Cost-effectiveness of zoledronic acid vs clodronic acid for newly-diagnosed multiple myeloma from the United Kingdom healthcare system perspective

Figures & data

Table 1.  Model parameters.

Estimate	Value
Weibull survival function parameters (monthly)
PFS
Lambda	0.1801
Gamma	0.5911
HR zoledronic acid vs clodronic acid	0.883
OS
Lambda	0.0282
Gamma	0.8483
HR zoledronic acid vs clodronic acid	0.842
Adverse events, probability (per month)
Clodronic acid; Osteonecrosis of the jaw	0.02%
Zoledronic acid; Osteonecrosis of the jaw	0.19%
Skeletal-related events, probability (per month), by month	Months 1–6	Months 7–12	Months 13–24	Months 25+
Clodronic acid
Radiation	2.55%	0.63%	0.22%	0.05%
Vertebral fractures	1.02%	0.26%	0.09%	0.02%
Other fractures	0.76%	0.19%	0.07%	0.02%
Surgery to bone lesions	0.67%	0.17%	0.06%	0.01%
Spinal cord compression	0.21%	0.05%	0.02%	0.00%
Zoledronic acid
Radiation	2.41%	0.31%	0.16%	0.05%
Vertebral fractures	0.65%	0.09%	0.05%	0.01%
Other fractures	0.58%	0.08%	0.04%	0.01%
Surgery to bone lesions	0.63%	0.09%	0.04%	0.01%
Spinal cord compression	0.16%	0.02%	0.01%	0.00%
Costs, £
Bisphosphonates, per administration
Zoledronic acid
Medication				174.14
Administration				52.94
Clodronic acid, per day				4.66
Thalidomide, per day of administration				10.66
Adverse events, per event; Osteonecrosis of the jaw				195.47
Skeletal-related events, per event
Vertebral fractures				250
Other fractures				6271
Surgery to bone lesions				3899
Spinal cord compression				3831
Follow-up/monitoring				206.09
Utilities
PFS
Baseline PFS				0.485
Monthly increase during PFS	Months 1–3	Months 4–12	Months 12+
Zoledronic acid	0.0267	0.0100	0.000
Clodronic acid	0.0233	0.0133	0.000
PPS			0.485

Figure 1.  Estimated PFS (a) and OS (b) for zoledronic acid and clodronic acid.

Table 2.  Base-case results.

Outcome measure	Zoledronic acid	Clodronic acid	Difference
Effectiveness
PFS (years)	2.94	2.65	0.29
PFS discounted (years)	2.63	2.40	0.23
PPS (years)	3.49	2.95	0.55
PPS discounted (years)	2.75	2.36	0.39
Life years	6.43	5.60	0.83
Life years, discounted	5.37	4.76	0.62
Quality adjusted life years	3.55	3.14	0.42
Quality adjusted life years, discounted	2.99	2.68	0.30
Expected lifetime costs, £
Bisphosphonates	4415	2590	1825
Thalidomide maintenance therapy	3423	3450	−27
SREs	877	1154	−277
ONJ	7	1	6
Routine follow-up and monitoring	1108	981	127
Total	9829	8176	1653
Cost per QALY gained			5443

Figure 2.  Cost-effectiveness acceptability curves for zoledronic acid and clodronic acid.

Table 3.  Deterministic sensitivity analyses.

No.	Scenario	Difference, Zoledronic acid vs Clodronic acid
		Costs, £	QALYs	ICER, £
1	Base case	1653	0.30	5443
2	HR PFS ZOL vs CLO 95%CIL	1706	0.32	5414
3	HR PFS ZOL vs CLO: 95%CIU	1646	0.30	5448
4	HR OS ZOL vs CLO: 95%CIL	1676	0.36	4684
5	HR OS ZOL vs CLO: 95%CIU	1632	0.25	6434
6	ZOL admin. costs = −50% vs BC	1139	0.30	3749
7	ZOL admin. costs = +50% vs BC	2168	0.30	7137
8	OS independent Kaplan Meier then independent Weibull	1610	0.20	7945
9	OS proportional hazard Kaplan Meier then proportional hazard Weibull	1692	0.35	4802
10	OS proportional hazard Weibull only	1692	0.36	5124
11	OS independent Weibull only	1780	0.17	10,608
12	Change from independent Kaplan Meier to proportional hazard Weibull at median OS (ZOL = 48 m; CLO = 43 m)	1639	0.27	6069
13	Price of ZOL generic (50% base-case price) after 2 years	939	0.30	3091
14	Price of ZOL generic (50% base-case price) after 1 year	326	0.30	1073
15	Price of ZOL generic (50% base-case price) at start of treatment	−1057	0.30	ZOL Dominant
16	ONJ costs = −50% vs base-case	1650	0.30	5433
17	ONJ costs = +50% vs base-case	1656	0.30	5453
18	Surgery of the jaw in 100% of ONJ cases (cost ONJ = £5101)	1808	0.30	5953
19	SRE costs = −50% vs base case	1792	0.30	5900
20	SRE costs = +50% vs base case	1515	0.30	4986
21	Disutility PFS vs perfect health = −50% vs base-case	1653	0.46	3578
22	Disutility PFS vs perfect health = +50% vs base-case	1653	0.15	11,367
23	Disutility PPS vs PFS @ 1 year (average of ZOL and CLO) = −50% vs BC	1653	0.27	6145
24	Disutility PPS vs PFS @ 1 year (average of ZOL and CLO) = +50% vs BC	1653	0.34	4885
25	Model timeframe 5 years	1499	0.08	19,378
26	Benefits of ZOL on PFS and OS for 5 years	1566	0.19	8405

AE, Adverse event; BC, Base case; CLO, Clodronic acid; KM Kaplan Meier; PFS, Progression-free survival; PH, Proportional hazard; PPS, Post-progression survival; SRE, Skeletal-related event; ZOL, Zoledronic acid; 95%CIL, Lower bound of 95% confidence interval; 95%CIL, Upper bound of 95% confidence interval.