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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 OShea1, 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. Josephs 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 xTAGTM RVP 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.
  21716-747.
• 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.
  351579-1581.
• 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. 411438-44.
• 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. 452965-2970.

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.