Cost-effectiveness of recombinant human activated protein C and the influence of severity of illness in the treatment of patients with severe sepsis.
OBJECTIVE
To evaluate the cost-effectiveness of recombinant human activated protein C (rhAPC) compared with usual therapy for patients with severe sepsis, and also to determine the influence that severity of illness exerts on cost-effectiveness.


METHODS
We use a Markov model-based cost-effectiveness analysis of treatment strategies for patients with severe sepsis. Therapy includes treatment with either rhAPC and usual therapy, or usual therapy alone. Probabilities for clinical outcomes were obtained from a large randomized clinical trial comparing the use of rhAPC with placebo (PROWESS study) and from outcomes literature for patients with severe sepsis and its complications. Cost estimates were based on Medicare reimbursement rates, Health Care Financing Administration information and the literature. Outcome measures include life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness.


RESULTS
Compared with usual therapy alone, rhAPC treatment for patients with very severe sepsis (APACHE II score > or = 25) was associated with an incremental cost-effectiveness ratio of $13 493/QALY. Treatment of patients with less severe sepsis with rhAPC (APACHE II score < 25) had an incremental cost-effectiveness ratio of $403,000/QALY. For patients with very severe sepsis the incremental cost-effectiveness ratio for treatment with rhAPC remained under $30,000/QALY, over a broad range of variables, including costs of rhAPC, costs of acute care and costs and probabilities of complications of treatment. For patients with less severe sepsis, drug costs would need to fall well below current market price before achieving cost-effectiveness. A probabilistic sensitivity analysis comparing rhAPC treatment with usual therapy for patients with very severe sepsis showed that < 1% of Monte Carlo simulations had incremental cost-effectiveness ratios > $50,000/QALY.


CONCLUSIONS
The use of rhAPC for the treatment of patients with very severe sepsis, as determined by APACHE II score > or = 25, appears cost-effective, while treatment of patients with APACHE II score < 25 is not cost-effective.
Division of General Medicine and Critical Care Medicine, Department of Medicine, Sunnybrook and women's College Health Sciences Centre, University of Toronto, Ontario, Canada. rob.fowler@swchsc.on.ca
Robert A
RA
Fowler
Marya
M
Hill-Popper
John
J
Stasinos
Constantia
C
Petrou
Gillian D
GD
Sanders
Alan M
AM
Garber
D018806:APACHE; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000191:economics* / Q000627:therapeutic use; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D017048:Health Care Costs; D006801:Humans; D008390:Markov Chains; D009010:Monte Carlo Method; D011336:Probability; D011486:Protein C / Q000191:economics* / Q000627:therapeutic use; D019057:Quality-Adjusted Life Years; D011994:Recombinant Proteins / Q000191:economics* / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000191:economics* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011486:Protein C; D011994:Recombinant Proteins