Supplements Treatment and Management Options for Reversible Airway Disease
The Cost Effectiveness of Levalbuterol Versus Racemic Albuterol
The lower mean number of treatments
with levalbuterol versus racemic albuterol
(19.0 vs 30.8; P <.001) was partly due to protocol-mandated differences in the dosing
schedules. (A published letter challenged
the study on this basis and also for using
average wholesale prices, which may be
different from what hospitals actually pay.
The study investigators responded that the
need for more frequent dosing with racemic
albuterol than with levalbuterol to achieve
an adequate clinical response was the very
point of the study, and that average wholesale
prices are standard in cost analyses.15)
However, the protocol did not account for
the fact that the mean duration of β2-agonist
treatment was 29% shorter with levalbuterol
than with racemic albuterol (5.5 vs 3.9
days), or that patients receiving levalbuterol
versus racemic albuterol required fewer
adjunctive treatments with ipratropium
(mean 9.4 vs 23.2; P <.001) and had a lower
30-day rehospitalization rate (mean 5.7% vs
16.4%; P = .01). This difference was noted
mainly in the subset of patients with COPD,
and other factors may have affected the risk
of readmission. Overall costs for delivering
nebulized medications were significantly
lower with levalbuterol than with racemic
albuterol (for all patients $61 vs $112, P
<.001; among asthma patients, $44 vs $99,
P <.005). Total hospital costs were numerically
lower (for all patients $2756 vs
$3225, P = .11; among asthma patients,
$1856 vs $2503). Regression analysis controlling
for baseline FEV1, diagnosis, and
ipratropium use showed that levalbuterol
was associated with a 0.9-day shorter stay
(P = .015), a 67% lower rate of rehospitalization
(P = .056), and total cost savings of
$556 per patient (P = .013).
The Economics of Asthma Care
Assessing the costs of asthma and its
treatment, and the cost effectiveness of specific
therapies, is a daunting task. A review
by Sculpher and Price16 outlines several of
the difficulties, starting with the fact that
looking at total direct and indirect costs does
not address the disproportionate share of
costs incurred by patients with severe asthma
or the unnecessary costs attributable to
suboptimal management. Moreover, published
reports employ such a variety of methods,
outcome measures, and definitions that
their findings are difficult to compile and
compare. Finally, most cost-effectiveness
data emerge from short-term studies of clinical
efficacy, safety, and tolerability, and such
findings are not necessarily predictive of
In an attempt to sort out the numerous
variables that must be considered in all
clinical-economic evaluations of drugs,
Eisenberg and colleagues17 proposed a 3-dimensional model: (1) type of analysis (cost
identification, cost effectiveness, cost benefit);
(2) point of view (patient, clinician,
insurer, society); and (3) types of outcome
measures (direct and indirect costs, morbidity
and mortality, intangible or unquantifiable
results). For example, quantifiable
clinical outcomes are usually of most interest
to physicians, less readily quantifiable
outcomes such as quality of life reflect the
patient's point of view, while cost-effectiveness
analyses aimed at obtaining the best
clinical outcome at the lowest cost are of
greatest concern to managed care, insurers,
Applying this model to asthma, the economic
comparison of levalbuterol versus
racemic albuterol involves cost-effectiveness
analysis from the point of view of the clinician
and the insurer, with the focus on
direct medical costs. Yet further definition is
necessary; for example, pharmacy services
may focus only on drug acquisition costs,
but the overall cost to the medical facility
and insurer may be more strongly affected by
such clinical outcomes as needed for hospitalization.
In the previously cited pediatric
study,13 the number needed to treat (with
levalbuterol instead of racemic albuterol) to
avert a hospitalization was only 10.6
patients; the incremental cost of levalbuterol
for such a small number of patients
is minuscule compared with the cost of a single
Most studies that reflect the interests of
the clinical audience have focused on objective
measures of efficacy, such as FEV1.
However, efficacy in the ideal setting of a
well-designed clinical trial is not the same as
effectiveness in the real-world setting of
actual clinical practice. For example, how
should a worsening FEV1 be interpreted in
clinical practice? Assuming adequate adherence
to treatment, it may be difficult to
determine whether the patient's condition is
becoming more severe or the drug is losing
its effectiveness. With the latter possibility,
loss of effectiveness may be an intrinsic
problem with the drug or the result of something
else happening in that patient, such as
a drug interaction that induces increased
metabolism of the asthma medication.
Just as it is difficult to gauge the overall
therapeutic worth of an asthma drug from
changes in FEV1 in a short-term controlled
clinical trial, it is difficult to assess a drug's
cost effectiveness by looking only at direct
medical expenditures recorded in that same
trial. A working group from the National
Heart, Lung, and Blood Institute reviewed
the role of health economics in planning
optimal asthma management strategies,
and offered a set of recommendations for
future research, including adoption of standardized
definitions and outcome measures,
a focus on long-term effectiveness
rather than short-term efficacy, and controls
for such variables as patients' age and
socioeconomic status, and the duration and
severity of asthma.18
From the evidence currently available, it
appears that levalbuterol represents a clinically
important advance over racemic
albuterol. The advantage in clinical efficacy
(ie, improved respiratory performance) is
matched by an advantage in cost effectiveness,
which leads to a reduction in the need
for hospitalization. Long-term follow-up in
the clinical practice setting may determine
the degree to which these short-term advantages
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