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Crit Care. 2007;11(5):R99.

Cost-effectiveness of activated protein C in real-life clinical practice.

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Department of Intensive Care, Cochin Port-Royal University Hospital, AP-HP, René Descartes University, Paris 5, Paris, France.



Recombinant human activated protein C (rhAPC) has been reported to be cost-effective in severely ill septic patients in studies using data from a pivotal randomized trial. We evaluated the cost-effectiveness of rhAPC in patients with severe sepsis and multiple organ failure in real-life intensive care practice.


We conducted a prospective observational study involving adult patients recruited before and after licensure of rhAPC in France. Inclusion criteria were applied according to the label approved in Europe. The expected recruitment bias was controlled by building a sample of patients matched for propensity score. Complete hospitalization costs were quantified using a regression equation involving intensive care units variables. rhAPC acquisition costs were added, assuming that all costs associated with rhAPC were already included in the equation. Cost comparisons were conducted using the nonparametric bootstrap method. Cost-effectiveness quadrants and acceptability curves were used to assess uncertainty of the cost-effectiveness ratio.


In the initial cohort (n = 1096), post-license patients were younger, had less co-morbid conditions and had failure of more organs than did pre-license patients (for all: P < 0.0001). In the matched sample (n = 840) the mean age was 62.4 +/- 14.9 years, Simplified Acute Physiology Score II was 56.7 +/- 18.5, and the number of organ failures was 3.20 +/- 0.83. When rhAPC was used, 28-day mortality tended to be reduced (34.1% post-license versus 37.4% pre-license, P = 0.34), bleeding events were more frequent (21.7% versus 13.6%, P = 0.002) and hospital costs were higher (47,870 euros versus 36,717 euros, P < 0.05). The incremental cost-effectiveness ratios gained were as follows: 20,278 euros per life-year gained and 33,797 euros per quality-adjusted life-year gained. There was a 74.5% probability that rhAPC would be cost-effective if there were willingness to pay 50,000 euros per life-year gained. The probability was 64.3% if there were willingness to pay 50,000 euros per quality-adjusted life-year gained.


This study, conducted in matched patient populations, demonstrated that in real-life clinical practice the probability that rhAPC will be cost-effective if one is willing to pay 50,000 euros per life-year gained is 74.5%.

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