Evidence-based Oncology
Volume 1 • Number 3 • September 2000
Copyright © 2000 Harcourt Brace & Company Ltd.
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95
Cost-effectiveness analysis
Pamidronate associated with high incremental costs per
adverse event avoided in patients with metastatic breast cancer
Hillner BE, Weeks JC, Desch CE, Smith TJ.
Pamidronate in prevention of bone complications in metastatic breast cancer: a cost-effectiveness analysis. J Clin Oncol
2000; 18: 72-79
QUESTION
Is pamidronate a cost-effective treatment for reducing bony complications in patients with metastatic breast cancer who have known osteolytic lesions?
DESIGN
A post-hoc evaluation of the
cost-effectiveness of pamidronate.
SETTING
Data from two randomized trials (Aredia
Breast Cancer Study Group Protocols 18 and 19) that evaluated pamidronate 90 mg
administered intravenously every month vs placebo were analyzed. Each protocol
was an international, multicenter, randomized, double-blind, parallel trial of
women with metastatic breast cancer with one or more
osteolytic lesions at least 1 cm in diameter. All women received systemic therapy.
The trials differed only in the initial systemic therapy administered (hormonal
or chemotherapy). Primary end-point of the trials was skeletal-related events
(SREs), an aggregate of all bony complications. Median age was approximately 57
years. Approximately 60% of women had bony involvement as their sole site of
metastates, and approximately 65% had an Eastern Cooperative Oncology Group
performance score of 0 or 1. Both trials clearly showed that pamidronate was
effective in reducing SREs.
PATIENTS
A hypothetical group of women meeting the
entry criteria for the two trials.
INTERVENTIONS
Total SREs, including surgery for
pathologic fracture, radiation for fracture or pain control, conservatively
treated pathologic fracture, spinal cord compression, or hypercalcemia, were taken directly from the trials. Using a societal
perspective, direct health-care costs were assigned to each SRE. Each group's
monthly survival was equal and was projected to decline using observed median
survivals. The cost of pamidronate reflected the average wholesale price of the
drug plus infusion. The value or disutility of an adverse event per month was
evaluated using a zero value (events avoided) or an assigned value (range,
0.2-0.8).
MAIN OUTCOME MEASURES
The analysis considered end-points of all
adverse events as well as assigned quality-of-life values for non-fatal
complications. Over a 24-month time horizon, the study projected direct
health-care costs, cost per adverse event avoided. The model's primary
end-points were cost per quality-adjusted life year (QALY).
MAIN RESULTS
The cost of pamidronate therapy exceeded
the cost savings from prevented adverse events. The difference between the
treated and placebo groups was larger with hormonal systemic therapy than with
chemotherapy (additional $7685 compared with $3968 per woman). The projected
net cost per SRE avoided was $3940 with chemotherapy and $9390 with hormonal
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therapy. The
cost-effectiveness ratios were $108,200 with chemotherapy and $305,300 with
hormonal therapy per quality-adjusted year (
Table 1 ).
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TABLE 1 -- Evidence
Table 1 *
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Costs per QALY ($) |
Costs per SRE avoided ($) |
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Base case |
108,200 |
3940 |
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Analytic strategy |
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Combined analysis of
both trials |
175,200 |
5860 |
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Symptomatic events
only (costs and quality of life for asymptomatic fractures excluded) |
134,700 |
3480 |
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Exclude hypercalcemia |
187,900 |
5200 |
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Costs |
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If 50% decrease in
cost of pamidronate ($378) |
Dominant
strategy |
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If decreased to $618 |
50,000 |
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If decreased to $484 |
Equivalent
cost |
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High range of costs
for each adverse event |
Dominant
strategy |
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If no refusals of therapy and
pamidronate continued until death |
122,200 |
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Quality of life/utility values |
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If the duration of
assigned quality of life decrease with each symptomatic adverse event is
doubled |
77,300 |
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If monthly quality of
life with pamidronate is decreased from 1.00 to 0.995 (20% reduction for 1
day) |
134,100 |
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*For the stated purpose
of increasing clarity, only the results of changes in the chemotherapy group
were presented by the authors in the sensitivity analysis. However, data under
'Analytic strategy' were pooled from both studies.
Lower costs and higher
quality-adjusted survival with pamidronate.
CONCLUSION
Although pamidronate is effective in
preventing a feared, common adverse outcome in metastatic breast cancer, its use is associated with high incremental
costs per adverse event avoided. The analysis is most sensitive to the costs of
pamidronate and pathologic fractures that were asymptomatic or treated
conservatively.
Sources of funding: Supported in part by a
Faculty Research Award from the American Cancer Society
Correspondence
to: B.E. Hillner, Virginia Commonwealth University, Box 980170, Richmond, BA
23298-0170 (e-mail: [log in to unmask]).
Martine Extermann MD
H. Lee Moffitt Cancer Center University of South Florida, Tampa, FL, USA
Commentary
Pamidronate has been demonstrated in three studies to reduce
complications from bone metastates in patients with metastatic breast cancer. As a result, pamidronate
is widely used for treating such patients. In their article, Hillner et al
explore the cost-effectiveness of this approach from an American societal
perspective and conclude that this is a costly approach, mostly sensitive to
the cost of pamidronate. This is a well-designed cost-effectiveness analysis,
with clearly stated sources and assumptions. Under a wide range of hypotheses
pamidronate, given in an American setting, has a marginal cost-effectiveness
above that commonly accepted as cost-effective. The authors use hypothetical patients
with a profile similar to those enrolled in two randomized studies. Their cost
calculation is based on a database from their institution and Medicare data.
This is weaker evidence than a direct prospective cost-effectiveness analysis
integrated into the study. However, if carefully conducted, this type of
approach can provide good cost-effectiveness assessments.
Can these results be transferred to other
countries? Not without validation. A Canadian cost utility analysis using similar data
concluded that in the Canadian health system, the marginal cost-effectiveness
of pamidronate was Can$ 18,700 (about US$ 12,700) per QALY gained over 1 year
for chemotherapy-treated patients.[1] This is markedly different from the
results of Hillner et al and falls well within the range of interventions
considered as cost-effective. It is interesting to note that the cost of
pamidronate administration was US$ 406, including infusion costs, compared to
US$ 621 wholesale price for the drug alone in the study of Hillner et al
reflecting major international pricing variations. In another country with a
high cost of living, Switzerland, the authorized retail price for the drug is
US$ 328.[2] The Canadian insurance system is
state-controlled, the Swiss system is private with state control against
medication overpricing, and the American system is private and state without
medication price control. As the authors themselves conclude,
cost-effectiveness considerations alone are unlikely to modify the clinical use
of pamidronate in metastatic breast cancer: pathological fractures are viewed by both
patients and physicians as a distressing event that needs to be avoided as much
as possible. Pamidronate being presently the only FDA-approved biphosphonate in
this indication, we will probably have to wait for future approval of competing
biphosphonates such as clodronate, alendronate or zolendronate before cost
considerations bear weight and can be used as a leverage. The example of the
Canadian and Swiss prices of pamidronate suggests that there may be large room
for maneuver.
Literature cited
1.
Dranitsaris G, Hsu T. Cost utility analysis of prophylactic
pamidronate for the prevention of skeletal related events in patients with
advanced breast cancer. Support Care Cancer 1999; 7: 271-279
Abstract
2.
Compendium Suisse des Medicaments, Documed SA ED, 2000; 21: 165.
CHF 546.65. Exchange rates 3/23/00.
Level and quality of evidence: At
this time the journal is not formally evaluating the quality of economic
analysis due to the lack of acceptable published rank of evidence in this
category.
Edward E.
Rylander, M.D.
Diplomat American
Board of Family Practice.
Diplomat American
Board of Palliative Medicine.