0
January 13, 1993, Vol 269, No. 2 >
ARTICLE | January 13, 1993

Cost-effectiveness of Monoclonal Antibodies to Gram-negative Endotoxin in the Treatment of Gram-negative Sepsis in ICU Patients FREE

Donald B. Chalfin, MD, MS; M. E. Blair Holbein, PhD; Alan M. Fein, MD; Graziano C. Carlon, MD
[+] Author Affiliations

Presented, in part, at the 19th Annual Educational and Scientific Symposium of the Society of Critical Care Medicine, San Francisco, Calif, May 29-June 1, 1990.

Reprint requests to Division of Pulmonary and Critical Care Medicine, Winthrop-University Hospital, 222 Station Plaza N, Suite 400, Mineola, NY 11501 (Dr Chalfin).


JAMA. 1993;269(2):249-254. doi:10.1001/jama.1993.03500020083037
Text Size: A A A
Published online
Article
References

Objective.  —To evaluate the fiscal impact and the cost-effectiveness of monoclonal antibodies against gram-negative endotoxin (MAbGNE) in the treatment of presumed gram-negative sepsis.

Design.  —A decision analysis model was developed from (1) data from two phase III trials that studied the E5 or HA-1A MAbGNE, and (2) financial data from 1405 septic patients who required intensive care at a large tertiary hospital.

Setting.  —Intensive care unit (ICU) patients with presumed gram-negative sepsis.

Patients.  —The E5 trial evaluated 468 patients, and the HA-1A study enrolled 543 patients with presumed gram-negative sepsis.

Interventions.  —The addition of MAbGNE to standard regimens or standard regimens alone.

Main Outcome Measures.  —Total expected charges and the expected probability of survival were determined for each option. Cost-effectiveness and marginal cost-effectiveness ratios were also derived. Multiple sensitivity and Monte Carlo analyses were performed to test the underlying assumptions.

Results.  —MAbGNE therapy always resulted in higher expected charges; however, these differences were less than its acquisition cost by $870. The cost-effectiveness ratio for MAbGNE, for $2000 and $4000 acquisition costs, was $71 674 and $74 900 per probability of survival, respectively. Sensitivity analysis showed that cost-effectiveness was most affected by diagnostic accuracy, patient selection, and acquisition cost. Monte Carlo analysis showed that MAbGNE was more costly for 71% of simulations, yet the most efficacious option for 79% of simulations.

Conclusions.  —From the perspective of acute care institutions, MAbGNE is expensive and cannot be justified on a cost-saving basis. However, it may be cost-effective throughout a reasonable range of assumptions.(JAMA. 1993;269:249-254)

REFERENCES

1 +
Centers for Disease Control.  Increase in national hospital discharge survey rates for septicemia— United States, 1979-1987. MMWR . 1990;;39:31-34.
2 +
Bone RC, Fisher CJ, Clemmer TP, et al.  Sepsis syndrome: a valid clinical entity. Crit Care Med . 1989;;17:389-393.
3 +
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.
4 +
Cullen DJ.  Results and costs of intensive care. Anesthesiology . 1977;;47:203-216.
5 +
Oye RK, Bellamy PE.  Patterns of resource consumption in medical intensive care. Chest . 1991;;99: 6875-6789.
6 +
Bone RC, Elpern EH.  Honoring patient preferences and rationing intensive care: are these compatible goals? Arch Intern Med . 1991;;151:1061-1063.
7 +
Goetzler RM, Moskowitz MA.  Changes in physician attitudes toward limiting care of critically ill patients. Arch Intern Med . 1991;;151:1537-1540.
8 +
Engleberg NC, Eisenstein BI.  The impact of new cloning techniques on the diagnosis and treatment of infectious disease. N Engl J Med . 1984;; 311:892-901.
9 +
Bogard WC Jr, Dunn DL, Abernethy K, Kilgarriff C, Kung PC.  Isolation and characterization of murine monoclonal antibodies specific for gram-negative bacterial lipopolysaccharide: association of cross-genus reactivity with lipid A specificity. Infect Immun . 1987;;55:899-908.
10 +
Harkonen S, Scannon P, Mischak RP, et al.  Phase I study of a murine monoclonal anti-lipid A antibody in bacteremia and nonbacteremic patients. Antimicrob Agents Chemother . 1988;;32:710-716.
11 +
Ziegler EJ, Fischer CJ, Sprung CL, et al.  Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. N Engl J Med . 1991;;324:429-436.
12 +
Parillo JE.  Septic shock in humans: advances in the understanding of pathogenesis, cardiovascular dysfunction and therapy. Ann Intern Med . 1990;; 113:227-242.
13 +
Ziegler EJ, McCutchan A, Fierer J, et al.  Treatment of gram-negative bacteremia and shock with human anti-serum to a mutant Escherichia coli. N Engl J Med . 1982;;307:1225-1230.
14 +
Greenman RL, Schein RMH, Martin MA, et al.  A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. JAMA . 1991;;266:1097-1102.
15 +
Schwartz WB, Mendelson DN.  Hospital cost containment in the 1980s: hard lessons learned and prospects for the 1990s. N Engl J Med . 1991;;324: 1037-1042.
16 +
Schulman KA, Glick HA, Rubin H, Eisenberg JM.  Cost-effectiveness of HA-1A monoclonal antibody for gram-negative sepsis: economic assessment of a new therapeutic agent. JAMA . 1991;;266: 3466-3471.
17 +
Weinstein MC, Fineberg HV. Clinical Decision Analysis . Philadelphia, Pa: WB Saunders Co; 1980;:12-34.
18 +
Sox HC, Blatt MA, Higgins MC, Marton KI. Medical Decision Making . Stoneham, Mass: Butterworths; 1988;:27-34.
19 +
Kassirer FP, Moskowitz AJ, Lau J, Pauker SG.  Decision analysis: a progress report. Ann Intern Med . 1987;;106:275-291.
20 +
Shepherd MF.  Criteria for use of antiendotoxin monoclonal antibodies (HA-1A and E5) in adult and pediatric inpatients. Clin Pharm . 1992;;11:257-260.
21 +
Finkler SA.  The distinction between costs and charges. Ann Intern Med . 1982;;96:102-109.
22 +
Marty AT, Matar AF, Danielson R, O'Reilly R.  The variation in hospital charges: a problem in determining the cost/benefit ratio for cardiac surgery. Ann Thorac Surg . 1977;;24:409-416.
23 +
Weinstein MC, Stason WB.  Foundations of cost-effectiveness analysis for health and medical practices. N Engl J Med . 1977;;296:716-721.
24 +
Jacobs P, Noseworthy TW.  National estimates of intensive care utilization and costs: Canada and the United States. Crit Care Med . 1990;;17:1282-1286.
25 +
Sloan FA, Morrisey MA, Valvona J.  Medicare prospective payment and the use of medical technologies in hospitals. Med Care . 1988;;26:837-853.
26 +
Spivack D.  The high cost of acute health care: a review of escalating costs and limitations of such exposure in intensive care units. Am Rev Respir Dis . 1987;;136:1007-1011.
27 +
Bekes C, Fleming S, Scott WE.  Reimbursement for intensive care services under diagnosis related groups. Crit Care Med . 1988;;16:478-481.
28 +
Ahmad M, Fergus L, Stothard P,  Harrington D, Sivak E, Farmer R. Impact of diagnosis-related groups' prospective payment on utilization of medical intensive care. Chest . 1988;;93:176-179.
29 +
Butler PW, Bone RC, Field T.  Technology under Medicare diagnosis-related groups prospective payment. Chest . 1985;;87:228-234.
30 +
Chalfin DB, Carlon GC, Munoz E.  Hospital cost of intensive care survivors and nonsurvivors under diagnostic related groups (DRGs). Crit Care Med . 1989;;17( (suppl) ):S86.
31 +
Cerra FB.  The multiple organ failure syndrome. Hosp Pract . 1990;;25:169-176.
32 +
Doubilet P, Begg CB, Weinstein MC, Braun P, McNeil BJ.  Probabilistic sensitivity analysis using Monte Carlo simulation. Med Decis Making . 1985;; 5:157-177.
33 +
Willard KE, Critchfield GN.  Probabilistic analysis of decision trees using Monte Carlo simulation. Med Decis Making . 1986;;6:85-92.
34 +
Hollenberg J. SML TREE: The All Purpose Decision Tree Builder . Boston, Mass: Pratt Medical Group; 1985;.
35 +
DeGroot MH. Probability and Statistics . Reading, Mass: Addison-Wesley Publishing Co; 1986;.
36 +
Wilkinson L. SYSTAT: The System for Statistics . Evanston, Ill: SYSTAT Inc; 1989;.
37 +
Wenzel RP.  Anti-endotoxin monoclonal antibodies: a second look. N Engl J Med . 1992;;326: 1151-1152.
38 +
Warren HS, Danner RL, Munford RS.  Antiendotoxin monoclonal antibodies. N Engl J Med . 1992;;326:1153-1156.
39 +
Cunnion RE.  Clinical trials of immunotherapy for sepsis. Crit Care Med . 1992;;20:721-723.
40 +
Laffel GL.  A cost-effectiveness model for coronary thrombolysis/reperfusion therapy. J Am Coll Cardiol . 1987;;10( (5 suppl B) ):79B-90B.
41 +
Fineberg HV, Scadden D, Goldman L.  Care of patients with a low probability of acute myocardial infarction: cost-effectiveness of alternatives to coronary-care-unit admission. N Engl J Med . 1984;; 310:1301-1307.
42 +
Beck JR, Pauker SG.  The Markov process in medical prognosis. Med Decis Making . 1983;;3:419-458.
43 +
Beck JR, Kassirer JP, Pauker SG.  A convenient approximation of life expectancy (the 'DEALE'). Am J Med . 1982;;73:883-888.

Figures

Tables

Interactive Graphics

Video

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 +
Centers for Disease Control.  Increase in national hospital discharge survey rates for septicemia— United States, 1979-1987. MMWR . 1990;;39:31-34.
2 +
Bone RC, Fisher CJ, Clemmer TP, et al.  Sepsis syndrome: a valid clinical entity. Crit Care Med . 1989;;17:389-393.
3 +
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.
4 +
Cullen DJ.  Results and costs of intensive care. Anesthesiology . 1977;;47:203-216.
5 +
Oye RK, Bellamy PE.  Patterns of resource consumption in medical intensive care. Chest . 1991;;99: 6875-6789.
6 +
Bone RC, Elpern EH.  Honoring patient preferences and rationing intensive care: are these compatible goals? Arch Intern Med . 1991;;151:1061-1063.
7 +
Goetzler RM, Moskowitz MA.  Changes in physician attitudes toward limiting care of critically ill patients. Arch Intern Med . 1991;;151:1537-1540.
8 +
Engleberg NC, Eisenstein BI.  The impact of new cloning techniques on the diagnosis and treatment of infectious disease. N Engl J Med . 1984;; 311:892-901.
9 +
Bogard WC Jr, Dunn DL, Abernethy K, Kilgarriff C, Kung PC.  Isolation and characterization of murine monoclonal antibodies specific for gram-negative bacterial lipopolysaccharide: association of cross-genus reactivity with lipid A specificity. Infect Immun . 1987;;55:899-908.
10 +
Harkonen S, Scannon P, Mischak RP, et al.  Phase I study of a murine monoclonal anti-lipid A antibody in bacteremia and nonbacteremic patients. Antimicrob Agents Chemother . 1988;;32:710-716.
11 +
Ziegler EJ, Fischer CJ, Sprung CL, et al.  Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. N Engl J Med . 1991;;324:429-436.
12 +
Parillo JE.  Septic shock in humans: advances in the understanding of pathogenesis, cardiovascular dysfunction and therapy. Ann Intern Med . 1990;; 113:227-242.
13 +
Ziegler EJ, McCutchan A, Fierer J, et al.  Treatment of gram-negative bacteremia and shock with human anti-serum to a mutant Escherichia coli. N Engl J Med . 1982;;307:1225-1230.
14 +
Greenman RL, Schein RMH, Martin MA, et al.  A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. JAMA . 1991;;266:1097-1102.
15 +
Schwartz WB, Mendelson DN.  Hospital cost containment in the 1980s: hard lessons learned and prospects for the 1990s. N Engl J Med . 1991;;324: 1037-1042.
16 +
Schulman KA, Glick HA, Rubin H, Eisenberg JM.  Cost-effectiveness of HA-1A monoclonal antibody for gram-negative sepsis: economic assessment of a new therapeutic agent. JAMA . 1991;;266: 3466-3471.
17 +
Weinstein MC, Fineberg HV. Clinical Decision Analysis . Philadelphia, Pa: WB Saunders Co; 1980;:12-34.
18 +
Sox HC, Blatt MA, Higgins MC, Marton KI. Medical Decision Making . Stoneham, Mass: Butterworths; 1988;:27-34.
19 +
Kassirer FP, Moskowitz AJ, Lau J, Pauker SG.  Decision analysis: a progress report. Ann Intern Med . 1987;;106:275-291.
20 +
Shepherd MF.  Criteria for use of antiendotoxin monoclonal antibodies (HA-1A and E5) in adult and pediatric inpatients. Clin Pharm . 1992;;11:257-260.
21 +
Finkler SA.  The distinction between costs and charges. Ann Intern Med . 1982;;96:102-109.
22 +
Marty AT, Matar AF, Danielson R, O'Reilly R.  The variation in hospital charges: a problem in determining the cost/benefit ratio for cardiac surgery. Ann Thorac Surg . 1977;;24:409-416.
23 +
Weinstein MC, Stason WB.  Foundations of cost-effectiveness analysis for health and medical practices. N Engl J Med . 1977;;296:716-721.
24 +
Jacobs P, Noseworthy TW.  National estimates of intensive care utilization and costs: Canada and the United States. Crit Care Med . 1990;;17:1282-1286.
25 +
Sloan FA, Morrisey MA, Valvona J.  Medicare prospective payment and the use of medical technologies in hospitals. Med Care . 1988;;26:837-853.
26 +
Spivack D.  The high cost of acute health care: a review of escalating costs and limitations of such exposure in intensive care units. Am Rev Respir Dis . 1987;;136:1007-1011.
27 +
Bekes C, Fleming S, Scott WE.  Reimbursement for intensive care services under diagnosis related groups. Crit Care Med . 1988;;16:478-481.
28 +
Ahmad M, Fergus L, Stothard P,  Harrington D, Sivak E, Farmer R. Impact of diagnosis-related groups' prospective payment on utilization of medical intensive care. Chest . 1988;;93:176-179.
29 +
Butler PW, Bone RC, Field T.  Technology under Medicare diagnosis-related groups prospective payment. Chest . 1985;;87:228-234.
30 +
Chalfin DB, Carlon GC, Munoz E.  Hospital cost of intensive care survivors and nonsurvivors under diagnostic related groups (DRGs). Crit Care Med . 1989;;17( (suppl) ):S86.
31 +
Cerra FB.  The multiple organ failure syndrome. Hosp Pract . 1990;;25:169-176.
32 +
Doubilet P, Begg CB, Weinstein MC, Braun P, McNeil BJ.  Probabilistic sensitivity analysis using Monte Carlo simulation. Med Decis Making . 1985;; 5:157-177.
33 +
Willard KE, Critchfield GN.  Probabilistic analysis of decision trees using Monte Carlo simulation. Med Decis Making . 1986;;6:85-92.
34 +
Hollenberg J. SML TREE: The All Purpose Decision Tree Builder . Boston, Mass: Pratt Medical Group; 1985;.
35 +
DeGroot MH. Probability and Statistics . Reading, Mass: Addison-Wesley Publishing Co; 1986;.
36 +
Wilkinson L. SYSTAT: The System for Statistics . Evanston, Ill: SYSTAT Inc; 1989;.
37 +
Wenzel RP.  Anti-endotoxin monoclonal antibodies: a second look. N Engl J Med . 1992;;326: 1151-1152.
38 +
Warren HS, Danner RL, Munford RS.  Antiendotoxin monoclonal antibodies. N Engl J Med . 1992;;326:1153-1156.
39 +
Cunnion RE.  Clinical trials of immunotherapy for sepsis. Crit Care Med . 1992;;20:721-723.
40 +
Laffel GL.  A cost-effectiveness model for coronary thrombolysis/reperfusion therapy. J Am Coll Cardiol . 1987;;10( (5 suppl B) ):79B-90B.
41 +
Fineberg HV, Scadden D, Goldman L.  Care of patients with a low probability of acute myocardial infarction: cost-effectiveness of alternatives to coronary-care-unit admission. N Engl J Med . 1984;; 310:1301-1307.
42 +
Beck JR, Pauker SG.  The Markov process in medical prognosis. Med Decis Making . 1983;;3:419-458.
43 +
Beck JR, Kassirer JP, Pauker SG.  A convenient approximation of life expectancy (the 'DEALE'). Am J Med . 1982;;73:883-888.

Letters

Submit a Letter
CME Course for:


You need to register in order to view this quiz.


To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
To view and print your certificate and access a summary of your CME courses go to My CME.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
Submit a Response

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

© 2012 American Medical Association. All Rights Reserved.
Powered bySilverchair Information Systems