Volume 4, 2001
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Health economic comparisons of rofecoxib versus conventional nonsteroidal antiinflammatory
drugs for osteoarthritis in the United Kingdom
RA Moore, CJ Phillips, JM Pellissier, SX Kong
Pages 1-17 ¦ Abstract ¦ PDF (129 KB)
Pharmacoeconomic analysis of the treatment of rheumatoid arthritis with lefluniomide
in comparison with the combination of infliximab and methotrexate
C Rubio-Terrés, A Domínguez-Gil
Pages 19-34 ¦ Abstract ¦ PDF (97 KB)
A cost utility model of interferon beta-1b in the treatment of relapsing-remitting
multiple sclerosis
CJ Phillips, L Gilmour, R Gale, M Palmer
Pages 35-50 ¦ Abstract ¦ PDF (83 KB)
The cost of osteoporotic fractures in the UK: projections for 2000-2020
RT Burge, D Worley, A Johansen, S Bhattacharyya, U Bose
Pages 51-62 ¦ Abstract ¦ PDF (80 KB)
The newer antipsychotics: evidence for cost-effectiveness and policy implications
RF Cookson
Pages 63-89 ¦ Abstract ¦ PDF (138 KB)
A comparison of evidence and practice in the treatment of constipation
A Haycox, SP Howard, A Partridge, T Wright
Pages 91-98 ¦ Abstract ¦ PDF (62 KB)
Economic evaluation of the use of enoxaparin for thromboprophylaxis in acutely
ill medical patients
AC Lloyd, PM Anderson, DJ Quinlan, A Bearne
Pages 99-113 ¦ Abstract ¦ PDF (91 KB)
Cost-effectiveness of combination chemotherapy (oxaliplatin or irinotecan in
combination with 5-FU/FA) compared with 5-FU/FA alone
CJ Nicholls, J Cassidy, N Freemantle, M Harrison, P Carita
Pages 115-125 ¦ Abstract ¦ PDF (71 KB)
Cost-effectiveness of oxaliplatin in combination with 5-FU/FA compared with 5-FU/FA
alone
CJ Nicholls, J Cassidy, N Freemantle, M Harrison, P Carita
Pages 127-135 ¦ Abstract ¦ PDF (68 KB)
Cost-utility of risperidone compared with standard conventional antipsychotics
in chronic schizophrenia
PI Oh, KL Lanctöt, N Mittmann, M Iskedjian, TR Einarson
Pages 137-156 ¦ Abstract ¦ PDF (108 KB)
Comparison of the effectiveness of eletriptan, sumatriptan and Cafergot® in reducing the time loss associated with migraine attacks
NEJ Wells
Pages 157-166 ¦ Abstract ¦ PDF (67 KB)
Costs of neoadjuvant chemotherapy and surgery in patients with liver metastases
from advanced colorectal cancer
G Poston, IS Benjamin, T Diamond, M Finch-Jones, RW Parks, JN Primrose, M Rees,
DJ Sherlock, S Yeung, P Carita, CJ Nicholls
Pages 167-177 ¦ Abstract ¦ PDF (85 KB)
Comparing olanzapine and ziprasidone in the treatment of schizophrenia: a case
study in modeling
I Alexeyeva, J Mauskopf, SR Earnshaw, VL Stauffer, JP Gibson, H Ascher-Svanum,
J Ramsey
Pages 179-192 ¦ Abstract ¦ PDF (97 KB)
Hospital management and costs of antidepressant overdose: multicentre comparison
of tricyclic antidepressants and selective serotonin reuptake inhibitors
N Kapur, A House, K Dodgson, C May, F Creed
Pages 193-197 ¦ Abstract ¦ PDF (50 KB)
An economic evaluation of ramipril in the treatment of patients at high risk
for cardiovascular events due to diabetes mellitus
SM Beard, L Gaffney, ME Backhouse
Pages 199-205 ¦ Abstract ¦ PDF (60 KB)
Cost-effectiveness of glatiramer acetate in the treatment of relapsing-remitting
multiple sclerosis
U Bose, D Ladkani, A Burrell, M Sharief
Pages 207-219 ¦ Abstract ¦ PDF (91 KB)
Moore RA, Phillips CJ, Pellissier JM, Kong SX
Health economic comparisons of rofecoxib versus conventional nonsteroidal antiinflammatory
drugs for osteoarthritis in the United Kingdom
J Med Econ 2001; 4: 1-17
Conventional NSAIDs cause major gastrointestinal complications and minor symptoms.
Most publications on the economic implications of NSAID gastropathy have examined
ulceration rates with endoscopy, adjusted for ulcers that are “silent,” i.e. never
require clinical treatment. Silent ulcer rates used range from 40% to 85%. Decision
analytic
modeling was done to examine the economic implications of switching all OA patients
currently treated with conventional NSAIDs to rofecoxib, from the perspective
of the National Health Service.
Analysis 1 was based on investigator observed perforations, symptomatic ulcers,
and bleeds (PUBs). Analyses 2 and 3 were based on endoscopic ulcers with adjustments
for silent ulcers of 85% and 40%, respectively. Analysis 1 showed that switching
patients currently treated with conventional NSAIDs to rofecoxib would cost the
NHS £0.32 extra per patient per day with cost per year of life saved estimated
at £15,647, a figure within accepted benchmarks for cost-effectiveness of medical
interventions. In Analyses 2 and 3, switching from conventional NSAIDs to rofecoxib
would be cost-saving to the NHS.
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Rubio-Terrés C, Domínguez-Gil A
Pharmacoeconomic analysis of the treatment of rheumatoid arthritis with lefluniomide
in comparison with the combination of infliximab and methotrexate
J Med Econ 2001; 4: 19-34
The objective of this study was to carry out a systematic review of efficacy
and toxicity and a cost-minimisation analysis, comparing a 1 year treatment of
rheumatoid arthritis with leflunomide and the combination of infliximab/methotrexate
in Spain.
Head-to-head clinical trials comparing both treatments are not available. The
response rate ACR20, after 1 year, was 53.0% (CI95%: 49.2%-56.4%) with leflunomide
and 42.0% (CI95%: 31.2%-52.5%) with the infliximab/methotrexate combination (p=0.051).
There were no statistically significant differences in the ACR50 response (27.0
vs 21.0, respectively; p=0.19). There were fewer infections with leflunomide than
with the combination, both respiratory (15.0% and 34.0%, respectively; p=0.0003)
and urinary (0.0% and 3.0%, respectively; p=0.10). In the basic case, the cost
per patient of a yearly treatment with leflunomide or with infliximab/methotrexate
is estimated to be 315,023 Ptas (Spanish pesetas) (1,893 euros) and 2,596,286
Ptas (15,604 euros), respectively. Therefore, the incremental cost of the combined
treatment would be 2,281,263 Ptas (13,711 euros).
The cost per patient after 1 year of treatment is higher with the infliximab/methotrexate
combination compared to leflunomide, this is due to the higher acquisition cost of infliximab (64.3% and 93.6% of the total
cost, respectively).
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Phillips CJ, Gilmour L, Gale R, Palmer M
A cost utility model of interferon beta-1b in the treatment of relapsing-remitting
multiple sclerosis
J Med Econ 2001; 4: 35-50
This study estimates the long-term cost effectiveness of Betaferon® (interferon beta-1b) in the treatment of relapsing-remitting multiple sclerosis
(RRMS). Clinical trial data, natural disease history information, and costs and
quality of life (EQ-5D) data, are linked using disease severity levels, via a
model that accounts for the number, severity and duration of relapses, and the
probability of disease progression. Previous attempts at modelling the cost effectiveness
of beta interferon have produced very high estimates of cost per QALY gained (CQG).
Increasing data availability enables the modification or replacement of many of
the assumptions underlying these models. In particular, longer term modelling
and the consideration of wider societal costs is appropriate in the context of
this chronic disease. The evidence presentd here provides much lower, and more
precise, estimates of CQG. The base case 20-year model estimates a CQG of £8,100.
These new estimates are in line with other recent estimates and demonstrates the
cost effectiveness of beta interferon.
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Burge RT, Worley D, Johansen A, Bhattacharyya S, Bose U
The cost of osteoporotic fractures in the UK: projections for 2000-2020
J Med Econ 2001; 4: 51-62
The prevalence of osteoporosis increases with age. The over-50-year-old population
is expected to grow by 10% and 25% by 2010 and 2020, respectively. There are already
3 million UK residents with osteoporosis and the public health impact of osteoporosis
will increase substantially over the next 20 years. A Markov model of the natural
history of osteoporosis was used to predict fracture numbers and corresponding
costs for the UK population aged 50-99 from 2000 to 2020. The model predicts 190,000
osteoporosis-related fractures at a cost of £1.8 billion in 2000. By 2020, annual
osteoporotic fractures will increase by 21% to 230,000 per year, with costs growing
by 20% to over £2.1 billion per year. Cumulative totals for 2000-2010 were 2.2
million fractures and £20.3 billion. Osteoporotic fractures will have substantial
and increasing impacts on UK health services unless highly effective preventative
interventions achieve widespread use.
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Cookson RF
The newer antipsychotics: evidence for cost-effectiveness and policy implications
J Med Econ 2001; 4: 63-89
The current reluctance in some health authorities to provide full funding for
the use of the new generation of antipsychotics is not in the best interests of
patients or the National Health Service. Schizophrenia is a complex and costly
disease, which relies too much on hospital care because of funding shortages elsewhere.
New research attitudes are required to assist health policy decisions. Economic
evaluations using evidence solely from randomised controlled trials (RCTs) are
insufficient and give a partial and potentially misleading picture. The complexity
of the illness and its outcomes in schizophrenia as well as the social influences
on hospital admission and discharge exaggerate methodological difficulties arising
from the nature of RCTs. The long-term, relapsing nature of the disease in many
patients means that long-term evidence must be considered from nonrandomised observational
studies.
This paper discusses recent reviews and major publications in order to examine
the economic arguments for newer atypicals as a class. The economic data published
to date consistently suggest that these newer agents should not increase the direct
costs of treating schizophrenia and may in fact reduce them. As there are undoubted
patient benefits, not least a reduction in side effects, especially extrapyramidal
symptoms (EPS) with the potential to improve compliance and reduce relapse, the
range of atypicals might be made available and the clinician allowed to make a
choice based on clinical not economic grounds.
The funding of these newer agents, although they are ultimately of benefit to
patients and to the NHS, stretches already sparse resources. The likely freeing
up of beds previously blocked by patients on older ‘conventional’ treatments will
allow them to be used by those patients who currently escape the net. This will
further increase funding requirements as more patients present for treatment.
There are ethical, clinical and political grounds for increasing funding for the
treatment of schizophrenia to take advantage of the biggest revolution in antipsychotic
therapy since the launch of the first neuroleptics.
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Haycox A, Howard SP, Partridge A, Wright T
A comparison of evidence and practice in the treatment of constipation
J Med Econ 2001; 4: 91-98
This paper reviews the evidence underlying pharmacological treatment for chronic
constipation at the primary care level and compares it with current patterns of
prescribing. The aim of the analysis is to identify the extent to which general
practitioners’ (GP) choices of treatment appear to be evidence-based. Evidence
from two systematic reviews of constipation were evaluated and updated. This evidence
was then reviewed for quality and compared with prescribing data taken from a
national prescribing database of over 700,000 patients. The quality of evidence
available to GPs is generally poor. The greatest evidence supports the use of
osmotic laxatives with an average weekly increase of 1.3 bowel movements. Osmotic
laxatives are used most widely by GPs, representing 40% of all prescriptions.
This may suggest that GPs are making the best use of the poor quality evidence
available to them in directing their prescribing decisions. In contrast, little
evidence was available to support the use of stimulant laxatives. The comparatively
high levels of co-prescribing and therapeutic switching, along with a high level
of repeat consultation appear to indicate therapeutic uncertainty and a certain
degree of dissatisfaction with currently available agents. The paucity of evidence
requires GPs to adopt ‘trial and error’ approaches, frequently switching therapies
in a therapeutic area that appears to be characterised by clinical uncertainty.
GPs are acutely aware of the limitations of current therapeutic strategies and
await the development of new therapeutic approaches that will enable them to treat
patients more effectively.
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Lloyd AC, Anderson PM, Quinlan DJ, Bearne A
Economic evaluation of the use of enoxaparin for thromboprophylaxis in acutely
ill medical patients
J Med Econ 2001; 4:99-113
The objective of this study was to assess the cost-effectiveness of prophylaxis
for venous thromboembolism (VTE) in acutely ill medical patients using 40 mg enoxaparin
od compared with unfractionated heparin (UFH) and placebo. An established decision
tree model based on epidemiological data, clinical trials, and a recent meta-analysis
was used to evaluate costs and consequences of alternative means of thromboprophylaxis
in medical patients. Primary outcome measures were episodes of VTE (deep vein
thrombosis or pulmonary embolism) and major bleeding. Secondary effectiveness
measures included estimated mortality. Inhospital drug costs and administration
time, in conjunction with long-term VTE complications up to 15 years and major
bleeding, were considered. Results were estimated for a hypothetical cohort of
100 patients. The expected cost per 100 patients was £9,992 with enoxaparin 40
mg od, £9,972 with UFH 5000 IU bd and £8,781 with no prophylaxis. The expected
number of episodes of VTE per 100 patients was 1.2 with enoxaparin 40 mg od, 1.4
with UFH 5000 IU bd and 3.2 with no prophylaxis. The expected number of episodes
of major bleeding per 100 patients was 1.7 with enoxaparin 40 mg od, 3.5 with
UFH 5000 IU bd and 1.1 with no prophylaxis. The cost-effectiveness ratios for
enoxaparin compared to no prophylaxis were £796 per VTE event avoided (taking
into account the small increase in bleeding). In acutely ill medical patients,
enoxaparin 40 mg od was found to be cost-effective compared with no thromboprophylaxis.
Compared to UFH prophylaxis, enoxaparin was found to be cost neutral.
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Nicholls CJ, Cassidy J, Freemantle N, Harrison M, Carita P
Cost-effectiveness of combination chemotherapy (oxaliplatin or irinotecan in
combination with 5-FU/FA) compared with 5-FU/FA alone
J Med Econ 2001; 4: 115-125
Combination therapies of oxaliplatin with 5-fluorouracil (5-FU) and folinic acid
(FA) and irinotecan with 5-FU/FA have been shown to offer comparable clinical
improvements in advanced colorectal cancer and are becoming part of routine clinical
practice in the UK. Using published key Phase III trials of these two combination
therapies (oxaliplatin trial, 620 patients; irinotecan trial, 387 patients) we
calculated incremental cost-effectiveness ratios for progression-free survival
and response rates compared with each regimen’s control arm. Average drug-acquisition
costs were used.
The incremental cost to achieve an additional progression-free year is £26,665
for oxaliplatin in combination therapy and £30,171 for irinotecan in combination
therapy. In terms of response rates, the costs incurred per year to achieve an
additional responding patient are £31,065 for oxaliplatin in combination therapy
and £46,343 for irinotecan combination therapy.
These analyses indicate that the two combination therapies offer comparable benefits
in terms of efficacy and cost-effectiveness compared with 5-FU/FA alone. The two
treatments differ in terms of their toxicity.
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Nicholls CJ, Cassidy J, Freemantle N, Harrison M, Carita P
Cost-effectiveness of oxaliplatin in combination with 5-FU/FA compared with 5-FU/FA
alone
J Med Econ 2001; 4:127-135
We performed a cost-effectiveness analysis to assess the cost-effectiveness of
oxaliplatin in combination with 5-fluorouracil (5-FU) and folinic acid (FA), compared
with 5-FU/FA alone to achieve an additional progression-free month or year from
the UK NHS perspective. Clinical data from a Phase III clinical trial were used
to determine efficacy, in terms of progression-free survival. The average drug-acquisition
cost for each cycle of treatment was then calculated. Any toxicities that resulted
in hospitalisation of the patient were determined, and the costs incurred were
calculated depending on the type of ward to which the patient was admitted. The
costs for oxaliplatin in combination with 5-FU/FA compared with 5-FU/FA alone
gave the incremental cost to achieve the improvement in progression-free survival.
Sensitivity analyses were performed on costs and progression-free survival to
give a range of possible values when costs and outcome were varied. The results
of the analysis indicate that the costs to achieve an additional progression-free
month are around £2,133. In the sensitivity analysis, the majority of scenarios
gave similar cost-effectiveness ratios. This gives an average incremental cost
of £25,600 to achieve an additional progression-free year. The cost-effectiveness
ratio is within acceptable limits and supports the use of oxaliplatin combination
therapy in the management of advanced colorectal cancer.
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Oh PI, Lanctöt KL, Mittmann N, Iskedjian M, Einarson TR
Cost-utility of risperidone compared with standard conventional antipsychotics
in chronic schizophrenia
J Med Econ 2001; 4: 137-156
The high costs and the efficacy of risperidone warrant a systematic pharmacoeconomic
evaluation in order to assess its relative cost-utility. The purpose of this study
was to evaluate the costs and utilities of treatment in chronic schizophrenia.
To achieve this, a cost-utility analysis, which compared risperidone to haloperidol
and two depot antipsychotics: haloperidol decanoate and fluphenazine decanoate
was conducted. A deterministic decision analysis was used to model chronic schizophrenia
over one year. Probabilities were obtained from clinical trials for each medication
that were combined using a random effects single arm metaanalysis. Utility values
for different health states were obtained by patient interview. A government payer
perspective was adopted for this analysis.
The study results demonstrate that risperidone is a dominant therapy in this
baseline analysis since it is associated with the lowest overall cost and highest
number of quality-adjusted life-years (QALYs). Compared with haloperidol, risperidone
might save $6,510 (CAN$) per year while producing 0.04 more QALYs per average
patient.
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Wells NEJ
Comparison of the effectiveness of eletriptan, sumatriptan and Cafergot® in reducing the time loss associated with migraine attacks
J Med Econ 2001; 4: 157-166
This study compared the effectiveness of different treatments for migraine in
reducing the time loss caused by attacks. Two dosage strengths of eletriptan (40
mg and 80 mg) were compared with Cafergot® (2 mg ergotamine tartrate plus 200 mg caffeine) and with sumatriptan (50 mg
and 100 mg) and placebo. Total Time Loss and Work Time Loss (including reduced
effectiveness whilst continuing to work during attacks as well as absenteeism)
were determined from patient questionnaires. Eletriptan at doses of 40 or 80 mg
led to a statistically significant reduction in Total Time Loss compared with
placebo. There was also a statistically significant reduction for both eletriptan
doses compared with
Cafergot®. For Work Time Loss, both doses of eletriptan were superior to placebo
and the 80 mg dose of eletriptan was superior to Cafergot®. The differences in Total and Work Time Loss between eletriptan and sumatriptan
were not statistically significant.
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Poston G, Benjamin IS, Diamond T et al
Costs of neoadjuvant chemotherapy and surgery in patients with liver metastases
from advanced colorectal cancer
J Med Econ 2001; 4:167-177
Liver metastases are found in 40-70% of patients with colorectal cancer. Surgery
is the only treatment for liver metastases that gives potential for long-term
survival. Studies with oxaliplatin combination therapy have reported significant
reduction of tumour bulk in the liver, allowing resection, with curative intent,
of previously unresectable liver metastases.
This study uses a simple decision model to estimate average chemotherapy costs
and surgical costs of treating advanced colorectal cancer patients with metastases
confined to the liver with either oxaliplatin combination therapy, or 5-FU/FA
alone. The incremental cost per life-year gained with oxaliplatin combination
therapy ranged between £5,489 and £15,624, and treatment could enable between
7.3% and 17.5% extra patients to be resected and therefore gain the chance of
long-term survival compared to 5-FU/FA treatment alone. To date, oxaliplatin combination
therapy is the only first-line treatment that has shown the possibility of long-term
survival in patients with unresectable liver metastases. This long-term survival
can be achieved at an acceptable cost.
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Alexeyeva I, Mauskopf J, Earnshaw SR et al
Comparing olanzapine and ziprasidone in the treatment of schizophrenia: a case
study in modeling
J Med Econ 2001; 4: 179-192
When a new drug is introduced to the market, the availability of head-to-head
data for comparisons of annual cost and health outcomes with other drugs already
on the market is usually insufficient. When only limited head-to-head data are
available, one alternative is to perform preliminary modeling using data from
the best available studies. In this paper, we synthesise data from the most comparable
available studies to create a model to compare the annual costs and health outcomes
when initiating treatment for schizophrenia with one of two antipsychotic drugs:
olanzapine, which was launched in the United States (US) market in September 1996,
and ziprasidone, which was approved by the US Food and Drug Administration (FDA)
in February 2001. Annual treatment costs were determined by response and relapse
rates as well as acquisition costs. The results indicate similar annual treatment
costs (US$48,676 for olanzapine; US$48,873 for ziprasidone), despite the lower
drug acquisition cost for ziprasidone. Annual health outcomes differed between
the olanzapine and ziprasidone groups with 23.5% and 25.2% relapsed, 36.7 and
37.4 hospital days, and 60.0 and 60.1 EPS days in the olanzapine and ziprasidone
groups respectively. A head-to-head naturalistic trial is needed to validate the
results of this modeling exercise.
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Kapur N, House A, Dodgson K, May C, Creed F
Hospital management and costs of antidepressant overdose: multicentre comparison
of tricyclic antidepressants and selective serotonin reuptake inhibitors
J Med Econ 2001; 4: 193-197
There is ongoing debate regarding the relative cost effectiveness of different
classes of antidepressants, but there has been little consideration of the cost
of deliberate self-poisoning. We examined the cost of antidepressant overdose
at six hospitals over a 5 month period and found that the cost of selective serotonin
reuptake inhibitor overdose was less than one-third that of tricyclic antidepressant
overdose (mean cost per episode £173 versus £634). The cost of overdose is often
ignored and should be considered in future analyses of the cost effectiveness
of different classes of antidepressant.
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Beard SM, Gaffney L, Backhouse ME
An economic evaluation of ramipril in the treatment of patients at high risk
for cardiovascular events due to diabetes mellitus
J Med Econ 2001; 4: 199-205
Cardiovascular disease (CVD) is a major cause of death and morbidity in the United
Kingdom (UK) and carries with it a significant financial cost through health care
resource use. More than one in three people die from CVD events, and the cost
to the UK National Health Service (NHS) was £1.6 billion in 19961. The recently
published MICRO-HOPE study evaluated the treatment of 3,577 patients at high risk
for cardiovascular events from diabetes mellitus and demonstrated significant
survival and morbidity benefits associated with ramipril.
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Bose U, Ladkani D, Burrell A, Sharief M
Cost-effectiveness of glatiramer acetate in the treatment of relapsing-remitting
multiple sclerosis
J Med Econ 2001; 4: 207-219
We have developed an economic model around the patient level data from the pivotal
clinical trial for Copaxone® (glatiramer acetate), combined with published cost and natural history data,
to demonstrate cost-effectiveness in relapsing-remitting multiple sclerosis (RRMS).
Based upon analysis over 8 years, the cost per relapse avoided and cost per disability
unit avoided was £11,000 and £8,862 respectively. To facilitate comparison with
other therapies and across other disease areas we also calculated the cost per
quality adjusted life year (QALY). Dependent upon the assumed utility loss associated
with duration of relapse, the cost per QALY ranged between £22,586 and £64,636
over 8 years analysis. Given the nature of the disease and compared to accepted
standards of cost-effectiveness in the UK, this analysis shows that glatiramer
acetate is demonstrably cost-effective versus best supportive care alone.
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