Cost-Effectiveness of Serum Galactomannan Surveillance during Mould-Active Antifungal Prophylaxis
Abstract
:1. Introduction
2. Methods
2.1. Model Structure
2.2. Model Inputs
2.3. Resource Use and Cost
2.4. Outcomes
2.5. Scenario Analysis
2.6. Sensitivity Analysis
3. Results
3.1. Base Case Analysis
3.2. Scenario Analysis
3.3. Deterministic Sensitivity Analysis
3.4. Probabilistic Sensitivity Analysis
4. Discussion
5. Transparency Declaration
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
- Kontoyiannis, D.P.; Marr, K.A.; Park, B.J.; Alexander, B.D.; Anaissie, E.J.; Walsh, T.J.; Ito, J.; Andes, D.R.; Baddley, J.W.; Brown, J.M.; et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: Overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin. Infect. Dis. 2010, 50, 1091–1100. [Google Scholar] [CrossRef]
- Pagano, L.; Caira, M.; Candoni, A.; Offidani, M.; Fianchi, L.; Martino, B.; Pastore, D.; Picardi, M.; Bonini, A.; Chierichini, A.; et al. The epidemiology of fungal infections in patients with hematologic malignancies: The SEIFEM-2004 study. Haematologica 2006, 91, 1068–1075. [Google Scholar] [PubMed]
- Pagano, L.; Caira, M.; Nosari, A.; van Lint, M.T.; Candoni, A.; Offidani, M.; Aloisi, T.; Irrera, G.; Bonini, A.; Picardi, M.; et al. Fungal infections in recipients of hematopoietic stem cell transplants: Results of the SEIFEM B-2004 study—Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne. Clin. Infect. Dis. 2007, 45, 1161–1170. [Google Scholar] [CrossRef]
- Slobbe, L.; Polinder, S.; Doorduijn, J.K.; Lugtenburg, P.J.; el Barzouhi, A.; Steyerberg, E.W.; Rijnders, B.J.A. Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: An observational study. Clin. Infect. Dis. 2008, 47, 1507–1512. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- De Pauw, B.; Walsh, T.J.; Donnelly, J.P.; Stevens, D.A.; Edwards, J.E.; Calandra, T.; Pappas, P.G.; Maertens, J.; Lortholary, O.; Kauffman, C.A.; et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin. Infect. Dis. 2008, 46, 1813–1821. [Google Scholar] [PubMed]
- Shah, A.A.; Hazen, K.C. Diagnostic accuracy of histopathologic and cytopathologic examination of Aspergillus species. Am. J. Clin. Pathol. 2013, 139, 55–61. [Google Scholar] [CrossRef] [Green Version]
- Herbrecht, R.; Letscher-Bru, V.; Oprea, C.; Lioure, B.; Waller, J.; Campos, F.; Villard, O.; Liu, K.; Natarajan-Amé, S.; Lutz, P.; et al. Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients. J. Clin. Oncol. 2002, 20, 1898–1906. [Google Scholar] [CrossRef]
- Harricharan, S.; Biederman, K.; Bombassaro, A.M.; Lazo-Langner, A.; Elsayed, S.; Fulford, A.; Delport, J.A.; Xenocostas, A. Adherence to, and outcomes of, a galactomannan screening protocol in high-risk hematology patients. Curr. Oncol. 2018, 25, e139–e145. [Google Scholar] [CrossRef] [Green Version]
- Maertens, J.; Theunissen, K.; Verhoef, G.; Verschakelen, J.; Lagrou, K.; Verbeken, E.; Wilmer, A.; Verhaegen, J.; Boogaerts, M.; van Eldere, J. Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: A prospective feasibility study. Clin. Infect. Dis. 2005, 41, 1242–1250. [Google Scholar] [CrossRef] [Green Version]
- Tan, B.H.; Low, J.G.H.; Chlebicka, N.L.; Kurup, A.; Cheah, F.K.; Lin, R.T.P.; Goh, Y.T.; Wong, G.C. Galactomannan-guided preemptive vs. empirical antifungals in the persistently febrile neutropenic patient: A prospective randomized study. Int J. Infect. Dis. 2011, 15, e350–e356. [Google Scholar] [CrossRef] [Green Version]
- Morrissey, C.O.; Chen, S.C.; Sorrell, T.C.; Milliken, S.; Bardy, P.G.; Bradstock, K.F.; Szer, J.; Halliday, C.L.; Gilroy, N.M.; Moore, J.; et al. Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high-risk haematology patients: A randomised controlled trial. Lancet Infect. Dis. 2013, 13, 519–528. [Google Scholar] [CrossRef]
- Cordonnier, C.; Pautas, C.; Maury, S.; Vekhoff, A.; Farhat, H.; Suarez, F.; Dhédin, N.; Isnard, F.; Ades, L.; Kuhnowski, F.; et al. Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: A randomized, controlled trial. Clin. Infect. Dis. 2009, 48, 1042–1051. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fung, M.; Kim, J.; Marty, F.M.; Schwarzinger, M.; Koo, S. Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia. PLoS ONE 2015, 10, e0140930. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cornely, O.A.; Maertens, J.; Winston, D.J.; Perfect, J.; Ullmann, A.J.; Walsh, T.J.; Helfgott, D.; Holowiecki, J.; Stockelberg, D.; Goh, Y.; et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N. Engl. J. Med. 2007, 356, 348–359. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ullmann, A.J.; Lipton, J.H.; Vesole, D.H.; Chandrasekar, P.; Langston, A.; Tarantolo, S.R.; Greinix, H.; de Azevedo, W.M.; Reddy, V.; Boparai, N.; et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N. Engl. J. Med. 2007, 356, 335–347. [Google Scholar] [CrossRef] [PubMed]
- Cornely, O.A. Galactomannan testing during mold-active prophylaxis. Clin. Infect. Dis. 2014, 59, 1703–1704. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Duarte, R.F.; Sánchez-Ortega, I.; Cuesta, I.; Arnan, M.; Patiño, B.; de Sevilla, A.F.; Gudiol, C.; Ayats, J.; Cuenca-Estrella, M. Serum galactomannan-based early detection of invasive aspergillosis in hematology patients receiving effective antimold prophylaxis. Clin. Infect. Dis. 2014, 59, 1696–1702. [Google Scholar] [CrossRef] [Green Version]
- Walsh, T.J.; Anaissie, E.J.; Denning, D.W.; Herbrecht, R.; Kontoyiannis, D.P.; Marr, K.A.; Morrison, V.A.; Segal, B.H.; Steinbach, W.J.; Stevens, D.A.; et al. Treatment of aspergillosis: Clinical practice guidelines of the Infectious Diseases Society of America. Clin. Infect. Dis. 2008, 46, 327–360. [Google Scholar] [CrossRef] [PubMed]
- Patterson, T.F.; Thompson, G.R., 3rd; Denning, D.W.; Fishman, J.A.; Hadley, S.; Herbrecht, R.; Kontoyiannis, D.P.; Marr, K.A.; Morrison, V.A.; Nguyen, M.H.; et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2016, 63, e1–e60. [Google Scholar] [CrossRef] [PubMed]
- Husereau, D.; Drummond, M.; Petrou, S.; Carswell, C.; Moher, D.; Greenberg, D.; Augustovski, F.; Briggs, A.H.; Mauskopf, J.; Loder, E.; et al. Consolidated Health Economic Evaluation Reporting Standards (CHEERS)—Explanation and elaboration: A report of the ISPOR Health Economic Evaluation Publication Guidelines Good Reporting Practices Task Force. Value Health 2013, 16, 231–250. [Google Scholar] [CrossRef] [Green Version]
- Appelbaum, F.R.; Gundacker, H.; Head, D.R.; Slovak, M.L.; Willman, C.L.; Godwin, J.E.; Anderson, J.E.; Petersdorf, S.H. Age and acute myeloid leukemia. Blood 2006, 107, 3481–3485. [Google Scholar] [CrossRef] [PubMed]
- Juliusson, G.; Lazarevic, V.; Horstedt, A.S.; Hagberg, O.; Hoglund, M.; Swedish Acute Leukemia Registry Group. Acute myeloid leukemia in the real world: Why population-based registries are needed. Blood 2012, 119, 3890–3899. [Google Scholar] [CrossRef] [Green Version]
- Drug Evaluation Methods & Process; Agency for Care Effectiveness, Ministry of Health: Singapore, 2018. Available online: www.ace-hta.gov.sg (accessed on 31 January 2019).
- Leeflang, M.M.G.; Debets-Ossenkopp, Y.J.; Wang, J.; Visser, C.E.; Scholten, R.J.P.M.; Hooft, L.; Bijlmer, H.A.; Reitsma, J.B.; Zhang, M.; Bossuyt, P.M.M.; et al. Galactomannan detection for invasive aspergillosis in immunocompromised patients. Cochrane Database Syst. Rev. 2015, 2015, CD007394. [Google Scholar] [CrossRef]
- Ananda-Rajah, M.R.; Grigg, A.; Downey, M.T.; Bajel, A.; Spelman, T.; Cheng, A.; Thursky, K.T.; Vincent, J.; Slavin, M.A. Comparative clinical effectiveness of prophylactic voriconazole/posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period. Haematologica 2012, 97, 459–463. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Herbrecht, R.; Denning, D.W.; Patterson, T.F.; Bennett, J.E.; Greene, R.E.; Oestmann, J.; Kern, W.V.; Marr, K.A.; Ribaud, P.; Lortholary, O. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N. Engl. J. Med. 2002, 347, 408–415. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jung, J.; Kim, M.Y.; Chong, Y.P.; Lee, S.; Choi, S.; Kim, Y.S.; Woo, J.H.; Kim, S. Clinical characteristics, radiologic findings, risk factors and outcomes of serum galactomannan-negative invasive pulmonary aspergillosis. J. Microbiol. Immunol. Infect. 2018, 51, 802–809. [Google Scholar] [CrossRef]
- Complete Life Tables 2015–2016 for Singapore Resident Population. Department of Statics S. Available online: www.singstat.gov.sg (accessed on 30 June 2018).
- Labour Market Statistical Information, Ministry of Manpower 2017, Singapore. Available online: http://stats.mom.gov.sg/Pages/Income-Summary-Table.aspx (accessed on 31 January 2019).
- Chai, L.Y.A.; Kullberg, B.; Johnson, E.M.; Teerenstra, S.; Khin, L.W.; Vonk, A.G.; Maertens, J.; Lortholary, O.; Donnelly, P.J.; Schlamm, H.T.; et al. Early serum galactomannan trend as a predictor of outcome of invasive aspergillosis. J. Clin. Microbiol. 2012, 50, 2330–2336. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- WHO Global Health Expenditure Atlas. World Health Organisation. 2012. Available online: www.who.int/nha/atlas.pdf (accessed on 31 January 2019).
- Calmettes, C.; Gabriel, F.; Blanchard, E.; Servant, V.; Bouchet, S.; Kabore, N.; Forcade, E.; Leroyer, C.; Bidet, A.; Latrabe, V.; et al. Breakthrough invasive aspergillosis and diagnostic accuracy of serum galactomannan enzyme immune assay during acute myeloid leukemia induction chemotherapy with posaconazole prophylaxis. Oncotarget 2018, 9, 26724–26736. [Google Scholar] [CrossRef]
- Marr, K.A.; Laverdiere, M.; Gugel, A.; Leisenring, W. Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay. Clin. Infect. Dis. 2005, 40, 1762–1769. [Google Scholar] [CrossRef] [PubMed]
- Vehreschild, J.J.; Rüping, M.J.G.T.; Wisplinghoff, H.; Farowski, F.; Steinbach, A.; Sims, R.; Stollorz, A.; Kreuzer, K.; Hallek, M.; Bangard, C.; et al. Clinical effectiveness of posaconazole prophylaxis in patients with acute myelogenous leukaemia (AML): A 6 year experience of the Cologne AML cohort. J. Antimicrob. Chemother. 2010, 65, 1466–1471. [Google Scholar] [CrossRef] [Green Version]
- Macesic, N.; Morrissey, C.O.; Liew, D.; Bohensky, M.A.; Chen, S.C.; Gilroy, N.M.; Milliken, S.T.; Szer, J.; Slavin, M.A. Is a biomarker-based diagnostic strategy for invasive aspergillosis cost effective in high-risk haematology patients? Med. Mycol. 2017, 55, 705–712. [Google Scholar] [CrossRef] [PubMed]
- Barnes, R.; Earnshaw, S.; Herbrecht, R.; Morrissey, O.; Slavin, M.; Bow, E.; McDade, C.; Charbonneau, C.; Weinstein, D.; Kantecki, M.; et al. Economic Comparison of an Empirical Versus Diagnostic-Driven Strategy for Treating Invasive Fungal Disease in Immunocompromised Patients. Clin. Ther. 2015, 37, 1317–1328.e2. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chai, L.Y.A.; jan Kullberg, B.; Earnest, A.; Johnson, E.M.; Teerenstra, S.; Vonk, A.G.; Schlamm, H.T.; Herbrecht, R.; Netea, M.G.; Troke, P.F. Voriconazole or amphotericin B as primary therapy yields distinct early serum galactomannan trends related to outcomes in invasive aspergillosis. PLoS ONE 2014, 9, e90176. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fisher, C.E.; Stevens, A.M.; Leisenring, W.; Pergam, S.A.; Boeckh, M.; Hohl, T.M. The serum galactomannan index predicts mortality in hematopoietic stem cell transplant recipients with invasive aspergillosis. Clin. Infect. Dis. 2013, 57, 1001–1004. [Google Scholar] [CrossRef] [Green Version]
- Marr, K.A.; Balajee, S.A.; McLaughlin, L.; Tabouret, M.; Bentsen, C.; Walsh, T.J. Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: Variables that affect performance. J. Infect. Dis. 2004, 190, 641–649. [Google Scholar] [CrossRef] [Green Version]
- Zhou, W.; Li, H.; Zhang, Y.; Huang, M.; He, Q.; Li, P.; Zhang, F.; Shi, Y.; Su, X. Diagnostic Value of Galactomannan Antigen Test in Serum and Bronchoalveolar Lavage Fluid Samples from Patients with Nonneutropenic Invasive Pulmonary Aspergillosis. J. Clin. Microbiol. 2017, 55, 2153–2161. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Parameters | Base-Case | Uncertainty (Range/Distribution) | Source |
---|---|---|---|
Events | |||
Probability of IA | |||
Non-mould-active prophylaxis | 0.08 | 0.06–0.10 (beta) | Cornely et al., 2007 [14] |
Mould-active prophylaxis | 0.02 | 0.015–0.025 (beta) | Cornely et al., 2007 [14] |
Probability of receiving empirical treatment | |||
No GM test while on non-mould-active prophylaxis | 0.34 | 0.26–0.43 (beta) | Morrissey et al., 2013 [11] |
No GM test while on mould-active prophylaxis | 0.23 | 0.17–0.29 (beta) | Morrissey et al., 2013 [11] |
GM test while on non-mould-active prophylaxis | 0.16 | 0.12–0.20 (beta) | Morrissey et al., 2013 [11] |
GM test while on mould-active prophylaxis | 0.16 | 0.12–0.20 (beta) | Morrissey et al., 2013 [11] |
Probability of test being positive (sensitivity) in IA patients | |||
Non-mould-active prophylaxis | 0.82 | 0.73–0.90 (beta) | Leeflang et al., 2015 [24] |
Probability of test being negative (specificity) in non-IA patients | |||
Non-mould-active prophylaxis | 0.81 | 0.72–0.90 (beta) | Leeflang et al., 2015 [24] |
Probability of all-cause death in IA patients | |||
No GM test | 0.25 | 0.19–0.31 (beta) | Chai et al., 2012 [30], post hoc analysis |
GM test positive | 0.28 | 0.21–0.35 (beta) | Jung et al., 2018 [27] |
GM test negative | 0.24 | 0.18–0.30 (beta) | Jung et al., 2018 [27] |
Probability of all-cause death in non-IA patients | 0.11 | 0.08–0.14 (beta) | local hospital data |
Probabilities of death after 16 weeks | |||
First year | age-specific AML cohort | local hospital data (NUH AML Database) | |
Subsequent year | life table | Department of Statistics, Singapore [28] | |
Costs (SGD) | |||
Investigation (GM test positive) | |||
Serum GM antigen index | 704 | 528–880 (gamma) | local hospital data |
Radiography | 547 | 517–577 (gamma) | local hospital data |
Septic work-up | 431 | 431–431 (gamma) | local hospital data |
Investigation (GM test negative) | |||
Serum GM antigen index (8 tests) | 704 | 528–880 (gamma) | local hospital data |
Radiography | 547 | 517–577 (gamma) | local hospital data |
Septic work-up | 431 | 431–431 (gamma) | local hospital data |
Additional investigations with bronchoscopy (including GM in BAL) | 971 | 971–971 (gamma) | local hospital data |
Investigation (No routine GM test) | |||
Serum GM antigen index on suspicions | 196 | 88–196 (gamma) | local hospital data |
Radiography | 547 | 517–577 (gamma) | local hospital data |
Septic work-up on suspicions | 431 | 431–431 (gamma) | local hospital data |
Additional investigations with bronchoscopy (including GM in BAL) | 971 | 971–971 (gamma) | local hospital data |
Treatment of IA | |||
IA infection (12-week course of voriconazole) | 14,280 | 11,900–16,660 (gamma) | local hospital data |
Outpatient visits | 196 | 98–256 (gamma) | local hospital data |
Productivity loss | 2116 | 1058–4232 (gamma) | local hospital data |
Laboratory investigation (liver, renal panel, and full blood count) | |||
IA patients | 609 | 483–736 (gamma) | local hospital data |
Non-IA patients | 165 | 143–154 (gamma) | local hospital data |
Hospitalisation | |||
IA patients | 5992 | 4494–8988 (gamma) | local hospital data |
Non-IA patients | 2996 | 2996–5992 (gamma) | local hospital data |
Strategy | Total Cost | Incremental Cost | QALYs Gained | Incremental QALY | ICER # |
---|---|---|---|---|---|
Routine GM assay during mould-active prophylaxis | SGD 11,227 (USD 8255) | - | 5.3272 | - | - |
Routine GM assay during non-mould-active prophylaxis | SGD 12,225 (USD 8989) | SGD 998 (USD 734) | 5.3053 | −0.0219 | dominated |
No GM assay during mould-active prophylaxis | SGD 14,437 (USD 10,615) | SGD 3210 (USD 2316) | 5.3266 | −0.0006 | dominated |
Strategy | Total Cost | Incremental Cost | QALYs Gained | Incremental QALY | ICER # |
---|---|---|---|---|---|
Routine GM assay during mould-active prophylaxis | SGD 9234 (USD 6790) | - | 1.1693 | - | - |
Routine GM assay during non-mould-active prophylaxis | SGD 10,132 (USD 7450) | SGD 898 (USD 660) | 1.1597 | −0.0096 | dominated |
No GM assay during mould-active prophylaxis | SGD 12,292 (USD 9039) | SGD 3058 (USD 2249) | 1.1691 | −0.0002 | dominated |
Sensitivity of GM Assay | Strategy | Total Cost | Incremental Cost | QALYs Gained | Incremental QALY | ICER # |
---|---|---|---|---|---|---|
- | No GM assay during mould-active prophylaxis | SGD 14,437 (USD 10,615) | 5.3266 | - | - | |
80% | Routine GM assay during mould-active prophylaxis | SGD 11,227 (USD 8255) | −SGD 3210 (USD 2316) | 5.3272 | 0.0006 | dominant |
70% | Routine GM assay during mould-active prophylaxis | SGD 11,227 (USD 8255) | −SGD 3206 (USD 2357) | 5.3274 | 0.0007 | dominant |
60% | Routine GM assay during mould-active prophylaxis | SGD 11,227 (USD 8255) | −SGD 3201 (USD 2354) | 5.3275 | 0.0009 | dominant |
50% | Routine GM assay during mould-active prophylaxis | SGD 11,227 (USD 8255) | −SGD 3196 (USD 2350) | 5.3276 | 0.0010 | dominant |
40% | Routine GM assay during mould-active prophylaxis | SGD 11,227 (USD 8255) | −SGD 3192 (USD 2347) | 5.3278 | 0.0012 | dominant |
30% | Routine GM assay during mould-active prophylaxis | SGD 11,227 (USD 8255) | −SGD 3187 (USD 2343) | 5.3279 | 0.0013 | dominant |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Khoo, A.L.; Zhao, Y.J.; Tan, G.S.E.; Teng, M.; Yap, J.; Tambyah, P.A.; Ng, C.H.; Lim, B.P.; Chai, L.Y.A. Cost-Effectiveness of Serum Galactomannan Surveillance during Mould-Active Antifungal Prophylaxis. J. Fungi 2021, 7, 417. https://doi.org/10.3390/jof7060417
Khoo AL, Zhao YJ, Tan GSE, Teng M, Yap J, Tambyah PA, Ng CH, Lim BP, Chai LYA. Cost-Effectiveness of Serum Galactomannan Surveillance during Mould-Active Antifungal Prophylaxis. Journal of Fungi. 2021; 7(6):417. https://doi.org/10.3390/jof7060417
Chicago/Turabian StyleKhoo, Ai Leng, Ying Jiao Zhao, Glorijoy Shi En Tan, Monica Teng, Jenny Yap, Paul Anantharajah Tambyah, Chin Hin Ng, Boon Peng Lim, and Louis Yi Ann Chai. 2021. "Cost-Effectiveness of Serum Galactomannan Surveillance during Mould-Active Antifungal Prophylaxis" Journal of Fungi 7, no. 6: 417. https://doi.org/10.3390/jof7060417