title: The influence of clinical study design on cost-effectiveness projections for the treatment of gram-negative sepsis with human anti-endotoxin antibody.
abstract: OBJECTIVE
  This study was performed to compare the effect of entry criteria, patient population, and study design on outcome and projected cost-effectiveness of human anti-endotoxin antibody (HA-1A).
  
  
  METHODS
  Patients with suspected or documented gram-negative bacteremia (GNB) with sepsis syndrome or shock received HA-1A during an open-label protocol. The patient characteristics and outcome measures of this series were compared with those of a placebo-controlled randomized clinical trial (RCT) of HA-1A. Both data sets were subjected to three published cost-effectiveness models of anti-endotoxin therapy, which were derived from RCT data.
  
  
  RESULTS
  One hundred thirty-one patients (43 with gram-negative bacteremia) received HA-1A during a 19-month open-label protocol. Comparison with the RCT results demonstrated greater severity of illness and higher 28-day mortality in the open-label protocol. When projected for open-label recipients, HA-1A was considerably less cost-effective than in the original projections based on RCT-derived data. This reduction in cost-effectiveness was consistent across all three models and their respective sensitivity analyses.
  
  
  CONCLUSIONS
  Extrapolating cost-effectiveness from RCT-derived analyses to open-label usage may yield widely inaccurate projections because of only small differences in patient population and the drug administration protocol.
authors.affiliation: Department of Anesthesiology, University of Pittsburgh Medical Center, PA, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Linden
authors.forename: D C
authors.initials: DC
authors.lastname: Angus
authors.forename: L
authors.initials: L
authors.lastname: Chelluri
authors.forename: R A
authors.initials: RA
authors.lastname: Branch
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000191:economics* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D016470:Bacteremia / Q000401:mortality / Q000628:therapy*; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D016527:Drug Costs; D005260:Female; D005544:Forecasting; D016905:Gram-Negative Bacterial Infections / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018803:Models, Economic; D016032:Randomized Controlled Trials as Topic; D012107:Research Design / Q000592:standards*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C068069:nebacumab