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December 25, 1991, Vol 266, No. 24 >
ARTICLE | December 25, 1991

Cost-effectiveness of HA-1A Monoclonal Antibody for Gram-Negative Sepsis: Title and subTitle BreakEconomic Assessment of a New Therapeutic Agent FREE

Kevin A. Schulman, MD; Henry A. Glick, MA; Harvey Rubin, MD; John M. Eisenberg, MD
[+] Author Affiliations

Reprint requests to Department of Medicine, Georgetown University Medical Center, 3800 Reservoir Rd NW, Washington, DC 20007-2197 (Dr Eisenberg).


JAMA. 1991;266(24):3466-3471. doi:10.1001/jama.1991.03470240088039
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Article
References

Objective.  —To assess the cost-effectiveness of the HA-1A monoclonal antibody for the treatment of gram-negative bacteremia.

Design.  —Cost-effectiveness analysis of a randomized, double-blind, placebo-controlled trial using clinical efficacy data reported in the medical literature.

Setting.  —Hospitalized patients with sepsis.

Patients.  —543 patients with sepsis and suspected gram-negative infection. Patients enrolled in the study met strict criteria for sepsis, including fever or hypothermia (<35.6°C or >38.3°C), tachycardia (>90 beats per minute), tachypnea (>20 breaths per minute), and hypotension or two of six signs of systemic toxicity.

Intervention.  —HA-1A vs placebo in addition to usual care.

Main Outcome Measures.  —We determined the range of possible cost-effectiveness ratios for HA-1 A therapy, using modeling techniques when clinical or economic variables were unknown. We subjected the model to rigorous sensitivity analysis. We calculated the incremental cost of care and years of life saved for patients with sepsis and modeled two different treatment strategies: treat all patients with sepsis or test and then treat only patients with positive test results.

Results.  —The cost-effectiveness of therapy based on our two models was $24100 per year of life saved based on the treat strategy and $14 900 based on the test strategy. In sensitivity analysis the ratios ranged from $5200 to $110 200 per year of life gained. Annual costs of care for these two strategies are $1.3 billion for the test strategy and $2.3 billion for the treat strategy.

Conclusion.  —Economic assessment of new technologies early in their development can be used to guide their efficient clinical introduction.(JAMA. 1991;266:3466-3471)

REFERENCES

1 +
Ziegler EJ, Fisher CJ, Sprung CL, et al.  Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin: a randomized, double-blind, placebo-controlled trial. N Engl J Med . 1991;;324:429-436.
2 +
Young LS.  Gram-negative sepsis.  In: Mandell GL, Douglas RG Jr, Bennett JE, eds. Principles and Practice of Infectious Diseases . 2nd ed. New York, NY: John Wiley & Sons Inc; 1985;.
3 +
 Increase in national hospital discharge survey rates for septicemia—United States, 1979-1987. MMWR . 1990;;39:31-34.
4 +
Fox JL.  Antibodies against sepsis. Biotechnology . 1990;;8:1240-1241.
5 +
Health Care Financing Administration, US Dept of Health and Human Services.  Medicare program: criteria and procedures for making medical service coverage decisions that relate to medical technology. Federal Register . (January 30) , 1989;;54:4302-4318.
6 +
Schulman KA, Lynn LA, Glick HA, Eisenberg JM.  Cost effectiveness of low-dose zidovudine therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection. Ann Intern Med . 1991;;114:798-802.
7 +
Length of Stay . Ann Arbor, Mich: Healthcare Knowledge Systems Publications; 1989;.
8 +
Statistical Abstract of the United States: 1990 . Washington, DC: US Dept of Commerce; 1990;.
9 +
Moussa MAA.  Analysis of underlying and multiple-cause mortality data: the life table methods. Comput Methods Programs Biomed . 1987;;24:3-19.
10 +
Cancer Statistics Review 1973-1986 . Bethesda, Md: National Cancer Institute; 1989;.
11 +
Panzram G.  Mortality and survival in type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia . 1987;;30:123-131.
12 +
Tanaka R, Tatsuya I, Nagashima H.  Follow-up study of 582 liver cirrhosis patients for 26 years in Japan. Liver . 1987;;7:316-324.
13 +
Brook RH, Appel FA, Avery C, Orman M, Stevenson RL.  Effectiveness of inpatient follow-up care. N Engl J Med . 1971;; 285:1509-1514.
14 +
Pessi TT.  Experiences gained in the intensive care unit of surgical patients. Ann Chir Gynaecol . 1973;;185( (suppl) ):3-72.
15 +
Cullen DJ, Ferrara LC, Briggs BA, Walker PF, Gilbert J.  Survival, hospitalization charges and follow-up results in critically ill patients. N Engl J Med . 1976;;294:982-987.
16 +
Nunn JF, Milledge JS, Singaraya J.  Survival of patients ventillated in an intensive care unit. BMJ . 1979;;1:1525-1527.
17 +
Thibault GE, Mulley AG, Barnett GO, et al.  Medical intensive care: indications, interventions, and outcomes. N Engl J Med . 1980;;302:938-942.
18 +
Chassin MR.  Costs and outcomes of medical intensive care: implications for cost control. Med Care . 1982;;20:165-179.
19 +
Parno J, Teres D, Lemeshow S, Brown RB.  Hospital charges and long-term survival of ICU versus non-ICU patients. Crit Care Med . 1982;;10:569-574.
20 +
Parno JR, Teres D, Lemeshow S, Brown RB, Avrunin JS.  Two-year outcome of adult intensive care patients. Med Care . 1984;;22:167-176.
21 +
Searle JF.  The outcome of mechanical ventilation: report of a five year study. Ann R Coll Surg Engl . 1985;;67:187-189.
22 +
Thoner J.  Outcome and costs of intensive care: a follow-up study on patients requiring prolonged mechanical ventilation. Acta Anaesthesiol Scand . 1987;;31:693-698.
23 +
Spicher JE, White DP.  Outcome and function following prolonged mechanical ventilation. Arch Intern Med . 1987;;147:421-425.
24 +
Ludwigs UG, Baehrendtz S, Wanecek M, Matell G.  Mechanical ventilation in medical and neurological diseases: 11 years of experience. J Intern Med . 1991;;229:117-124.
25 +
Daley C, Lim I, J Modra, Wilkinson I.  Comparative evaluation of nonradiometric BACTEC and improved oxoid signal blood culture systems in a clinical laboratory. J Clin Microbiol . 1990;;28:1586-1590.
26 +
Weinstein MP, Mirrett S, Wilson ML, Harrell LJ, Stratton CW, Reller LB.  Controlled evaluation of BACTEC Plus 26 and Roche Septi-Chek aerobic blood culture bottles. J Clin Microbiol . 1991;;29:879-882.
27 +
Fant WK.  Selecting patients for monoclonal antibody therapy. Am J Hosp Pharm . 1990;;47( (suppl 3) ):16-19.
28 +
Van Deventer SJH, Buller HR, Ten Cante JW, Sturk A, Pauw W.  Endotoxaemia: an early predictor of septicemia in febrile patients. Lancet . 1988;;1:605-609.
29 +
Yamagami S, Adachi T, Sugimura T, et al.  Detection of endotoxin antibody in long-term dialysis patients. Int J Artif Organs . 1990;;13:205-210.
30 +
Roth RI, Levin J, Behr S.  A modified Limulus amebocyte lysate test with increased sensitivity for detection of bacterial endotoxin. J Lab Clin Med . 1989;;114:306-311.
31 +
Obayashi T.  A new endotoxin-specific assay. Adv Exp Med Biol . 1990;;256:215-223.
32 +
Eisenberg JM, Hershey JC.  Derived thresholds: determining the diagnostic probabilities at which clinicians initiate testing and treatment. Med Decis Making . 1983;;3:155-168.
33 +
Beier JC, Perkins PV, Koros JK, et al.  Malaria sporozoite detection by dissection and ELISA to assess infectivity of afrotropical Anopheles (Diptera: Culcidae). J Med Entomol . 1990;;27:377-384.
34 +
Chiodi F, Sundqvist VA, Norrby E, Mavra M, Link H.  Measles IgM antibodies in cerebrospinal fluid and serum in subacute sclerosing panencephalitis. J Med Virol . 1986;;18:149-158
35 +
Field PR, Ho DW, Cunningham AL.  Evaluation of rubella immune status by three commercial enzyme-linked immunosorbent assays. J Clin Microbiol . 1988;;26:990-994.
36 +
Linde A, Kallin B, Dillner J, et al.  Evaluation of enzyme-linked immunosorbent assays with two synthetic peptides of Epstein-Barr virus for diagnosis of infectious mononucleosis. J Infect Dis . 1990;;161:903-909.
37 +
Rosoff JD, Sanders CA, Sonnad SS, et al.  Stool diagnosis of giardiasis using a commercially available enzyme immunoassay to detect Giardia-specific antigen 65 (GSA 65). J Clin Microbiol . 1989;;27:1997-2002.
38 +
Schwartz JS, Kinosian BP, Pierskalla WP, Lee H.  Strategies for screening blood for human immunodeficiency virus antibody: use of a decision support system. JAMA . 1990;;264:1704-1710.
39 +
Teplizki H, Buskila D, Alkan M, Coates ARM, Baumgarten A, Shoenfeld Y.  ELISA measurement of antibody titer to purified protein derivative and mycobacteria-derived phosphoglycolipids: tool for diagnosing active pulmonary tuberculosis. Isr J Med Sci . 1987;;23:1121-1124.
40 +
Donham CS, Maple BT, Singer N.  Health care indicators. Health Care Financ Rev . 1990;;11:169-196.
41 +
Kinosian BP, Eisenberg JM.  Cutting into cholesterol: cost-effective alternatives for treating hypercholesterolemia. JAMA . 1988;;259:2249-2254.
42 +
Eisenberg JM, Kitz DS.  Savings from outpaoutpa- antibiotic therapy for osteomyelitis. JAMA . 1986;;255:1584-1588.

Figures

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Ziegler EJ, Fisher CJ, Sprung CL, et al.  Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin: a randomized, double-blind, placebo-controlled trial. N Engl J Med . 1991;;324:429-436.
2 +
Young LS.  Gram-negative sepsis.  In: Mandell GL, Douglas RG Jr, Bennett JE, eds. Principles and Practice of Infectious Diseases . 2nd ed. New York, NY: John Wiley & Sons Inc; 1985;.
3 +
 Increase in national hospital discharge survey rates for septicemia—United States, 1979-1987. MMWR . 1990;;39:31-34.
4 +
Fox JL.  Antibodies against sepsis. Biotechnology . 1990;;8:1240-1241.
5 +
Health Care Financing Administration, US Dept of Health and Human Services.  Medicare program: criteria and procedures for making medical service coverage decisions that relate to medical technology. Federal Register . (January 30) , 1989;;54:4302-4318.
6 +
Schulman KA, Lynn LA, Glick HA, Eisenberg JM.  Cost effectiveness of low-dose zidovudine therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection. Ann Intern Med . 1991;;114:798-802.
7 +
Length of Stay . Ann Arbor, Mich: Healthcare Knowledge Systems Publications; 1989;.
8 +
Statistical Abstract of the United States: 1990 . Washington, DC: US Dept of Commerce; 1990;.
9 +
Moussa MAA.  Analysis of underlying and multiple-cause mortality data: the life table methods. Comput Methods Programs Biomed . 1987;;24:3-19.
10 +
Cancer Statistics Review 1973-1986 . Bethesda, Md: National Cancer Institute; 1989;.
11 +
Panzram G.  Mortality and survival in type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia . 1987;;30:123-131.
12 +
Tanaka R, Tatsuya I, Nagashima H.  Follow-up study of 582 liver cirrhosis patients for 26 years in Japan. Liver . 1987;;7:316-324.
13 +
Brook RH, Appel FA, Avery C, Orman M, Stevenson RL.  Effectiveness of inpatient follow-up care. N Engl J Med . 1971;; 285:1509-1514.
14 +
Pessi TT.  Experiences gained in the intensive care unit of surgical patients. Ann Chir Gynaecol . 1973;;185( (suppl) ):3-72.
15 +
Cullen DJ, Ferrara LC, Briggs BA, Walker PF, Gilbert J.  Survival, hospitalization charges and follow-up results in critically ill patients. N Engl J Med . 1976;;294:982-987.
16 +
Nunn JF, Milledge JS, Singaraya J.  Survival of patients ventillated in an intensive care unit. BMJ . 1979;;1:1525-1527.
17 +
Thibault GE, Mulley AG, Barnett GO, et al.  Medical intensive care: indications, interventions, and outcomes. N Engl J Med . 1980;;302:938-942.
18 +
Chassin MR.  Costs and outcomes of medical intensive care: implications for cost control. Med Care . 1982;;20:165-179.
19 +
Parno J, Teres D, Lemeshow S, Brown RB.  Hospital charges and long-term survival of ICU versus non-ICU patients. Crit Care Med . 1982;;10:569-574.
20 +
Parno JR, Teres D, Lemeshow S, Brown RB, Avrunin JS.  Two-year outcome of adult intensive care patients. Med Care . 1984;;22:167-176.
21 +
Searle JF.  The outcome of mechanical ventilation: report of a five year study. Ann R Coll Surg Engl . 1985;;67:187-189.
22 +
Thoner J.  Outcome and costs of intensive care: a follow-up study on patients requiring prolonged mechanical ventilation. Acta Anaesthesiol Scand . 1987;;31:693-698.
23 +
Spicher JE, White DP.  Outcome and function following prolonged mechanical ventilation. Arch Intern Med . 1987;;147:421-425.
24 +
Ludwigs UG, Baehrendtz S, Wanecek M, Matell G.  Mechanical ventilation in medical and neurological diseases: 11 years of experience. J Intern Med . 1991;;229:117-124.
25 +
Daley C, Lim I, J Modra, Wilkinson I.  Comparative evaluation of nonradiometric BACTEC and improved oxoid signal blood culture systems in a clinical laboratory. J Clin Microbiol . 1990;;28:1586-1590.
26 +
Weinstein MP, Mirrett S, Wilson ML, Harrell LJ, Stratton CW, Reller LB.  Controlled evaluation of BACTEC Plus 26 and Roche Septi-Chek aerobic blood culture bottles. J Clin Microbiol . 1991;;29:879-882.
27 +
Fant WK.  Selecting patients for monoclonal antibody therapy. Am J Hosp Pharm . 1990;;47( (suppl 3) ):16-19.
28 +
Van Deventer SJH, Buller HR, Ten Cante JW, Sturk A, Pauw W.  Endotoxaemia: an early predictor of septicemia in febrile patients. Lancet . 1988;;1:605-609.
29 +
Yamagami S, Adachi T, Sugimura T, et al.  Detection of endotoxin antibody in long-term dialysis patients. Int J Artif Organs . 1990;;13:205-210.
30 +
Roth RI, Levin J, Behr S.  A modified Limulus amebocyte lysate test with increased sensitivity for detection of bacterial endotoxin. J Lab Clin Med . 1989;;114:306-311.
31 +
Obayashi T.  A new endotoxin-specific assay. Adv Exp Med Biol . 1990;;256:215-223.
32 +
Eisenberg JM, Hershey JC.  Derived thresholds: determining the diagnostic probabilities at which clinicians initiate testing and treatment. Med Decis Making . 1983;;3:155-168.
33 +
Beier JC, Perkins PV, Koros JK, et al.  Malaria sporozoite detection by dissection and ELISA to assess infectivity of afrotropical Anopheles (Diptera: Culcidae). J Med Entomol . 1990;;27:377-384.
34 +
Chiodi F, Sundqvist VA, Norrby E, Mavra M, Link H.  Measles IgM antibodies in cerebrospinal fluid and serum in subacute sclerosing panencephalitis. J Med Virol . 1986;;18:149-158
35 +
Field PR, Ho DW, Cunningham AL.  Evaluation of rubella immune status by three commercial enzyme-linked immunosorbent assays. J Clin Microbiol . 1988;;26:990-994.
36 +
Linde A, Kallin B, Dillner J, et al.  Evaluation of enzyme-linked immunosorbent assays with two synthetic peptides of Epstein-Barr virus for diagnosis of infectious mononucleosis. J Infect Dis . 1990;;161:903-909.
37 +
Rosoff JD, Sanders CA, Sonnad SS, et al.  Stool diagnosis of giardiasis using a commercially available enzyme immunoassay to detect Giardia-specific antigen 65 (GSA 65). J Clin Microbiol . 1989;;27:1997-2002.
38 +
Schwartz JS, Kinosian BP, Pierskalla WP, Lee H.  Strategies for screening blood for human immunodeficiency virus antibody: use of a decision support system. JAMA . 1990;;264:1704-1710.
39 +
Teplizki H, Buskila D, Alkan M, Coates ARM, Baumgarten A, Shoenfeld Y.  ELISA measurement of antibody titer to purified protein derivative and mycobacteria-derived phosphoglycolipids: tool for diagnosing active pulmonary tuberculosis. Isr J Med Sci . 1987;;23:1121-1124.
40 +
Donham CS, Maple BT, Singer N.  Health care indicators. Health Care Financ Rev . 1990;;11:169-196.
41 +
Kinosian BP, Eisenberg JM.  Cutting into cholesterol: cost-effective alternatives for treating hypercholesterolemia. JAMA . 1988;;259:2249-2254.
42 +
Eisenberg JM, Kitz DS.  Savings from outpaoutpa- antibiotic therapy for osteomyelitis. JAMA . 1986;;255:1584-1588.

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