This presentation is part of: Poster Session - Clinical Strategies; Judgment and Decison Making
QUANTIFYING THE EXPECTED BENEFIT OF DROTRECOGIN ALFA (ACTIVATED) IN THE TREATMENT OF SEVERE SEPSIS WITH A PATIENT-SPECIFIC DECISION SUPPORT TOOL
Daniel P. Schauer, MD1, Joseph A. Johnston, MD, MSc2, Richard W. Hornung, DrPH1, Anthony Leonard, PHD1, and Mark H. Eckman, MD, MS1. (1) University of Cincinnati, Internal Medicine, Cincinnati, OH, (2) Eli Lilly, US Outcomes Research, Indianapolis, IN
PURPOSE: The expected benefit of treating severe sepsis with drotrecogin alfa (activated) for an individual patient may depend upon a number of clinical factors including disease severity. Our purpose was to create a decision support tool incorporating patient-specific inputs to estimate the balance of treatment risks and benefits for individual patients. METHODS: The decision support tool has two components. Logistic regression models were developed to calculate patient-specific mortality risk with and without treatment, which were then used as inputs into a seventy-five state Markov model. Data from the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial and subsequent open-label studies were used to develop the logistic models and the Markov model. Patient-specific inputs included patient age, gender and twelve readily available clinical characteristics. Expected patient outcomes were expressed in quality-adjusted life years (QALYs). RESULTS: The expected benefit from drotrecogin alfa (activated) treatment was most dependent upon the underlying disease severity. For example, treatment of a 55 year-old white male with severe sepsis and a 28-day mortality risk of 45% resulted in an expected gain of 3.1 QALYs (16.0 v. 12.9). In a similar patient with less severe disease (28-day mortality risk = 20%), the expected net benefit from drotrecogin alfa (activated) therapy would be 0.8 QALYs (19.6 v. 18.8). However, the treatment decision is sensitive to bleeding risk. If this same patient (28-day mortality risk = 20%) were at an increased risk of serious bleeding prior to treatment (28-day probability of bleeding = 7% vs. baseline of 2%) and an increased relative risk of serious bleeding with treatment (RR of 5.5 vs. baseline of 1.8) then not treating with drotrecogin alfa (activated) would yield the most QALYs (18.7 vs 18.6). CONCLUSION: A customizable decision model using patient-specific inputs can be used to inform the treatment decision when considering the use of drotrecogin alfa (activated) therapy by weighing the risks versus the benefits of therapy in the treatment of severe sepsis.
