Cost-effectiveness analysis of intradiscal condoliase injection vs. surgical or conservative treatment for lumbar disc herniation

Figures & data

Figure 1. Schematic diagram of the study design. ^*1A cost comparison was performed between surgery for patients with inadequate efficacy at 13 weeks after condliase treatment and surgery from the beginning. If the efficacy is equal in both groups, the cost after the second year of treatment can be considered equivalent. Therefore, the analysis period was set to one year. Since conservative treatment is no longer necessary once patients are completely cured, medical costs for conservative treatment were calculated by setting an upper limit on the number of treatment. ^*2The time horizon for this analysis was set at 2 years. As a sensitivity analysis, the efficacy at 3 and 4 years after treatment were also calculated. Since QOL data during longer condliase treatment than 1 year were not available, the analysis was performed assuming that the QOL at 1 year in this analysis persisted. It was assumed that conservative treatment in the condliase group remained the same for two years after condliase administration as in the conservative treatment group (conservative conditions unfavorable to condliase). Therefore, medical costs for conservative treatment would be offset in both groups. ^*3The response rate for condoliase was assumed to be 72.0%, which is the response rate at 13 weeks after treatment with condoliase (95% CI: 62.2–81.7%)⁹, and the remaining 28.0% were assumed to undergo open surgery at 13 weeks.

Table 1. Attributes and levels of conjoint cards.

Attribute	Level
Wound size	0mm		2cm		5cm
Degree of pain associated with treatment	0	1	2	3	4	5
Duration of pain associated with treatment	0 days		1 day		7 days
Anesthesia method	Local			General
Percentage of back and leg pain due to hernia that improves by more than half after treatment	60%		70%		90%
Co-payment	10,000 yen		50,000 yen		200,000 yen

The six attributes included wound size, pain duration, pain level, anesthesia method, response rate, and treatment-associated co-payment. The Wong-Baker FACES Pain Rating Scale with six levels (0–5) was used for the pain scale.

Table 2. An example of a conjoint card used in the online survey.

Wound size	2 cm
Degree of pain associated with treatment	5 Unbearably painful
Duration of pain associated with treatment	7 days
Anesthesia method	Local (Conscious)
Percentage of back and leg pain due to hernia that improves by more than half with treatment	60%
Co-payment	10,000 yen

Each respondent was presented with two different cards with illustrations and asked to choose their preferred card. Twenty sets of conjoint cards were presented to each respondent.

Figure 2. ΔIntangible cost of each attribute. The results of the conjoint analysis in Table 3 are visualized on the wound size, pain duration, pain level, and the response rate with linear interpolation between each level.

Table 3. Results of the conjoint analysis for group 1.

Attribute	Level	Utility				ΔIntangible cost
		Mean	SE	U95%	L95%	Mean	U95%	L95%
Wound size	0mm	0	0	0	0	¥0	¥0	¥0
	2cm	–0.095	0.046	–0.005	–0.184	¥7,161	¥373	¥13,948
	5cm	–0.117	0.045	–0.030	–0.205	¥8,877	¥2,267	¥15,487
Degree of pain associated with treatment	0	0	0	0	0	¥0	¥0	¥0
	1	–0.145	0.065	–0.018	–0.272	¥10,957	¥1,353	¥20,560
	2	–0.261	0.058	–0.149	–0.374	¥19,758	¥11,236	¥28,280
	3	–0.769	0.062	–0.649	–0.890	¥58,163	¥49,048	¥67,277
	4	–1.072	0.063	–0.949	–1.196	¥81,089	¥71,723	¥90,455
	5	–1.650	0.068	–1.517	–1.783	¥124,764	¥114,686	¥134,841
Duration of pain associated with treatment	0 days	0	0	0	0	¥0	¥0	¥0
	1 day	–0.055	0.045	0.033	–0.143	¥4,151	¥–2,488	¥10,791
	7 days	–0.290	0.044	–0.204	–0.376	¥21,921	¥15,415	¥28,427
Anesthesia method	Local	0	0	0	0	¥0	¥0	¥0
	General	–0.017	0.036	0.054	–0.087	¥1,248	¥–4,058	¥6,553
Response rate	60%	–0.782	0.046	–0.691	–0.872	¥59,093	¥52,246	¥65,940
	70%	–0.430	0.043	–0.345	–0.514	¥32,484	¥26,082	¥38,886
	90%	0	0	0	0	¥0	¥0	¥0
Co-payment	¥10,000	0	0	0	0
	¥50,000	–0.529	0.045	–0.440	–0.618
	¥200,000	–1.358	0.047	–1.266	–1.450

The monetary value of each attribute was calculated by conjoint analysis (conditional logit model) using data from online survey among the general public in group 1. The pain duration, pain level and response rate tended to be more important than wound size or anesthesia method.

Table 4. Results of the questionnaire for group 2.

Treatment	Wound size associated with treatment (mm)		Degree of pain associated with treatment (0 ∼ 5)		Duration of pain associated with treatment (day)		Days of absence from work at the time of treatment (day)
	mean	SD	mean	SD	mean	SD	mean	SD
(1) Condoliase	20.4	30.3	2.5	1.1	5.3	10.3	6.4	14.3
(2) Endoscopic surgery	25.3	28.5	1.9	1.3	9.6	17.4	22.4	47.6
(3) Open surgery	73.4	63.7	2.5	1.5	8.9	12.3	28.4	29.1

The average response value for each treatment-experienced respondent in group 2 is shown. We excluded a response considered to be an outlier (only one respondent indicated 365 days as the treatment-related pain duration). The in/out ratio of patients with condoliase was 63/153.

Table 5. Results of the cost analyses.

(I) Condoliase + open surgery (for non-responders to condoliase) vs. open surgery from the beginning
( I )	A：Condoliase + open surgery (for non-responder to condoliase)			B：Open surgey	BーA
	(1) Whole	(2) Condoliase only	(3) Condoliase + open surgery
Percentage		72.0%	28.0%
Treatment cost	¥430,613	¥163,497	¥1,117,481	¥953,985	¥523,372
Re-checkup cost	¥33,783	¥25,312	¥55,564	¥30,252	¥-3,531
Medical cost due to adverse events	¥6,345	¥2,583	¥16,019	¥13,436	¥7,091
Productivity loss	¥147,204	¥65,643	¥356,932	¥291,289	¥144,086
Intangible cost	¥83,699	¥62,405	¥138,455	¥76,050	¥-7,649
Total	¥701,643	¥319,440	¥1,684,452	¥1,365,012	¥663,369
(II) Condoliase + endoscopic surgery (for non-responders to condoliase) vs. endoscopic surgery from the beginning
( II )	A: Condoliase + endoscopic surgery (for non-responder to condoliase)			B: Endoscopic surgery	BーA
	(1) Whole	(2) Condoliase only	(3) Condoliase + endoscopic surgery
Percentage		72.0%	28.0%
Treatment cost	¥398,597	¥163,497	¥1,003,141	¥839,645	¥441,047
Re-checkup cost	¥33,783	¥25,312	¥55,564	¥30,252	¥-3,531
Medical cost due to adverse events	¥3,223	¥2,583	¥4,870	¥2,286	¥-937
Productivity loss	¥129,972	¥65,643	¥295,392	¥229,749	¥99,777
Intangible cost	¥78,333	¥62,405	¥119,290	¥56,885	¥-21,448
Total	¥643,909	¥319,440	¥1,478,257	¥1,158,817	¥514,909

The cost included tangible (treatment, adverse events, postoperative follow-up) and intangible costs (mental and physical burden on patients calculated from conjoint analysis, denoted simply as intangible cost in the table, and productivity loss).

Table 6. Frequency of adverse events and medical costs of condoliase.

Treatment	Adverse event	Frequency (%)	Cost (outpatient)	Cost (inpatient)
Condoliase	Anaphylaxis	0.44%	¥322,130	¥250,860
	Neutropenia	2.62%	¥36,440	¥36,440
	Lymphadenitis	0.44%	¥49,812	¥49,812
	Skin symptoms	2.62%	¥4,044	¥2,624
	Total		¥2,685	¥2,336

Frequency was based on the combined results of the phase II/III studies^8,15. Although no anaphylaxis was reported in these phase II/III studies (229 study subjects), one case has been reported from the study launch to the present. Since the frequency was unknown, it was conservatively calculated as 1/229.

Table 7. Frequency of adverse events and medical costs of surgery.

Treatment	Adverse event	Frequency (%)	Cost
Open surgery	Dural injury	2.74%	¥59,460
	Caudaial disorder	0.22%	¥625,350
	Nerve root disorder	0.89%	¥159,040
	Postoperative hematoma	0.89%	¥359,300
	Deep wound infection	0.67%	¥873,602
	Tooth damage	0.02%	¥20,900
	Total		¥13,436
Treatment	Adverse event	Frequency (%)	Cost
Endoscopic surgery	Dural injury	1.64%	¥59,460
	Caudaial disorder	0.08%	¥657,450
	Nerve root disorder	0.12%	¥183,460
	Postoperative hematoma	0.10%	¥405,220
	Deep wound infection	0.02%	¥903,542
	Misidentification of level	0.02%	¥0
	Articular process fracture	0.02%	¥3,137
	Conversion to direct surgery	0.14%	¥0
	Tooth damage	0.02%	¥20,900
	Total		¥2,286

The frequency was calculated based on¹⁰ for open surgery and^9,10 for endoscopic surgery by using the total number of cases. The hospitalization duration for open/endoscopic surgery was assumed to be 16/10 days each, based on the “Survey of Discharged Patients” conducted by the Ministry of Health, Labor, and Welfare (MHLW), to evaluate the impact of DPC introduction in the fiscal year 2019.

Table 8. QOL changes after condoliase treatment.

	Subscale	Conversion coefficient	Baseline				After 13 weeks				After 52 weeks
			placebo		1.25U		placebo		1.25U		placebo		1.25U
			mean	SD	mean	SD	mean	SD	mean	SD	mean	SD	mean	SD
SF-36	Physical functioning	0.00370	55.9	20.9	58.8	20.4	73.1	21.5	80.9	17.6	76.2	26.2	85.2	18.0
	Role physical	–0.00024	41.0	26.8	47.6	25.9	67.4	25.2	76.7	24.3	71.9	30.0	82.3	24.9
	Bodily pain	0.00286	28.1	13.5	30.8	14.3	50.7	20.2	60.2	21.6	55.5	25.5	67.9	24.0
	General health	0.00052	52.9	14.9	55.0	15.3	55.9	16.7	60.7	17.1	57.1	17.8	62.5	17.5
	Vitality	–0.00063	41.0	21.4	42.7	18.8	54.9	21.4	59.4	19.9	57.4	22.6	61.7	19.8
	Social functioning	0.00110	54.5	26.1	56.6	27.9	72.1	26.8	81.9	22.9	78.1	28.4	88.4	20.5
	Role emotional	0.00024	60.8	33.4	59.1	28.9	75.4	26.2	81.7	23.5	79.9	27.0	85.6	22.6
	Mental health	0.00256	59.6	21.1	58.9	17.3	70.6	18.6	70.9	20.9	71.4	20.3	74.0	18.4
	Intercept	0.03256	1	0	1	0	1	0	1	0	1	0	1	0
EQ-5D (estimated)		QOL	0.539		0.556		0.704		0.771		0.737		0.823
		L95%	0.515		0.533		0.679		0.747		0.707		0.799
		U95%	0.562		0.578		0.730		0.795		0.768		0.847

The mean values of the SF-36 subscales at 13 and 52 weeks were reported in¹⁵. The estimated QOL was calculated by multiplying each of the eight subscales by the conversion coefficient shown in¹¹ and summing them. 1.25 U refers to the patient group treated with 1.25 U of condoliase.

Chiba K, Matsuyama Y, Seo T, et al. Condoliase for the treatment of lumbar disc herniation: a randomized controlled trial. Spine. 2018;43(15):E869–E876.

 PubMed Web of Science ®Google Scholar

Matsuyama Y, Chiba K. Condoliase for treatment of lumbar disc herniation. Drugs Today. 2019;55(1):17–23.

 PubMed Web of Science ®Google Scholar

Abdullah F, Bai A, Sahil F, et al. Lumbar disc herniation: comparing pain relief after medical and surgical intervention. Cureus. 2021;13(6):e15885.

 PubMed Web of Science ®Google Scholar

Matsuyama Y, Chiba K, Iwata H, et al. A multicenter, randomized, double-blind, dose-finding study of condoliase in patients with lumbar disc herniation. J Neurosurg Spine. 2018;28(5):499–511.

 PubMed Web of Science ®Google Scholar

Matsumoto M, Hasegawa T, Ito M, et al. Annual Report 2008 of the spinal endoscopic surgery in Japan. J Jpn Orthop Assoc. 2009;83(12):1022–1027. Japanese.

 Google Scholar