Cost-effectiveness of subdermal implantable buprenorphine versus sublingual buprenorphine to treat opioid use disorder

Figures & data

Figure 1. Markov model structure.

Figure 2. Modeled monthly cohort disposition among health states. The death health state is not shown due to low incidence by 52 weeks (BSI = 0.20% vs SL-BPN = 0.30%). BSI, buprenorphine subdermal implant; SL-BPN, sublingual buprenorphine.

Figure 3. Net monetary benefit and probability of cost effectiveness at various WTP. BSI, buprenorphine subdermal implant; NMB, net monetary benefit; QALY, quality-adjusted life-year; SL-BPN, sublingual buprenorphine; WTP, willingness-to-pay.

Table 1. Modeled outcomes at 12 months.

	BSI	SL-BPN	Difference
Direct Medical Costs	$19,367	$22,031	−$2,665
Acquisition	$9,414	$2,922	$6,492
Administration	$864	$1,101	−$237
Diversion	$0	$250	−$250
Supplemental Use	$54	$37	$18
New HCV Infection	$0	$75	−$75
Emergency Room and Hospitalization	$8,444	$16,484	−$8,040
Rehabilitation Services	$591	$1,153	−$563
Pediatric Poisonings	$0	$9	−$9
Non-Medical Costs	$1,367	$3,088	−$1,721
Criminal Justice	$1,265	$2,476	−$1,212
Lost Wages, Productivity, and OOP Costs	$102	$612	−$510
Base Case Summary Outcomes
Total Costs	$20,733	$25,119	−$4,386
Abstinent Patients	751	537	214
Retained Patients	776	577	199
QALYs	0.832	0.801	0.031

BSI, buprenorphine subdermal implant; HCV, hepatitis C virus; OOP, out-of-pocket; QALY, quality-adjusted life-year; SL-BPN, sublingual buprenorphine.

Figure 4. Scatterplot of PSA cost (y-axis) per QALY (x-axis) outcomes (n = 1,000 iterations). Q1 BSI is more costly and more effective than SL-BPN, >$50,000 per QALY (10%); Q1 BSI is more costly and more effective than SL-BPN, ≤$50,000 per QALY (5%); Q2 BSI is more costly and less effective than SL-BPN (1%); Q3 BSI is less costly and less effective than SL-BPN (0%); Q4 BSI is less costly and more effective than SL-BPN (84%). BSI, buprenorphine subdermal implant; PSA, probabilistic sensitivity analysis; QALY, quality-adjusted life year; SL-BPN, sublingual buprenorphine.

Table

Variables	Base Case	Range^r	Distribution	Source / Derived From
Probabilities and Utilization
Health State Transitions
A to B (BSI)^a	0.0257	N/A	N/A	Rosenthal et al.^15
A to B (SL-BPN)^a	0.0550	0.0293–0.0854	Beta	Rosenthal et al.^15
B to C^b	0.1630	0.1467–0.1793	Beta	Campbell et al.^40
B to D	0.00023	0.00021–0.00025	Beta	Degenhardt et al. (AU)^41
C to D	0.00066	0.00059–0.00072	Beta	Degenhardt et al. (AU)^41
Proportion of Deaths Attributable to Overdose
From State B	0.7500	N/A	Static	Degenhardt et al. (AU)^41
From State C	0.8101	N/A	Static	Degenhardt et al. (AU)^41
Proportion of Deaths Attributed to Suicide
From State B	0.2500	N/A	Static	Degenhardt et al. (AU)^41
From State C	0.1899	N/A	Static	Degenhardt et al. (AU)^41
Probability of Pediatric Poisoning^c	0.00012	0.00011–0.00013	Beta	Lavonas et al.^42
Supplemental Use
Tablets per Event – BSI	16	N/A	Static	US FDA^43
Tablets per Event – SL-BPN	12	N/A	Static	US FDA^43
Monthly Probability
BSI	0.0328	0.0295–0.0361	Beta	US FDA^43
SL-BPN	0.0263	0.0237–0.0290	Beta	US FDA^43
Diversion
Probability of Diversiond	0.2500	0.2250–0.2750	Beta	Larance et al. (AU)^44
Proportion of Diversions Refilled^e	0.2484	0.2235–0.2732	Beta	Lofwall et al.^45
Probability of Relapse to Heroin Use^f	0.2202	0.1982–0.2423	Beta	Rosenthal et al.^15
Relapse-Associated Events
Emergency Room^g	0.0887	0.0798–0.0975	Beta	Clark et al.^26, Inocencio et al.^6
Hospital^g	0.0521	0.0469–0.0574	Beta	Clark et al.^26, Inocencio et al.^6
Intensive Outpatient Rehabilitation	0.0172	0.0155–0.0189	Beta	Clark et al.^26, Inocencio et al.^6
Inpatient Rehabilitation post-Hospitalization	0.1000	0.0900–0.1100	Beta	Author Judgment
New HCV infection from IDU	0.0012	0.0011–0.0014	Beta	Jordan et al.^46
Probability of IV Misuse of SL-BPN^h	0.6800	0.6120–0.7480	Beta	Eiden et al. (FR)^47
Probability of Arrest	0.0550	0.0290–0.0810	Beta	Clark et al.^26
Probability Multipliers
Arrest Increase in State C^i	2.0700	1.6900–2.5400	Gamma	Kopak et al.^25
Relapse Events in State C	1.7300	N/A	Static	Clark et al.^26
Direct Medical Costs
BSI
Acquisition (per 6 month course)	$4,950	N/A	Static	Braeburn Pharmaceuticals^48
Administration^j	$112	(SD) $31.20	Gamma	Jones et al.^27
Implant^k	$299	$269–$329	Gamma	Author Judgment
Explant^k	$389	$350–$428	Gamma	Author Judgment
Implant and Explant^k	$521	$469–$573	Gamma	Author Judgment
SL-BPN
Acquisition^l	$298	N/A	Static	Massachusetts Dept. of Health^49
Administration^j	$112	(SD) $31.20	Gamma	Jones et al.^27
New HCV Infection^m	$75,169	$67,652–$82,686	Gamma	Le et al.^50
Hospitalization^n	$37,112	$33,401–$40,823	Gamma	Chandwani et al.^51
Emergency Room^n	$18,392	$16,553–$20,231	Gamma	Chandwani et al.^51
Intensive Outpatient Rehabilitation (10 weeks)	$7,871	$7,084–$8,659	Gamma	Lee^52
Inpatient Rehabilitation (28 days)	$21,868	$19,682–$24,055	Gamma	Lee^52
Pediatric Poisoning
Grade 1 (Mild)	$1,655	N/A	Static	Lavonas et al.^42
Grade 2-3 (Moderate–Severe)	$9,444	N/A	Static	Lavonas et al.^42
Grade 4 (Life-Threatening)	$10,779	N/A	Static	Lavonas et al.^42
Grade 5 (Death)	$18,181	N/A	Static	Lavonas et al.^42
Indirect Non-Medical and Non-Medical Costs
Out-of-Pocket^o	$48	$42–$52	Gamma	Jones et al.^27
Criminal Justice^p	$114,460	$103,014–$125,906	Gamma	ICER^53
Monthly Wage^q	$4,131	N/A	Static	US Census Bureau^54
Utilities
State A	0.8670	(SD) 0.152	Beta	Schackman et al.^24
State B (Relapsed to Heroin Use)	0.6330	(SD) 0.208	Beta	Schackman et al.^24
State B (Relapsed to Prescription Abuse)	0.6830	(SD) 0.204	Beta	Schackman et al.^24
State C (Relapsed to Heroin Use)	0.5880	(SD) 0.202	Beta	Schackman et al.^24
State C (Relapsed to Prescription Abuse)	0.6780	(SD) 0.217	Beta	Schackman et al.^24
State D	0.0000	N/A	Static	N/A
Disutility from Arrest	−25%	−20%–40%	Gamma	Lengyel and Brown^55

^a The minimum and maximum values for SL-BPN were based on the 95% confidence interval for the relative difference reported in the cited source, and therefore there are no minimum and maximum values listed for BSI.

^b For BSI and SL-BPN, we used the retention curve for treatment-experienced patients with any positive urines. No difference between treatment cohorts was assumed due to a non-significant difference in the clinical trial¹⁵.

^c Proportions by severity were as follows: 0.211 (Mild), 0.237 (Moderate), 0.368 (Severe), 0.158 (Life-Threatening), and 0.026 (Death).

^d This was applied to any cohort proportion receiving SL-BPN, which included the proportion of the BSI cohort receiving supplemental SL-BPN.

^e Derived from the weighted average of lost medication refills per physician survey (assumes upper limit of each group interval).

^f Derived from the clinical trial¹⁵ as the weighted average across both treatment arms.

^g It was assumed based on the proportion of overdose ER visits subsequently hospitalized (from Inocencio et al.⁶) that the 15.8 per 1,000 from Clark et al.²⁶ (low buprenorphine dose group) for relapse events would be as is reported in the table.

^h Among those who have relapsed and who have been prescribed SL-BPN.

ⁱ The range was derived from the odds ratio and 95% confidence interval for patients on treatment vs not on treatment.

^j Included the following components for office-based administration: Physician ($32.61), Nursing ($12.78), Administrative ($20.88), Adjustment for Missed Visits ($19.98), and Urine Testing ($25.90).

^k BSI patients initially incurred an implant procedure. Those who did not discontinue after 6 months incurred an implant and explant procedure. Data for costs reimbursed for the insertion and removal of BSI rods were not available at the time of this analysis. The assumed values were considered conservative insofar as they add costs to the BSI group given that they are higher than reimbursement rates from the 2017 National Medicare Physician Fee Schedule average allowables for a single nonbiodegradable implant⁵⁶: (insertion = $299 vs $143), (removal = $389 vs $163), and (insertion + removal = $521 vs $226). Those who discontinued by 6 months incurred an explant procedure.

^l 2 mg tablet q4 daily = $2.48 × 4 = $9.92 per day ×30 days = $297.60 per cycle (month).

^m Included the following components: Inpatient Services ($8,416.26), Emergency Room ($511.15), Outpatient Services ($9,800.34), and Boceprevir Drug Regimen ($56,441.04).

ⁿ Adjusted mean charges per-event for opioid abuse-related emergency department visits and inpatient admission.

^o Included the following components per administration: Travel Time ($13.36), Visit Time ($6.84), Childcare ($2.24), and Transportation ($25.22).

^p Used per person annual criminal justice costs (law enforcement, victimization, and lost productivity) reduced to monthly costs and prorated for the time of year of the arrest. State B was 25% and State C was 75%. We assumed that State B would incur 25% of these costs and State C would incur 75%.

^q Monthly wage is equal to the average personal per capita income in the United states in 2016, divided by 12 months.

^r When unavailable from the source, ranges were calculated as the mean value ±10%.

AU, the cited source included an exclusively Australian study cohort; BSI, buprenorphine subdermal implant; FDA, Food and Drug Administration; FR, the cited source included an exclusively French study cohort; HCV, hepatitis C virus; IDU, intravenous drug use; IV, intravenous; SD, standard deviation; SL-BPN, sublingual buprenorphine; US, United States.

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