Cost-effectiveness analysis of pregabalin for treatment of chronic low back pain in patients with accompanying lower limb pain (neuropathic component) in Japan

Figures & data

Figure 1 Cohort simulation using a Markov model.

Note: Arrows indicate transitions for the indicated time periods.

Figure 2 Design of the physician questionnaire for determining resource utilization.

Table 1 Estimated direct costs

Pain severity	Cost, ¥
	First month	Second month	Third month
Direct costs other than pregabalin acquisition, median (interquartile range)a
No/mild pain	–	10,614 (6,576–13,988)	7,877 (4,803–9,404)
Moderate pain	25,050 (13,692–29,175)	15,256 (7,636–22,987)	11,154 (6,176–19,464)
Severe pain	26,525 (16,661–33,559)	14,791 (8,063–29,474)	18,059 (8,088–30,868)
Pregabalin costs, mean (95% confidence interval)b
No/mild pain	–	3,759 (3,398–4,119)	Assumed to be the same as second month
Moderate pain	3,742 (3,361–4,124)	4,040 (3,671–4,410)	Assumed to be the same as second month
Severe pain	3,752 (3,342–4,162)	4,429 (3,898–4,960)	Assumed to be the same as second month

Notes:

a Based on results from an internet-administered physician survey in which physicians provided information on treatment for CLBP-NeP patients for each of monthly treatment periods based on pain severity transitions and assuming either moderate or severe pain as the initial pain category;

b based on a noninterventional study.²⁰

Table 2 Costs of outpatient visits, imaging, and drugs

Category	¥
Outpatient visits, unit cost
First visit	2,820
Second or later visit	720
Imaging, unit cost
X-ray (head to spine)	850
X-ray (other parts)	430
X-ray (photographing)	680
MRI	13,300
Medications, cost/day
Acetaminophen (paracetamol)	36.45
Neurotropin	129.60
Tramadol	154.40
Nonsteroidal anti-inflammatory drugs (loxoprofen)	52.50

Table 3 Base case analysis

	Costs, ¥					QALYs	ICER, ¥/QALY
	Direct medical	Pregabalin	Hospitalization	Indirect	Total
Payer perspective
Pregabalin	147,007	41,945	32,133	–	221,085	0.7657	–
Usual care	152,699	0	40,062	–	192,761	0.7517	–
Difference	−5,692	41,945	−7,928	–	28,324	0.0140	2,024,901
Societal perspective
Pregabalin	147,007	41,945	32,133	465,148	686,233	0.7657	–
Usual care	152,699	0	40,062	473,404	666,165	0.7517	–
Difference	−5,692	41,945	−7,928	−8,257	20,068	0.0140	1,434,637

Note: Negative values indicate cost savings with pregabalin relative to usual care.

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

Table 4 Sensitivity analysis on key variables

Variable	Total costs, ¥			QALYs			ICER, ¥/QALY
	Pregabalin	Usual care	Difference	Pregabalin	Usual care	Difference
Post-surgery assumption
NRS Pain score =0	221,085	192,761	28,324	0.7664	0.7525	0.0138	2,049,492
NRS Pain score =5	221,449	193,214	28,235	0.7646	0.7504	0.0142	1,982,802
Discontinuation results in NRS pain score of previous visit	221,085	192,761	28,324	0.7657	0.7517	0.0140	2,024,901
Initial pain severity
All moderate	205,161	178,792	26,370	0.7771	0.7639	0.0132	1,999,629
All severe	258,182	225,304	32,878	0.7390	0.7231	0.0159	2,073,877
Actual EQ-5D-5L score from a NIS^Citation20	221,085	192,761	28,324	0.7642	0.7516	0.0126	2,244,983

Abbreviations: EQ-5D-5L, five-level, five-dimension EuroQol health status measure; ICER, incremental cost-effectiveness ratio; NIS, noninterventional study; QALY, quality-adjusted life-year; NRS, numerical rating scale.

Figure 3 Tornado diagram of the 20 most sensitive parameters in the one-way sensitivity analysis.

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

Figure 4 Cost-effectiveness acceptability curve for pregabalin.

Table S1 Information for determining health care resource utiilization

Items	Data
Frequency of outpatient visits	Frequency per month
Tests	Proportion of patients having the test listed Frequency of the test per month
Medications	Drug name Daily dose

Table S2 Method of cost calculation

	First month	Second month	Third month
No/mild pain	NA	xx yen	xx yen
Moderate pain	xx yen	xx yen	xx yen
Severe pain	xx yen	xx yen	xx yen

Note: xx yens were calculated from each physician’s answer.

Abbreviation: NA, not applicable.

Table S3 Number of outpatient visits per month

	Median (interquartile range)
First month
No/mild pain	–
Moderate pain	3 (2–4)
Severe pain	4 (2–4)
Second month
No/mild pain	2 (1–2)
Moderate pain	2 (2–3)
Severe pain	2 (2–4)
Third month
No/mild pain	1 (1–1)
Moderate pain	2 (1–2)
Severe pain	2 (2–4)

Table S4 Proportion of patients having X-ray

	Median (interquartile range)
First month
No/mild pain	–
Moderate pain	100% (100%–100%)
Severe pain	100% (100%–100%)
Second month
No/mild pain	0% (0%–30%)
Moderate pain	10% (0%–60%)
Severe pain	20% (0%–100%)
Third month
No/mild pain	0% (0%–0%)
Moderate pain	0% (0%–50%)
Severe pain	30% (0%–100%)

Table S5 Number of X-ray tests per month in patients having one or more tests in each month

	Median (interquartile range)
First month
No/mild pain	–
Moderate pain	–
Severe pain	1 (1–1)
Second month
No/mild pain	1 (1–1)
Moderate pain	1 (1–1)
Severe pain	1 (1–1)
Third month
No/mild pain	1 (1–1)
Moderate pain	1 (1–1)
Severe pain	1 (1–1)

Table S6 Proportion of patients having an MRI

	Median (interquartile range)
First month
No/mild pain	–
Moderate pain	50% (11%–70%)
Severe pain	50% (20%–90%)
Second month
No/mild pain	0% (0%–10%)
Moderate pain	10% (0%–35%)
Severe pain	20% (0%–55%)
Third month
No/mild pain	0% (0%–0%)
Moderate pain	0% (0%–28%)
Severe pain	20% (0%–70%)

Table S7 Number of MRI tests per month in patients having one or more tests in each month

	Median (interquartile range)
First month
No/mild pain	–
Moderate pain	1 (1–1)
Severe pain	1 (1–1)
Second month
No/mild pain	1 (1–1)
Moderate pain	1 (1–1)
Severe pain	1 (1–1)
Third month
No/mild pain	1 (1–1)
Moderate pain	1 (1–1)
Severe pain	1 (1–1)

Table S8 Proportion of physicians reporting use of acetaminophen (paracetamol)

	Proportion of physicians
First month
No/mild pain	–
Moderate pain	50.5%
Severe pain	46.2%
Second month
No/mild pain	31.3%
Moderate pain	44.9%
Severe pain	34.8%
Third month
No/mild pain	29.3%
Moderate pain	33.7%
Severe pain	33.2%

Table S9 Acetaminophen (paracetamol) use, mg per day

	Proportion of physicians
First month
No/mild pain	–
Moderate pain	800 (600–1,200)
Severe pain	950 (600–1,200)
Second month
No/mild pain	600 (400–1,350)
Moderate pain	900 (600–1,200)
Severe pain	1,088 (450–1,425)
Third month
No/mild pain	600 (400–975)
Moderate pain	900 (600–1,250)
Severe pain	1,200 (800–1,500)

Table S10 Proportion of physicians reporting use of neurotropin

	Proportion of physicians
First month
No/mild pain	–
Moderate pain	42.6%
Severe pain	41.3%
Second month
No/mild pain	32.8%
Moderate pain	36.2%
Severe pain	29.0%
Third month
No/mild pain	28.8%
Moderate pain	34.1%
Severe pain	29.8%

Table S11 Use of neurotropin, units per day

	Proportion of physicians
First month
No/mild pain	–
Moderate pain	16 (4–16)
Severe pain	16 (8–16)
Second month
No/mild pain	16 (8–16)
Moderate pain	16 (4–16)
Severe pain	10 (4–16)
Third month
No/mild pain	12 (4–16)
Moderate pain	13 (4–16)
Severe pain	16 (4–16)

Table S12 Proportion of physicians reporting use of tramadol

	Proportion of physicians
First month
No/mild pain	–
Moderate pain	31.7%
Severe pain	44.2%
Second month
No/mild pain	23.9%
Moderate pain	55.1%
Severe pain	68.1%
Third month
No/mild pain	13.7%
Moderate pain	43.9%
Severe pain	62.0%

Table S13 Tramadol use, mg per day

	Proportion of physicians
First month
No/mild pain	–
Moderate pain	75 (50–109)
Severe pain	100 (50–178)
Second month
No/mild pain	63 (31–100)
Moderate pain	100 (74–150)
Severe pain	100 (75–200)
Third month
No/mild pain	75 (25–100)
Moderate pain	88 (50–150)
Severe pain	150 (75–200)

Table S14 Proportion of physicians reporting use of nonsteroidal anti-inflammatory drugs

	Proportion of physicians
First month
No/mild pain	–
Moderate pain	91.1%
Severe pain	88.5%
Second month
No/mild pain	67.2%
Moderate pain	81.2%
Severe pain	81.2%
Third month
No/mild pain	64.9%
Moderate pain	74.1%
Severe pain	70.7%

Table S15 Use of nonsteroidal anti-inflammatory drugs (loxoprofen), mg per daya

	Proportion of physicians
First month
No/mild pain	–
Moderate pain	180 (180–180)
Severe pain	180 (180–180)
Second month
No/mild pain	180 (120–180)
Moderate pain	180 (120–180)
Severe pain	180 (130–180)
Third month
No/mild pain	180 (100–200)
Moderate pain	180 (120–180)
Severe pain	180 (150–180)

Note:

a Loxoprofen doses are shown as this was the most frequent nonsteroidal anti-inflammatory drug reported by physicians in the survey.

Table

Parameters	Deterministic parameter				Probabilistic parameter				Source
	Expected	Range setting	Lower value	Upper value	Distribution type	Parameter 1	Parameter 2	PSA parameter description
Model assumption
Age, years	70.4	–	–	–	–	–	–	–	NIS
Time horizon, months	12	Assumption	3	24	–	–	–	–	Assumption
Pain NRS score after surgery	2	–	–	–	–	–	–	–	Assumption
Probability parameter
Initial probability of moderate pain	0.7	95% CI	0.648	0.751	Beta	212	91	Alpha and beta	NIS
Initial probability of severe pain	0.3	95% CI	0.249	0.352	Beta	91	212	Alpha and beta	NIS
Withdrawal rate of pregabalin group	0.116	95% CI	0.063	0.169	Beta	16	122	Alpha and beta	NIS
Transition probability of moderate pain at 0-week evaluation point to no pain at 4-week evaluation point of pregabalin group	0.390	95% CI	0.281	0.499	Beta	30	47	Alpha and beta	NIS
Transition probability of moderate pain at 0-week evaluation point to severe pain at 4-week evaluation point of pregabalin group	0.104	95% CI	0.036	0.172	Beta	8	69	Alpha and beta	NIS
Transition probability of severe pain at 0-week evaluation point to no pain at 4-week evaluation point of pregabalin group	0.289	95% CI	0.156	0.421	Beta	13	32	Alpha and beta	NIS
Transition probability of severe pain at 0-week evaluation point to moderate pain at 4-week evaluation point of pregabalin group	0.444	95% CI	0.299	0.59	Beta	20	25	Alpha and beta	NIS
Transition probability of no pain at 4-week evaluation point to moderate pain at 8-week evaluation point of pregabalin group	0.209	95% CI	0.088	0.331	Beta	9	34	Alpha and beta	NIS
Transition probability of no pain at 4-week evaluation point to severe pain at 8-week evaluation point of pregabalin group	0.023	95% CI	0	0.068	Beta	1	42	Alpha and beta	NIS
Transition probability of moderate pain at 4-week evaluation point to no pain at 8-week evaluation point of pregabalin group	0.322	95% CI	0.203	0.441	Beta	19	40	Alpha and beta	NIS
Transition probability of moderate pain at 4-week evaluation point to severe pain at 8-week evaluation point of pregabalin group	0.102	95% CI	0.025	0.179	Beta	6	53	Alpha and beta	NIS
Transition probability of severe pain at 4-week evaluation point to no pain at 8-week evaluation point of pregabalin group	0.150	95% CI	0	0.306	Beta	3	17	Alpha and beta	NIS
Transition probability of severe pain at 4-week evaluation point to moderate pain at 8-week evaluation point of pregabalin group	0.350	95% CI	0.141	0.559	Beta	7	13	Alpha and beta	NIS
Transition probability of moderate pain at 0-week evaluation point to no pain at 4-week evaluation point of usual care group	0.262	95% CI	0.185	0.339	Beta	33	93	Alpha and beta	NIS
Transition probability of moderate pain at 0-week evaluation point to severe pain at 4-week evaluation point of usual care group	0.079	95% CI	0.032	0.127	Beta	10	116	Alpha and beta	NIS
Transition probability of severe pain at 0-week evaluation point to no pain at 4-week evaluation point of usual care group	0.128	95% CI	0.023	0.233	Beta	5	34	Alpha and beta	NIS
Transition probability of severe pain at 0-week evaluation point to moderate pain at 4-week evaluation point of usual care group	0.513	95% CI	0.356	0.67	Beta	20	19	Alpha and beta	NIS
Transition probability of no pain at 4-week evaluation point to moderate pain at 8-week evaluation point of usual care group	0.237	95% CI	0.102	0.372	Beta	9	29	Alpha and beta	NIS
Transition probability of no pain at 4-week evaluation point to severe pain at 8-week evaluation point of usual care group	0.026	95% CI	0	0.077	Beta	1	37	Alpha and beta	NIS
Transition probability of moderate pain at 4-week evaluation point to no pain at 8-week evaluation point of usual care group	0.223	95% CI	0.143	0.304	Beta	23	80	Alpha and beta	NIS
Transition probability of moderate pain at 4-week evaluation point to severe pain at 8-week evaluation point of usual care group	0.136	95% CI	0.07	0.202	Beta	14	89	Alpha and beta	NIS
Transition probability of severe pain at 4-week evaluation point to no pain at 8-week evaluation point of usual care group	0.083	95% CI	0	0.194	Beta	2	22	Alpha and beta	NIS
Transition probability of severe pain at 4-week evaluation point to moderate pain at 8-week evaluation point of usual care group	0.292	95% CI	0.11	0.474	Beta	7	17	Alpha and beta	NIS
Surgery risk	0.017	95% CI	0.148	0.164	Beta	0.975	0.001	Average and SE for 10-month survival rate	MDV claims data analysis
Cost parameter
Direct cost of moderate pain at 0-week evaluation point, ¥/month	25,050	25th percentile–75th percentile	13,692	29,175	Gamma	25,050	25,050	Average and SE	Physician survey
Direct cost of severe pain at 0-week evaluation point, ¥/month	26,525	25th percentile–75th percentile	16,661	33,559	Gamma	26,525	26,525	Average and SE	Physician survey
Direct cost of no pain at 4-week evaluation point, ¥/month	10,614	25th percentile–75th percentile	6,567	13,988	Gamma	10,614	10,614	Average and SE	Physician survey
Direct cost of moderate pain at 4-week evaluation point, ¥/month	15,256	25th percentile–75th percentile	7,636	22,987	Gamma	15,256	15,256	Average and SE	Physician survey
Direct cost of severe pain at 4-week evaluation point, ¥/month	14,791	25th percentile–75th percentile	8,063	29,474	Gamma	14,791	14,791	Average and SE	Physician survey
Direct cost of no pain at 8-week evaluation point, ¥/month	7,877	25th percentile–75th percentile	4,803	9,404	Gamma	7,877	7,877	Average and SE	Physician survey
Direct cost of moderate pain at 8-week evaluation point, ¥/month	11,154	25th percentile–75th percentile	6,176	19,464	Gamma	11,154	11,154	Average and SE	Physician survey
Direct cost of severe pain at 8-week evaluation point, ¥/month	18,059	25th percentile–75th percentile	8,088	30,868	Gamma	18,059	18,059	Average and SE	Physician survey
Pregabalin cost of moderate pain at 0-week evaluation point, ¥/month	3,742	95% CI	3,361	4,124	Gamma	3,742	195	Average and SE	NIS
Pregabalin cost of severe pain at 0-week evaluation point, ¥/month	3,752	95% CI	3,342	4,162	Gamma	3,752	209	Average and SE	NIS
Pregabalin cost of no pain at 4-week evaluation point, ¥/month	3,759	95% CI	3,398	4,119	Gamma	3,759	184	Average and SE	NIS
Pregabalin cost of moderate pain at 4-week evaluation point, ¥/month	4,040	95% CI	3,671	4,410	Gamma	4,040	188	Average and SE	NIS
Pregabalin cost of severe pain at 4-week evaluation point, ¥/month	4,429	95% CI	3,898	4,960	Gamma	4,429	271	Average and SE	NIS
Cost of surgery, ¥	1,343,474	95% CI	1,329,725	1,357,222	Gamma	1,343,474	7,015	Average and SE	MDV claims data analysis
Total indirect cost of no pain, ¥/month	34,775	–	–	–	–	–	–	–	NIS
Total indirect cost of moderate pain, ¥/month	35,864	–	–	–	–	–	–	–	NIS
Total indirect cost of severe pain, ¥/month	56,778	–	–	–	–	–	–	–	NIS
Absenteeism indirect cost of no pain, ¥/month	2,081	–	–	–	–	–	–	–	NIS
Absenteeism indirect cost of moderate pain, ¥/month	964	–	–	–	–	–	–	–	NIS
Absenteeism indirect cost of severe pain, ¥/month	0	–	–	–	–	–	–	–	NIS
QOL weight parameter
Coefficient of pain NRS score	−0.037	95% CI	−0.042	−0.032	Normal	−0.037	0.002	Average and SE	NIS
QOL weight of no pain	0.867	–	–	–	–	–	–	–	NIS
QOL weight of moderate pain	0.738	–	–	–	–	–	–	–	NIS
QOL weight of severe pain	0.61	–	–	–	–	–	–	–	NIS

Abbreviations: CI, confidence interval; MDV, Medical Data Vision Co, Ltd; NIS, noninterventional study; NRS, numerical rating scale; PSA, probabilistic sensitivity analysis; QOL, quality of life; SE, standard error.

TaguchiTIgarashiAWattSEffectiveness of pregabalin compared with usual care for the treatment of chronic low back pain with a neuropathic component in Japan; the patient’s perspectiveJ Pain Res2015848749726346468

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