Table 1.
Model inputs
| Parameter | Value | Reference(s) | |
|---|---|---|---|
| Clinical inputs | EPFX | Vancomycin | |
| Clinical response 2 days after EOT (%) | 78.0 | 82.1 | Guery et al. 201715 |
| RR (95% CI)a | 0.95 (0.86‒1.05) | derived from Guery et al. 201715 | |
| Recurrence at Day 40 (%) | 1.4* | 19.7 | derived from Guery et al. 201715 |
| RR (95% CI)a | 0.07 (0.02–0.30) | calculated | |
| Recurrence at Day 55 (%) | 4.3* | 21.1 | derived from Guery et al. 201715 |
| RR (95% CI)a | 0.21 (0.09–0.48) | calculated | |
| Recurrence at Day 90 (%) | 7.2* | 22.4 | derived from Guery et al. 201715 |
| RR (95% CI)a | 0.32 (0.17–0.63) | calculated | |
| AEs (all-grade), (%)b | |||
| anaemia | 2.8 | 5.5 | Guery et al. 201715 |
| cardiac failure | 2.2 | 5.5 | Guery et al. 201715 |
| clostridial infectionc | 3.9 | 13.3 | Guery et al. 201715 |
| constipation | 5.5 | 2.8 | Guery et al. 201715 |
| diarrhoea | 5.5 | 6.6 | Guery et al. 201715 |
| pneumonia | 2.8 | 5.5 | Guery et al. 201715 |
| pyrexia | 3.9 | 6.6 | Guery et al. 201715 |
| sepsis | 0.6 | 5.0 | Guery et al. 201715 |
| urinary tract infection | 3.3 | 6.6 | Guery et al. 201715 |
| Deaths, n (%) | |||
| Days 1–12 | 12 (3.3) | Guery et al. 201715 | |
| Days 13–27 | 13 (3.6) | Guery et al. 201715 | |
| Days 28–90 | 40 (11.0) | Guery et al. 201715 | |
| Probability of mortality (%) | |||
| Days 0 to <10 | 1.39 | see Table S2 | |
| Days 10 to <15 | 1.28 | see Table S2 | |
| Days 15 to <25 | 1.20 | see Table S2 | |
| Days 25 to <30 | 1.03 | see Table S2 | |
| Days 30 to <90 | 0.92 | see Table S2 | |
| Days 90+ | 0 | see Table S2 | |
| Costs (£) | Fidaxomicind | Vancomycine | |
| Drug acquisition | |||
| per pack | 1350.00 | 132.47 | BNF 201625 |
| per course | 1350.00 | 189.24 | BNF 201625 |
| Hospitalization for CDI episode | |||
| per 10 day admittance | 8214.00 | DoH 201226; ONS 201624 | |
| rescue treatment | 4107.00 | assumption | |
| AEsf | |||
| anaemia | 46.35 | ONS 201624; Curtis & Burns 201527 | |
| cardiac failure | 7305.97 | ONS 201624; NICE 201536 | |
| clostridial infection | 0 | assumption | |
| constipation | 1414.96 | DoH 201526; ONS 201624 | |
| diarrhoea | 1414.96 | DoH 201526; ONS 201624 | |
| pneumonia | 1992.84 | DoH 201526; ONS 201624 | |
| pyrexia | 1026.66 | DoH 201526; ONS 201624 | |
| sepsis | 2215.78 | DoH 201526; ONS 201624 | |
| urinary tract infection | 0 | assumption | |
| Utilities | |||
| Health state utilities | |||
| CDI initial episodeg | 0.33 | derived from Slobogean et al. 201018 | |
| clinical failure (first recurrence)g | 0.30 | derived from Slobogean et al. 201018 | |
| clinical failure (second recurrence)g | 0.27 | derived from Slobogean et al. 201018 | |
| clinical response (initial episode) | 0.78 | derived from Slobogean et al. 201018 | |
| clinical response (recurrence) | 0.56 | derived from Slobogean et al. 201018 | |
| disease-free | 0.78 | derived from Slobogean et al. 201018 | |
| AE decrements | |||
| anaemia | −0.081 | NICE 201020 | |
| cardiac failure | −0.108 | NICE 201522 | |
| clostridial infection | 0 | assumption | |
| constipation | −0.007 | NICE 201020 | |
| diarrhoea | −0.007 | NICE 201020 | |
| pneumonia | −0.008 | Marti et al. 201323 | |
| pyrexia | −0.001 | NICE 201020 | |
| sepsis | −0.171 | NICE 201521 | |
| urinary tract infection | −0.00282 | NICE 201522 | |
BNF, British National Formulary; CDI, Clostridium difficile infection; DoH, Department of Health; EOT, end of treatment; EPFX, extended-pulsed fidaxomicin; RR, relative risk.
Asterisks indicate P<0.001 according to Cochran–Mantel–Haenszel test adjusted for stratificiation factors.
EPFX versus vancomycin.
Treatment-emergent AEs reported in ≥5% of patients in either the EPFX or vancomycin arm.
All CDI recurrences.
A pack includes 20 × 200 mg tablets and a course requires 20 × 200 mg tablets.
A pack includes 28 × 125 mg capsules and a course requires 40 × 125 mg capsules.
Anaemia, assumed to be the cost of one general practitioner visit; clostridial infections, assumed to be captured in the hospitalization costs; constipation, sum of weighted NHS reference costs for gastrointestinal infections (currency codes, FZ36G, FZ36H, FZ36J, FZ36K, FZ36L, FZ36M, FZ36N, FZ36P, FZ36Q); diarrhoea, assumed to be the same as for constipation; pneumonia, sum of weighted NHS reference costs for lobar, atypical or viral pneumonia (currency codes, DZ11K–V); pyrexia, sum of weighted NHS reference costs for fever of unknown origin (currency codes, WJ07A–D); sepsis, sum of weighted NHS reference costs for sepsis (currency codes, WJ06A–H, and WJ06J); urinary tract infection, assumed to be captured in the hospitalization costs.
Utility value applies for first-, second- and third-line therapies.