An evaluation of the cost effectiveness of drotrecogin alfa (Activated) relative to the number of organ system failures

Background: While drotrecogin alfa (activated) was shown to decrease absolute 28-day mortality by 6.1% in patients with severe sepsis in the Recombinant Human Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study, no mortality benefit was observed in the subset of patients with only one organ system failure. Consequently, some institutions restrict drotrecogin alfa (activated) use to patients with severe sepsis with greater than or equal to2 organ system failures. Objective: To measure the cost effectiveness of drotrecogin alfa (activated) for treatment of severe sepsis in relation to the number of organ system failures and determine the economic impact of-restricting drotrecogin alfa (activated) use based on the number of organ system failures. Perspective: Policy perspective specific to our 340-bed, level I trauma centre. Methods: A Monte Carlo simulation analysis was conducted to evaluate a hypothetical cohort of 10 000 patients with severe sepsis in four scenarios restricting treatment with drotrecogin alfa, (activated) to patients with greater than or equal to1, greater than or equal to2, greater than or equal to3 or greater than or equal to4 organ system failures. The primary outcomes of 28-day all-cause mortality and serious bleeding were obtained from the PROWESS study. Costs (year 2002 values) were obtained from institutional financial records and literature estimates. The incremental cost per life saved at 28 days with drotrecogin alfa (activated) plus best standard care versus best standard care alone (placebo) was calculated. The incidence of severe sepsis and number of drotrecogin alfa (activated) candidates were estimated through chart review, and projected annual institutional expenditures were derived according to these data. Results: With increasing number of organ system failures, the proportion of lives saved with drotrecogin alfa (activated) increased, and consequently the ICER decreased. Restriction of drotrecogin alfa (activated) to patients with greater than or equal to4 organ system failures was the most cost-effective scenario (0.11 lives saved; $US56 727 per life saved). For the nine patients that would be treated annually by our institution under this policy, one life would be saved at a total additional cost of $US56 160 per year. Use of the drug in patients with greater than or equal to1 or greater than or equal to2 organ system failures would save the greatest number of lives per year (4-5); however, restricting drotrecogin alfa (activated) to patients with greater than or equal to2 organ system failures would be the cheaper alternative (total additional cost $US356 022 vs $US462 204). Conclusion: While restriction of drotrecogin alfa (activated) use to patients with sepsis with greater than or equal to4 organ system failures is the most cost-effective alternative, restriction to those with greater than or equal to2 organ system failures is the preferred alternative for our institution according to the number of lives saved and available financial resources.