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(Drug information on filgrastim), Neupogen), yeast-derived granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim(Drug information on sargramostim), Leukine), and erythropoietin(Drug information on erythropoietin) (EPO, epoetin alfa(Drug information on 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.
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 studies, 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 studies, 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.
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.