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Table 2 Model parameters for cohort proportions, diagnostic test performance and costs

From: The potential of a multiplex high-throughput molecular assay for early detection of first and second line tuberculosis drug resistance mutations to improve infection control and reduce costs: a decision analytical modeling study

   PE Range   Source, scenario
Cohort proportions
  Proportion of PTB patients who are sputum-smear positive 0.64 0.62 0.65 [29] α
  Susceptible to all first line drugs, or resistance to either streptomycin, ethambutol or pyrazinamide, or combinations of those. 0.71 0.75 0.55 [29] α
  IHN mono resistance, which may or may not include resistance to other first line drugs streptomycin, ethambutol, and/or pyrazinamide (poly resistance), but not rifampicin 0.127 0.128 0.122 [29] α
Footnote (a)
  Rifampicin resistance with- or without INH resistance, without additional resistance to 2nd line drugs. Resistance to ethambutol and/or pyrazinamide may or may not be present. 0.108 0.073 0.212 [29] α
  MDR with additional resistance to ≥1 fluoroquinolone(s) but not to second-line injectable drugs (pré-XDR) 0.008 0.006 0.015 [29] α
  MDR with additional resistance to ≥1 SLID but not fluoroquinolones (pré-XDR) 0.044 0.032 0.087 [29] α
  XDR: MDR with additional resistance to ≥1 fluoroquinolones and ≥1 SLID. 0.008 0.007 0.014 [29] α
Diagnostic accuracy parameters
  Sensitivity of molecular tests in detecting rifampicin resistance (assumed to be the same as LiPA) 0.99 0.96 1.00 [28] α
  Sensitivity of molecular tests in detecting INH resistance (assumed to be the same as LiPA) 0.96 0.93 1.00 [28] α
  Sensitivity of molecular tests in detecting resistance to fluoroquinolones 0.831 0.787 0.867 [9] δ
  Sensitivity of molecular tests in detecting resistance to SLID, taken as the sensitivity of LiPA sl to detect capreomycin resistance 0.795 0.583 0.914 [9] δ
  Specificity of molecular tests in detecting rifampicin resistance (assumed to be the same as LiPA) 0.99 0.98 1.00 [28] α
  Specificity of molecular tests in detecting INH resistance (assumed to be the same as LiPA) 1.00 0.99 1.00 [28] α
  Specificity of molecular tests in detecting resistance to fluoroquinolones 0.977 0.943 0.991 [9] δ
  Specificity of molecular tests in detecting resistance to SLID, taken as the sensitivity of LiPA sl to detect capreomycin resistance 0.958 0.934 0.973 [9] δ
  Sensitivity and specificity of DST for resistance to 1st and 2nd line drugs 1 -   model assumption β
Repeat testing (Proportion of tests with invalid results requiring repeat testing, for:)
  Xpert MTB/RIF 0.011 0.0004 0.020 [30] γ
  LiPA 0.027 0.007 0.068 [3] γ
  mycobacterial culture 0.052 0.048 0.057 [31] γ
  high-throughput MRD-assay 0.027    same as LiPA; δ model assumption
  phenotypic DST 0    model assumption; β footnote (b)
Median number of days to resulta days sd   source
  MTBDRplus assay (LiPA) 3.0 1.7   [4]; γ footnote (c)
  LJ culture 34.1 11.3   [4] β
  MGIT culture 8.9 3.9   [4] γ
  LJ DST 67.5 15.0   [4] β
  MGIT DST 21.6 9.3   [4] β
  high-throughput MRD assay in scenarios A and C 6.0 3.0   Model assumption; footnote (d)
  high-throughput MRD assay in scenario B 3.0 1.5   Model assumption; footnote (e)
  Xpert MTB/RIF 0    Model assumption; γ footnote (f)
Median days from lab result until clinical review and treatment initiation
  for a standard treatment regimen (1st line or empirical 2nd line) 1    [32] α
  for an individualized regimen (assuming additional consultation) 4    Model assumption α
Median days from treatment initiation to sputum culture conversion
  in patients with susceptible TB or INHmono resistance (days, sd) 34 26   [3335] α
  in patients with MDR-TB on an appropriate regimen, (days, 95 % CI) 61 59 67 [13] α
  in patients with XDR-TB in high-throughput RMD scenario (days, 95 % CI) 75 60 90 [14] δ
  Increase in duration of préXDR (SLID res) in baseline 0.55    [15] β
  Increase in duration of préXDR (FQ res) in baseline 0.72    [15] β
Time to failure     
  Months to failure on a first-line regimen 5    (15;30) α
  Months to failure on a second-line regimen 4    (15;30) α
  Infectious time in XDR patients who fail 24    Model assumption (duration of treatment) α
Per-test unit cost for diagnostic tests US$ 2013 (min, max)
  Sputum smear [2] 3.34 2.42 5.08 [17] α
  Xpert PEPFAR pricing 17.29 15.66 18.92 [18] γ
  high-throughput MRD-assay - ratio compared to per-test unit costs of LiPA 2 0.5 4 model assumption δ
  DST 1st line (MGIT) 44.56 40.05 49.07 [18] β
  DST 2nd line (LJ) 25.35 20.68 30.02 [18] β
  Line Probe Assay (LiPA) 21.32 18.45 24.18 [18] γ
  LJ culture 18.48 11.08 33.30 [17] γ
  MGIT culture 18.48 11.08 33.30 [17] γ
Treatment cost parameters US$ 2013 (min, max)     
  First-line treatment courseb 945 629 1419 [19] α
  Second-line treatment course for MDR 4176 2341 7449 [19] α
  Ratio of pré-XDR regimen cost compared to MDR regimen cost 2    [20] α
  Ratio of XDR regimen cost compared to MDR regimen cost 3    [20] α
  Hospitalization for MDR/XDR, cost per dayb 67    [1] α
  1. The modeled scenarios are: Base Case; MRD-A. Rapid MRD assay following culture; MRD-B. Improved analytical sensitivity; MRD-C. Improved clinical accuracy. The Greek symbol in the first column indicates to which scenarios the parameter apply: α to all four scenarios; β to the Base Case only; γ to the Base Case, MRD-A and -C but not to MRD–B; δ to the MRD scenarios (A, B, C) but not the Base Case
  2. (a): low end of the range reflects the distribution among new patients and high end the distribution among previously treated patients.(b): if an isolate is obtained on culture, we assume DST will always give a valid result. (c): adjusted (was 4.2 days in the publication in a special study performing assays 2–3 times a run per week on 2–8 samples per run. We adjusted for current practice where LiPAs are run daily (50–60 samples per week). (d) assumes a batch of ± 50 once a week. (e): assumes a patient volume that requires batch testing of ± 50 every 1–2 (working) days. (f): Time counts from TB diagnosis and Rifampicin result comes at the same time as the TB diagnostic result
  3. Abbreviations; PE point estimate, PTB pulmonary tuberculosis, MDR multi-drug resistance, defined as resistance to rifampicin and isoniazid [2], SLID second-line injectable drugs, XDR extensively drug-resistant, INH isoniazide, LiPA line probe assay, LJ Löwenstein-Jensen, MGIT Mycobacterial Growth Inhibitor Tube, DST Drug Susceptibility Testing, sd standard deviation, CI confidence interval
  4. aExcluding requirement for repeat testing
  5. bFirst-line treatment applies to catI and catII treatment; hospitalization costs are estimated from studies in the same region [21] and average number of hospital days in 2012 [36]