An assessment of nucleic acid amplification testing for active mycobacterial infection

Test parameters

As NAAT is an add-on test, and as accuracy of NAAT differs by AFB result, accuracy estimates of NAAT used in the model are separated by AFB status.

Accuracy estimates used in the economic evaluation are based on the results of the meta-analyses of all patients, in all tissue types, as presented in the clinical assessment (Table ). As accuracy estimates reported in studies that were conducted in low-incidence countries (Canada, France etc.) may be more applicable to the Australian context, these estimates will be used in the base-case analysis, with 95%CI tested in sensitivity analyses. Given that countries in a low-incidence setting form the minority of results for the accuracy of AFB (k=11) and NAAT by AFB status (k=4), sensitivity analyses will be presented using the results for these parameters from all studies included in the clinical assessment.

Table Test parameters used in the economic evaluation

Test	k	Sensitivity [95%CI]	Specificity [95%CI]	Source
Base case (low-incidence countries)	--	--	--	--
AFB for TB	11	56% [44, 68]	98% [94, 100]	Figure
NAAT in AFB+ for TB	4	98% [94, 100]	97% [1, 100]	Figure
NAAT in AFB– for TB	4	70% [51, 84]	99% [94, 100]	Figure
NAAT for rifampicin resistance	8	92% [81, 97]	99% [96, 100]	Figure
Sensitivity analyses (all countries)	-	-	-	-
AFB for TB	68	62% [54, 69]	98% [97, 99]	Figure
NAAT in AFB+ for TB	25	99% [96, 100]	78% [53, 92]	Figure
NAAT in AFB– for TB	39	80% [69, 87]	94% [88, 97]	Figure
NAAT for rifampicin resistance	11	93% [85, 97]	91% [78, 96]	Figure

AFB = acid-fast bacilli test; NAAT = nucleic acid amplification test; TB = tuberculosis

Healthcare resources

Test costs

The PASC protocol does not provide a proposed item fee for NAAT but indicates that the New South Wales (NSW) Mycobacterium Reference Laboratory charges $200 per NAAT, while that in Victoria charges $88. Both these laboratories were contacted during the assessment to confirm these costs and seek further information that may explain the differences in cost (e.g. commercial versus in-house, or if separate tests are conducted for resistance mutation testing). The Victorian laboratory indicated that an in-house NAAT costs $82 and that using the commercial Xpert kit is $130, met primarily through the Victorian State Government—only private patients & non-Australian residents are billed for testing²¹. It is unclear if the in-house PCR cost includes that of rpoB sequencing. This laboratory also indicated that rifampicin resistance mutations identified using Xpert are confirmed by in-house rpoB sequencing before results are released. These costs are assumed to be additional to the $130 test cost. No further information was provided by the NSW laboratory.

A search of pathology providers across the country indicated that at least two NSW public (bulk-billing) services²² bill ‘TB-PCR’ under MBS item 69494 ($28.65). It is unclear if this is indicative of the cost of NAAT for TB, or if it is used as a partial subsidy and the NSW State Government is responsible for the difference. A private pathology provider in Victoria charges $100.50 for ’Mycobacterium TB-PCR’ with no Medicare funding²³.

The Mycobacterium Reference Laboratories in the other states (South Australia (SA), Western Australia (WA) and Queensland) were also contacted during the assessment to gather information regarding current NAAT use and costs. The laboratory in SA indicated that they conduct NAAT using the commercial Xpert kit at a cost of $70, which is currently funded by the SA State Government²⁴. In WA, NAAT is conducted using either the Xpert kit or in-house real-time PCR (the choice of which depends on microscopy result, specimen type and clinical history), with an approximate cost of $40 per test, met predominantly by the laboratory and/or public health authorities²⁵.

The applicant has indicated that they are charged approximately $100 by their state reference laboratory; however, the applicant assumes that this cost includes NAAT in addition to TB antigen and high-performance liquid chromatography testing, and so the approximate cost is not indicative of NAAT alone²⁶.

In the absence of further information regarding NAAT costs, the base-case analysis assumes a test cost of $130 (based on the Victorian reference lab Xpert cost, as per advice from the Department of Health Policy Area). ICERs using alternative item fees for NAAT are presented in Appendix .

As diagnostic AFB and C&S testing applies to all patients in both model arms, costs associated with these tests will not be considered.

Treatment costs

Costs were sourced for medications used commonly to treat susceptible TB and MDR-TB (Street et al. 2012). Sources included the Pharmaceutical Benefits Schedule (PBS), where listed, and Chemist Warehouse, where not listed on the PBS. However, not all medications used in the treatment of TB are marketed for use in Australia, and so are only available through the Special Access Scheme. In these instances, and where costs could not be sourced alternatively, they were sourced from a public hospital pharmacy²⁷. Some medications require co-administration with pyridoxine; these costs have been included in the analysis.

For the treatment of susceptible TB, the standard regimen consists of 2 months’ treatment with isoniazid, rifampicin, pyrazinamide and ethambutol (intensive phase), followed by a further 4 months with isoniazid and rifampicin (continuation phase). Daily doses are assumed based on the maximum dose per day (Street et al. 2012).

For the treatment of MDR-TB it is assumed that the organism is resistant to isoniazid and rifampicin. The intensive phase of treatment consists of pyrazinamide, ethambutol, amikacin, moxifloxacin and prothionamide for 6 months, followed by 12 months of pyrazinamide, ethambutol, moxifloxacin and prothionamide (Street et al. 2012). Amikacin is initially given intravenously via a peripherally inserted central catheter 5 days per week for the first 3 months and 3 days per week for the following 3 months (Jenkins, Dedicoat & Cook 2013). A one-off catheterisation cost has been applied in the model to account for the insertion of the catheter (MBS item 13815, $85.25). After the initial hospitalisation period (see ‘Hospitalisation’), administration is assumed to occur in the home (Jenkins, Dedicoat & Cook 2013) at a cost of $234 per administration (Victoria State Government Department of Health 2014) (see Table , Appendix ).

Costs per month have been calculated and are presented in Table . These costs are assumed to apply each month while on treatment.

Table Resource items associated with treatment of TB used in the economic evaluation

Type of resource item	Natural unit of measurement	Unit cost	Source of unit cost	Cost per month