Quality of life benefits and cost impact of prolonged release oxycodone/naloxone versus prolonged release oxycodone in patients with moderate-to-severe non-malignant pain and opioid-induced constipation: a UK cost-utility analysis

Figures & data

Figure 1.  Model structure.

Figure 2.  Major model inputs.

Table 1.  Costs of pain and laxative therapy.

	OXN	OXY	Difference
Pain therapy
Cost/mg	£0.078	£0.055	£0.02
Average dose/day (mg)14	32.2	33	−0.8
Average cost/week [Dj]	£17.48	£12.71	£4.77
Laxative (bisacodyl)
Cost/5 mg tablet	£0.03	£0.03	0
Average number of 5 mg tablets/4 weeks14	1.83	4.37	−2.54
Average cost/week [Lj]	£0.01	£0.04	−£0.03

Unit costs taken from British National Formulary 60 September 201022.

Table 2.  Additional healthcare costs.

	% of patients requiring resource	Frequency over course of opioid	Cost/unit (£)	Weighted cost (£)
Enema administered by patient	10	2.40	7.98	1.92
Enema administered by practice nurse	13	2.10	19.98	5.29
Enema administered by district nurse	12	2.30	34.98	9.90
Primary care physician consultation	34	2.90	36.00	35.29
Home visit by primary care physician	13	1.70	120.00	26.72
Home visit by district nurse	24	2.80	27.00	18.30
Home visit by practice nurse	10	1.00	20.00	2.00
Outpatient appointment	6	1.20	268.00	20.58
Endoscopy/colonoscopy	4	1.20	956.00	49.33
Accident and emergency attendance	4	1.40	87.00	4.87
Manual evacuation	3	1.10	991.00	30.52
Haemorrhoid stapling	3	1.00	1219.00	31.69
Average cost/patient per course of therapy				236.40
Average weekly cost/per patient of additional therapies				5.50 [V]

Costs taken from British National Formulary 60 September 201022, Curtis 201023, National Tariff 2009/201024.

Table 3.  Percentage of constipated patients over time [P_ij].

	% of patients
	OXN (n = 158)	OXY (n = 158)	Difference
Week 0	91	88	−3
Week 1	63	82	19
Week 2	56	79	23
Week 4	58	77	19
Week 8	51	75	24
Week 12	49	67	18
Week 64*	27	–	–

*Extension phase data for patients randomised to OXN in the study by Simpson et al.

The constipation status at week 64 (i.e., 64 weeks after randomisation in the study by Simpson et al.) was not applied in the model.

Table 4.  Base case EQ-5D utility values.

		OXN*	OXY^†	Difference (95% CI)	p-value
Week 0	Raw mean (SE)	0.4776 (0.0137)	0.4792 (0.0116)	–0.0015 (−0.034, 0.037)	0.9319
Week 1	Adjusted mean^‡ (SE)	0.5008 (0.0076)	0.4829 (0.0077)	0.0180 (−0.0035, 0.0395)	0.1006
Week 12	Adjusted mean^‡ (SE)	0.5029 (0.0115)	0.4640 (0.0117)	0.0388 (0.0065, 0.071)	0.0185

*n = 162 at weeks 0 and 1; n = 159 at week 12.

^†n = 160 at weeks 0 and 1; n = 156 at week 12.

^‡Least squares mean with baseline as a covariate based on Manca et al.28 and Willan and Briggs29.

SE, standard deviation; CI, confidence interval.

Table 5.  Deterministic sensitivity analysis inputs.

Sensitivity analysis	Input	Comments
Key variables
Incremental utility values OXY	±25%	To determine which inputs had the most significant impact on model results (and the direction of impact), a simple sensitivity analysis involved increasing and decreasing key variables by 25% as a change of this magnitude would be sufficient to indicate any trends (except for probability of constipation, which was adjusted by 10% to prevent values exceeding 100%)
Total weekly dose of OXY/OXN	±25%
Treatment duration (weeks)	±25%
Probability of constipation in OXY group	±10%
Probability of constipation in OXN group	±10%
Cost of additional resources for constipated patients	±25%
Cost of laxative	±25%
Mapping functions
Rowen et al.21 unadjusted for baseline	Week 0: 0.4776 (OXN); 0.4792 (OXY)	To test whether adjusting baseline utility values impacts the model results
	Week 1: 0.5003 (OXN); 0.4849 (OXY)
	Week 12: 0.5032 (OXN); 0.4652 (OXY)
SF-6D mapping equation (Brazier et al.33)	Week 0: 0.60169 (OXN); 0.59811 (OXY)	To test whether the mapping function impacts the model results
	Week 1: 0.61216 (OXN); 0.59624 (OXY)
	Week 12: 0.61901 (OXN); 0.58664 (OXY)
Constipation utility values		To test how application of constipated and non-constipated utility values from the literature impacts the model results
Non-advanced illness34	Not constipated 0.6500; constipated 0.3100
Uncontrolled chronic functional constipation35	Not constipated 1; constipated 0.74
Controlled chronic functional constipation35	Not constipated 1; constipated 0.9
Cancer patients with OIC36	Not constipated 0.63; constipated 0.39
Average utility value from the literature	Not constipated 0.8200; constipated 0.5850
Cost of constipation		To test how application of non-UK cost of constipation studies impacts the model results
Kwong et al.10	Incremental cost constipation £370.81
Iyer et al.11	Incremental cost constipation £555.58
Hjalte et al.12	Incremental cost constipation £42.16

OIC, opioid-induced constipation.

Table 6.  Base case results.

	Cost (£)
	OXN	OXY	Difference
Pain therapy	751.64	546.53	205.11
Laxatives	0.43	1.72	−1.29
Other resource costs	121.00	165.14	−44.14
Total	873.07	713.39	159.68
QALY	0.4152	0.3878	0.0273
ICER			£5841.56

QALY, quality-adjusted life-year; ICER, incremental cost-effectiveness ratio.

Table 7.  Results of sensitivity analyses.

Sensitivity analysis	Incremental cost (£)	Incremental QALY	Incremental ICER (£)
Key variables
Incremental utility values OXY −25%	159.68	0.0205	7788.75
Incremental utility values OXY +25%	159.68	0.0342	4673.25
Total weekly dose of OXY/OXN −25%	108.08	0.0273	3953.91
Total weekly dose of OXY/OXN +25%	211.28	0.0273	7729.21
Treatment duration (weeks) −25%	118.43	0.0191	6198.47
Treatment duration (weeks) +25%	197.18	0.0348	5663.50
Probability of constipation in OXY group −10%	176.20	0.0273	6445.68
Probability of constipation in OXY group +10%	143.17	0.0273	5237.45
Probability of constipation in OXN group −10%	147.58	0.0273	5398.92
Probability of constipation in OXN group +10%	171.78	0.0273	6284.21
Cost of additional resources for constipated patients −25%	170.72	0.0273	6245.23
Cost of additional resources for constipated patients +25%	148.65	0.0273	5437.90
Cost of laxatives −25%	160.01	0.0273	5853.36
Cost of laxatives +25%	159.23	0.0273	5824.85
Mapping functions
Rowen et al.21 unadjusted for baseline	159.68	0.0263	6080.47
SF-6D mapping equation (Brazier et al.33)	159.68	0.0230	6939.44
Constipation utility values
Non-advanced illness34	159.68	0.0525	3043.24
Uncontrolled chronic functional constipation35	159.68	0.0401	3979.63
Controlled chronic functional constipation35	159.68	0.0154	10347.03
Cancer patients with OIC36	159.68	0.0370	4311.26
Average utility value from the literature	159.68	0.0363	4402.99
Cost of constipation
Kwong et al.10	−2771.97	0.0273	OXN dominant
Iyer et al.11	−4254.70	0.0273	OXN dominant
Hjalte et al.12	−134.54	0.0273	OXN dominant

QALY, quality-adjusted life-year; ICER, incremental cost-effectiveness ratio; OIC, opioid-induced constipation.

Figure 3.  Cost effectiveness acceptability curve for the OXN utility model.

Figure 4.  Cost effectiveness plane.

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