A cost-utility study of the use of pregabalin in treatment-refractory neuropathic pain

Figures & data

Figure 1.  Structure of pregabalin versus usual care stochastic simulation model.

Table 1.  Details of clinical studies describing the effectiveness of pregabalin in the management of NeP.

Study details	No of patients	Study location	Study duration	Population	Pain score results	End-points
Stacey et al.14	81	US	15 months	• Refractory patients	Mean VAS SF-MPQ decreased	15 month study; 3-monthly pain
				• Combination of DPN/PHN	from 73.4 at baseline to 48.5 at	score intervals
				• Moderate-to-severe pain despite use of GBP a tricyclic and a third medication	study end-point
Douglas et al.15	30	Borders, Scotland	3 months	• Refractory	Mean pain intensity score on 0–10	Pain score at 1 month and
				• All NP	NRS changed from 7.79	at 3 months
				• Failed or could not tolerate tricyclic and GBP	(SD: 1.7) at baseline to 4.9 (SD: 1.9) at 3 months (p < 0.001)
Allen16	26	Pain Management	6 months	• Refractory	Average score on the BPI	Pain score at 3 weeks, 3 months
		Unit, Royal		• All NP sources	decreased from a score of ∼7.0	and 6 months
		Berkshire Hospital, Reading		• Uncontrolled on GBP	to ∼5.0 after 3 months and 4.2 after 6 months of pregabalin treatment (estimated from figure)
Freynhagen et al.17	55	Anaesthetist-based	1 month	• Refractory	The mean pain intensity score	Pain score at week 2 and week 4
		pain clinics in		• All NP sources	decreased from 6.5 (SD: 1.8) at
		Germany		• PG naive	baseline to 4.9 (SD: 1.8) at day 28 (p < 0.0001)

Table 2.  Pain scores and patient numbers of the four studies providing clinical data input to the model.

Time point (weeks)	Comparator pain scores (patient numbers)				Treatment pain scores (patient numbers)
	Freynhagen	Allen	Douglas	Stacey	Freynhagen	Allen	Douglas	Stacey
0 (baseline)	6.5 (n = 54)	6.7 (n = 26)	7.8 (n = 30)	7.34 (n = 81)	6.5 (n = 54)	6.7 (n = 26)	7.8 (n = 30)	7.34 (n = 81)
2					5.5 (n = 54)
3						4.5 (n = 19)
4					4.9 (n = 51)		6 (unknown)
12				7.6 (n = 71)		4.7 (n = 15)	5 (unknown)	4.72 (n = 71)
24				7.6 (n = 62)		4.6 (n = 4)		4.79 (n = 62)
36				7.4 (n = 52)				3.78 (n = 52)
48				7.5 (n = 51)				4.15 (n = 51)
60								4.17 (n = 56)

Figure 2.  Clinical data input: pregabalin and usual care pain profiles.

Table 3.  Adverse event and withdrawal profile of the treatment cohort.

	Total treatment-related AEs	Withdrawals due to treatment-related AEs	Other withdrawals
15 Month rate	73/106 (69%)	11/73 (15%)	34/106 (32%)
Weekly probabilities	1.93%	15.07%*	0.64%

*Withdrawal percentage applies to the sub-group of patients that have experienced an adverse event, i.e., the total treatment-related AE withdrawals would be calculated as 15.07% of the 1.93% of patients that have already experienced an adverse event.

Figure 3.  Utility data from the new pain survey by pain score.

Table 4.  Quantities and costs of treatment and treatment-related resources (weekly cost and quantities) in refractory patients.

Resource category	Unit cost^a	Comparator (no. of units)	Treatment (no. of units)
Pregabalin	£20.13^b	Not applicable	1.00
Other pain medications (Usual care)	£10.56^c	3.12	3.71
Hospital Consultant	£88	0.07	0.06
Hospital Clinic	£222^d	0.07	0.07
GP Visit	£24^e	0.23	0.22
GP Nurse/HC Assistant	£9	0.09	0.07
NHS Walk In Centre/NHS Direct	£17.69^f	0.02	0.09
Nurse Home Visit	£12	0.04	0.01
Other HC Professional	£22^g	0.06	0.05
Social Services	£17 ^h	0.11	0.26

^aAnalysis of British National Formulary and Prescription Pricing Authority drug costs by licensed indication. Treatment costs sourced from Netten and Curtis21.

^bWeekly cost of a mixture of BID and TID dosing.

^cMid-point of minimum and maximum average weekly cost of medication categories from the survey.

^dBased on first appointment at a neurology clinic21.

^eCost of a standard 10-min consultation21.

^fMid-point cost of NHS Walk in Centre (£20.27, from Salisbury et al.22) and NHS Direct (£15.11, from National Audit Office23).

^gNetten and Curtis²¹—average of a 1-h session with a community physiotherapist (£27), community chiropodist (£23), and local area health worker (£16).

^hNetten and Curtis²¹—hourly cost of a social work assistant.

Table 5.  Pricing of other pain medication usage.

Category	Min	Max	Comment
Paracetamol tablets	£0.01	£0.69	OTC
Ibuprofen tablets	£0.02	£0.24	OTC
Aspirin tablets	£0.01	£0.64	OTC
Co-codamol tablets	£0.03	£1.17	OTC
Celebrex	£0.72	£1.44	Max. 2 weeks
Froben	£0.31	£1.47
Preservex	£0.32	£0.32
Rheumox	£0.31	£0.62
Zacin	£2.15	£2.15	1 tube per week
Axsain	£1.74	£1.74	1 tube per week
Kaolin	£0.35	£0.46	1 tube (200 g) per week
Ibugel	£0.86	£0.86	1 tube per week
Voltarol	£1.00	£1.00	1 tube per week
Codeine tablets	£0.03	£0.31
Morphine	£0.30	£1.20
Palladone	£5.67	£5.67
Tramadol	£0.03	£0.34
Zamadol	£0.08	£0.95
Tegretol tablets	£0.03	£2.10
Carbagen	£0.04	£0.79
Trileptal tablets	£0.80	£3.20
Neurontin	£0.46	£8.23
Lamictal	£0.03	£7.29
Epanutin tablets	£0.05	£6.25
Triptafen	£0.10	£1.71
Cymbalta	£0.99	£1.60
Yentreve	£1.10	£2.20
Tetracycline	£0.73	£1.09
Motilium tablets	£0.28	£0.75
Maxolon tablets	£0.19	£0.19
Kaolin, morphine	£0.18	£0.18	PPA
Versatis	£2.41	£2.41
Rapydan	£3.80	£15.20
Mean cost (per day)	£0.76	£2.26
Mean weekly cost	£5.33	£15.79
Mean weekly cost (Avg. of Min/Max)	£10.56

Figure 4.  Simulated pain profiles of the treatment and comparator cohort over the model time horizon.

Table 6.  Cost-effectiveness results (base case analysis).

Strategy	Cost (£)	Incremental cost (£)	Effect (QALY)	Incremental effect (QALY)	Incremental cost effectiveness (£ per QALY)
Base case analysis
Usual care	15,624		0.43
Pregabalin	18,372	2748	0.68	0.25	10,803

Table 7.  Cost-effectiveness results (deterministic sensitivity analyses).

Strategy	Incremental cost (£)	Incremental effect (QALY)	Incremental cost effectiveness (£ per QALY)
Base case analysis	2748	0.25	10,803
S1: Alternative source of utility inputs	2748	0.12	22,116
S2 a: Cost of usual care = £0	2164	0.25	8505
S2 b: Cost of usual care = £5.33	2459	0.25	9666
S2 c: Cost of usual care = £15.79	3038	0.25	11,942
S3 a: Cost of pregabalin = £16.10	2370	0.25	9318
S3 b: Cost of pregabalin = £24.15	3126	0.25	12,288
S4: AE frequency and withdrawal rate +100%	1549	0.13	11,667
S5 a: Utility decrement of adverse events = 0	2749	0.26	10,704
S5 b: Utility decrement of adverse events = 0.12	2749	0.25	10,908
S6 a: Probability of withdrawal for non-AE reasons = 0%	5025	0.48	10,515
S6 b: Probability of withdrawal for non-AE reasons = 1%	2091	0.19	11,004
S6 c: Probability of withdrawal for non-AE reasons = 2%	1287	0.11	11,517
S6 d: Probability of withdrawal for non-AE reasons = 3%	905	0.07	12,073
S6 e: Probability of withdrawal for non-AE reasons = 4%	696	0.06	12,646
S7 a: AE cost = £0	2698	0.25	10,607
S7 b: AE cost = £48	2805	0.26	11,000
S8: Increasing AE effect period (AE cost and utility decrement × 4)	2898	0.25	11,724
S9 a: Time horizon = 1 year	1214	0.11	11,517
S9 b: Time horizon = 2 years	1933	0.18	11,036
S9 c: Time horizon = 3 years	2310	0.21	10,912
S9 d: Time horizon = 4 years	2595	0.24	10,834

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