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Wu Q, Li Q, Zhang J, Luo Z, Zhou J, Chen J, Luo Y. Comparison of Primary and Secondary Prophylaxis Using PEGylated Recombinant Human Granulocyte-Stimulating Factor as a Cost-Effective Measure in Malignant Neoplasms: A Multicenter Retrospective Study. Front Pharmacol 2021; 12:690874. [PMID: 34776940 PMCID: PMC8586644 DOI: 10.3389/fphar.2021.690874] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 08/09/2021] [Indexed: 02/05/2023] Open
Abstract
Purpose: The aim of the study was to evaluate the cost-effectiveness of PEGylated recombinant human granulocyte-stimulating factor (PEG-rhG-CSF) as a means of achieving primary and secondary prophylaxis against chemotherapy-induced neutropenia cancer cases. Methods: Individuals who underwent PEG-rhG-CSF therapeutics were monitored for 12 months, together with thorough examination of individual medical records for extracting medical care costs. Both prophylaxis-based therapeutic options (primary/secondary) were scrutinized for cost-effectiveness, using a decision-making analysis model which derived the perspective of Chinese payers. One-way and probabilistic sensitivity analyses were used to assess the robustness of the model. Results: In summary, 130 clinical cases treated using PEG-rhG-CSF prophylaxis were included in this study: 51 within the primary prophylaxis (PP) group and 79 within the secondary prophylaxis (SP) group. Compared with SP, PP-based PEG-rhG-CSF successfully contributed to a 14.3% reduction in febrile neutropenia. In general, PP was estimated to reduce costs by $4,701.81 in comparison to SP, with a gain of 0.02 quality-adjusted life years (QALYs). Equivalent results were found in differing febrile neutropenia (FN) risk subgroups. Sensitivity analyses found the model outputs to be most affected for the average time of hospitalization and for the cost of FN. Conclusion: From the perspective of Chinese payers, PP with PEG-rhG-CSF should be considered cost-effective compared to SP strategies in patients who received chemotherapy regimens with a middle- to high-risk of FN.
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Affiliation(s)
- Qiuji Wu
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Qiu Li
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jun Zhang
- Department of Oncology, The Third People’s Hospital of ChengduChengdu, China
| | - Zhumei Luo
- Department of Oncology, The Third People’s Hospital of ChengduChengdu, China
| | - Jin Zhou
- Department of Medical Oncology, Sichuan Cancer HospitalChengdu, China
| | - Jing Chen
- Department of Medical Oncology, Sichuan Cancer HospitalChengdu, China
| | - Yong Luo
- Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, China
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Edelsberg J, Weycker D, Bensink M, Bowers C, Lyman GH. Prophylaxis of febrile neutropenia with colony-stimulating factors: the first 25 years. Curr Med Res Opin 2020; 36:483-495. [PMID: 31834830 DOI: 10.1080/03007995.2019.1703665] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Filgrastim prophylaxis, both primary and secondary, was rapidly incorporated into clinical practice in the 1990s. When pegfilgrastim became available in 2002, it quickly replaced filgrastim as the colony-stimulating factor (CSF) of choice for prophylaxis. Use of prophylaxis increased markedly in the first decade of this century and has stabilized during the present decade. Data concerning real-world CSF prophylactic practice patterns are limited but suggest that both primary and secondary prophylaxis are common, and that use is frequently inappropriate according to guidelines. The extent of inappropriate use is controversial, as are issues concerning the cost-effectiveness of prophylaxis versus no prophylaxis and the cost-effectiveness of primary prophylaxis versus secondary prophylaxis. Nevertheless, CSF prophylaxis is firmly established as a valuable adjunct to chemotherapy and will almost certainly continue to be widely used for the foreseeable future. In this article, we chronicle the use and impact of CSF prophylaxis in US patients receiving myelosuppressive chemotherapy for non-myeloid malignancies. We emphasize the interplay of expert opinion, clinical evidence, and economic factors in shaping the use of CSFs in clinical practice over time, and, with the recent introduction of new CSF agents and options, we aim to provide useful clinical and economic information for healthcare decision makers.
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Affiliation(s)
| | | | | | | | - Gary H Lyman
- Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA
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Gao L, Li SC. Cost-effectiveness analysis of lipegfilgrastim as primary prophylaxis in women with breast cancer in Australia: a modelled economic evaluation. Breast Cancer 2018; 25:671-680. [PMID: 29802592 DOI: 10.1007/s12282-018-0872-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 05/19/2018] [Indexed: 11/24/2022]
Abstract
OBJECTIVES To examine the cost-effectiveness of lipegfilgrastim versus pegfilgrastim as primary prophylaxis in women with early stage breast cancer. METHODS Two Markov models including a chemotherapy and a post-chemotherapy models were constructed with a time horizon of 12 weeks and 30 years, respectively. All the transition probabilities and utility weights were derived from clinical trials and/or published literatures. The costs populated in the chemotherapy model were extracted from Medicare, Pharmaceutical Benefit Scheme and the Independent Hospital Pricing Authority. No cost was considered in the post-chemotherapy model. Sensitivity analyses were performed to test the robustness of the results. RESULTS From the first chemotherapy model, lipegfilgrastim was associated with fewer episodes of severe neutropenia (SN) (N = 142 per 1000 patients treated), febrile neutropenia (FN) (N = 29 per 1000 patients treated), infection (N = 17 per 1000 patients treated) and chemotherapy delayed (N = 170 per 1000 patients treated) and lower cost ($116.88 less per patient treated). The post-chemotherapy model indicated lipegfilgrastim led to higher gains in both life years (18.72 versus 18.61) and quality-adjusted life years (17.28 versus 17.18) in comparison to pegfilgrastim. Sensitivity analysis showed that the results from the chemotherapy model is very sensitive to the baseline risk of SN; while from the probabilistic sensitivity analysis, lipegfilgrastim was likely to be more cost-effective than pegfilgrastim based on two models. CONCLUSIONS Lipegfilgrastim was likely to be a cost-effective alternative to pegfilgrastim as primary prophylaxis. The sensitivity analysis showed the confidence interval for the cost and benefit outcomes overlapped to a great extent, suggesting an insignificant difference.
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Affiliation(s)
- Lan Gao
- Deakin Health Economics, Centre for Population Health Research, Faculty of Health, Deakin University, 1 Gheringhap St, Geelong, VIC, 3220, Australia.
| | - Shu-Chuen Li
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, Callaghan, NSW, Australia
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Akpo EIH, Jansen IR, Maes E, Simoens S. Cost-Utility Analysis of Lipegfilgrastim Compared to Pegfilgrastim for the Prophylaxis of Chemotherapy-Induced Neutropenia in Patients with Stage II-IV Breast Cancer. Front Pharmacol 2017; 8:614. [PMID: 28955224 PMCID: PMC5601405 DOI: 10.3389/fphar.2017.00614] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 08/23/2017] [Indexed: 11/13/2022] Open
Abstract
Background: Lipegfilgrastim (Lonquex®) has demonstrated to be non-inferior to pegfilgrastim (Neulasta®) in reducing the duration of severe neutropenia (SN) in patients with stage II-IV breast cancer. Compared to pegfilgrastim, lipegfilgrastim also demonstrated statistically significant lower time to ANC recovery in cycles 1-3, lower incidence of SN in cycle 2 and lower depth of absolute neutrophil count (ANC) nadir in cycles 2 and 3. The aim of this study was to quantify the cost utility of lipegfilgrastim compared to pegfilgrastim in stage II-IV breast cancer patients, taking the perspective of the Belgian payer over a lifetime horizon. Methods: Two Markov models were developed to track on- and post-chemotherapy related complications, including SN, febrile neutropenia (FN), chemotherapy dose delay, chemotherapy relative dose intensity of less than 85%, infection, death rates, and quality-adjusted life years (QALYs). Data on costs (2015 value) and effects were obtained from literature, national references, and complemented by a survey of clinical experts using a modified Delphi method. Both deterministic and probabilistic sensitivity analyses were carried out. Outcomes measures included costs, QALYs and life-years (LY). Results: At current equivalent price of €1,169, treatment with lipegfilgrastim was associated with overall costs of €9,845 vs. €10,208 for pegfilgrastim and overall QALYs of 13.977 vs. 13.925 for pegfilgrastim. Life expectancy was increased by 21 days (or 0.058 LY gained). The difference in costs stem from avoided infection, SN and FN cases in the lipegfilgrastim compared to the pegfilgrastim group. Similarly, the difference in QALYs was explained by the difference in the number of patients in the chemotherapy/G-CSF Markov state followed by infection and FN between lipegfilgrastim and pegfilgrastim. The probability of lipegfilgrastim to be cost-effective compared to pegfilgrastim was 68, 79, and 83% at the willingness-to-pay thresholds (WTP) of €10,000, €30,000 and €50,000 per QALY gained, respectively. At a WTP threshold of €30,000 per QALY gained, lipegfilgrastim was cost-effective up to €1,500 across all age bands and cancer stages, compared to the current price. Conclusions: Lipegfilgrastim is a cost-effective use of health care resources in patients with stage II-IV breast cancer.
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Affiliation(s)
- Esse I. H. Akpo
- Market Access Strategy and Health EconomicsDeloitte (Belgium), Zaventem, Belgium
| | - Irshaad R. Jansen
- Market Access Strategy and Health EconomicsDeloitte (Belgium), Zaventem, Belgium
| | - Edith Maes
- Market Access Strategy and Health EconomicsDeloitte (Belgium), Zaventem, Belgium
| | - Steven Simoens
- Department of Pharmaceutical and Pharmacological SciencesKU Leuven, Leuven, Belgium
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Fust K, Li X, Maschio M, Villa G, Parthan A, Barron R, Weinstein MC, Somers L, Hoefkens C, Lyman GH. Cost-Effectiveness Analysis of Prophylaxis Treatment Strategies to Reduce the Incidence of Febrile Neutropenia in Patients with Early-Stage Breast Cancer or Non-Hodgkin Lymphoma. PHARMACOECONOMICS 2017; 35:425-438. [PMID: 27928760 PMCID: PMC5357483 DOI: 10.1007/s40273-016-0474-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
OBJECTIVE The objective of this study was to evaluate the cost effectiveness of no prophylaxis, primary prophylaxis (PP), or secondary prophylaxis (SP) with granulocyte colony-stimulating factors (G-CSFs), i.e., pegfilgrastim, lipegfilgrastim, filgrastim (6- and 11-day), or lenograstim (6- and 11-day), to reduce the incidence of febrile neutropenia (FN) in patients with stage II breast cancer receiving TC (docetaxel, cyclophosphamide) and in patients with non-Hodgkin lymphoma (NHL) receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) over a lifetime horizon from a Belgian payer perspective. METHODS A Markov cycle tree tracked FN events during chemotherapy (3-week cycles) and long-term survival (1-year cycles). Model inputs, including the efficacy of each strategy, risk of reduced relative dose intensity (RDI), and the impact of RDI on mortality, utilities, and costs (in €; 2014 values) were estimated from public sources and the published literature. Incremental cost-effectiveness ratios (ICERs) were assessed for each strategy for costs per FN event avoided, life-year (LY) saved, and quality-adjusted LY (QALY) saved. LYs and QALYs saved were discounted at 1.5% annually. Deterministic and probabilistic sensitivity analyses (DSAs and PSAs) were conducted. RESULTS Base-case ICERs for PP with pegfilgrastim relative to SP with pegfilgrastim were €15,500 per QALY and €14,800 per LY saved for stage II breast cancer and €7800 per QALY and €6900 per LY saved for NHL; other comparators were either more expensive and less effective than PP or SP with pegfilgrastim or had lower costs but higher ICERs (relative to SP with pegfilgrastim) than PP with pegfilgrastim. Results of the DSA for breast cancer and NHL comparing PP and SP with pegfilgrastim indicate that the model results were most sensitive to the cycle 1 risk of FN, the proportion of FN events requiring hospitalization, the relative risk of FN in cycles ≥2 versus cycle 1, no history of FN, and the mortality hazard ratio for RDI (<90% vs ≥90% [for NHL]). In the PSAs for stage II breast cancer and NHL, the probabilities that PP with pegfilgrastim was cost effective or dominant versus all other prophylaxis strategies at a €30,000/QALY willingness-to-pay threshold were 52% (other strategies ≤24%) and 58% (other strategies ≤24%), respectively. CONCLUSION From a Belgian payer perspective, PP with pegfilgrastim appears cost effective compared to other prophylaxis strategies in patients with stage II breast cancer or NHL at a €30,000/QALY threshold.
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Affiliation(s)
- Kelly Fust
- Optum, 950 Winter St, Waltham, MA, 02451, USA.
| | - Xiaoyan Li
- Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA
| | - Michael Maschio
- Optum, 5500 North Service Road, Suite 501, Burlington, ON, L7L 6W6, Canada
| | | | | | - Richard Barron
- Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA
| | - Milton C Weinstein
- Harvard T.H. Chan School of Public Health, 718 Huntington Avenue, Boston, MA, 02115, USA
| | - Luc Somers
- OncoLogX bvba, Arthur Boelstraat 66, 2990, Wuustwezel, Antwerp, Belgium
| | | | - Gary H Lyman
- Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA, 98109, USA
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Fust K, Parthan A, Maschio M, Gu Q, Li X, Lyman GH, Tzivelekis S, Villa G, Weinstein MC. Granulocyte colony-stimulating factors in the prevention of febrile neutropenia: review of cost-effectiveness models. Expert Rev Pharmacoecon Outcomes Res 2017; 17:39-52. [DOI: 10.1080/14737167.2017.1276829] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Kelly Fust
- Health Economics & Outcomes Research, Optum, Boston, MA, USA
| | - Anju Parthan
- Health Economics & Outcomes Research, Optum, Boston, MA, USA
| | - Michael Maschio
- Health Economics & Outcomes Research, Optum, Burlington, ON, Canada
| | - Qing Gu
- Health Economics & Outcomes Research, Optum, Boston, MA, USA
| | - Xiaoyan Li
- Global Health Economics, Amgen Inc., Thousand Oaks, CA, USA
| | - Gary H. Lyman
- Public Health Sciences Division and Clinical Research Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | | | - Guillermo Villa
- Global Health Economics, Amgen (Europe) GmbH, Zug, Switzerland
| | - Milton C. Weinstein
- Department of Health Policy and Management; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
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Klastersky J, Paesmans M, Aoun M, Georgala A, Loizidou A, Lalami Y, Dal Lago L. Clinical research in febrile neutropenia in cancer patients: Past achievements and perspectives for the future. World J Clin Infect Dis 2016; 6:37-60. [DOI: 10.5495/wjcid.v6.i3.37] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 12/02/2015] [Accepted: 06/03/2016] [Indexed: 02/06/2023] Open
Abstract
Febrile neutropenia (FN) is responsible for significant morbidity and mortality. It can also be the reason for delaying or changing potentially effective treatments and generates substantial costs. It has been recognized for more than 50 years that empirical administration of broad spectrum antibiotics to patients with FN was associated with much improved outcomes; that has become a paradigm of management. Increase in the incidence of microorganisms resistant to many antibiotics represents a challenge for the empirical antimicrobial treatment and is a reason why antibiotics should not be used for the prevention of neutropenia. Prevention of neutropenia is best performed with the use of granulocyte colony-stimulating factors (G-CSFs). Prophylactic administration of G-CSFs significantly reduces the risk of developing FN and consequently the complications linked to that condition; moreover, the administration of G-CSF is associated with few complications, most of which are not severe. The most common reason for not using G-CSF as a prophylaxis of FN is the relatively high cost. If FN occurs, in spite of prophylaxis, empirical therapy with broad spectrum antibiotics is mandatory. However it should be adjusted to the risk of complications as established by reliable predictive instruments such as the Multinational Association for Supportive Care in Cancer. Patients predicted at a low level of risk of serious complications, can generally be treated with orally administered antibiotics and as out-patients. Patients with a high risk of complications should be hospitalized and treated intravenously. A short period of time between the onset of FN and beginning of empirical therapy is crucial in those patients. Persisting fever in spite of antimicrobial therapy in neutropenic patients requires a special diagnostic attention, since invasive fungal infection is a possible cause for it and might require the use of empirical antifungal therapy.
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Wallbillich JJ, Forde B, Havrilesky LJ, Cohn DE. A personalized paradigm in the treatment of platinum-resistant ovarian cancer - A cost utility analysis of genomic-based versus cytotoxic therapy. Gynecol Oncol 2016; 142:144-149. [PMID: 27106017 DOI: 10.1016/j.ygyno.2016.04.024] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2016] [Revised: 04/17/2016] [Accepted: 04/18/2016] [Indexed: 01/11/2023]
Abstract
OBJECTIVE To assess the cost-effectiveness of a strategy employing genomic-based tumor testing to guide therapy for platinum-resistant ovarian cancer. METHODS A decision model was created to compare standard of care (SOC) cytotoxic chemotherapy to a genomic-based treatment strategy. The genomic arm included tumor testing with treatment directed at targets identified. Overall survival was assumed to be similar between strategies; quality of life (QOL) was assumed superior during targeted therapy compared to chemotherapy. Pertinent uncertainties (cost of targeted therapy and genomic testing, response to targeted therapy, probability of a tumor having a targetable alteration, and impact on QOL) were evaluated in a series of one-and two-way sensitivity analyses. RESULTS The genomic testing strategy was more expensive ($90,271 vs. $74,926) per patient than SOC. The incremental cost-effectiveness ratio (ICER) of the genomic strategy was $479,303 per quality-adjusted life year saved (QALY). Model results were insensitive to the cost of genomic testing, differences in QOL, and the probability of identifying a targetable alteration. However, the model was sensitive to the cost of targeted therapy. For example, when the cost of targeted therapy was reduced to 56% of its current cost (or $6400/cycle), the genomic strategy became more cost-effective with an ICER of $96,612/QALY. CONCLUSIONS Genomic-based tumor testing and targeted therapy in patients with platinum-resistant ovarian cancer is not cost-effective compared with SOC. However, reducing the cost of targeted therapy (independently, or in combination with reducing the cost of the genomic test) provides opportunities for improved value in cancer care.
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Affiliation(s)
- J J Wallbillich
- The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - B Forde
- Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - L J Havrilesky
- Duke University Medical Center, Durham, NC, United States
| | - D E Cohn
- The Ohio State University Wexner Medical Center, Columbus, OH, United States.
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