Incorporating ulipristal acetate in the care of symptomatic uterine fibroids: a Canadian cost-utility analysis of pharmacotherapy management

Figures & data

Figure 1 Structure of the economic model.

Note: This decision tree illustrates the structure of the model alongside the health states that were incorporated into this model.
Abbreviation: w/, with.

Table 1 Summary of model parameters

Type of Parameter	Parameter	Ulipristal				Leuprolide				Reference
		Base-case value	Range in univariate sensitivity-analysis	Type of distribution	Values for probabilistic analysis	Base-case value	Range in univariate sensitivity-analysis	Type of distribution	Values for probabilistic analysis
Costs§	Pharmaceuticals-related
	Monthly cost of treatment drug	$343.80	N/A	N/A	N/A	$347.18	N/A	N/A	N/A	^Citation23
	Monthly cost of add-back therapy	N/A	N/A	N/A	N/A	$43.26	$30.28–$56.24	Gamma	α: 42.68 β: 1.01 SD: 6.62**	McKesson Ontario pricing (March, 2013)
	Pharmacy up-charge	8.00%	5.60%–10.40%	N/A	N/A					^Citation21
	Health professional fees*
	Specialist consultation	$101.70	$71.19–$132.21	Normal	SD: 15.57**
	Cost of injection (with medical visit billed)	N/A	N/A	N/A	N/A	$3.89	$2.72–$5.06	Normal	SD: 0.60**
	Cost of injection (without medical visit billed): applicable to first injection	N/A	N/A	N/A	N/A	$6.75	$4.73–$8.78	Normal	SD: 1.03**
	Specialist medical visit: first visit following consultation	$47.45	$33.22–$61.69	Normal	SD: 7.26**
	Specialist medical visit: subsequent	$26.35	$18.45–$34.26	Normal	SD: 4.03**
	GP medical visit	$38.35	$26.85–$49.86	Normal	SD: 5.87**
	Pharmacist’s dispensing fee	$8.40	$5.88–$10.92	Normal	SD: 1.29**					^Citation22
	Productivity*
	Hourly salary of females	$22.10	$15.47–$28.73	Normal	SD: 3.38^†					^Citation31
Resource utilization	Health care related
	Number of pharmacy dispensation	2	1–3	Gamma	α: 10.82 β: 0.18 SD: 0.608**	3	1–3	Gamma	α: 24.35 β: 0.12 SD: 0.608**	Assumption
	Number of surgical consult	1	N/A	N/A	N/A	1	N/A	N/A	N/A	Assumption
	Number of specialists or GP follow-up visits	1	1–3	Gamma	α: 2.71 β: 0.37 SD: 0.608**	3	1–3	Gamma	α: 24.35 β: 0.12 SD: 0.608**	Clinical opinion
	Productivity
	Proportion of full-time employed females	0.89	0.804–0.947	Beta	α: 74.76 β: 9.24 SD: 0.033					IMS Brogan# chart audit
	Total hours of missed work over a month if bleeding uncontrolled	7.5	5.25–9.75	Normal	SD: 1.148
	Hours of lost work due to medical visit/injection	2	0–8	Gamma	α: 1 β: 2 SD: 2					Assumption
Utility (yearly)	Controlled bleeding	0.73	0.716–0.744	Beta	α: 2965.02 β: 1096.65 SD: 0.007					^Citation20
	Uncontrolled bleeding	0.55	0.542–0.558	Beta	α: 7321.20 β: 5990.08 SD: 0.004
	Increment from oral administration	0.02	0.011–0.029	Beta	α: 18.17 β: 890.39 SD: 0.005
	Decrement from hot flashes	0.06	0.045–0.075	Beta	α: 59.21 β: 927.62 SD: 0.008
Probability	Probability of achieving controlled bleeding	0.903	0.820–0.952	Beta	α: 80.83 β: 8.68 SD: 0.031	0.891	0.805–0.944	Beta	α: 81.08 β: 9.92 SD: 0.032	^Citation14
	Days of uncontrolled bleeding	5.226	3.208–7.572	Gamma	α: 22.04 β: 0.24 SD: 1.113	10.268	7.434–13.241	Gamma	α: 48.04 β: 0.21 SD: 1.481
	Proportion of patients suffering moderate-to-severe hot flashes on ulipristal	0.113	0.061–0.198	Beta	α: 10.85 β: 85.15 SD: 0.032	0.396	0.302–0.499	Beta	α: 39.6 β: 60.4 SD: 0.049

Notes: For parameters that are the same in both arms of the model, they are only presented once under the ulipristal column.

* The high and low values for the parameters were defined as ±30% of the base-case value. For the remaining parameters, the high and low value represents the 95% confidence interval.

** The standard error of mean for these parameters was estimated by fitting a normal distribution across the high and low parameter values.

§ 2013 Canadian dollars.

# IMS Brogan is the Canadian business unit of IMS Health that provides anonymized medical claims data.

Abbreviations: GP, general practitioner; SD, standard deviation; N/A, not applicable.

Figure 2 Probabilistic sensitivity analysis base-case (health care payer perspective).

Notes: The incremental cost-effectiveness plane demonstrates the joint distribution in costs (y-axis) and QALYs (x-axis), recalculated over 1,000 replications of the study parameters using Monte Carlo simulation technique. Each point in the graph represents a single iteration of the Monte Carlo simulation.
Abbreviation: QALYs, quality-adjusted life years.

Table 2 Expected results under the base-case scenario

	Total		Incremental
	Costs	QALYs	Costs	QALYs	ICUR
Leuprolide	$1,365.58	0.165	-reference-	-reference-
Ulipristal	$1,273.44	0.177	$-92.13	0.012	Ulipristal dominates leuprolide

Note: Costs in 2013 Canadian dollars.

Abbreviations: QALYs, quality-adjusted life years; ICUR, incremental cost-utility ratio.

Table 3 Expected cost breakdown under the base-case scenario (deterministic results)

Type of costs	Ulipristal	Leuprolide	Difference (ie, ulipristal – leuprolide)
Drug-related costs ($)
Drug costs	1,113.91	1,124.86	-10.95
Pharmacist dispensation	8.40	25.20	-16.80
Drug administration	0.00	113.44	-113.44
Total drugs	1,122.31	1,263.50	-141.19
Non-drug costs
Medical visits*	149.15	101.7	47.45
Total direct health care costs	1,271.46	1,365.20	-93.74
Cost from time lost from work due to symptoms	66.13	93.23	-27.10
Cost from time lost from work due to medical visits	78.68	157.35	-78.67
Total indirect health care costs	144.81	250.58	-105.77

Notes:

* Medical visits in which patients are assessed by the physician and receive an injection are not captured here. Rather, such costs have been classified under “drug administration”. Costs in 2013 Canadian dollars.

Table 4 Results of one-way univariate sensitivity analysis of the base-case parameters

Parameter description	Lower range		Upper range
	Parameter value	ICUR result	Parameter value	ICUR result
Base-case model parameters
Monthly cost of “add-back”-therapy, norethindrone acetate: 5 mg	$30.28	Dominant	$56.24	Dominant
Pharmacy upcharge	5.60%	Dominant	10.40%	Dominant
ObGyn: consultation for initial diagnosis (20 minutes)	$71.19	Dominant	$132.21	Dominant
Cost of injection – medical visit billed alongside	$2.72	Dominant	$5.06	Dominant
Cost of first injection – sole reason (ie, no visit)	$4.73	Dominant	$8.78	Dominant
ObGyn: specific assessment	$33.22	Dominant	$61.69	Dominant
ObGyn: partial assessment	$18.45	Dominant	$34.26	Dominant
GP: re-assessment during administration of GnRH	$26.85	Dominant	$49.86	Dominant
Pharmacist’s dispensing fee	$5.88	Dominant	$10.92	Dominant
Number of times ulipristal dispensed	1	Dominant	3	Dominant
Number of times leuprolide injected	1	Dominant	3	Dominant
Number of specialists follow-up visits for ulipristal	1	Dominant	3	Dominant
Proportion of females working full-time	0.804	Dominant	0.947	Dominant
Proportion of hours lost to total hours worked if bleeding uncontrolled	0.001	Dominant	0.127	Dominant
Proportion of patients with one absenteeism due to uncontrolled bleeding	0.274	Dominant	0.515	Dominant
Hours worked per month	168	Dominant	184	Dominant
Hours of lost work due to medical visit or injection	0	Dominant	8	Dominant
Yearly utility of controlled bleeding	0.716	Dominant	0.744	Dominant
Yearly utility uncontrolled bleeding	0.542	Dominant	0.558	Dominant
Yearly utility increment for oral administration	0.011	Dominant	0.029	Dominant
Yearly utility decrement from hot flashes	0.045	Dominant	0.075	Dominant
Days of uncontrolled bleeding (leuprolide)	7.434	Dominant	13.241	Dominant
Days of uncontrolled bleeding (ulipristal)	3.208	Dominant	7.572	Dominant
Proportion of patients suffering moderate-to-severe hot flashes (leuprolide)	0.302	Dominant	0.499	Dominant
Proportion of patients suffering moderate-to-severe hot flashes (ulipristal)	0.061	Dominant	0.198	Dominant
Probability of achieving controlled bleeding (leuprolide)	0.805	Dominant	0.944	Dominant
Probability of achieving controlled bleeding (ulipristal)	0.820	Dominant	0.952	Dominant

Note: Costs in 2013 Canadian dollars.

Abbreviations: ICUR, incremental cost-utility ratio; ObGyn, obstetrics and gynecology; GnRH, gonadotropin-releasing hormone; GP, general practitioner.

Figure 3 Cost-effectiveness acceptability curve (CEAC) – when medical assessments are not billed alongside each leuprolide injection.

Notes: The probabilistic sensitivity analysis is based on 1,000 Monte Carlo simulations. The CEAC shows the likelihood to which ulipristal is cost-effective compared to leuprolide across a range of cost-effectiveness threshold values (x-axis). For each cost-effectiveness threshold (increasing from left to right) on the x-axis, the proportion of iterations having ICUR at or below that threshold is plotted on the y-axis.
Abbreviation: ICUR, incremental cost-utility ratio.

Table 5 Expected results under different methodological assumptions

	Strategy	Total		Incremental
		Costs	QALYs	Costs	QALYs	ICUR
Utility increment of “oral administration” removed	Leuprolide	$1,365.49	0.165	-reference-	-reference-
	Ulipristal	$1,273.15	0.172	$-92.34	0.007	Ulipristal dominates leuprolide
Utility decrement of “hot flashes” removed	Leuprolide	$1,365.51	0.171	-reference-	-reference-
	Ulipristal	$1,274.06	0.178	$-91.45	0.008	Ulipristal dominates leuprolide
Medical visits not billed during injection	Leuprolide	$1,262.77	0.165	-reference-	-reference-
	Ulipristal	$1,274.24	0.177	$11.48	0.012	$1,015.65/QALY

Note: Costs in 2013 Canadian dollars.

Abbreviations: QALYs, quality-adjusted life years; ICUR, incremental cost-utility ratio.

Figure 4 Probabilistic results when comparator is 11.25 mg, 3-month leuprolide (intramuscular).

Notes: (A) Probabilistic sensitivity analysis. (B) Cost-effectiveness acceptability curve. The probabilistic sensitivity analysis is based on 1,000 Monte Carlo simulations.
Abbreviation: QALYs, quality-adjusted life years.

Table 6 Expected results under different scenarios analyses

Scenario	Total		Incremental
	Costs	QALYs	Costs	QALYs	ICUR
1. Inclusion of add-back therapy
Scenario a: 100% on add-back, no hot flashes in the leuprolide arm
Leuprolide	$1,366.36	0.171	-reference-	-reference-
Ulipristal	$1,273.47	0.177	$-92.89	0.006	Ulipristal dominates leuprolide
Scenario b: 39% on add-back, no hot flashes in the leuprolide arm
Leuprolide	$1,365.00	0.171	-reference-	-reference-
Ulipristal	$1,273.66	0.177	$-91.34	0.006	Ulipristal dominates leuprolide
Scenario c: 39% on add-back, 50% reduction in hot flashes in the leuprolide arm
Leuprolide	$1,366.24	0.168	-reference-	-reference-
Ulipristal	$1,273.11	0.177	$-93.14	0.009	Ulipristal dominates leuprolide
2. 11.25 mg leuprolide
Leuprolide	$1,271.14	0.165	-reference-	-reference-
Ulipristal	$1,273.08	0.177	1.93	0.012	168.39
3. Societal perspective
Leuprolide	$1,614.50	0.165	-reference-	-reference-
Ulipristal	$1,416.77	0.177	$-197.74	0.012	Ulipristal dominates leuprolide

Note: Costs in 2013 Canadian dollars.

Abbreviations: QALYs, quality-adjusted life years; ICUR, incremental cost-utility ratio.

Figure 5 Probabilistic sensitivity analysis based on 1,000 Monte Carlo simulations – under a societal perspective.

Abbreviation: QALYs, quality-adjusted life years.

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