INTRODUCTION

1. INTRODUCTION METHODS RESULTS RESULTS SUMMARY REFERENCES COST ANALYSIS OF MULTIPLEX PCR (xTAGTM RVP) FOR DIAGNOSING RESPIRATORY VIRUS INFECTIONS IN A TERTIARY CARE HOSPITAL James Mahony1,4, Gord Blackhouse3, Jesse Babwah1, Marek Smieja2,3,4, Sonya Buracond4, William Ciccotelli1, Tim O’Shea1, Daifallah Alnakhli1, May Griffiths-Turner4, Sylvia Chong4, and Ron Goeree3 Department of Pathology & Molecular Medicine1, Department of Medicine2, PATH Research Institute3, McMaster University and the Regional Virology laboratory, St. Joseph’s Healthcare4, Hamilton, Ontario, CANADA Commercial tests using multiplex PCR have recently been introduced for the detection of respiratory viruses (1). The xTAGTM RVP Test is the first multiplex PCR test to be cleared by the FDA and detects ten additional respiratory virus types or subtypes not detected by DFA and shell vial culture (2). Since molecular tests are often more expensive than traditional tests we performed a cost analysis study using decision tree modeling to determine whether the use of the xTAGTM RVP Test is a cost effective strategy for diagnosing respiratory virus infections in a pediatric population in a tertiary care hospital in Hamilton. Table 2. Calculation of weighted costs for each diagnostic strategy using proportions and actual costs. The cost per case was highest for DFA plus culture at $3,914 and the lowest for xTAGTM RVP alone at $3,623 while the costs of DFA alone ($3,911) and DFA plus xTAGTM RVP ($3,849) were intermediate (Table 2). In our study almost all of the savings were due to a shortened length of stay in hospital. Since the prevalence of respiratory virus infection varies by season and geographical area, a sensitivity analysis was undertaken to estimate which testing strategy was the least costly according to true prevalence rates.When all four testing strategies were compared the least costly strategy was xTAGTM RVP when the prevalence of infection was 11% or higher and when the prevalence was lower than 11%, DFA was the least costly strategy. Based on investigating 1,820 pediatric inpatients per year for respiratory virus infections, the model predicts a savings of $291 CDN per case if the xTAGTM RVP alone strategy was used in place of the DFA plus culture testing strategy currently in place in Hamilton resulting in a savings of $529,520 per year in direct costs for the four Hamilton hospitals. The savings for total inpatient work (pediatric plus adult) for the Hamilton region serving a population of 1 million would be $756,600 per year based on investigating 2,700 patients with respiratory tract infection. • Decision tree model: A decision tree model was used to compare the costs of four different testing strategies for respiratory virus diagnosis viz. DFA alone, DFA plus culture, xTAGTM RVP alone, or DFA plus xTAGTM RVP. The tree was constructed to represent the number of patients by testing status including true positive (TP), false positive (FP), true negative (TN) and false negative (FN) for each of the four testing strategies. • Chart review: A chart review of 661 patients was performed to determine the proportion of patients in each arm of the tree, the length of hospital stay, number of days in isolation, antibiotic usage and other medical procedures. • Hospital costs: The costs for hospitalization days (semi private and isolation) and all medical procedures were determined from the Ontario Hospital Association rates and were applied to each arm of the tree to arrive at a weighted cost per patient for each diagnostic strategy using the average cost per patient and the number of patients in each arm of the decision tree. Costs for performing DFA, SVC and xTAGTM RVP were determined using list prices for diagnostic reagents and an average technologist salary plus benefits ($28/hr + 30% FB) for performing the testing. • Test performance: The sensitivity of DFA was based on literature values where DFA was compared to at least one other test including at least one molecular test and where test performance was calculated using a combined reference standard for positivity and was set at 70% (3,4). The sensitivity for shell vial culture was set at 72% reflecting a 2% increase in the positive pick up rate using shell vial culture during the study period. The sensitivity of RVP was set at 94% reflecting the median sensitivity for 12 respiratory viruses detected by this test (2,5). The specificity for each test was set at 98%. • We performed a cost analysis study using decision tree modeling to determine whether the use of multiplex PCR testing for respiratory viruses (xTAGTM RVP Test) is a more or less costly strategy than the status quo testing of DFA plus SVC for diagnosing respiratory virus infections in pediatric patients. • The decision tree model was constructed using four testing strategies for respiratory virus detection viz. DFA alone, DFA plus SVC, xTAGTM RVP test alone, or DFA plus xTAGTM RVP. • When all four diagnostic strategies were compared, the least costly strategy was xTAGTM RVP testing alone strategy. The cost per case for DFA plus SVC was the highest at $3,914 CDN while the xTAGTM RVP alone was lowest at $3,623 (Table 3). • These data indicated a savings of $291 CDN per case investigated if the xTAGTMRVP alone strategy was used to replace DFA plus SVC (Table 3), resulting in a savings of $529,620 per year in direct costs for the Hamilton hospitals based on testing specimens from 1,820 pediatric inpatients. If adult patients are included in the model then the savings for the four Hamilton hospitals would be $756,600 CDN per year based on testing a total of 2,700 inpatients. • We conclude that the xTAGTM RVP test is the least costly strategy for diagnosing respiratory virus infections in pediatric inpatients and that the use of xTAGTM RVP test would result in a significant savings for hospitals compared with the cost of performing DFA plus SVC. Figure 1. Graphical representation of one node of the decision tree showing one of the four diagnostic strategies, the true testing status for each strategy and costs (c) associated with each status. Table 3. Component costs used to calculate the weighted cost per case for the four testing strategies. • Mahony, J. B. (2008). Detection of Respiratory Viruses by Molecular Methods. Clin. Micro Rev. 21:716-747. • Krunic, N., T. D. Yager, D. Himsworth, F. Merante, S. Yaghoubian, R. Janeczko. 2007. xTAG RVP assay: analytical and clinical performance. J. Clin. Virol. 40(Suppl): S39-S46. • Woo, P. C. Y., S. S. Chiu, W-E. Seto and M. Peiris. (1997). Cost-Effectiveness of Rapid diagnosis of Viral Respiratory Tract Infections in Pediatric Patients. J. Clin. Microbio. 35:1579-1581. • Oosterheert, J. et al. (2005). Impact of Rapid Detection of Viral and Atypical Bacterial Pathogens by Real-Time Polymerase Chain Reaction for Patients with Lower Respiratory Tract infection. Clin. Infect. Dis. 41:1438-44. • Mahony, J., S. Chong, F. Merante, S. Yaghoubian, T. Sinha, C. Lisle, R. Janeczko. (2007). Development of a respiratory virus panel test for detection of twenty human respiratory viruses by use of multiplex PCR and a fluid microbead-based assay. J. Clin. Microbiol. 45:2965-2970. Table 1. Breakdown of cost per case by true infection status. The total cost per case was determined by the model using weighted test costs and weighted hospital costs as shown in Table 2 and broken down into component costs.