Economic Outcomes Associated With Hematopoietic Growth Factors

Economic Outcomes Associated With Hematopoietic Growth Factors

ABSTRACT: The myeloid growth factors G-CSF and GM-CSF have had an impact on the supportive care of cancer patients as well as on the strategies utilized in chemotherapy dose intensification. Therapy with these factors has not been associated with improvements in survival, and hence an examination of their effects on economic outcomes is central to rational decision making regarding their use. Erythropoietin therapy has been shown to decrease transfusion requirements in anemic cancer patients undergoing chemotherapy and to improve the quality of life in responding patients. The available data on the economic outcomes associated with the use of these three factors in oncology practice are reviewed. [ONCOLOGY 9(Suppl):93-105, 1995]


Escalating health care costs mandate that a rigorous assessment
of economic outcomes be included in the overall evaluation of
a new technology. At the same time, the effect of a new treatment
on the quality of life of cancer patients is increasingly recognized
as a legitimate goal of treatment and an important outcome to
consider in the overall assessment of the costs and benefits of
a new therapy. Because it is likely that, with time, the results
of these two less traditional outcome analyses in oncology will
increasingly guide clinical decision making, it is important that
they accurately reflect the true impact of the technology in community
practice and that clinicians fully understand the methodologies
involved in these analyses and their findings.

The hematopoietic growth factors are a class of glycoproteins
involved in the regulation of hematopoiesis and mature effector
cell function. The recombinant human forms of three of these factors-granulocyte
colony-stimulating factor (G-CSF, filgrastim, Neupogen), yeast-derived
granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim,
Leukine), and erythropoietin (EPO, epoetin alfa, Epogen, Procrit)-have
shown sufficient efficacy in clinical trials to be approved for
community use in oncology practice in the United States. While
all three factors have shown significant efficacy in the supportive
care of oncology patients in various clinical settings, none has
been shown to increase survival or tumor response rates; hence,
economic and quality of life outcome assessments have become particularly
important components of the overall assessment of these new technologies.

Unfortunately, there are relatively few directly measured data
available regarding the economic or quality of life impacts of
any of these factors, and the available analyses are based largely
upon assumptions drawn from the clinical effects measured directly
in randomized clinical trials. For G-CSF and GM-CSF, some directly
measured data regarding impact on health care charges are available,
but few data are available regarding the effects of these factors
on the quality of life of the cancer patient. For EPO the situation
is reversed: The impacts of this factor on the quality of life
of the cancer patient have been directly measured in both phase
III and phase IV studies, but there are no published data regarding
the economic impact of the use of this factor in oncology practice.

Perspective, Scope, and Types of Economic

In approaching the study of the economic outcomes of relatively
expensive new drugs such as the hematopoietic growth factors,
it is important to state clearly the perspective and scope of
the analysis. While cost studies focused on a particular component
of the health care system, such as the hospital pharmacy, are
important for budgeting purposes, the results of these studies
cannot be used to estimate the true cost impact of the new technology
or to support responsible clinical decision making. For these
purposes, the perspective of the cost analysis should be the health
care system or society as a whole, and the scope of the analysis
should include all the costs, both direct and indirect, associated
with the new therapy, including the treatment of any drug-related
toxicities and all of the direct and indirect costs that the new
therapy eliminates.

Studies such as these, which compare the health care costs associated
with two alternative approaches to treatment, are termed cost-minimization
, and are typically utilized when the two approaches
yield equivalent clinical outcomes such as tumor response rates
and survival. If a cost-minimization analysis shows that the new
therapy is associated with increased overall costs, decisions
regarding its use will then depend upon which outcomes, if any,
are improved. In these broader scope analyses, termed cost-benefit
, the increased costs associated with the new treatment
are balanced against improvements in nonclinical outcomes such
as improved quality of life, improved functional status, and decreased
indirect costs, including lost days from work.

The hematopoietic growth factors are unique new technologies in
that they are applied to a broad spectrum of patients at varying
risks for the complications they may prevent, such as febrile
neutropenia, prolonged hospitalization, and red blood cell transfusions.
These complications have associated costs, and the initial question
about economic impact focuses on to what extent the savings associated
with preventing these complications offset the cost of the growth
factor. These cost offsets will depend, in part, upon the risk
of the prevented complication in that subset of patients.

Figure 1 presents the results of a hypothetical cost-minimization
study for a hematopoietic growth factor. In this example, as the
risk of a preventable complication, such as severe anemia or febrile
neutropenia, increases (as the magnitude of the efficiency variable
rises), the efficiency of the use of the factor increases and
the cost offsets associated with its use increase. At the threshold
value of the efficiency variable, these offsets fully cover the
cost of the factor, and at higher values, the use of the factor
becomes cost saving.

Cost-minimization studies such as these are an important first
step in the economic evaluation of the growth factor. They provide
two useful pieces of information: First, these studies suggest
that in select subgroups of patients, the use of the growth factor
can be justified on the basis of direct cost savings alone. Second,
they provide estimates of the magnitude of the increase in direct
health care expenditures associated with growth factor therapy
in the remaining subgroups of patients. These estimates can be
used in future cost-benefit analyses that take into account any
additional benefits of therapy with the growth factor, such as
improved quality of life or decreased indirect costs to the health
care system or society.

This paper will review the published data regarding the economic
impacts of the hematopoietic growth factors in oncology practice.
It will include a brief description of the seminal randomized
clinical trials, with an emphasis on their implications for economic
analyses, followed by a synopsis of the available cost-minimization
and quality of life studies of the use of these factors in the
treatment of cancer. Finally, this paper will summarize our current
understanding of the cost-benefit balance for these factors and
point out gaps in the data where further studies are needed for
a more mature assessment of the impact of these agents.

The Clinical Trials

Any cost assessment of hematopoietic growth factors must begin
with a review of the state of knowledge regarding the technical
aspects of their use, such as dose and schedule, clinical efficacy,
and toxicities. For obvious reasons, the review should focus on
randomized, controlled clinical trials, to ensure that any effects
attributed to the growth factors are actually associated with
their use. As will be seen, randomized clinical trials designed
to demonstrate clinical efficacy usually do not define the optimal
cost-effective use. Still, these studies are a necessary and important
starting point for economic analyses.

The Myeloid Growth Factors in Cancer Treatment

There are three distinct rationales for the use of myeloid growth
factors in the care of the cancer patient. The first is as part
of supportive care during chemotherapy given at standard doses.
In this approach, the goal of growth factor therapy is to decrease
the duration or severity of neutropenia and thereby decrease the
incidence of serious infections. In studies done to date, the
risk of infections has been estimated by measuring the incidence
of febrile neutropenia. While much remains to be learned about
this supportive care application, it is best characterized from
both a clinical and a cost standpoint.

The second rationale is the facilitation of chemotherapy dose
intensification, with or without the use of autologous hematopoietic
progenitor cells. In this approach, the goal of growth factor
therapy is to increase the dose intensity of the administered
chemotherapy and thereby improve tumor outcomes. Because the efficacy
of dose intensification in improving tumor outcomes is likely
to vary with tumor type and stage of disease, and because the
demonstration of improvement in survival requires large studies
of long duration that have not yet been completed, this is the
most difficult application of hematopoietic growth factors to
fully analyze from a cost-benefit standpoint.

The third rationale is the treatment of established infection
in patients who are neutropenic following myelosuppressive chemotherapy.
In this approach, the goal of growth factor therapy is to decrease
the duration of febrile neutropenia and, hence, to decrease the
cost of caring for these patients. The appropriate clinical trial,
and type and scope of cost analysis, depends upon the rationale
and goals of myeloid growth factor therapy. Table 1 lists the
three rationales for myeloid growth factor therapy and their implications
for clinical trials and cost analyses.


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