Research Article: Cost-effectiveness of molecular diagnostic assays for the therapy of severe sepsis and septic shock in the emergency department

Date Published: May 24, 2019

Publisher: Public Library of Science

Author(s): Ioannis M. Zacharioudakis, Fainareti N. Zervou, Fadi Shehadeh, Eleftherios Mylonakis, Chiara Lazzeri.


Sepsis presents a major burden to the emergency department (ED). Because empiric inappropriate antimicrobial therapy (IAAT) is associated with increased mortality, rapid molecular assays may decrease IAAT and improve outcomes. We evaluated the cost-effectiveness of molecular testing as an adjunct to blood cultures in patients with severe sepsis or septic shock evaluated in the ED.

We developed a decision analysis model with primary outcome the incremental cost-effectiveness ratio expressed in terms of deaths averted. Costs were dependent on the assay price and the patients’ length of stay (LOS). Three base-case scenarios regarding the difference in LOS between patients receiving appropriate (AAT) and IAAT were described. Sensitivity analyses regarding the assay cost and sensitivity, and its ability to guide changes from IAAT to AAT were performed.

Under baseline assumptions, molecular testing was cost-saving when the LOS differed by 4 days between patients receiving IAAT and AAT (ICER -$7,302/death averted). Our results remained robust in sensitivity analyses for assay sensitivity≥52%, panel efficiency≥39%, and assay cost≤$270. In the extreme case that the LOS of patients receiving AAT and IAAT was the same, the ICER remained≤$20,000/death averted for every studied sensitivity (i.e. 0.5–0.95), panel efficiency≥34%, and assay cost≤$313. For 2 days difference in LOS, the bundle approach was dominant when the assay cost was≤$135 and the panel efficiency was≥77%.

The incorporation of molecular tests in the management of sepsis in the ED has the potential to improve outcomes and be cost-effective for a wide range of clinical scenarios.

Partial Text

Sepsis presents a major burden to U.S. emergency departments (ED), with up to 850,000 estimated visits annually between 2009–2011 [1]. Treatment of septic patients places a significant financial burden on the U.S. healthcare system with estimated $20.3 billion spent in 2011 [2], and the annual rate of increase of the average cost of hospital stay for sepsis is three-times the rate for hospital costs overall [3].

We designed a decision analysis model to examine the cost-effectiveness of a bundle approach that involves collection of both a rapid diagnostic molecular test and blood cultures at the time of presentation of a patient with severe sepsis or septic shock in the ED (Fig 1). Data for the model were extrapolated from the literature as described below.

We evaluated three base case scenarios in which the hospital LOS differed by 0, 2 and 4 days between patients on AAT and IAAT, as detailed in the Methods. In the base case scenarios, the bundle approach that included the simultaneous collection of blood cultures and molecular assay upon presentation to the ED had an estimated cost of $6,929, $7,019 and $7,109 per patient for a difference in LOS of 0, 2 and 4 days, respectively. The relevant costs when only blood cultures were collected were $6,774, $6.999 and $7,223 per patient.

In this study, we examined the cost-effectiveness of the use of a rapid molecular diagnostic test for patients who present with severe sepsis or septic shock in the ED. Under baseline assumptions, we found that this bundle is cost-saving in cases that the length of hospital stay differs by 4 days between patients receiving AAT and IAAT. Our results remained robust in sensitivity analyses for assay sensitivity ≥52%, panel efficiency ≥39%, and cost ≤$270. Even in the extreme scenario where the LOS was the same between patients receiving AAT and IAAT, the use of the molecular test as an adjunct to blood cultures remained cost-effective for a willingness to pay ≤$20,000 per death averted for every examined assay sensitivity (0.5–0.95), panel efficiency ≥34%, or cost ≤$313.