Patients at Risk for Severe Neutropenia From Cancer Chemotherapy
Patients at Risk for Severe Neutropenia From Cancer Chemotherapy
Study Objectives: Previous studies have used direct hospital costs to determine the threshold at which the cost of prophylactic use of colony-stimulating factor (CSF) is offset by savings from the lower risk of hospitalization for febrile neutropenia. By conducting a survey of patients in whom febrile neutropenia had developed during treatment with chemotherapy, we sought to reassess these costs by including estimates of indirect costs associated with febrile neutropenia as well as new categories of direct costs that were not previously available. Costs were included in an existing cost-minimization model, and their effect on the risk threshold at which the prophylactic use of CSF becomes cost saving was determined.
Patients: A sample survey of 26 patients with ovarian cancer who were treated with chemotherapy and developed febrile neutropenia.
Intervention: Analysis of data from patients' questionnaires containing survey items on indirect costs and additional direct costs associated with febrile neutropenia.
Measurements and Main Results: Estimates of indirect costs and other direct costs from the questionnaires were included in an existing cost-minimization model, and risk thresholds were recalculated. Before modification, the model showed cost neutrality for prophylactic use of CSF when the risk of hospitalization for febrile neutropenia was approximately 23%. Including previously excluded direct costs and indirect costs ranging from $1000-5000 attributable to severe neutropenia in the model lowered the risk threshold for hospitalization for febrile neutropenia at which the prophylactic use of CSF becomes cost neutral to between 22% and 18%.
Conclusion: Including additional direct as well as indirect costs associated with chemotherapy-induced neutropenia permits a more realistic assessment of the possible effect of prophylactic use of CSF from a societal perspective. Despite the limited size of the survey, this study shows a cost-benefit rationale to support prophylactic use of CSF in a greater proportion of patients treated with chemotherapy.
Chemotherapy-induced neutropenia, one of the most common toxic effects of cancer chemotherapy, can lead to febrile neutropenia and frequently results in delays or reductions in chemotherapy doses, which may compromise outcomes. Prophylactic use of colony-stimulating factor (CSF) can reduce the frequency and severity of chemotherapy-induced neutropenia and the risk of infection and hospitalization for febrile neutropenia. Despite the benefits of CSFs in the management of chemotherapy-induced neutropenia, they are not routinely administered prophylactically to patients with cancer who receive myelosuppressive chemotherapy because of the costs associated with them.
Economic cost-minimization models, which are used to determine the most cost-effective treatment among different equivalent alternatives, have estimated the threshold for the risk of hospitalization due to febrile neutropenia at which prophylactic use of CSF becomes cost saving. These models have been based exclusively on economic criteria and have not considered any difference between administration of CSF and no therapy; they have been based on the risk of febrile neutropenia and the efficacy of CSFs in randomized clinical trials and the direct costs of hospitalization for febrile neutropenia. These models have also assumed that all patients with febrile neutropenia were hospitalized and treated with intravenous antibiotics.
The costs used in our model were the direct costs associated with hospitalization for febrile neutropenia and the total cost of prophylactic CSF use, including the costs of the agent and its administration. Sensitivity analyses have shown that the total cost of treatment for febrile neutropenia increases as the risk for febrile neutropenia increases, and these costs increase more rapidly in patients not treated with CSF. Based on the original estimated direct cost of hospitalization of $1000/day, the reduction of cost of hospitalization with the use of prophylactic CSF equals the cost of the CSF when the risk of febrile neutropenia is 40%. When the risk of hospitalization for febrile neutropenia exceeds 40%, the prophylactic use of CSF reduces the overall costs. Below this risk threshold, CSF administration increases the costs of treatment (Figure 1). This 40% value was used to support the current guidelines of the American Society of Clinical Oncology for prophylactic use of CSF. These guidelines support the use of prophylactic CSF when the chemotherapy regimen is associated with a risk of febrile neutropenia of 40% or higher.
(Enlarge Image)
Cost-minimization model based on direct hospitalization costs for deriving risk thresholds for cost reductions with prophylactic colony-stimulating factor (CSF). The initial model used $1000/day; an updated analysis used $1750/day. (Adapted with permission from reference 12.)
In an updated economic analysis that used more current and inclusive fixed and variable direct costs of hospitalization of $1750/day, the risk threshold for cost reductions with prophylactic CSF was lowered to approximately 23% (Figure 1). Similar risk thresholds were obtained when estimates of the risk of febrile neutropenia and the efficacy of CSF were determined in a recent meta-analysis of data from randomized clinical trials of prophylactic use of CSF.
Estimating expenditures additional to the cost of hospitalization from the societal perspective is more inclusive, attempting to include all expenses borne by everyone affected by the treatment process. Since this perspective encompasses the category of indirect or productivity costs, it is arguably the most appropriate one to use in public health. With this perspective, important differences in the outcome of such decisions are often revealed.
Indirect costs are divided into two categories: morbidity costs -- those associated with lost or impaired ability to work -- and mortality costs -- those associated with lost productivity due to premature death. Indirect costs can be difficult to measure; they usually require detailed patient or employer surveys of changes in work patterns.
The additional indirect costs associated with cancer and its treatment are a substantial portion of the economic burden of the disease. One study estimated these costs to be more than 71% of the total cost of cancer care. Direct costs of cancer care account for approximately 5% of total health care expenditures in the United States. However, when indirect costs are included, total costs of cancer care account for approximately 20% of all U.S. health care spending.
In this study, we evaluated the effect of including, in a cost-minimization model that previously used only the direct costs of hospitalization, the indirect costs attributable to chemotherapy-induced neutropenia. We also incorporated into this model additional direct costs, such as costs associated with laboratory work and drugs prescribed, that were not captured in the earlier analysis. These additional direct costs did not include any costs incurred outside hospital-based care. Our objective was to determine whether this approach might produce a lower threshold for the risk of hospitalization for febrile neutropenia at which prophylactic use of CSF becomes cost saving. Such an outcome would indicate that from a societal perspective of economic considerations, a greater proportion of patients with cancer who receive chemotherapy would be appropriate candidates for CSF prophylaxis.
Study Objectives: Previous studies have used direct hospital costs to determine the threshold at which the cost of prophylactic use of colony-stimulating factor (CSF) is offset by savings from the lower risk of hospitalization for febrile neutropenia. By conducting a survey of patients in whom febrile neutropenia had developed during treatment with chemotherapy, we sought to reassess these costs by including estimates of indirect costs associated with febrile neutropenia as well as new categories of direct costs that were not previously available. Costs were included in an existing cost-minimization model, and their effect on the risk threshold at which the prophylactic use of CSF becomes cost saving was determined.
Patients: A sample survey of 26 patients with ovarian cancer who were treated with chemotherapy and developed febrile neutropenia.
Intervention: Analysis of data from patients' questionnaires containing survey items on indirect costs and additional direct costs associated with febrile neutropenia.
Measurements and Main Results: Estimates of indirect costs and other direct costs from the questionnaires were included in an existing cost-minimization model, and risk thresholds were recalculated. Before modification, the model showed cost neutrality for prophylactic use of CSF when the risk of hospitalization for febrile neutropenia was approximately 23%. Including previously excluded direct costs and indirect costs ranging from $1000-5000 attributable to severe neutropenia in the model lowered the risk threshold for hospitalization for febrile neutropenia at which the prophylactic use of CSF becomes cost neutral to between 22% and 18%.
Conclusion: Including additional direct as well as indirect costs associated with chemotherapy-induced neutropenia permits a more realistic assessment of the possible effect of prophylactic use of CSF from a societal perspective. Despite the limited size of the survey, this study shows a cost-benefit rationale to support prophylactic use of CSF in a greater proportion of patients treated with chemotherapy.
Chemotherapy-induced neutropenia, one of the most common toxic effects of cancer chemotherapy, can lead to febrile neutropenia and frequently results in delays or reductions in chemotherapy doses, which may compromise outcomes. Prophylactic use of colony-stimulating factor (CSF) can reduce the frequency and severity of chemotherapy-induced neutropenia and the risk of infection and hospitalization for febrile neutropenia. Despite the benefits of CSFs in the management of chemotherapy-induced neutropenia, they are not routinely administered prophylactically to patients with cancer who receive myelosuppressive chemotherapy because of the costs associated with them.
Economic cost-minimization models, which are used to determine the most cost-effective treatment among different equivalent alternatives, have estimated the threshold for the risk of hospitalization due to febrile neutropenia at which prophylactic use of CSF becomes cost saving. These models have been based exclusively on economic criteria and have not considered any difference between administration of CSF and no therapy; they have been based on the risk of febrile neutropenia and the efficacy of CSFs in randomized clinical trials and the direct costs of hospitalization for febrile neutropenia. These models have also assumed that all patients with febrile neutropenia were hospitalized and treated with intravenous antibiotics.
The costs used in our model were the direct costs associated with hospitalization for febrile neutropenia and the total cost of prophylactic CSF use, including the costs of the agent and its administration. Sensitivity analyses have shown that the total cost of treatment for febrile neutropenia increases as the risk for febrile neutropenia increases, and these costs increase more rapidly in patients not treated with CSF. Based on the original estimated direct cost of hospitalization of $1000/day, the reduction of cost of hospitalization with the use of prophylactic CSF equals the cost of the CSF when the risk of febrile neutropenia is 40%. When the risk of hospitalization for febrile neutropenia exceeds 40%, the prophylactic use of CSF reduces the overall costs. Below this risk threshold, CSF administration increases the costs of treatment (Figure 1). This 40% value was used to support the current guidelines of the American Society of Clinical Oncology for prophylactic use of CSF. These guidelines support the use of prophylactic CSF when the chemotherapy regimen is associated with a risk of febrile neutropenia of 40% or higher.
(Enlarge Image)
Cost-minimization model based on direct hospitalization costs for deriving risk thresholds for cost reductions with prophylactic colony-stimulating factor (CSF). The initial model used $1000/day; an updated analysis used $1750/day. (Adapted with permission from reference 12.)
In an updated economic analysis that used more current and inclusive fixed and variable direct costs of hospitalization of $1750/day, the risk threshold for cost reductions with prophylactic CSF was lowered to approximately 23% (Figure 1). Similar risk thresholds were obtained when estimates of the risk of febrile neutropenia and the efficacy of CSF were determined in a recent meta-analysis of data from randomized clinical trials of prophylactic use of CSF.
Estimating expenditures additional to the cost of hospitalization from the societal perspective is more inclusive, attempting to include all expenses borne by everyone affected by the treatment process. Since this perspective encompasses the category of indirect or productivity costs, it is arguably the most appropriate one to use in public health. With this perspective, important differences in the outcome of such decisions are often revealed.
Indirect costs are divided into two categories: morbidity costs -- those associated with lost or impaired ability to work -- and mortality costs -- those associated with lost productivity due to premature death. Indirect costs can be difficult to measure; they usually require detailed patient or employer surveys of changes in work patterns.
The additional indirect costs associated with cancer and its treatment are a substantial portion of the economic burden of the disease. One study estimated these costs to be more than 71% of the total cost of cancer care. Direct costs of cancer care account for approximately 5% of total health care expenditures in the United States. However, when indirect costs are included, total costs of cancer care account for approximately 20% of all U.S. health care spending.
In this study, we evaluated the effect of including, in a cost-minimization model that previously used only the direct costs of hospitalization, the indirect costs attributable to chemotherapy-induced neutropenia. We also incorporated into this model additional direct costs, such as costs associated with laboratory work and drugs prescribed, that were not captured in the earlier analysis. These additional direct costs did not include any costs incurred outside hospital-based care. Our objective was to determine whether this approach might produce a lower threshold for the risk of hospitalization for febrile neutropenia at which prophylactic use of CSF becomes cost saving. Such an outcome would indicate that from a societal perspective of economic considerations, a greater proportion of patients with cancer who receive chemotherapy would be appropriate candidates for CSF prophylaxis.
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