An assessment of nucleic acid amplification testing for active mycobacterial infection
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- Implications for false-positive and false-negative results
- Inputs to the economic evaluation
- Prevalence of MDR-TB
| Figure 34 Decision analytic structure of the economic evaluation, intervention (AFB plus NAAT) model arm
AFB = acid-fast bacilli test; C = culture; MDR = multidrug-resistant; NAAT = nucleic acid amplification test; R = resistance; RIF res = rifampicin resistant; RIF suscept = rifampicin susceptible; Rif_res = prevalence of rifampicin resistance in TB; sensAFB = sensitivity of AFB for TB; sensNAAT_AFBn = sensitivity of NAAT for TB in AFB-negative; sensNAAT_AFBp = sensitivity of NAAT for TB in AFB-positive; sensNAAT_rif_res = sensitivity of NAAT for rifampicin resistance; specAFB = specificity of AFB for TB; specNAAT_AFBn = specificity of NAAT for TB in AFB-negative; specNAAT_AFBp = specificity of NAAT for TB in AFB-positive; specNAAT_rif_res = specificity of NAAT for rifampicin resistance; S = susceptibility; TB = tuberculosis; TB_high = prevalence of TB in high clinical suspicion population; TB_low = prevalence of TB in low clinical suspicion population
Table 44 Summary of decision tree outcome states in the economic evaluation
C&S = culture and sensitivity; FRN = false resistance negative; FRP = false resistance positive; MDR = multidrug-resistant; TB = tuberculosis; TBFN = tuberculosis false negative; TBFP = tuberculosis false positive; TBTN = tuberculosis true negative; TBTP = tuberculosis true positive; TRN = true resistance negative; TRP = true resistance positive False-negative results (i.e. initially untreated TB (± MDR) or initial standard treatment in MDR-TB) As there was no indication from the clinical assessment that a treatment delay of up to 2 months leads to an increase in disease severity (van der Oest, Kelly & Hood 2004), the economic modelling will assume treatment duration and QoL (from the time of correct diagnosis) as for those correctly treated. However, there is some indication that a delay in treatment leads to an increased risk of TB transmission (Ponticiello et al. 2001). A cost and utility penalty are applied to account for the treatment costs and utility decrement associated with secondary infections; see ‘TB transmissions’ and Utility penalty for active TB transmissions’ for further details. Treatment outcomes in MDR-TB patients treated initially with the standard regimen are assumed to be poorer than for those initially untreated, as treatment is ineffective and associated with AEs (i.e. outcomes equal to those untreated who then have a disutility associated with treatment applied).
Patients that are truly negative for TB who undergo initial TB (± MDR) treatment are assumed to have the cost and disutility of 2 months of the applicable treatment applied. As these patients may have a range of alternative diagnoses that present with similar symptoms (associated with differing costs and outcomes), the delay to treatment for the alternative diagnosis is not considered in the assessment. Patients with true susceptible TB that are treated initially with MDR regimen are assumed to be effectively treated but have poorer overall health outcomes than those treated with the standard regimen because of the increased AEs associated with MDR treatment.
Prevalence of TBThe prevalence of TB, defined as culture-positive, in studies included for the diagnostic accuracy of NAAT conducted in a low TB incidence country (k=11) was 24% (range 660%) (Table 93, Appendix D). A reliable estimate for the prevalence of TB in the population with clinical signs and symptoms of active TB in Australia was not identified during the assessment, nor were estimates of the respective prevalences where that patient group is divided into those considered to have either a high or low clinical suspicion of TB. This introduces considerable uncertainty in the economic modelling, as the cost-effectiveness is likely to be sensitive to these variables. Given the uncertainties in prevalence estimates identified, further information was provided by the applicant (an Australian pathology provider)20. It was estimated that 1020% of patients would be considered to have a high clinical suspicion of TB, of which 5070% would have TB. In those considered to have a low clinical suspicion of TB (the remaining 8090% of patients) the prevalence is estimated to be in the range 510%. Using the upper limits of these estimates provides an overall prevalence estimate of 22% (Table 45). This value is reasonably similar to the prevalence of TB reported in the diagnostic accuracy studies conducted in low incidence countries (24%, Table 93, Appendix D), and so appears to have face validity. It would be expected that the higher the proportion of patients with true TB that are treated based on clinical judgement, the less cost-effective NAAT will be, as there are fewer benefits of NAAT for patients managed this way; therefore, using the upper limit of these estimates is the conservative choice and will be used in the base-case analysis of the economic evaluation. However, it should be noted that if the overall prevalence of TB is an overestimate, the cost-effectiveness of NAAT may too be overestimated. Given that these are best-guess estimates, sensitivity analyses around these estimates will be presented. Additional scenarios are presented to examine the extent to which treatment initiation decisions based on clinical suspicion affect the ICER. The base-case prevalence of 22% is maintained in these scenarios; however, all are managed as though they have either low or high clinical suspicion of TB, depending on the scenarios (Table 45). Table 45 Prevalence estimates used in previously published economic evaluations of NAAT
NAAT = nucleic acid amplification testing; TB = tuberculosis Prevalence of MDR-TBThe Australian Mycobacterium Reference Laboratory Network reported 1,051 bacteriologically confirmed cases of TB in 2010 (Lumb et al. 2013). Results of susceptibility testing to first-line treatments were available for 1,050 cases (99.9%) and multidrug resistance was reported in 37 cases (3.5%). However, 16 patients with MDR-TB were Papua New Guinea nationals who accessed health services in the Torres Strait Protection Zone. The remaining 21 MDR-TB patients were people who lived in Australia. This represents 2.0% of the bacteriologically confirmed cases of TB. This estimate will be used as the base-case estimate for the prevalence of MDR-TB in TB cases in the economic analysis. An upper limit of 3.5% will be tested in sensitivity analyses, to reflect the proportion of MDR-TB in all bacteriologically confirmed cases of TB in 2010; a lower limit of 0.5% will be used, which reflects the lowest proportion observed by the Australian Mycobacterium Reference Laboratory Network since 1995 (Figure 35). This is consistent with proportions observed in Victoria during 2002–07 (0.6%–2.2%) (Lavender, Brown & Johnson 2009). 
Figure 35 Percentage of TB cases that exhibited multidrug resistance in Australia, 1995–2010 MDR-TB = multidrug-resistant tuberculosis; TSPZ = Torres Strait Protection Zone Source: Figure 2, Lumb et al. (2013) Directory: internet internet -> Applications and limitations internet -> L. and Gossypium barbadense internet -> Natural Resources Conservation Service Conservation Practice Standard internet -> Practice Exercise Created By Stavros Charalambous The Internet internet -> It’s a good Topic internet -> National Preventative Health Strategy – the roadmap for action internet -> Downloading gps gr-3 Surveys Summary of Procedure internet -> 3G300m-how to setup the 3g router Mode? Product line: 3g question categories: Function configurations Note internet -> Installation Work has never been simpler or easier Download 12.08 Mb. Share with your friends:
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