Table 3.
Incremental costs, effects, and cost efficacy ratios for the probiotics vs comparator (placebo/no treatment/usual care)
| Reference | Costs inputs | Clinical effects inputs (healthcare-associated infections avoided, life-years or QALYS gained) | Incremental outputs (incremental costs, incremental cost benefit or cost effectiveness ratios - cost per healthcare associated-infection avoided or life-years or QALYS gained) | Subgroup analysis | Sensitivity analysis | Most economically attractive drug |
|---|---|---|---|---|---|---|
| Allen et al. (2013) |
Total healthcare costs per patient did not differ significantly between the probiotic (£8020; 95% CI, 7620 to 8420) and placebo arms (£8010; 95% CI, 7600 to 8420) Probiotics: (15,629 CAD; 95% CI, 14,850 to 16,409) Placebo: (15,601 CAD; 95% CI, 14,811 to 16,409) |
Probiotics and occurrence of AAD/CDAD: No difference with probiotics usage and placebo for AAD: 10.8 vs 10.4%, RR, 1.04; 95% CI, 0.84 to 1.28; P = 0.71 or CDAD: probiotics (12/1470, 0.8%), vs placebo (17/1491, 1.2%); RR, 0.71; 95% CI, 0.34 to 1.47; P = 0.35 |
Incremental Cost (AAD): 8.74 GBP; 95% CI, 4.32 to 21.78 17.03 CAD; 95% CI, -8.42 to 42.44 ICER: base case analysis: 22,701 GBP per QALY (44,239.07 CAD per QALY) |
Yes | Yes | No difference (base case) |
| Branch-Elliman et al. (2015) |
VAP: 15,975 USD [7,000–35,000] per case (22,623 CAD [9,913–49,566]) Probiotics cost: 2.18 USD; range, 1–10 3.09 CAD; range, 1.42–14.16 |
Primary outcome: VAP risk reduction (RR): 0.48 (range, 0.1–0.9) (Model effects inputs: 83.8% ICU survivors, 20% VAP, 15.4% mortality, 1% remained in ICU) |
Incremental cost benefit ratio: low estimate for VAP: 7,000–14,000 USD (9,913–19,826 CAD) vs willingness to pay threshold of 50,000–100,000 (70,809–141,617 CAD) per VAP case Prophylactic probiotics and subglottic endotracheal tube are cost-effective for preventing VAP |
Yes | Yes | Probiotics, suction ETT, VAP bundle (base case) |
| Kamdeu Fansi et al. (2012)*** |
Hospital care for CDAD patient (per day hospitalized): 1,424.16 USD (2,016.85 CAD) 2.50 USD (3.55 CAD) (Lactobacillus acidophilus/casei, per dose-unit) |
Probiotic-double dose (Pro-2) (15.5%) lower AAD vs probiotic-single dose (Pro-1) (28.2%) with each probiotic lower AAD incidence vs placebo (44.1%). In patients with AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter symptom duration vs placebo (6.4 days). Pro-2 (1.2%) had lower CDAD incidence vs Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs placebo (23.8%). Gastrointestinal symptoms were less common in the treatment groups vs placebo and in Pro-2 vs Pro-1. |
Estimated mean per patient’s savings (incremental cost): 1,968 USD (2,152 CAD) - single dose 2,661 USD (2,910 CAD) - double dose Compared with the placebo option (if used an average of 13 days by all patients at risk of developing AAD and CDAD) |
Yes | Yes | Probiotics (base case) |
| Leal et al. (2016) |
Cost of probiotics: 24 CAD/treatment (2018): 24.94 CAD Costs of CDAD: 11,862 CAD (12,326.60 CAD 2018) |
Risk of CDAD vs cost of probiotics Lower risk of CDI: 5.5 vs 2.0% |
Incremental cost: cost-savings: 518 CAD (539 CAD 2018)/patient Patients treated with oral probiotics lower overall cost compared with usual care (CAD 327 [340 CAD 2018] vs 845 [878 CAD 2018]) |
Yes | Yes | Probiotics (base case) |
| Lenoir-Wijnkoop et al. (2014)*** |
Non-severe CDAD patient (1st, 2nd, 3rd line): 2502, 3104, 2808 GBP (4,745, 5,587, 5,226 CAD) Severe CDAD patient (1st, 2nd, 3rd line): 6292, 6236, 5110 GBP (11,933, 11,827, 9,691 CAD) |
Probiotic group, 12% (7/57) developed AAD compared with 34% (19/56) in the placebo group (P = 0.007). None of the patients randomized to the FM with probiotic developed CDAD, while 17% (9/53) in the placebo group developed CDAD (P = 0.001). Risk ratio (RR) for the total population from Hickson’s study was 0.35 (12/34) |
Incremental cost: Probiotic intervention to prevent AAD generated estimated mean cost savings of £339 (643 CAD) per hospitalized patient over the age of 65 years and treated with antibiotics, compared to no preventive probiotic. Incremental cost-savings: 243 GBP (461 CAD)/case treated with antibiotics by preventing non-CDAD 96 GBP (182)/case treated with antibiotics through preventing CDAD |
Yes | Yes | Probiotics (base case) |
| Shen et al. (2017) |
CDAD (inpatient cost per case): 7,670 USD [3,830–11,500] CDAD (outpatient cost per case): 440 USD [210–620] CDAD (inpatient cost per case): 10,502.98 CAD [5,244.65-15,747.62] CDAD (outpatient cost per case): 602.52 CAD [287.57–849.00] |
Probiotic efficacy vs no treatment: <0.73 RR, baseline risk CDAD >1.6%, risk of probiotic-associated bacteremia/fungemia (<0.26%) |
Incremental cost: cost-savings of 840 USD (1,150 CAD)/case of CDAD averted Base case (age, 65–84; CDI risk, 2.9%); probiotics dominant (-13 USD incremental cost [18 CAD], +0.00005 QALYs); probiotics dominated no probiotics (less costly, greater QALYs) ICERs (scenarios): Probiotics RR 0.51 (WTP: 100,000 USD (135,348 CAD)) Age 18-44, CDI risk 0.6%: ICER 884,100 USD/QALY (1,196,609 CAD/QALY) - not cost effective Age, 45–64; CDI risk, 1.5%; ICER, 156,100 USD/QALY (211,278 CAD/QALY) - not cost effective Age, 65–84; CDI risk, 1.2%; ICER, 1,257,100 USD/QALY (1,701,456 CAD/QALY) - not cost effective Age >85; CDI risk, 3.8%; probiotics dominant (-31 USD incremental cost [42 CAD], +0.00014 QALYs) ICER, 19,200 USD (26,292 CAD)/QALY if baseline CDAD risk was low <1.2% |
Yes | Yes | Probiotics (in certain scenarios: base case - age 65–84 & CDI risk 2.9%, age >85, CDI risk 3.8%) |
| Vermeersch et al.*** (2018) |
AAD – non-complicated (cost per case): €277 or 418 CAD (hospital): €2150.30 or 3237.78 CAD (societal) CDAD - complicated (inpatient cost per case): €588.80 or 886.58 CAD (hospital): €2239.10 or 3,371.49 CAD (societal) |
Base case: AAD: 9.6% (71/743 patients), CDAD 5.6% (4/71 AAD patients) AAD RRR 48% S. boulardii vs no treatment CDAD RRR 47% S. boulardii vs no treatment |
Incremental cost: cost savings of €50.03 or 75.74 CAD (bottom-up) and €28.10 or 42.31 CAD (top-down) per AAD patient treated with antibiotics (healthcare provider) Incremental cost: cost savings of €95.20 or 143.35 CAD (bottom-up) and €14.70 or 22.13 CAD (top-down) per AAD patient treated with antibiotics (hospital/societal) |
Yes | Yes |
Probiotics (base case) |
AAD = antibiotic-associated diarrhea; CAD = Canadian dollar; CDAD = Clostridium Difficile-associated diarrhea; CDI = Clostridium Difficile infection; CI = confidence interval; ETT = endotracheal tube; GBP = Great Britain pound; ICER = incremental cost-effectiveness ratio; RR = risk reduction; RRR = relative risk reduction; USD = United States dollar; VAP = ventilator associated pneumonia; WTP = willingness-to-pay threshold.
*** Industry-sponsored study.
Adjusted to Canadian dollar (CAD) – 2018.