Use of opioid substitution therapies in the treatment of opioid use disorder: results of a UK cost-effectiveness modelling study

Figures & data

Figure 1. Decision tree model structure (adapted from Connock et al.¹⁰).

Table 1. Level and nature of drug misuse and utility values (derived from Connock et al.¹⁰).

Parameter	Input
Proportions
OST and not drug misusing	0.3850
OST and drug misusers (injectors)	0.4400
OST and drug misusers (non-injectors)	0.5600
No OST and not drug misusing^a	0.0000
No OST and drug misusers (injectors)	0.6100
No OST and drug misusers (non-injectors)	0.3900
Weighted treatment specific utility values
OST: Buprenorphine
Week 1–2	0.7039
Week 3–52	0.7455
OST: Methadone
Week 1–2	0.7017
Week 3–52	0.7458
No OST	0.6231

^a Patients who dropped out of treatment were assumed to return to their previous drug misuse habits.

OST: opioid substitution therapy.

Table 2. Comparison of Connock et al.¹⁰ model, with the replicated model results (2004 costs).

	QALYs		NHS/PSS costs		Societal costs
	Connock et al.^10 model	Replication	Connock et al.^10 model	Replication	Connock et al.^10 model	Replication
BMT	0.6774	0.6773	£2,491	£2,221	£30,992	£30,721
MMT	0.6990	0.6899	£1,971	£1,916	£28,345	£28,307
Difference of replication from Connock et al.^10 model
BMT	−0.0001		−£270		−£271
MMT	−0.0001		−£55		−£38

BMT: buprenorphine maintenance treatment; MMT: methadone maintenance treatment; NHS: National Health Service; PSS: personal social services; QALY: quality-adjusted life year.

Table 3. Resource use (derived from the Connock et al.¹⁰) and costs (2016 values).

Parameter	Resource use^10	Unit cost	Source
Drug costs (per mg)^a
Methadone		£0.0126	NHSBSA^26; 2016
Buprenorphine		£0.0803
Subutex^b		£0.3739	BNF^27; 2016
Suboxone^b		£0.3739
Dispensing fees (per treatment dispensed)
Buprenorphine, Subutex, Suboxone		£1.13	PSNC^28; 2016
Methadone		£1.13
Controlled drug fee (per treatment dispensed)
Buprenorphine, Subutex, Suboxone		£1.28
Methadone		£2.50
Supervised self-administration (per administration)
Buprenorphine, Subutex, Suboxone		£3.00	Thurrock Council^29; 2016
Methadone		£1.50
Counseling session per week	1.0	£10.91	Connock et al.^10; 2007^c
Urine test per week	0.5	£1.43	Connock et al.^10; 2007^c
GP visit per year
Successful health state	5.6	£36.00	Curtis^30, 2016
Unsuccessful health state	3.6
A&E visit per year
Successful health state	0.8	£163.24	NHS reference costs^31, 2015/16
Unsuccessful health state	0.7
Inpatient hospital stay per year
Successful health state	2.8	£470.21
Unsuccessful health state	1.75
Out-patient mental health visit per year
Successful health state	0.8	£101.46
Unsuccessful health state	1.3
Inpatient mental health visit per year
Successful health state	0.4	£429.00
Unsuccessful health state	1.5
Rate of drug arrests per year^e
Successful health state	0.80	£5,592.11	Connock et al.^10; 2007^d
Unsuccessful health state	0.30
Rate of acquisitive crime arrests per year^e
Successful health state	1.60	£2,119.68
Unsuccessful health state	1.35
Average time held in police custody per year (nights)^e
Successful health state	1.20	£108.66
Unsuccessful health state	2.00
Rate of court appearances per year^e
Successful health state	1.40	£1,100.78
Unsuccessful health state	2.20
Time spent in prison per year (days)^e
Successful health state	34.00	£108.44
Unsuccessful health state	36.00
Annual victim costs (per person on or off OST)^f
Successful health state		£14,004.69
Unsuccessful health state		£48,546.33

A&E: accident and emergency; BNF: British National Formulary; CPI: consumer price index; GP: general practitioner; HCHS: Hospital and Community Health Services; OST: opioid substitution therapy; PSNC: Pharmaceutical Services Negotiating Committee.

^a The model assumes a flexible dosing regimen and uses data on mean dose derived from Connock et al.¹⁰. Methadone cost/mg: Methadone Cost for 500 ml (1 mg/ml). Buprenorphine cost/mg: 30% at buprenorphine price for 7 tab (2 mg/tab) and 70% at buprenorphine price for 7 tab (8 mg/tab). Subutex cost/mg: 30% at Subutex price for 7 tab (2 mg/tab) and 70% at Subutex price for 7 tab (8 mg/tab). Suboxone cost/mg: 30% at Suboxone price for 7 tab (2 mg/tab) and 70% at Suboxone price for 7 tab (8 mg/tab).

^b Used in the sensitivity analysis only.

^c Inflated to 2016 using HCHS inflator³⁰.

^d Inflated to 2016 using CPI³².

^e Includes existing and new contacts with criminal justice services both on and off OST.

^f Includes costs incurred in anticipation of crime, e.g. installation of burglar alarms, as well as direct costs such as material or physical damage or loss.

Table 4. Expanded model inputs.

Parameter	Input	Source
Proportions
Infection rate for patients who are on OST and not current drug misusers
HIV	0.0019	Calculated prevalence plus annual incidence calculated from Public Health England, Home office and Office of National Statistics 2016 data^33–37. Calculations shown below^a to^c
HCV	0.4961
HIV/HCV	0.0078
Infection rate among drug misusers (injecting)
HIV	0.0033
HCV	0.5396
HIV/HCV	0.0130
Infection rate among drug misusers (non-injecting)
HIV	0.0033
HCV	0.4908
HIV/HCV	0.0130
Costs
HIV infection (annual cost)
Direct cost: cost of treatment (triple therapy) and health service costs	£31,141.78	Mandalia et al.^38, 2010*
HCV infection (annual cost)
Direct cost of standard treatment (peginterferon alfa and ribavirin) and health service costs	£1,152.92	Calculated from NICE^39, 2009 (lifetime costs), Messina et al.^40, 2015 (genotype prevalence) and Campos et al.^41, 2007 (average duration of HCV)* Calculations shown below^d
Direct cost of new treatments** (interferon-free treatments) and health service costs	£44,852.00	Barclay et al.^42, 2016
Utilities†
OST and not drug misusing
No HIV/HCV	0.8673	Connock et al.^10, 2007
HIV	0.7806	Calculated using Zaric et al.^43, 2000‡
HCV	0.7806	Assumption§
OST and drug misusers (injectors)
No HIV/HCV	0.6332	Connock et al.^10, 2007
HIV	0.5699	Calculated using Zaric et al.^43, 2000‡
HCV	0.5699	Assumption§
OST and drug misusers (non-injectors)
No HIV/HCV	0.6834	Connock et al.^10, 2007
HIV	0.6151	Calculated using Zaric et al.^43, 2000‡
HCV	0.6151	Assumption§
No OST and not drug misusing
No HIV/HCV	0.8673	Connock et al.^10, 2007
HIV	0.7806	Calculated using Zaric et al.^43, 2000‡
HCV	0.7806	Assumption§
No OST and drug misusers (injectors)
No HIV/HCV	0.5880	Connock et al.^10, 2007
HIV	0.5292	Calculated using Zaric et al.^43, 2000‡
HCV	0.5292	Assumption§
No OST and drug misusers (non-injectors)
No HIV/HCV	0.6780	Connock et al.^10, 2007
HIV	0.6102	Calculated using Zaric et al.^43, 2000‡
HCV	0.6102	Assumption§

Calculations

^a Calculation of infection rate for patients who are on OST and not current drug misusers:

HIV: ((Prevalence HIV among persons who inject drugs in UK³³ × (Proportion of 16–59 year olds who took Opioids in the last 3 months³⁴) × UK Population 16 to 59 years in 2015³⁵) + ( Population with New HIV Diagnosis in 2015³⁶ × Proportion of 16-59 year olds who took Opioids in the last 3 months³⁴)) ÷ (Proportion of 16–59 year olds who took Opioids in the last 3 months³⁴ × UK Population 16 to 59 years in 2015³⁵).

HCV: ((Prevalence HCV among persons who inject drugs in UK³³ × (Proportion of 16–59 year olds who took Opioids in the last 3 months³⁴) × UK Population 16 to 59 years in 2015³⁵) ÷ (Proportion of 16-59 year olds who took Opioids in the last 3 months³⁴ × UK Population 16 to 59 years in 2015³⁵)).

^b Calculation of infection rate among drug misusers (injecting):

HIV: ((Prevalence HIV among persons who inject drugs in UK³³ × (Proportion of 16–59 year olds who took Opioids in the last 3 months³⁴ × UK Population 16–59 years in 2015³⁵)) + (Population with New HIV Diagnosis who inject drugs³⁶) ÷ (Proportion of 16–59 year olds who took Opioids in the last 3 months³⁴) × UK Population 16–59 years in 2015³⁵).

HCV: (((Prevalence HCV among persons who inject drugs in UK³³ × (Proportion of 16–59 year olds who took Opioids in the last 3 months³⁴ × UK Population 16–59 years in 2015³⁵)) ÷ Proportion of 16–59 year olds who took Opioids in the last 3 months³⁴ × UK Population 16–59 years in 2015³⁵ + Proportion of injectors who contract HCV)³⁷).

^c Calculation of infection rate among drug misusers (non-injecting):

HIV: ((Prevalence HIV among persons who inject drugs in UK³³ × (Proportion of 16–59 year olds who took Opioids in the last 3 months³⁴ × UK Population 16–9 years in 2015³⁵) + Population with New HIV Diagnosis who take non-inject drugs³⁶) ÷ (Proportion of 16–59 year olds who took Opioids in the last 3 months³⁴) × UK Population 16–59 years in 2015³⁵).

HCV: ((Prevalence of HCV among persons who inject drugs in UK³³ × (Proportion of 16-59 year olds who took Opioids in the last 3 months³⁴ × UK Population 16 to 59 years in 2015³⁵)) ÷ (Proportion of 16–59 year olds who took Opioids in the last 3 months³⁴ × UK Population 16 to 59 years in 2015³⁵)).

^d Calculation of HCV annual cost = ((AVERAGE (Lifetime costs for Genotype 1 {Std treatment duration} in NICE 2009 (Lui study)³⁹, Lifetime costs Genotype 1 {Short treatment duration} in NICE 2009 (Lui study)³⁹, Lifetime costs Genotype 1 {Std treatment duration} in NICE 2009 (Yu study)³⁹, Lifetime costs Genotype 1{Short treatment duration} in NICE 2009 (Yu study)³⁹) × (Population with HCV Genotype 1[40]/(Population with HCV Genotype 1⁴⁰ + Population with HCV Genotype 2⁴⁰ + Population with HCV Genotype 3⁴⁰))) + (AVERAGE (Lifetime costs Genotype 2 & 3 {Std treatment duration} in NICE 2009 (Wagner study)³⁹, Lifetime costs Genotype 2 & 3 {Short treatment duration} in NICE 2009 (Wagner study)³⁹) × ((Population with HCV Genotype 2⁴⁰ + Population with HCV Genotype 3⁴⁰)/(Population with HCV Genotype 1⁴⁰ + Population with HCV Genotype 2⁴⁰ + Population with HCV Genotype 3⁴⁰)))) ÷ Average duration of HIV infection⁴¹.

HCV, hepatitis C virus; HCHS, Hospital and Community Health Services; HIV, human immunodeficiency virus; NHS, National Health Service; NICE, National Institute for Health and Care Excellence; ONS, Office for National Statistics; OST, opioid substitution therapy

* Inflated to 2016 using HCHS inflator³⁰.

** It was assumed a proportion of patients with HCV would receive the new interferon-free treatments that results in a cure. The proportion was estimated from the increase in HCV treatment on previous years reported by Public Health England in the 2016 report, Hepatitis C in the UK³⁷.

† HIV/HCV co-infection utilities were calculated by combining the utility values for HIV and HCV using methodology recommended by the NICE decision support unit⁴⁴.

‡ A quality adjustment multiplier of 0.90 was applied to the utility values of patients with no HIV/HCV to account for the reduced quality-of-life associated with HIV⁴³.

§ It was assumed that the adjustment in utility as a result of having HCV was the same as that for HIV, based on a study comparing the utility values across HIV and HCV⁴⁵.

Table 5. Results of the cost-effectiveness analysis.

	Cost (£)	Cost (£) difference	QALYs	QALY difference	ICER (£/QALY) vs no OST
NHS/PSS perspective
No OST	9,647		0.5883
BMT	10,362	716	0.6398	0.0514	13,923
MMT	10,541	895	0.6514	0.0630	14,206
Societal perspective
No OST	69,274		0.5883
BMT	55,243	–14,032	0.6398	0.0514	Dominant
MMT	52,100	–17,174	0.6514	0.0630	Dominant

BMT: buprenorphine maintenance treatment; ICER: incremental cost-effectiveness ratio; MMT: methadone maintenance treatment; NHS: National Health Service; OST: opioid substitution therapy; PSS: personal social services; QALY: quality-adjusted life year.

Table 6. Impact of OST on healthcare resource and non-clinical outcomes.

Outcome	BMT	MMT	No OST
Healthcare resource use (over 1 year)
GP visits	4.51	4.72	3.60
Rate of A&E visits	0.75	0.76	0.70
Rate of inpatient hospital stays	2.23	2.34	1.75
Rate of out-patient mental health visits	1.07	1.02	1.30
Rate of inpatient mental health visits	1.00	0.89	1.50
Criminal justice and victim costs (over 1 year)
Victim costs	£32,824	£29,282	£48,546
Rate of drug arrests	0.53	0.58	0.30
Rate of acquisitive crime arrests	1.46	1.49	1.35
Average time held in police custody (nights)	1.64	1.55	2.00
Rate of court appearances	1.84	1.75	2.20
Time spent in prison (days)	35.09	34.88	36.00

A&E: accident and emergency; BMT: buprenorphine maintenance treatment; MMT: methadone maintenance treatment; GP: General Practitioner; OST: opioid substitution therapy.

Figure 2. Incremental cost-effectiveness plane for BMT vs No OST. BMT, buprenorphine maintenance treatment; OST: opioid substitution therapy.

Figure 3. Incremental cost-effectiveness plane for MMT vs No OST. MMT, methadone maintenance treatment; OST: opioid substitution therapy.

Figure 4. Cost-effectiveness acceptability curve for BMT vs No OST. BMT, buprenorphine maintenance treatment; OST: opioid substitution therapy.

Figure 5. Cost-effectiveness acceptability curve for MMT vs No OST. MMT, methadone maintenance treatment; OST: opioid substitution therapy.

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