost were established for
one patient per year – 3095 USD. CONLUSIONS:
The
treatment with pegintron and rebetol (by body
weight) reaches 19421 USD in patients with
genotype 1 resp. 13694 in patients with genotypes
2 and 3. This treatment is costeffective in
Slovakia.
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PGI7 |
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VALUING HEALTH STATES USING
UTILITY WEIGHTS TO CAPTURE THE IMPACT OF DISEASE
PROGRESSION IN CHRONIC HEPATITIS B (CHB)
Lam CL1, Levy A2, Lozano-Ortega G2, Tafesse
E3, Mukherjee J3, Iloeje U4, Briggs AH5, 1The
University of Hong Kong, Hong Kong, China, 2Oxford
Outcomes, Vancouver, British Columbia, Canada,
3BMS, Wallingford, CT, USA, 4Bristol-Myers Squibb
Company, Wallingford, CT, USA, 5University of
Glasgow, Glasgow, United
Kingdom
OBJECTIVE:
Approximately 8% of people in Hong Kong
are chronically infected with the hepatitis B
virus (HBV). Without treatment, infected
individuals may progress through increasingly
severe disease states before death. Utility
weights are useful for estimating the combined
impact of morbidity and mortality and estimate
quality adjusted life years (QALYs) in
cost-effectiveness analyses. The objective was to
elicit utility weight estimates associated with
six hepatitis B-related disease states. METHODS:
Three hepatologists characterized the typical
effects of HBV symptoms on health-related quality
of life. We elicited preferences from 100
uninfected subjects and 100 subjects chronically
infected with HBV in Hong Kong using: 1) a visual
analogue scale (VAS) based on a `feeling’
thermometer anchored between 0 (death) and 1
(perfect health), and 2) standard gamble (SG)
utility weights using probability wheels with
2-color pie charts for the relative probabilities
of perfect health and death. RESULTS:
For infected
subjects, the mean age was 45 years (range: 18 to
80) and 79% were male. Mean utility weights
elicited from infected subjects using SG were:
0.69 (95% confidence interval: 0.63-0.74) for
chronic hepatitis B; 0.71 (0.66-0.77) for
compensated cirrhosis; 0.27 (0.22-0.32) for
decompensated cirrhosis; 0.64 (0.58-0.69) for
first year after liver transplant; 0.71
(0.65-0.76) for subsequent years after liver
transplant and 0.36 (0.30-0.42) for hepatocellular
carcinoma. Mean utility weights elicited from
uninfected subjects had the same relative rankings
and similar numerical values. VAS ratings were
generally lower than SG utilities and ranked in
the same order for infected and uninfected
subjects. CONLUSIONS:
In this, the first study of
its kind in Hong Kong, we observed that the health
states were associated with substantial loss in healthrelated quality of life. The lowest utility
estimates were associated with decompensated
cirrhosis and hepatocellular carcinoma. This
information can be used in estimating QALYs for
incremental cost-utility analyses.
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PGI8 |
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TREATMENT PREFERENCE AND
IMPROVEMENTS IN HEALTH RELATED QUALITY OF LIFE
(HRQOL) IN RENAL TRANSPLANT RECIPIENTS WITH
GASTROINTESTINAL (GI) COMPLAINTS CONVERTED FROM
MYCOPHENOLATE MOFETIL (MMF) TO ENTERIC-COATED
MYCOPHENOLATE SODIUM (EC-MPS)
Bonney MA1, Fassett R2, Kark A3, Faull R4,
Hutchison B5, Walker R6, Mahony J7, Goodman D8,
Pussell B9, Ierino F10, Kurstjens N1, 1Novartis
Pharmaceuticals Australia, Sydney, NSW, Australia,
2Launceston General Hospital, Launceston, TAS,
Australia, 3Royal Brisbane Hospital, Brisbane,
QLD, Australia, 4Royal Adelaide Hospital,
Adelaide, SA, Australia, 5Sir Charles Gairdner
Hospital, Perth, WA, Australia, 6Royal Melbourne
Hospital, Melbourne, VIC, Australia, 7Royal North
Shore Hospital, Sydney, NSW, Australia, 8St
Vincents Hospital, Melbourne, VIC, Australia,
9Prince of Wales Hospital, Sydney, NSW, Australia,
10Austin Hospital, Melbourne, VIC, Australia
OBJECTIVE:
GI complaints are common side-effects
of immunosuppressive agents, but dose reductions
to ameliorate symptoms may compromise efficacy.
This study evaluated changes in GI symptoms and
HRQoL after renal transplant patients were
converted from MMF to EC-MPS. A substudy gained
additional information on patients’ utility and
preference for treatment. METHODS:
An open-label,
multi-centre study; patients with GI complaints on
MMF were switched to EC-MPS (Gp1); asymptomatic
patients remained on MMF (Gp2). Patients completed
the Gastrointestinal Symptom Rating Scale (GSRS),
Gastrointestinal Quality of Life Index (GIQLI),
and Psychological General Well-Being Index (PGWB)
at baseline and four-six weeks. Of the 328
patients, 90 were Australian – they also completed
the EQ-5D and SF-6D utility instruments and
treatment preference questions. Non-parametric
tests were used. RESULTS:
In the Australian ITT
population there was no significant difference
between Gp1(n=56)and Gp2(n=34) with respect to age
(45.8 vs 49.6 yrs), male gender (55% vs 62%) or
time post-transplant (4.6 vs 3.5 yrs). At
baseline, Gp1 had significantly more symptoms and
HRQoL impairment compared to Gp2 (p<0.01, all
scores). At follow-up, patients converted to
EC-MPS demonstrated significant improvement
(p<0.01) in four of five GI symptoms. HRQoL also
improved, as measured by the GIQLI (p<0.001) and
PGWB (p=0.003); (EQ-5D/SF-6D, ns). Scores for Gp2
remained generally stable. Of the 56 patients
converted, 28 (50%) stated a preference for
EC-MPS; 20 (35.7%) had no preference; 6(10.7%)
preferred MMF (p=0.001). Patients preferring ECMPS
had greater improvement in HRQoL compared to those
with no preference or a preference for MMF (GIQLI
p<0.001, PGWB p=0.002, EQ-5D p=0.017, SF-6D
p=0.035). CONLUSIONS:
Converting patients with GI
complaints to EC-MPS resulted in significant
improvement in GI symptoms and HRQoL.Generic
utility instruments were less sensitive to changes
in GI complaints. Overall, HRQoL improvements were
consistent with reduced GI symptom severity, and
this was ultimately reflected in patients’
preference for treatment.
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PGI9 |
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SYSTEMATIC REVIEW OF ECONOMIC
EVALUATIONS IN DRUG DECISION-MAKING: AN EXAMPLE
FROM ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS B
Sun X1, Li Y2, Zhou R3, Hu S4, 1The Chinese
Cochrane Centre, West China Hospital, Sichuan
University, Chengdu, China, 2Chinese
Evidence-Based Medicine Center, West China
Hospital, Chengdu, Sichuan, China, 3West China
Hospital, Sichuan University, Chengdu, China,
4Fudan University (former Shanghai Medical
University), Shanghai, China
OBJECTIVE:
To investigate the applicability of
systematic review of economic evaluations in drug
decision-making, by systematic reviewing lamivudine for chronic hepatitis B (CHB) as an
example. METHODS:
Medline, Cochrane Database, CBMDisc and SCI-E were searched, with
complementary searching of references of eligible
studies. Full economic evaluations on single and
combined therapy of lamivudine for patients with
CHB were eligible. Quality was appraised by
Drummond’s 36-item checklist and transferability
assessed by 12-item checklist developed by the
research group. The eligibility of studies for
informing drug decision-making was weighted by the
overall quality and transferability, as assessed
by independent investigators, with consensus
reached by panel agreement. A matrix-based summary
of outcomes were conducted. RESULTS:
Fifteen
studies were included. Ten trial-based studies
were conducted in China, and five modelling
studies from Australia, USA and Poland. Eight
studies compared lamivudine with interferon, four
with interferon and no treatment, one with
thomycin, one with four alternative strategies,
and one with placebo. Thirteen studies adapted
health care-sector perspective, and two US studies
from third-payer perspective. Quality of Chinese
studies was poor to moderate (4/10 moderate) with
concerns in costing methods, while foreign studies
were at least moderate in quality. Transferability
of foreign studies was low due to variations of
clinical practice pattern and costing sources. The
short-term analyses from 13 studies consistently
indicated that lamivudine was more effective in
seroconversion and cost-effective compared with
interferon or thymosin, and 11 studies further
indicated that lamiuvdine was cost-saving. The
long-term analyses were not available in Chinese
studies. Three studies indicated that lamiuvudine
was cost-saving and life-extending in Australia,
but was less cost-effective in US. CONLUSIONS:
Lamiuvdine was cost-effective in short-term
analysis in the Chinese setting, but remained
unclear for long-term results. It suggested that
systematic review was helpful for drug
decision-making, though difficult to address all
questions of interest.
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