Skip to main content
Top
Published in: PharmacoEconomics 7/2004

01-05-2004 | Review Article

Economic Evaluations of Treatments for Systemic Fungal Infections

A Systematic Review of the Literature

Authors: Dr Simon Dixon, Emma McKeen, Margaret Tabberer, Suzy Paisley

Published in: PharmacoEconomics | Issue 7/2004

Login to get access

Abstract

We systematically reviewed published economic evaluations of systemic antifungal therapies and assessed their strengths and weaknesses. The study identified all economic evaluations published before May 2002 and critically appraised their methods using a published checklist. Over 1000 papers on antifungal treatments and costs were retrieved, 40 of which were economic evaluations. Fifteen of these were evaluations of systemic antifungal therapy. The majority of studies examined prophylaxis (11 out of 15), two examined empiric treatment and two examined the treatment of confirmed infections.
Methods varied quite dramatically and the quality of the studies was, in general, very poor. Consequently, we were unable to find a coherent body of economic evidence for any particular patient group and/or indication. Three methodological issues were identified as requiring improvement in future economic evaluations of the prevention and treatment of systemic mucoses: cost estimates, outcome measures and evidence of effectiveness.
Costs of both antifungal infection and treatment are important, and despite this, seven of the studies only collected cost information on drug acquisition costs. This is such a fundamental flaw that these studies should not be used to inform decision making on the use of antifungal medication. The estimation of costs in the other studies appeared appropriate, although limited reporting obscured other important issues, such as the appropriate use of per diem costs.
Outcome measures were necessarily produced in all evaluations, yet only two studies produced cost-effectiveness ratios. This makes comparisons across studies very difficult. Also, small samples sizes meant that ‘hard’ outcome measures such as life-years saved could not be used, as deaths were rare within the studies. Both studies that produced incremental cost-effectiveness ratios were model-based studies. These allow simulations to be run on large cohorts of hypothetical patients, thus allowing differences in mortality between treatments to be evaluated.
Evidence of effectiveness was limited, with many of the studies based on non-randomised clinical studies and consequently open to bias. Future clinical trials of the effectiveness of antifungal prophylaxis and treatment need to incorporate the collection of costs and economic outcome measures. Even quite simple analyses can be quite powerful, particularly when combined with modelling work to allow other data sources to be added.
Literature
1.
go back to reference Beck Sague CM, Jarvis WR. Secular trends in the epidemiology of noscomial fungal infections in the United States, 1980–1990. National Noscomial Infections Surveillance System. JInfectDis 1993; 167: 1247–51CrossRef Beck Sague CM, Jarvis WR. Secular trends in the epidemiology of noscomial fungal infections in the United States, 1980–1990. National Noscomial Infections Surveillance System. JInfectDis 1993; 167: 1247–51CrossRef
2.
go back to reference Guiot HF, Fibbe WE, van’t Wout JW. Risk factors for fungal infection in patients with malignant hematologic disorders: implications for empirical therapy and prophylaxis. Clin Infect Dis 1994; 18: 525–32PubMedCrossRef Guiot HF, Fibbe WE, van’t Wout JW. Risk factors for fungal infection in patients with malignant hematologic disorders: implications for empirical therapy and prophylaxis. Clin Infect Dis 1994; 18: 525–32PubMedCrossRef
3.
go back to reference Wey SB, Mori M, Pfaller MA, et al. Risk factors for hospitalacquired candidemia: a matched case-controlled study. Arch Intern Med 1989; 149: 2349–53PubMedCrossRef Wey SB, Mori M, Pfaller MA, et al. Risk factors for hospitalacquired candidemia: a matched case-controlled study. Arch Intern Med 1989; 149: 2349–53PubMedCrossRef
4.
go back to reference Pinner RW, Teutsch SM, Simonsen L, et al. Trends in infectious diseases mortality in the United States. JAMA 1996; 275: 189–93PubMedCrossRef Pinner RW, Teutsch SM, Simonsen L, et al. Trends in infectious diseases mortality in the United States. JAMA 1996; 275: 189–93PubMedCrossRef
5.
go back to reference Kao AS, Brandt ME, Pruitt WR, et al. The epidemiology of candidemia in two United States cities: results of a populationbased active surveillance. Clin Infect Dis 1999; 29 (5): 1164–70PubMedCrossRef Kao AS, Brandt ME, Pruitt WR, et al. The epidemiology of candidemia in two United States cities: results of a populationbased active surveillance. Clin Infect Dis 1999; 29 (5): 1164–70PubMedCrossRef
6.
go back to reference Banerjee SN, Emori TG, Culver DH, et al. Secular trends in nosocomial primary bloodstream infections in the United States, 1980–1989. National Nosocomial Infections Surveillance System. Am J Med 1991; 91: 86S-9SCrossRef Banerjee SN, Emori TG, Culver DH, et al. Secular trends in nosocomial primary bloodstream infections in the United States, 1980–1989. National Nosocomial Infections Surveillance System. Am J Med 1991; 91: 86S-9SCrossRef
7.
go back to reference Pfaller MA, Jones RN, Doern GV, et al. International surveillance of bloodstream infections due to Candida species: frequency of occurrence and antifungal susceptibilities of isolates collected in 1997 in the United States, Canada, and South America for the SENfRY Program. The SENTRY Participant Group. J Clin Microbiol 1998; 36: 1886–9PubMed Pfaller MA, Jones RN, Doern GV, et al. International surveillance of bloodstream infections due to Candida species: frequency of occurrence and antifungal susceptibilities of isolates collected in 1997 in the United States, Canada, and South America for the SENfRY Program. The SENTRY Participant Group. J Clin Microbiol 1998; 36: 1886–9PubMed
8.
go back to reference Edmond MB, Wallace SE, McClish DK, et al. Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 1999; 29: 239–44PubMedCrossRef Edmond MB, Wallace SE, McClish DK, et al. Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 1999; 29: 239–44PubMedCrossRef
9.
go back to reference Fraser DW, Ward J, Ajello L, et al. Aspergillosis and other systemic mycoses: the growing problem. JAMA 1979; 242: 1631–5PubMedCrossRef Fraser DW, Ward J, Ajello L, et al. Aspergillosis and other systemic mycoses: the growing problem. JAMA 1979; 242: 1631–5PubMedCrossRef
10.
go back to reference Groll AH, Shah PM, Mentzel C, et al. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J Infect 1996; 33: 23–32PubMedCrossRef Groll AH, Shah PM, Mentzel C, et al. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J Infect 1996; 33: 23–32PubMedCrossRef
11.
go back to reference Yamazaki T, Kurre H, Murase S, et al. Epidemiology of visceral mycoses: analysis of data in annual of the pathological autopsy cases in Japan. J Clin Microbiol 1999; 37: 1732–8PubMed Yamazaki T, Kurre H, Murase S, et al. Epidemiology of visceral mycoses: analysis of data in annual of the pathological autopsy cases in Japan. J Clin Microbiol 1999; 37: 1732–8PubMed
12.
go back to reference Wilson L, Reyes C, Stolpman M, et al. The direct cost and incidence of systemic fungal infections. Value Health 2002; 5: 26–34PubMedCrossRef Wilson L, Reyes C, Stolpman M, et al. The direct cost and incidence of systemic fungal infections. Value Health 2002; 5: 26–34PubMedCrossRef
13.
go back to reference Rentz AM, Halpern MT, Bowden R. The impact of candidemia on length of hospital stay, outcome, and overall cost of illness. Clin Infect Dis 1998; 27: 781–8PubMedCrossRef Rentz AM, Halpern MT, Bowden R. The impact of candidemia on length of hospital stay, outcome, and overall cost of illness. Clin Infect Dis 1998; 27: 781–8PubMedCrossRef
14.
go back to reference Dasbach EJ, Davies GM, Teutsch SM. Burden of aspergillosisrelated hospitalizations in the United States. Clin Infect Dis 2000; 31: 1524–8PubMedCrossRef Dasbach EJ, Davies GM, Teutsch SM. Burden of aspergillosisrelated hospitalizations in the United States. Clin Infect Dis 2000; 31: 1524–8PubMedCrossRef
15.
go back to reference NHS Centre for Reviews and Dissemination. Making costeffectiveness information accessible: the NHS Economic Evaluation Database Project: CRD guidance for reporting critical summaries of economic evaluations. (CRD reports; no.6) York: NHS CRD, 1996 NHS Centre for Reviews and Dissemination. Making costeffectiveness information accessible: the NHS Economic Evaluation Database Project: CRD guidance for reporting critical summaries of economic evaluations. (CRD reports; no.6) York: NHS CRD, 1996
16.
go back to reference Drummond M, O’Brien B, Stoddart GL, et al. Methods for the economic evaluation of health care programmes. London: Oxford University Press, 1997 Drummond M, O’Brien B, Stoddart GL, et al. Methods for the economic evaluation of health care programmes. London: Oxford University Press, 1997
17.
go back to reference Drummond M, Jefferson T, on behalf of the BMJ Economic Evaluation Working Party. Guidelines for authors and peer reviewers of economic submissions to the BMJ. BMJ 1996; 313: 275–83PubMedCrossRef Drummond M, Jefferson T, on behalf of the BMJ Economic Evaluation Working Party. Guidelines for authors and peer reviewers of economic submissions to the BMJ. BMJ 1996; 313: 275–83PubMedCrossRef
18.
go back to reference Adams ME, McCall NT, Gray DT, et al. Economic analysis in randomized control trials. Med Care 1992; 30: 231–43PubMedCrossRef Adams ME, McCall NT, Gray DT, et al. Economic analysis in randomized control trials. Med Care 1992; 30: 231–43PubMedCrossRef
19.
go back to reference Buxton MJ, Dubois DJ, Turner RR, et al. Cost implications of alternative treatments for AIDS patients with cryptococcal meningitis: comparison of fluconazole and amphotericin Bbased therapies. J Infect 1991; 23: 17–31PubMedCrossRef Buxton MJ, Dubois DJ, Turner RR, et al. Cost implications of alternative treatments for AIDS patients with cryptococcal meningitis: comparison of fluconazole and amphotericin Bbased therapies. J Infect 1991; 23: 17–31PubMedCrossRef
20.
go back to reference Cagnoni PJ, Walsh TJ, Prendergast MM, et al. Pharmacoeconomic analysis of liposomal amphotericin B versus conventional amphotericin B in the empirical treatment of persistently febrile neutropenic patients. J Clin Oncol 2000; 18: 2476–83PubMed Cagnoni PJ, Walsh TJ, Prendergast MM, et al. Pharmacoeconomic analysis of liposomal amphotericin B versus conventional amphotericin B in the empirical treatment of persistently febrile neutropenic patients. J Clin Oncol 2000; 18: 2476–83PubMed
21.
go back to reference Dranitsaris G, Phillips P, Rotstein C, et al. Economic analysis of fluconazole versus amphotericin B for the treatment of candidemia in non-neutropenic patients. Pharmacoeconomics 1998; 13 (5): 509–18PubMedCrossRef Dranitsaris G, Phillips P, Rotstein C, et al. Economic analysis of fluconazole versus amphotericin B for the treatment of candidemia in non-neutropenic patients. Pharmacoeconomics 1998; 13 (5): 509–18PubMedCrossRef
22.
go back to reference Flynn TN, Kelsey SM, Hazel DL, et al. Cost effectiveness of amphotericin B plus G-CSF compared with amphotericin B monotherapy: treatment of presumed deep-seated fungal infection in neutropenic patients in the UK. Pharmacoeconomics 1999; 16 (5 Pt 2): 543–50PubMedCrossRef Flynn TN, Kelsey SM, Hazel DL, et al. Cost effectiveness of amphotericin B plus G-CSF compared with amphotericin B monotherapy: treatment of presumed deep-seated fungal infection in neutropenic patients in the UK. Pharmacoeconomics 1999; 16 (5 Pt 2): 543–50PubMedCrossRef
23.
go back to reference Krupova Y, Novotny J, Sabo A, et al. Aetiology, cost of antimicrobial therapy and outcome in neutropenic patients who developed bacteraemia during antimicrobial prophylaxis: a case-control study. Int J Antimicrob Agents 1998; 10: 313–6PubMedCrossRef Krupova Y, Novotny J, Sabo A, et al. Aetiology, cost of antimicrobial therapy and outcome in neutropenic patients who developed bacteraemia during antimicrobial prophylaxis: a case-control study. Int J Antimicrob Agents 1998; 10: 313–6PubMedCrossRef
24.
go back to reference Manfredi R, Mastroianni A, Coronado OV, et al. Fluconazole as prophylaxis against fungal infection in patients with advanced HIV infection. Arch Intern Med 1997; 157: 64–9PubMedCrossRef Manfredi R, Mastroianni A, Coronado OV, et al. Fluconazole as prophylaxis against fungal infection in patients with advanced HIV infection. Arch Intern Med 1997; 157: 64–9PubMedCrossRef
25.
go back to reference Persson U, Tennvall GR, Andersson S, et al. Cost-effectiveness analysis of treatment with liposomal amphotericin B versus conventional amphotericin B in organ or bone marrow transplant recipients with systemic mycoses. Pharmacoeconomics 1992; 2 (6): 500–8PubMedCrossRef Persson U, Tennvall GR, Andersson S, et al. Cost-effectiveness analysis of treatment with liposomal amphotericin B versus conventional amphotericin B in organ or bone marrow transplant recipients with systemic mycoses. Pharmacoeconomics 1992; 2 (6): 500–8PubMedCrossRef
26.
go back to reference Poirier JM, Hardy S, Isnard F, et al. Plasma itraconazole concentrations in patients with neutropenia: advantages of a divided daily dosage regimen. Ther Drug Monit 1997; 19: 525–9PubMedCrossRef Poirier JM, Hardy S, Isnard F, et al. Plasma itraconazole concentrations in patients with neutropenia: advantages of a divided daily dosage regimen. Ther Drug Monit 1997; 19: 525–9PubMedCrossRef
27.
go back to reference Sajben P, Minarik T, TomasikE, et al. Fluconazol plus ofloxacin in prophylaxis of infections in patients with acute leukemia: a comparative study. Support Care Cancer 1993; 1: 214–6PubMedCrossRef Sajben P, Minarik T, TomasikE, et al. Fluconazol plus ofloxacin in prophylaxis of infections in patients with acute leukemia: a comparative study. Support Care Cancer 1993; 1: 214–6PubMedCrossRef
28.
go back to reference Schaffner A, Schaffner M. Effect of prophylactic fluconazole on the frequency of fungal infections, amphotericin B use, and health care costs in patients undergoing intensive chemotherapy for hematologic neoplasias. J Infect Dis 1995; 172: 1035–41PubMedCrossRef Schaffner A, Schaffner M. Effect of prophylactic fluconazole on the frequency of fungal infections, amphotericin B use, and health care costs in patients undergoing intensive chemotherapy for hematologic neoplasias. J Infect Dis 1995; 172: 1035–41PubMedCrossRef
29.
go back to reference Scharfstein JA, Paltiel AD, Freedberg KA. The cost-effectiveness of fluconazole prophylaxis against primary systemic fungal infections in AIDS patients. Med Decis Making 1997; 17: 373–81PubMedCrossRef Scharfstein JA, Paltiel AD, Freedberg KA. The cost-effectiveness of fluconazole prophylaxis against primary systemic fungal infections in AIDS patients. Med Decis Making 1997; 17: 373–81PubMedCrossRef
30.
go back to reference Schroder CP, de Vries EG, Mulder NH, et al. Prevention of febrile leucopenia after chemotherapy in high-risk breast cancer patients: no significant difference between granulocytecolony stimulating growth factor or ciprofloxacin plus amphotericin B. J Antimicrob Chemother 1999; 43: 741–3PubMedCrossRef Schroder CP, de Vries EG, Mulder NH, et al. Prevention of febrile leucopenia after chemotherapy in high-risk breast cancer patients: no significant difference between granulocytecolony stimulating growth factor or ciprofloxacin plus amphotericin B. J Antimicrob Chemother 1999; 43: 741–3PubMedCrossRef
31.
go back to reference Skinner JL, Harris C, Aaron MF, et al. Cost-benefit analysis of extended antifungal prophylaxis in ventricular assist devices. ASAIO J 2000; 46: 587–9PubMedCrossRef Skinner JL, Harris C, Aaron MF, et al. Cost-benefit analysis of extended antifungal prophylaxis in ventricular assist devices. ASAIO J 2000; 46: 587–9PubMedCrossRef
32.
go back to reference Tollemar J, Hockerstedt K, Ericzon BG, et al. Liposomal amphotericin B prevents invasive fungal infections in liver transplant recipients: a randomized, placebo-controlled study. Transplantation 1995; 59: 45–50PubMedCrossRef Tollemar J, Hockerstedt K, Ericzon BG, et al. Liposomal amphotericin B prevents invasive fungal infections in liver transplant recipients: a randomized, placebo-controlled study. Transplantation 1995; 59: 45–50PubMedCrossRef
33.
go back to reference Wakerly L, Craig AM, Malek M, et al. Fluconazole versus oral polyenes in the prophylaxis of Imminocomprorrused patients: a cost-minimization analysis. J Hosp Infect 1996; 33: 35–48PubMedCrossRef Wakerly L, Craig AM, Malek M, et al. Fluconazole versus oral polyenes in the prophylaxis of Imminocomprorrused patients: a cost-minimization analysis. J Hosp Infect 1996; 33: 35–48PubMedCrossRef
34.
go back to reference Kind P. The EuroQol instrument: an index of health-related quality oflife. In: Spilker B, editor. Quality oflife and pharmacoeconomics in clinical trials. 2nd ed. Philadelphia (PA): Lippincott-Raven, 1996: 191–201 Kind P. The EuroQol instrument: an index of health-related quality oflife. In: Spilker B, editor. Quality oflife and pharmacoeconomics in clinical trials. 2nd ed. Philadelphia (PA): Lippincott-Raven, 1996: 191–201
35.
go back to reference Sheldon T. Problems of using modelling in the economic evaluation of health care. Health Econ 1996; 5: 1–11PubMedCrossRef Sheldon T. Problems of using modelling in the economic evaluation of health care. Health Econ 1996; 5: 1–11PubMedCrossRef
36.
go back to reference McCabe C, Dixon S. Testing the validity of cost-effectiveness models. Pharmacoeconomics 2000; 17 (5): 501–13PubMedCrossRef McCabe C, Dixon S. Testing the validity of cost-effectiveness models. Pharmacoeconomics 2000; 17 (5): 501–13PubMedCrossRef
37.
go back to reference Buxton MJ, Drummond MF, van Hout BA, et al. Modelling in economic evaluation: an unavoidable fact of life. Health Econ 1997; 6: 217–27PubMedCrossRef Buxton MJ, Drummond MF, van Hout BA, et al. Modelling in economic evaluation: an unavoidable fact of life. Health Econ 1997; 6: 217–27PubMedCrossRef
38.
go back to reference O’Brien B. Economic of pharmaceuticals: Frankenstein’s monster or vampire of trials? Med Care 1996; 34: DS99-DS108 O’Brien B. Economic of pharmaceuticals: Frankenstein’s monster or vampire of trials? Med Care 1996; 34: DS99-DS108
39.
go back to reference Schulman KA, Buxton M, Glick H, et al. Results of the economic evaluation of the FIRST study: a multinational prospective economic evaluation. Int J Technol Assess Health Care 1996; 12: 698–713PubMedCrossRef Schulman KA, Buxton M, Glick H, et al. Results of the economic evaluation of the FIRST study: a multinational prospective economic evaluation. Int J Technol Assess Health Care 1996; 12: 698–713PubMedCrossRef
Metadata
Title
Economic Evaluations of Treatments for Systemic Fungal Infections
A Systematic Review of the Literature
Authors
Dr Simon Dixon
Emma McKeen
Margaret Tabberer
Suzy Paisley
Publication date
01-05-2004
Publisher
Springer International Publishing
Published in
PharmacoEconomics / Issue 7/2004
Print ISSN: 1170-7690
Electronic ISSN: 1179-2027
DOI
https://doi.org/10.2165/00019053-200422070-00002

Other articles of this Issue 7/2004

PharmacoEconomics 7/2004 Go to the issue

Adis Pharmacoeconomic Drug Evaluation

Drotrecogin Alfa (Activated)