Cost-Effectiveness Study of Criteria for Screening Cerebrospinal Fluid To Determine the Need for Herpes Simplex Virus PCR Testing

Abstract

The absence of markers of inflammation in the cerebrospinal fluid (CSF) commonly predicts the absence of herpes simplex virus (HSV) central nervous system (CNS) infection. Consequently, multiple authors have proposed and validated criteria for deferring HSV PCR testing of CSF in immunocompetent hosts with normal CSF white blood cell and protein levels (≤5 cells/mm³ and ≤50 mg/dl, respectively). Hosts are considered immunocompetent if they are ≥2 years old and have not had HIV or an organ transplant. Adoption of the criteria may erroneously exclude HSV-infected persons from a necessary diagnostic test or, alternatively, reduce the costs associated with HSV tests with minimal to no effect on patient care. Little is known about the cost-effectiveness of this approach. A decision analysis model was developed to evaluate the adoption of criteria for screening HSV tests of CSF. Estimates of input parameter values combined available literature with a multiyear multisite review at two of the largest health care systems in the United States. Adoption of criteria to screen for HSV test need proved cost-effective when less than 1 in 200 patients deferred from testing truly had an HSV CNS infection. Similar to prior studies, none of the deferred cases had HSV encephalitis (n = 3120). Adoption of these criteria in the United States would save an estimated $127 million ($95 million to $158 million [±25%]) annually. The model calculations remained robust to variation in test cost, prevalence of HSV infection, and random variation to study assumptions. The adoption of criteria to screen HSV PCR tests in CSF represents a cost-effective approach.

Keywords: cost-effectiveness; herpes simplex virus; polymerase chain reaction.

FIG 1

One-way sensitivity analysis. As the probability of HSV infection in a patient with normal CSF WBC and protein levels increases, the criteria for screening for HSV PCR become less reliable. A less reliable screen for HSV PCR decreases the incremental cost-effectiveness ratio (ICER). The ICER declines because fewer dollars are required by the intervention (i.e., HSV PCR of all patients) to gain one quality-adjusted life year (QALY) relative to the strategy to screen for HSV PCR.

FIG 2

Two-way sensitivity analysis. (A and B) x- and y-axis parameters were varied over a range. For a given (x, y) point on the graph, the values of the two parameters listed on the two axes were used as inputs to compare using a strategy for screening for HSV PCR and not using a screening strategy. The shading indicates the most cost-effective strategy at a given (x, y) point. A standard value for the willingness to pay, $100,000/QALY, was used.

FIG 3

Probabilistic sensitivity analysis. At a given willingness to pay, the parameters listed in Table 1 were iteratively drawn from random distributions (i.e., beta distributions for probability parameters and utility estimates). For each iteration, the two strategies were compared to determine the most cost-effective strategy given the randomly drawn parameter values. For each strategy, the proportion of each iteration representing the most cost-effective strategy at a given willingness to pay is graphed.

FIG 4

Decision tree for evaluating the cost-effectiveness of herpes simplex virus (HSV) PCR testing strategies. Patients entering the decision tree have an age greater than 2 years and neither HIV nor solid organ transplant (i.e., heart, liver, or kidney). Components 1, 2, and 3 flow together in sequential order. Square nodes represent decisions, while circular nodes represent probabilistic events.