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To the Editors:

In the guest editorial titled, "Meeting Unmet Needs in Patients With Sepsis: The Role of Drotrecogin Alfa (Activated)" (March 2003:94–97), Dr Morris offers compelling arguments for this contemporary addition to our armamentarium against sepsis in the intensive care unit. I am, however, troubled by the author’s assertion that, "If a therapeutic agent is available that can significantly reduce mortality, and a patient meets the guidelines mandated by the Food and Drug Administration (FDA) for treatment, then rationing that treatment could be considered unethical."

The FDA approved drotrecogin alfa (activated) in November 2001 for use in adult patients with severe sepsis who are at high risk of death.¹ In doing so, the FDA acknowledged the scientific validity of data submitted by Eli Lilly and Company. The manufacturer labeling approved by the FDA is for the reduction of mortality in adult patients with severe sepsis (sepsis associated with acute organ dysfunction) who have a high risk of death.² The FDA did not mandate treatment of severe sepsis with drotrecogin alfa (activated), nor did they mandate specific guidelines for its use.

Apt evaluation of the ethical elements involved with administration of new and costlier agents must include not only a patient risk benefit analysis but an institutional and healthcare system risk benefit analysis as well. If practitioners blithely empty their entire inventory of interventions and supplies on every critically ill patient, institutions and, ultimately, our entire healthcare system will be bankrupt.

Despite our best efforts to integrate evidence-based medicine into our practices, no scientific assurance can determine that a specific patient will benefit from any given treatment. Assuring the financial integrity of our institutions through formulary-driven policies that incorporate the best available evidence is ethically imperative; it is at least as imperative as having an FDA-approved agent in hand and a compelling patient before us.

Mike McEvoy, PhD, RN, CCRN
Albany, NY

REFERENCES

1. FDA. FDA approves first biologic treatment for sepsis [press release]. Available at: http://www.fda.gov/bbs/topics/NEWS/2001/NEW00780.html. Accessed March 1, 2003.
2. Eli Lilly and Co. Label for Xigris drotrecogin alfa (activated). Available at: http://www.fda.gov/cber/label/droteli112101LB.pdf. Accessed March 1, 2003.

Dr McEvoy crystallizes the ongoing difficulties of practitioners in their attempt to appropriately incorporate information from the medical literature into our everyday practice. Practitioners struggle with weighing a study’s efficacy and safety profile. An added complexity occurs when the proposed addition to our practice comes with significant cost.

Although cost-benefit analysis studies are based on many assumptions, they do provide another means to help address Dr McEvoy’s concerns. In the literature, there are now 3 studies that examine the cost-benefit profile of activated protein C (drotrecogin alfa [activated]) in severe sepsis patients. One was funded by Eli Lilly¹ and based on a subpopulation of patients enrolled in the Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial.² Another was an independent, retrospective analysis based on a Canadian population.³ The third has been presented in abstract form.⁴

From these analyses, there emerges a confirmation of the cost-effectiveness of drotrecogin alfa (activated) for use in patients with severe sepsis and an APACHE II score of greater than 25. These studies provide a foundation of scientific evidence and will hopefully assist practitioners, like Dr McEvoy, with the incorporation of drotrecogin alfa (activated) into their local formularies and practice.

Peter E. Morris, MD
REFERENCES

1. Angus DC, Linde-Zwirble WT, Clermont G, et al. Cost-effectiveness of drotrecogin alfa [activated] in the treatment of severe sepsis. Crit Care Med. 2003;31:1–11.[Medline]
2. Bernard GR, Vincent JL, Laterre PF, et al. Recombinant Human Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant activated human protein C for severe sepsis. N Engl J Med. 2001;344:699–709.[Abstract/Free Full Text]
3. Manns BJ, Lee H, Doig CJ, Johnson D, Donaldson C. An economic evaluation of activated protein C treatment for severe sepsis. N Engl J Med. 2002;347:993–1000.[Abstract/Free Full Text]
4. Fowler R, Hill-Popper M, Petrou C, Stasinos J, Sanders G, Garber A. Cost-effectiveness of human recombinant activated protein C in the treatment of patients with severe sepsis. Paper presented at: 24th Annual Meeting of the Society of Medical Decision Making. October 21, 2002; Baltimore, Md.

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