Background: In 1990, annual costs of the diagnosis and
treatment of cancer reached nearly $100 billion and currently constitutes
approximately 10% of health care expenditures in the United States.
As new and often more expensive therapies for cancer treatment become available,
the health care decision-maker must consider the cost effectiveness of
the therapy.
Methods: Key principles of economic analyses and the
inherent differences among these analyses are reviewed.
Results: While pharmacoeconomic analyses are increasingly
being used in treatment decision-making, several issues relating to study
design, data collection, and research methods are controversial.
Conclusions: Pharmacoeconomics analyses are necessary
in the current health care environment, but the assumptions used within
the analyses warrant careful evaluation.
Introduction
As health care expenditures in the United States continue
to increase, many involved in the provision of health care are being asked
to make difficult decisions concerning new interventions in an environment
of limited resources. Economic analysis is a tool that determines the value
(ie, quality divided by cost) of an intervention and is used by those who
are involved in decisions concerning the allocation of limited resources.
It can be used to evaluate many types of interventions, including screening
and diagnostic tests or procedures and medical or surgical interventions.
Pharmacoeconomics refers to the economic analysis of a drug or drug regimen.
In simple terms, pharmacoeconomics is a tool to help health care decision-makers
determine if a drug is "worth the price." In the following article, we
briefly review the economic evaluation of cancer therapies.
Economic Burden of Cancer
The economic burden of cancer is considerable and is
a growing concern to purchasers and payers. The National Cancer Institute
(NCI) estimates that the overall annual costs of cancer diagnosis and treatment
was nearly $100 billion in 1990, a figure that includes $27 billion for
direct medical costs, $10 billion for morbidity costs (cost of lost productivity),
and $59 billion for mortality costs.
1 More recent estimates
suggest that the direct medical costs of cancer in the United States represent
approximately 10% of all health care expenditures, or about $100 billion
each year.
2
Several new cancer therapies have been marketed in
the past few years (Table 1), and numerous promising drugs are being developed
that offer hope for cancer patients. For example, trastuzumab (Herceptin
[Genentech, Inc, San Francisco, Calif]) is a monoclonal antibody that shows
promise in the treatment of metastatic breast cancer in the subset of women
who overexpress the HER2 (human epidermal growth factor 2) oncogene. Two
thrombopoietic growth factors are also being developed: thrombopoietin
(TPO) and pegylated megakaryocyte growth and development factor (peg-rhMGDF).
The availability of some of these new therapies is related in part to new
initiatives by the Food and Drug Administration (FDA) to improve patient
access to promising therapies. Historically, prior to drug approval, the
FDA has required that a manufacturer of a pharmaceutical with antineoplastic
activity prove that the agent demonstrate reasonable safety, efficacy,
and improvements in survival time or quality of life. Unfortunately, this
system often delayed access to potentially life-saving therapies and occasionally
forced American cancer patients to seek alternative therapies available
only outside the United States. In response to these concerns, the FDA
announced in 1996 an initiative to accelerate the approval process. This
initiative allows the FDA to now approve a new pharmaceutical based on
objective evidence of tumor shrinkage and permits the manufacturer to provide
additional evidence of increased survival and/or improved quality of life
associated with that therapy after the marketing of the drug.
Table 1. -- Recently Approved New
Drugs Used in the Treatment of Cancer |
| Drug |
Tradename |
FDA-Approved Indication |
Approval Date |
| Amifostine |
Ethyol |
Prevention of
cisplatin-induced nephrotoxicity |
Dec 1995 |
| Capcitabine |
Xeloda |
Treatment of breast
carcinoma |
April 1998 |
| Carmustine implant |
Gliadel |
Treatment of glioblastoma |
Sept 1996 |
| Dexrazoxane |
Zinecard |
Prevention of
anthracycline-induced cardiomyopathy |
May 1995 |
| Dolasetron |
Anzemet |
Chemotherapy-induced nausea
and vomiting |
Sept 1997 |
| Docetaxel |
Taxotere |
Treatment of breast
carcinoma |
May 1996 |
| Irinotecan |
Camptosar |
Treatment of colorectal
carcinoma |
June 1996 |
| Gemcitabine |
Gemzar |
Treatment of pancreatic
carcinoma |
May 1996 |
| Oprelvekin |
Neumega |
Chemotherapy-induced
thrombocytopenia |
Nov 1997 |
| Rituximab |
Rituxan |
Treatment of
non-Hodgkin’s lymphoma |
Nov 1997 |
| Topotecan |
Hycamtin |
Treatment of ovarian cancer |
May 1996 |
| Tretinoin |
Vesanoid |
Treatment of acute
promyelocytic leukemia |
Nov 1995 |
| Vinorelbine |
Navelbine |
Treatment of non-small cell
lung cancer |
Dec 1994 |
The availability of new and often expensive therapies
presents health care decision-makers with the challenge of determining
the value of the new agents. The Health Services Research Committee of
the American Society of Clinical Oncology (ASCO) recognizes patient outcomes,
particularly survival and quality of life, as important considerations
in assessing the role of a particular therapy.3 The Committee
also included cost effectiveness as an important outcome to consider, particularly
when the benefits of treatment are modest or the costs are high. These
cost-effectiveness analyses can provide oncologists, payers, and purchasers
with a reference point from which to compare the value of different cancer
therapies as well as the value compared to other medical treatments.
Pharmacoeconomic Studies
Economic analysis is a tool to determine the value of
a specific drug or drug regimen. These analyses are particularly important
for expensive agents that can add considerable cost to overall treatment
costs. Few economic analyses of drugs used to treat cancer have been conducted,
and even fewer have been published.
4 Following is a discussion
of key principles of economic analyses and a review of selected published
pharmacoeconomic studies. Reviews of principles of economic evaluation
are published elsewhere.
5-7
Perspective
The perspective (point of view) of the analysis is
important because it determines the types of costs included, the cost of
each resource unit, and, in some instances, which measures of outcomes
are included. The costs of care generally fall into two categories: (1)
health care resources (also referred to as direct medical costs) and (2)
patient and family resources.
The health care resources consumed include the costs
of providing that intervention -- hospitalization, physician visits, procedures,
laboratory tests, nursing home visits, drugs, etc. It includes both fixed
(or overhead) and variable costs. Patient and family resources consumed
include any out-of-pocket expenses incurred by the patient, family members,
or other caregivers, such as transportation costs, meals, and housing,
and the value of their time, including the value of time of the patient
seeking and receiving medical care or of family members serving as caregivers.
The time lost could be from either leisure activities or work.
The societal perspective is the broadest, and studies
conducted from this perspective usually include all costs, regardless of
who incurs them. Some economic analyses may state that the analysis is
conducted from a societal perspective but then omit the cost of patient
or family resources consumed. Although the societal perspective is recommended
by the Public Health Service Panel on Cost-Effectiveness Studies,7
most studies are not conducted from this perspective because of the difficulty
(and expense) associated with measurement of costs other than direct medical
costs.
Most studies are conducted from the payer or provider
perspective, a perspective that usually includes only direct medical costs.
Studies conducted from a provider perspective should be analyzed carefully
because they often include only those consumed by that provider rather
than all health care resources consumed. For example, studies conducted
from the hospital perspective may not include professional fees, outpatient
services, or prescription drugs dispensed outside of the hospital. As health
care becomes more integrated, however, institutions will increasingly be
asked to pay for all of the medical costs of cancer therapy, including
supportive care (growth factors, antiemetics, etc). When a payer perspective
is used, it is important to understand the differences between various
payers. Because cancer is primarily a disease of older adults, Medicare
is a major payer of cancer care in the United States. Therefore, many economic
evaluations of new cancer therapies use cost estimates from Medicare data.
For more than a decade, Medicare has paid a fixed amount for a hospitalization
based on the diagnosis-related group. If a study is conducted from a payer
perspective, and that payer pays a fixed amount per hospitalization, any
changes in the costs that the provider incurred in caring for that patient
would not affect payer costs. However, those changes could determine the
amount of the profit or loss that the provider incurs in providing care
for that patient.
It is important to recognize that outpatient drug
costs may not be included in studies conducted from some perspectives.
For example, only a portion of outpatient drug costs would be included
in studies analyzed from a hospital or health system perspective because
many patients obtain their drugs from their local community pharmacy. Furthermore,
traditional fee-for-service Medicare does not reimburse for the cost of
most orally administered drugs.
Costs
The perspective of the study determines the types
of costs included and the cost for each resource unit. Many issues should
be considered when costs are calculated, including the method used to calculate
costs, whether costs and benefits were discounted, and whether all relevant
costs are included. The length of the study period, or time horizon, should
be considered, particularly for interventions such as high-dose chemotherapy
with stem cell rescue where most of the costs are accrued "up front" but
the benefits are experienced over a lifetime. Although charges and costs
are often used interchangeably, they are clearly not the same.8
Charges are inflated from actual cost and are not comparable among providers.
They are based on other factors such as accounting methodology, payer mix,
and bad debt and are designed to maximize revenues. Charges can be used
as a proxy for costs when all patients are treated in the same institution
by the same group of physicians and when a uniform billing system is used.
Actual charges should not be used as a proxy for costs in multicenter trials
because charges for the same resource vary widely among institutions.
Most published economic analyses are conducted from
either a provider or payer perspective. A payer’s cost is the amount paid
to the provider (eg, hospital, physician) for providing the service. That
amount can vary by payer. For example, a managed care organization may
pay a different amount than Medicare pays for the same intervention. Studies
conducted from a provider perspective require that the actual cost of providing
that service be included. Many institutions, however, either do not know
or are unwilling to share their actual costs. Provider costs vary among
different regions of the United States and also among different health
care systems in the same region. Many studies use the institution’s Medicare
cost-to-charge ratio to estimate cost. Measurement of the actual cost of
physician services can be difficult; how is the actual cost of a physician’s
time calculated in an academic medical center where the physician spends
time in patient care, research, and teaching? In addition, physicians in
private practice also must include overhead expenses into their actual
costs.
Several different methods can be used to calculate
cost. For studies analyzed from a provider perspective, the institution’s
Medicare cost-to-charge ratio is commonly used. Alternatively, one can
use a cost accounting method to calculate provider cost. The institution’s
cost-to-charge ratio is based on a number of factors such as the utilization
rate of equipment used for a specific procedure, the payer mix, and reimbursement
policies for that procedure. Some payers limit treatment to selected centers
("centers of excellence") to decrease costs and to ensure quality. As centers
treat more patients, the utilization rate of equipment increases. Thus,
these fixed costs are spread out over a larger number of patients, which
increases the efficiency of those centers. In addition, allocation of overhead
varies from hospital to hospital and may not be indicative of actual resource
use.
Two methods are generally used to calculate costs
for studies analyzed from a payer perspective. One widely used method is
to collect resource units (hospital days, ICU days, etc) and convert them
to costs by multiplying each unit by the amount reimbursed by a payer.
When the payer is Medicare, data can be obtained from the Health Care Financing
Administration (ie, MEDPAR). For nongovernment payers, data can be obtained
from the payers themselves, from providers, or from health care information
companies. Another method is to use the actual amount reimbursed (based
on bills), which can vary depending on the payer.
The study should include all relevant costs appropriate
for that specific perspective. Studies analyzed from a hospital or health-system
perspective often do not include the cost of physician visits or outpatient
care provided after patients are discharged from the treatment center.
When not all costs are included, the impact of these omissions on the results
of the study should be considered.
Once costs have been determined, it may be necessary
to adjust costs and benefits to present value -- a procedure referred to
as discounting. Costs and benefits need to be discounted if the
time horizon of the study is longer than one year. All values must be in
the same time period to compare alternatives. This incorporates the economic
concept of time preference. Briefly, this concept states that, even
in a world with zero inflation and no bank interest, most individuals would
prefer to receive a benefit earlier or to incur a cost later because it
gives the individual more options. If the costs or benefits are incurred
or accrued more than one year in the future, then they need to be adjusted
to present value. Various methods can be used for this adjustment, including
the institution’s yearly charge inflation rate, rate of inflation as estimated
by the Consumer Price Index for Hospitalization Costs, or Consumer Price
Indices for Medical Care. Many studies use a discount rate of 5%, although
the recently published Public Health Service guidelines recommend that
a discount rate of 3% be used.7
Study Types
An understanding of the different types of economic
analyses is important because many studies do not correctly use economic
terms.
9
Cost-Minimization Analysis
The simplest form of economic analysis is the cost-minimization
analysis. In this type of study, costs are expressed in monetary units
(eg, dollars), and patient outcome is assumed to be the same in both groups.
Thus, a cost-minimization analysis is actually a special form of cost-effectiveness
analysis where the consequences of the alternatives being compared are
equivalent. The objective of this type of analysis is to identify the least
expensive alternative.
Cost-Effectiveness Analysis
In a cost-effectiveness analysis, costs are expressed
in the numerator in monetary units (eg, dollars), and effectiveness is
expressed in the denominator in some unit of effectiveness. The units are
usually the same as those clinical outcomes used to measure effectiveness
in clinical trials or practice. When comparing two or more alternative
interventions, the analyst will select a common clinical outcome.
A disadvantage in a cost-effectiveness analysis is
that a comparison of results is difficult when effectiveness is expressed
in different units. As a result, medical interventions used to treat different
diseases often cannot be compared with each other when decision-makers
are trying to allocate resources. This can be particularly problematic
when the interventions do not prolong life. When the intervention prolongs
life, the most appropriate measure is life-years gained or saved. For example,
when comparing two alternative cancer therapies, the difference in survival
between the two therapies is often the focus of interest. In that situation,
investigators involved in the economic evaluation determine the differences
in average cost and survival (average number of life-years gained or saved)
between the two interventions. The differences in cost and survival between
the two interventions is expressed as a cost-effectiveness ratio, with
the difference in cost in the numerator and the difference in survival
in the denominator.
Health care decision-makers can use cost-effectiveness
analyses to compare different interventions to determine which intervention
will result in the most life-years gained for a given dollar value. However,
even this approach has its limitations because it does not incorporate
all aspects that may be important to the physician and the patient such
as utility (ie, patient preference).
Cost-Utility Analysis
Cost-utility analysis is a specific type of cost-effectiveness
analysis in which utility is measured and the units of effectiveness are
quality-adjusted life-years (QALYs). The major advantage of using QALY
as an outcome measure is that it incorporates changes in both quantity
(mortality) and quality (morbidity) of life. With this type of analysis,
new therapies that greatly reduce morbidity can increase the number of
QALYs even without an increase in survival time. The major disadvantage
of cost-utility analyses is that utility data are not usually collected
in clinical trials because of the additional costs of the data collection
and the complex nature of the methods used in utility assessments.
Utility scores measure the strength of a patient’s
preference for a given health state or outcome.10,11 Although
values, preferences, and utilities are terms that
are often used interchangeably, values reflect preferences without risk
(or uncertainty), while utilities reflect preferences with risk. The utility
approach assigns numerical values on a scale from 0 (death) to 1 (optimal
or "perfect" health). It provides a single number that summarizes all of
health-related quality of life; some researchers have described utility
as a global measure of health-related quality.
Several techniques can be used in utility assessment.
Two techniques derived from utility theory are standard gamble and time
tradeoff. Because of their complexity, some researchers prefer to use rating
scales and multi-attribute techniques to measure patient preferences. Examples
of generic preference-based approaches include the Health Utilities Index,
Quality of Well-Being Scale, and Disability/Distress Index. Utility approaches
are particularly useful in pharmacoeconomic studies because they provide
a single summary score of the net change in health-related quality of life
-- the gains from the positive effects of treatment minus the burden of
adverse effects.
Cost-utility analysis is a valuable technique to
evaluate new chemotherapeutic regimens that offer some treatment benefit
but do not prolong survival in comparison with other therapeutic options.
This type of analysis is particularly important with cancer therapies because
they are often associated with potentially serious or intolerable adverse
effects. Cost-utility analysis is also attractive because it is similar
to the approach that many oncologists use when discussing treatment options
with their patients. Tradeoffs between the potential benefits of
treatment vs the burdens of treatment-related adverse effects are always
considered by both the patient and oncologist in decisions concerning treatment.
Cost-Benefit Analysis
In a cost-benefit analysis, both cost and benefits
are expressed in the same units, usually monetary units (eg, dollars).
In a cost-benefit analysis, all health benefits such as disability days
avoided, life-years gained, and medical complications avoided would be
translated into monetary units. While theoretically attractive, it is often
difficult to determine the cost of health benefits in a cost-benefit analysis.
For example, what dollar value is assigned to a life-year gained for a
homeless person or a homemaker? This type of analysis is therefore not
widely used in the economic analysis of drugs or technology.
Interpretation of Pharmacoeconomic Studies
Interventions do not have to be cost saving (ie, reduce
health care cost) to be cost effective. Most medical interventions that
are of benefit will increase cost. When an intervention is considered to
be cost effective, it implies that the therapeutic benefit of that intervention
is worth the cost.
Since economic analyses are often used to assist
decision-makers in making policy decisions concerning adoption of that
technology in a population, there must be some consensus as to what constitutes
a "cost-effective intervention." In the United States, interventions that
prolong life and have a cost-effectiveness ratio in the range of $50,000
per life year gained are generally considered to be cost effective. This
value of $50,000 is considered by many experts as a societal benchmark
because it represents the additional cost of dialysis (covered by Medicare)
compared with no treatment in patients with end-stage renal disease.
Pharmacoeconomic studies must be critically analyzed
because of the nature of economic analyses and because most studies are
funded by the pharmaceutical industry. Table 2 shows a checklist that can
be used to assess economic evaluations. Most economic evaluations use data
from multiple sources, require that many assumptions be made, and use some
modeling. As a result, investigators may influence the study design, data
sources, or underlying assumptions in order to achieve results that are
positive for the sponsor’s product.12 Because decision-makers
often lack the necessary knowledge and background to critically analyze
pharmacoeconomic studies, the results of studies that are scientifically
flawed or biased are sometimes used to make decisions or policies. Because
of the perceptions of bias, some journals have specific policies for publication
of pharmacoeconomic studies.13
Table 2. -- Checklist for Assessing Economic
Evaluations |
| 1. Was a well-defined question posed in answerable form? |
| 2. Was a comprehensive description of the competing
alternatives given (ie, can you tell who did what to whom, where, and how often)? |
| 3. Was the effectiveness of the programs or services
established? |
| 4. Were all the important and relevant costs and
consequences for each alternative identified? |
| 5. Were costs and consequences measured accurately in
appropriate physical units (eg, hours of nursing time, number of physician visits, lost
work-days, gained life-years)? |
| 6. Were costs and consequences valued credibly? |
| 7. Were costs and consequences adjusted for differential
timing? |
| 8. Was an incremental analysis of costs and consequences
of alternatives performed? |
| 9. Was allowance made for uncertainty in the estimates of
costs and consequences? |
| 10. Did the presentation and discussion of study results
include all issues of concern to users? |
| |
| Adapted from Drummond et al.5 |
Economic analyses usually compare two or more interventions.
In many analyses, the investigators select the "comparator" and make assumptions
concerning clinical practices. The comparator and the assumptions in the
study must be carefully evaluated. For example, treatment with a new anticancer
drug may be reported as cost effective when compared with best supportive
care. In the United States, however, best supportive care is not usually
the community standard because most patients expect or demand some form
of therapy. The most appropriate comparator to use in most analyses is
another anticancer drug or drug regimen. Similarly, it is important to
carefully evaluate other assumptions in the analysis, such as drug dose,
dose schedule, duration of infusion, and use of supportive care drugs (eg,
antiemetics and growth factors).
For pharmacoeconomic studies that use economic modeling,
it is important not only to ensure that the study includes a sensitivity
analysis, but also to carefully evaluate that analysis. A sensitivity analysis
tests the robustness of the results by modifying the assumptions in various
scenarios. Sensitivity analysis allows the analyst to ask a variety of
"what if" questions, which is important for economic analyses due to the
many assumptions that often have to be made. It identifies the variables
that drive the analysis. More confidence is given to a conclusion that
is "robust" when subjected to different scenarios.
For economic analyses of new drugs, the acquisition
cost of the new drug can be varied in the sensitivity analysis. Since the
acquisition cost varies considerably, many pharmacoeconomic studies use
the average wholesale price, which is usually higher than the actual acquisition
cost. If the drug is investigational, the analyst can evaluate the effect
of different acquisition costs on the results.
Sensitivity analysis also allows the analyst to determine
the cost-effectiveness of a new drug or intervention in different subsets
of patients. Health care decision-makers use this type of analysis to determine
which patients should receive the new drug or intervention.
Economic Evaluation of Cancer Treatment
Clinical oncology researchers and the FDA have traditionally
demanded objective evidence of antitumor response for new cancer therapies.
We often assume that cancer patients have the same preferences as the health
care professionals caring for them -- that they value cure more highly
than prolonged survival and value prolonged survival more highly than tumor
shrinkage (Figure). Even if we assume that cancer patients would value
prolonged survival over tumor shrinkage, we do not know how
much
more they would value one outcome over another. Although relief of symptoms
clearly has a beneficial impact on a patient’s health-related quality of
life, we do not know how patients would value relief of symptoms as a therapeutic
goal as compared with more objective endpoints, such as tumor shrinkage
or prolonged survival. In one study conducted in the United Kingdom, many
cancer patients were willing to accept the adverse effects associated with
an intensive chemotherapy regimen for the potential benefit of relief of
symptoms.
14 In contrast, only a small percentage of the individuals
without cancer (control group), oncology nurses, general practitioners,
or oncology physicians were willing to accept that treatment under the
identical scenario. We also do not know what factors influence those preferences.
For example, we expect that the severity of the treatment-related toxicities
would influence cancer patient’s preferences for a specific therapy. Similarly,
we expect that the magnitude of the treatment benefit, such as the degree
of tumor shrinkage or the duration of the survival benefit, would influence
a patient’s preferences.
Cost-Minimization Analyses
Cost-minimization analyses are useful when a drug reduces
the risk of a clinical event associated with significant resource utilization,
such as febrile neutropenia. The additional cost are the costs of the more
expensive drug (or drug regimen), drug administration, drug monitoring,
adverse effects, etc, and the benefits are the "downstream" cost savings
(sometimes referred to as costs offsets) associated with fewer clinical
events.
Cost-minimization analyses have been conducted to
evaluate the economic benefit of filgrastim-mobilized peripheral-blood
progenitor-cell (PBPC) transplantation over autologous bone marrow transplantation
(ABMT). These studies show that the high initial cost of growth factors
for PBPC mobilization are more than offset by the "downstream" cost savings
that result from shorter hospital stay and decreased use of health care
resources such as drugs, blood products, physician visits, hyperalimentation,
and laboratory and diagnostic tests.
Several clinical trials have reported that hematopoietic
recovery, particularly platelet recovery, is more rapid in patients who
receive PBPC transplants than in those who have undergone ABMT.15,16
A concurrent economic analysis was performed prospectively as part of one
of these studies.17 Resource utilization data were converted
to costs based on the cost of each resource unit at an academic medical
center in the United States. The analysis divided treatment into three
phases: (1) stem cell collection, (2) high-dose chemotherapy (HDC) administration,
and (3) recovery until discharge. The total cost included all direct medical
costs of HDC, beginning with the cost of stem cell collection and continuing
until patients were discharged after the initial hospital stay. Overall,
the total cost of HDC was $14,000 less in the PBPC group than in the ABMT
group. Most of the cost savings occurred during the hospitalization phase
($10,740 less in the PBPC group), which was primarily related to the more
rapid hematologic recovery in the PBPC arm. Furthermore, a shorter hospital
course resulted in savings due to decreased use of drugs, blood products,
physician visits, hyperalimentation, and laboratory and diagnostic tests.
Cost-Effectiveness Analyses
Cost-effectiveness analyses are useful in evaluating
various therapeutic modalities that prolong survival in patients with cancer
(Table 3). In the treatment of breast cancer, cost-effectiveness analyses
have evaluated the role of adjuvant therapy in various subgroups of women
and the role of HDC in women with metastatic disease.
Table 3. -- Cost-Effectiveness of
Cancer Treatment4,18-22 |
| Intervention |
Incremental CE Ratio* |
| Autologous bone marrow transplantation vs standard chemotherapy for
limited metastatic breast cancer |
116,000 |
| Adjuvant tamoxifen for early-stage breast cancer (premenopausal ER-
woman) |
57,000-214,000 |
| Adjuvant chemotherapy for early-stage breast cancer (75-year-old woman) |
44,000 |
| Adjuvant interferon alfa-2b for high-risk malignant melanoma |
32,600 |
| Autologous bone marrow transplantation vs salvage chemotherapy for
Hodgkin’s disease (second relapse only) |
26,200 |
| Paclitaxel + cisplatin vs cyclophosphamide + cisplatin for advanced
ovarian cancer |
21,222 |
| Vinorelbine + cisplatin vs vindesine + cisplatin for non-small cell
lung cancer |
15,500 |
| Adjuvant chemotherapy vs no treatment for node-negative, early-stage
breast cancer (45-year-old woman) |
15,400 |
| Adjuvant chemotherapy vs no treatment for early-stage breast cancer
(45-year-old woman) |
4,900 |
| |
| * Cost-effectiveness (CE) ratio is expressed as dollars
(US) per life year gained or quality-adjusted life year. |
In 1991, Hillner and Smith18 evaluated
the cost effectiveness of adjuvant chemotherapy in women with node-negative
breast cancer. The analysis was initiated based on a Clinical Alert in
1988 by the NCI that stated that "chemotherapy can have a meaningful impact
on the natural history of node-negative breast cancer patients." This statement
was interpreted by many clinicians at the time as a recommendation for
adjuvant therapy in these women. Implementation of this approach was estimated
to cost $338 million for the entire group of such patients in the United
States. Using the best data available in 1989, the investigators developed
a decision analytic model that incorporated the natural history of node-negative
breast cancer, effect and toxicity of chemotherapy, and costs of treatment.
In the hypothetical cohort, the patient was either a 45-year-old woman
or a 60-year-old woman who had undergone surgery for stage I or II breast
cancer that was node negative and estrogen-receptor negative. Using a five-year
time horizon, the authors estimated that the cost-effectiveness ratio for
adjuvant chemotherapy was $15,400 per QALY in the 45-year-old cohort and
$18,800 per QALY in the 60-year-old cohort.
HDC with autologous hematopoietic stem cell rescue
has become a widely utilized treatment option for many women with breast
cancer and has been associated with increased long-term survival. Unfortunately,
this procedure is expensive with estimated charges ranging between $75,000
and $150,000 for ABMT. As a result, insurers are sometimes reluctant to
approve payment for HDC, often claiming that the therapy is experimental.
In an effort to assist policy-makers with their decision to cover the cost
of HDC, Hillner and colleagues19 published a cost-effectiveness
analysis. The researchers developed a decision analysis model that compared
HDC with ABMT vs standard-dose chemotherapy in an attempt to determine
the optimal approach for treatment of early metastatic breast cancer and
the associated cost effectiveness. The cost effectiveness of HDC with ABMT
depends on the magnitude of the difference in survival. If the difference
is small (eg, only a few months), HDC is not likely to be cost effective.
However, if the difference is large and if there is evidence of a survival
plateau (which may indicate that some patients have been cured), HDC is
likely to be cost effective and may even be considered the treatment of
choice. The hypothetical cohort in the analysis was a 45-year-old patient
with stage IV breast cancer. She was unresponsive to hormonal therapy and
had no bone marrow involvement or comorbidities. The cost of HDC was estimated
to be more than $50,000 higher than that of standard chemotherapy ($89,700
vs $36,100). On the basis of a review of the medical literature, the authors
concluded that the average survival benefit with HDC was 6.0 months (5-year
time horizon). The incremental cost-effectiveness ratio of HDC was $115,800
per life-year gained (5-year time horizon, costs and benefits discounted
at 5%). The model was sensitive to assumptions about long-term survival.
When a survival tail was assumed (patients who were free of disease at
5 years would have a normal life expectancy), the incremental cost-effectiveness
ratio decreased to $28,600 per life-year gained.
The costs of HDC in this analysis were estimated
from charges for a small number of patients treated at their medical center
in 1990, before hematopoietic growth factors were commercially available
and PBPCs were widely used. They also analyzed how the cost-effectiveness
ratio would change with routine administration of hematopoietic growth
factors and PBPC transplantation. For this analysis, the researchers made
three assumptions: the duration of hospitalization would decrease from
40 to 30 days, the total cost of HDC would decrease to $60,000, and the
treatment-related mortality rate would decrease to 3%. It is important
to note that with the routine use of growth factors and PBPCs, all three
assumptions are true today. With these assumptions considered, the incremental
cost-effectiveness ratio would decrease from $115,800 to $48,700 per life-year
gained, even without changes in the average survival benefit.
Cost-effectiveness analyses can also determine the
value of an intervention when long-term survival or cure is not an anticipated
outcome (Table 3). Examples of these interventions include vinorelbine
in non-small-cell lung cancer,20 paclitaxel and cisplatin in
recurrent epithelial ovarian carcinoma,21 and adjuvant interferon
alfa-2b in high-risk malignant melanoma.22
Cost-Utility Analyses
Although cost-utility analyses are valuable techniques
to evaluate new chemotherapeutic regimens, few such analyses have been
published. Hutton et al23 recently reported a cost-utility analysis
of