Cost-effectiveness analysis on the use of fidaxomicin and vancomycin to treat Clostridium difficile infection in France

Figures & data

Figure 1. Markov model structure.

Table 1. Efficacy inputs as 10-day probabilities used in the base-case model and sub-group analyses derived using data from published studies^{9,10,12,22,33}.

Efficacy estimate	Base-case				Severe CDI^a				Recurrent CDI^a				Elderly (≥ 65 years)				Concomitant antibiotics				Cancer patients				Renal failure
	FDX		VAN		FDX		VAN		FDX		VAN		FDX		VAN		FDX		VAN		FDX		VAN		FDX		VAN
	n	%	n	%	n	%	n	%	n	%	n	%	n	%	n	%	n	%	n	%	n	%	n	%	n	%	n	%
Clinical cure (index episode)	539	88	566	86	175	80	184	83	–	–	–	–	264	85	283	84	134	84	139	76	87	85	96	74	295	84	315	85
First recurrence	395	13	408	25	140	11	152	28	–	–	–	–	224	16	239	29	155	17	145	26	74	14	71	30	249	17	269	28
Clinical cure (recurrent infection)^b	88	84	90	84	88	84	90	84	88	84	90	84	264	85	283	84	134	84	139	76	87	85	96	74	295	84	315	85
Subsequent recurrence^b	79	20	80	33	79	20	80	33	79	20	80	33	224	16	283	29	155	17	145	26	74	14	71	30	249	17	269	28

CDI: C. difficile infection; FDX: fidaxomicin; VAN: vancomycin.

^a “Clinical cure (recurrent infection)” and “Subsequent recurrence” assumed the same as in trials.

^b For patients with cancer, renal failure or taking concomitant antibiotics, the probability of clinical cure for recurrent infection assumed to be the same as for the index episode, and the probability of subsequent recurrence the same as first recurrence.

Table 2. Parameter inputs and distributions used in deterministic and probabilistic sensitivity analysis.

Parameter	Distribution	Base case value	Lower 95% CI	Upper 95% CI
Probability of clinical cure—initial infection^33
Fidaxomicin	1-Beta (65,474)	88%	85%	91%
Vancomycin	1-Beta (78,488)	86%	83%	89%
Probability of first recurrence^22
Fidaxomicin	Beta (51,344)	13%	10%	16%
Vancomycin	Beta (101,307)	25%	21%	29%
Probability of clinical cure—recurrent infection^22
Fidaxomicin	Beta (74,14)	84%	76%	91%
Vancomycin	Beta (76,14)	84%	76%	91%
Probability of subsequent recurrence^22
Fidaxomicin	Beta (16,63)	20%	12%	30%
Vancomycin	Beta (26,54)	33%	23%	43%
Proportion of recurrence that is re-infection^49
Fidaxomicin	Beta (4,24)	14%	4%	29%
Vancomycin	Beta (11,51)	18%	9%	28%
Attributable CDI mortality^36	Beta (29,891)	3%	2%	4%
All-cause mortality^35	Beta (100,29)	1.26%	1.02%	1.52%
Hospitalization cost—CDI (excess)^39	Gamma (16,0.002)	€9,024	€5,158	€13,953
Recurrence hospital cost^39	Gamma (118,0.012)	€10,093	€8,354	€11,993
GP visit cost^24	Gamma (16,0.696)	€23	€13	€35

CDI: C. difficile infection; CI: confidence interval; GP: general practitioner.

Table 3. Cost breakdown per patient by treatment strategy for the base-case analysis (all patients).

	Cost (€)
	Fidaxomicin	Vancomycin	Difference
Initial infection
Treatment	1,205^a	0^b	1,205
Hospitalization	7,494	7,571	–77
Total	8,699	7,571	1,128
Recurrence
Treatment	487	0^b	487
Hospitalization	3,479	5,123	–1,645
Total	3,965	5,123	–1,158

^a The cost of fidaxomicin in the treatment of initial infection was less than the cost of a full 10-day treatment course²⁴, as some patients entered the model with recurrent infection, the drug costs for which were accounted for under recurrence.

^b Vancomycin costs included with hospitalization costs.

Table 4. Total costs and health outcomes at 12 months by treatment strategy, base case and patient sub-groups, reported as deterministic value (probabilistic mean [95% CI]).

Patient group	Costs (€)		Number of recurrences per 100 patients		Sustained cure (%)
	FDX	VAN	FDX	VAN	FDX	VAN
All	12  646(12 618 [9295, 17 013])	12  717(12 710 [9107, 17 369])	19%(19% [15%, 23%])	35%(36% [29%, 43%])	97%(97% [96%, 98%])	95%(95% [93%, 97%])
Severe	12 348(12 322 [8459, 17 274])	12 982(12 978 [8762, 18 261])	18%(18% [12%, 24%])	40%(40% [30%, 51%])	96%(96% [95%, 97%])	96%(96% [94%, 97%])
First recurrence	14 084(14 097 [11 839, 16 618])	13 810(13 877 [11 220, 16 816])	24%(24% [16%, 33%])	37%(38% [26%, 51%])	95%(95% [92%, 97%])	92%(92% [88%, 95%])
Cancer	12 202(12 379 [8344, 17 516])	12 502(12 958 [8453, 18 504])	17%(18% [10%, 31%])	35%(40% [24%, 64%])	98%(98% [96%, 99%])	93%(92% [86%, 96%])
Concomitant antibiotics	12 859(12 819 [8805, 18 156])	12 255(12 201 [7978, 17 572])	22%(22% [16%, 30%])	32%(32% [22%, 44%])	96%(96% [94%, 97%])	93%(93% [89%, 96%])
Renal failure	12 370(12 334 [8406, 17 375])	12 889(12 863 [8621, 18 235])	18%(18% [14%, 22%])	39%(39% [30%, 49%])	98%(98% [97%, 98%])	97%(97% [95%, 98%])
≥65 years	12 727(12 813 [8845, 17 973])	12 927(13 055 [8848, 18 557])	21%(22% [17%, 29%])	39%(41% [31%, 52%])	97%(97% [96%, 98%])	97%(96% [95%, 98%])

FDX: fidaxomicin; VAN: vancomycin.

Recurrence and cure rates are simulated over a 12-month time horizon and, therefore, differ from the 30-day rates reported in clinical trials (see Table 1).

Figure 2. Impact of parameters and assumptions on cost difference between fidaxomicin (FDX) and vancomycin (VAN).

Figure 3. Representation of the results of 1,000 PSA simulations on the cost-effectiveness plane.

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