Cost effectiveness of pharmacological maintenance treatment of people with opioid use disorder

Pharmacological maintenance treatment is a treatment option for people with severe opioid dependence due to prolonged use of heroine or other opioids. In Sweden, maintenance treatment is always combined with psychological treatment or psychosocial support and pharmacological substances commonly used are methadone and buprenorphine.

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SBU Enquiry Service

Consists of structured literature searches to highlight studies that can address questions received by the SBU Enquiry Service from Swedish healthcare or social service providers. We assess the risk of bias in systematic reviews and when needed also quality and transferability of results in health economic studies. Relevant references are compiled by an SBU staff member, in consultation with an external expert when needed.

Question

What systematic reviews are there on the cost effectiveness of pharmacological maintenance treatment of opioid use disorder?

Identified literature

Three systematic review with low to moderate risk of bias were identified [1–3] together with six systematic reviews with high risk of bias [4–9]. Two of the systematic reviews with low to moderate risk of bias did not identify any primary studies, due to a narrower choice of population [2,3]. Within the nine systematic reviews, 59 relevant primary studies were identified [10–64].

Table 1. Systematic reviews with low/medium risk of bias.
* Alla kostnadsuppgifter från litteraturen är omräknade till svenska kronor år 2021 med hjälp av den metod som rekommenderas av The Cochrane and Campbell Economic Methods Group, det vill säga med PPPs (köpkraftsjusterade valutakurser) via CCEMG - EPPI-Centre Cost Converter v.1.63. https://eppi.ioe.ac.uk/costconversion/default.aspx.
** Källdata var ej tillgängligt för konvertering från amerikanska dollar till svenska kronor äldre än år 1980. Då kostnaderna från dessa studier var äldre än så (1975 & 1976) så har dessa värden därför köpkraftsjusterats utifrån prisåret 1980.

BMT = Buprenorphine Maintenance Treatment; ICER = Incremental Cost-Effectiveness Ratio; MMT = Metadone Maintenance Treatment; MT = Maintenance Treatment; QALY = Quality-Adjusted Life-Year; SEK = Swedish kronor (currency)
Included studies Population/Intervention Outcome and Results
Connock et al, 2007
Methadone and buprenorphine for the management of opioid dependence: A systematic review and economic evaluation. [3]
Included studies:
11 studies were included for data extraction

MMT vs other or no treatment:
8 studies
BMT vs MMT:
3 studies

All costs have been converted with purchasing power parity (PPP) and is expressed in Swedish kronor year 2021*
 Population:
People who are dependent on opioids
Intervention:
Buprenorphine or methadone employed in maintenance irrespective of dose
Control:
Any comparator regime used in MT (including no therapy or placebo) or the intervention drug used in withdrawal/detoxification therapy		 MMT vs drug-free treatment:
ICER: 74 371 SEK per life-year gained

BMT vs MMT:
ICER: 2768 SEK per heroin-free days (MMT Dominated).

BMT vs MMT:
Cost per QALY excluding costs attributed to crime.
ICER: 44 2847 SEK per QALY

MMT vs MMT + heroin: MMT+ heroin dominated

MMT vs metadone detoxification treatment: ICER: 207 474 SEK per life-year saved

MMT vs 5 treatment options in addition to MMT:
ICER: 238 181–241 625 SEK per life-year saved

MMT in 4 populations with different HIV prevalence: ICER: 86 755–150 100 SEK per QALY

BMT vs conventional treatment:
If 5% HIV prevalence:
ICER: 198 298–1 166 377 SEK cost per QALY
If 40% HIV prevalence:
ICER: 148 723–918 505 SEK cost per QALY

MMT vs therapeutic community programme (TCP):
Cost [2] per “successful” patient:
MMT 3605 SEK, TCP 5959 SEK
Cost per heroin-free patient: MMT 1495 SEK, TCP 2992 SEK

MMT vs 5 modalities of care: Total dollar-benefit** to society of ~ 8.3 million SEK

MMT vs no MMT:
Benefit–cost ratio over a lifetime was 37.72
Authors' conclusion:
“Eight studies assessed the cost-effectiveness of methadone and two assessed buprenorphine for opiate abuse. Five studies were cost–utility analyses, with the ICER reported as a cost per QALY gained. There were three cost-effectiveness analyses and two cost–benefit analyses. Six papers reported use of an economic model: two used Markov models, one used a Monte Carlo simulation and three used a dynamic model. Direct comparisons of the ICERs between the studies is not possible because of their different approaches to modelling, different time horizons, comparators and perspectives, countries of origin, sources of preference weights and effectiveness data used.”

 

Table 2. All relevant primary studies from the included systematic reviews
* Referens till de systematiska översikter som inkluderat respektive primärstudie.

ART = Antiretroviral therapy; BMT = Buprenorphine Maintenance Treatment; CBA = Cost-Benefit Analysis; CBR =Cost-benefit ratio; CEA = Cost-Effectiveness Analysis; CEAC = Cost-effectiveness acceptability curve; CEAPF = Cost-effectiveness frontier; CUA = Cost-Utility Analysis; DFD = Drug free days; EMU = Effectiveness Measure Units; EQ5D = EuroQol; LAAM = Levo-Alpha Acetyl Methadol; LYG = Life-Year Gained; LYS = Life year saved; MDT = Methadone detoxification; MMT = Metadone Maintenance Treatment; M/BMT = MethadoneorBuprenorphine Maintenance Treatment; OAFW = Opiate abuse free weeks; PSI = Psychosocial intervention; TCP = Therapeutic community programme; QALY = Quality-Adjusted Life-Year
Author, Year
Country, Ref		 Intervention vs control Method/Outcome
Societal perspective		 Model structure Source*
Maintenance treatment vs alternative or no treatment
Barnett
1999 [12]
USA		 MMT vs drug-free treatment CEA/LYG
No Barnett		 Markov model [1,5–7]
Zarkin et al
2005 [64]
USA		 MMT vs no MMT CBA/CBR
Yes		 Microsimulation [1,4,5]
Masson et al
2004 [39]
USA		 MMT vs MDT CEA & CUA/LYG & QALY
No		 Markov model [1,4–6]
Goldschmidt
1976 [29]
USA		 MMT vs TCP CEA/EMU
Yes		 None [1]
Warren et al
2006 [60]
Australia		 MMT vs no treatment CEA/DFD
No		 None [7]
Schackman et al
2012 [47]
USA		 BMT + Naloxone vs no treatment CUA/QALY
Yes		 Markov model [4–6,8]
Stephen et al
2012 [51]
USA		 MMT vs deep brain stimulation CUA/QALY
Yes		 Decision tree [4,6,8]
Tran et al
2012 [56]
Vietnam		 MMT vs no MMT CUA/ Avoided HIV & QALY
No		 Decision tree [6,8]
Bansback et al
2018 [11]
Canada		 Hydromorphone vs MMT CUA/QALY
Yes		 Markov model [4,9]
Jackson et al
2015 [32]
USA		 Naltrexone vs M/BMT CEA/DFD
No		 Markov model [4,5,8]
Kenworthy et al
2017 [34]
England		 M/BMT vs no treatment CUA/QALY
No		 Decision tree [4,9]
Nosyk et al
2012 [43]
Canada		 Injectable heroin vs MMT CUA/QALY
Yes		 Markov model [7]
Strang et al
2000 [52]
England		 Injectable vs oral MMT CEA/DFD
No		 None [8]
Vanagas et al
2010 [57]
Lithuania		 MMT vs no MMT CUA/QALY
Yes		 None [8]
Schwartz et al
2014 [48]
USA		 MMT with or without counseling CBA/CBR
Yes		 None [8]
Basu et al
2008 [16]
USA		 MMT vs institution care CBA/CBR
Yes		 None [8]
Xing et al
2012 [61]
China		 MMT vs no MMT CEA/ Avoided HIV
No		 None [8]
Wammes et al
2012 [59]
Indonesia		 MMT vs usual care CEA/ Avoided HIV
Yes		 Other [8]
Alistar et al
2011 [10]
Ukraine		 MMT + ART vs usual care CUA/QALY
No		 Dynamical [8]
Tran et al
2013 [53]
Vietnam		 MMT vs no MMT CUA/EQ-5D
No		 None [8]
Tran et al
2012 [54]
Vietnam		 MMT vs no MMT CUA/QALY
No		 None [8]
Moore et al
2007 [40]
Australia		 BMT/MMT vs rehabilitation or prison CEA/Drug free
Yes		 None [8]
Clark et al
2015 [21]
USA		 BMT/MMT vs therapy CEA/Relapse
No		 None [8]
Clark et al
2011 [22]
USA		 BMT or MMT vs therapy or no therapy CEA/Health consumption
No		 None [8]
Byford et al
2013 [19]
England		 MMT vs injectable heroin CUA/QALY
Yes		 None [8]
Polsky et al
2010 [44]
USA		 BMT vs buprenorfin detox CUA/QALY
No		 None [8]
Ruger et al
2012 [46]
Malaysia		 BMT vs naltrexone CEA/Drug free
Yes		 None [8]
Idrisov et al
2017 [31]
Russia		 MMT vs no MMT CUA/DALY
No		 Decision tree [9]
Vuong et al
2016 [58]
Vietnam		 Voluntary MMT vs forced rehabilitation CEA/DFD
No		 None [9]
Gisev et al
2015 [28]
Australia		 MMT vs no MMT CEA/ Avoided deaths
No		 None [9]
Krebs et al
2018 [36]
USA		 MMT vs observation CUA/QALY
Yes		 Markov model [9]
Busch et al
2017 [18]
USA		 BMT + Naloxone vs community treatment CEA/DFD
No		 None [9]
Dunlop et al
2017 [26]
Australia		 BMT + Naloxone vs waitlist CEA/DFD
No		 None [9]
Premkumar et al
2019 [45]
USA		 MMT/BMT vs detox CUA/QALY
No		 Markov model [9]
Marsden et al
2019 [38]
England		 MMT/BMT with PSI vs without CUA/QALY
Yes		 None [9]
Maintenance treatment with Methadone (MMT) vs Buprenorphine (BMT)
Connock et al
2007 [1]
England		 MMT vs BMT CUA/QALY
No		 Decision tree [4,8]
Jones et al
2009 [33]
USA		 MMT vs BMT CEA/Drug free
No		 None [8]
Maas et al
2013 [37]
England		 MMT vs BMT CEA/Drug free
No		 None [8]
Barnett et al
2001 [14]
USA		 BMT vs MMT CUA/QALY
No		 Dynamical [8]
Doran et al
2003 [24]
Australia		 BMT vs MMT CEA & CUA / DFD & QALY
No		 None [1,5–7]
Harris et al
2005 [30]
Australia		 BMT vs MMT CEA & CUA/ DFD & QALY
Yes		 None [1,7]
Doran et al
2006 [23]
Australia		 BMT vs LAAM vs MMT CEA/DFD
No		 None [7]
Comparison of different treatment modalities or other
Morozova et al
2018 [41]
Ukraine		 Upscaling of MMT/BMT vs usual care CUA/QALY
No		 Dynamic [9]
Barocas et al
2019 [15]
USA		 Buprenorphine+ Naloxone on site vs off-site CUA/QALY
No		 Microsimulation [9]
Dunlap et al
2018 [25]
USA		 Patient-centered MMT vs MMT CEA/DFD
No		 None [9]
Bell et al
2007 [17]
Australia		 Observed BMT vs unobserved BMT CEA/Drug free
No		 None [8]
Barnett et al
2010 [13]
USA		 MMT with high adherence vs worse adherence CUA/QALY
No		 Decision tree [8]
Zaric et al
2000 [63]
USA		 MMT in four populations (HIV) CUA/LYG & QALY
No		 Dynamic [1,5–7]
Zaric et al
2000 [62]
USA		 MMT in two populations (HIV) CUA/ LYG & QALY
No		 Dynamic [1,5,6]
Sheerin et al
2004 [49]
New Zealand		 MMT vs five treatment strategies CEA/LYS
No		 Markov model [1,6]
Dijkgraaf et al
2005 [65]
Netherlands		 MMT vs MMT + heroin CUA/QALY
Yes		 None [1,7]
Sirotnik et al
1975 [50]
USA		 MMT in different settings CBA/CBR
Yes		 None [1]
Negrin et al
2006 [42]
Spain		 MMT with three intensities CEA/ CEAC & CEAPF
No		 Other [6]
Carter et al
2017 [20]
USA		 Implantable vs oral buprenorfin CUA/QALY
Yes		 Markov model [4,5,9]
King et al
2016 [35]
USA		 Office- vs clinic-based MMT CEA/OAFW
No		 Markov model [4,5,9]
Ritter et al
2016 [66]
Australia		 Rehabilitation vs MMT/BMT vs counseling Other/LYS
Yes		 Microsimulation [5]
Kraft et al
1997 [67]
USA		 MMT with three intensities CEA/Drug free<
No		 None [7]
Avants et al
1999 [68]
USA		 MMT with two intensities CEA/Drug free
No		 None [7]
Mojtabi et al
2003 [69]
USA		 MMT with different treatment strategies CEA/Drug free
No		 None [7]

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Published: Report no: ut202126 Registration no: SBU 2021/412
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Literature search

SocINDEX via EBSCO 24 August 2021

Economical evaluations of opiate substitution treatment.
The final search result, usually found at the end of the documentation, forms the list of abstracts.

AB = Abstract; AU = Author; DE = Term from the thesaurus; MH= Exact Subject Heading from CINAHL Subject Headings; MM = Major Concept; TI = Title; TX = All Text. Performs a keyword search of all the database's searchable fields; ZC = Methodology Index; * = Truncation; “ “ = Citation Marks; searches for an exact phrase; N = Near Operator (N) finds the words if they are a maximum of x words apart from one another, regardless of the order in which they appear.; W = Within Operator (W) finds the words if they are within x words of one another, in the order in which you entered them.
Search terms Items found
Population: Opioid dependence
1. (DE "HEROIN abuse" OR DE "METHADONE abuse" OR DE "SUBSTANCE-induced disorders" OR DE "INTRAVENOUS drug abuse")) OR (TI ((Opioid OR heroin OR opiate OR substance) N2 (use OR abuse OR misuse OR dependen*))) OR (AB ((Opioid OR heroin OR opiate OR substance) N2 (use OR abuse OR misuse OR dependen*))) 29 851
Intervention: Opioid substitution treatment
2. (DE "METHADONE treatment programs") OR (TI (methadone or buprenorphine or methadose or Subutex OR ((substitution OR maintenance) N1 (treatment* OR therap*)))) OR (AB (methadone or buprenorphine or methadose or Subutex OR ((substitution OR maintenance) N1 (treatment* OR therap*)))) 4 401
Study types: Systematic reviews
3. PT Reviews OR ((Systematic* N3 review*) OR “Meta-analysis”) OR (AB (Systematic* N3 review*) OR “Meta-analysis”) 10 247
Health economic aspects
4. (DE Economics OR DE “COST effectiveness”) OR (TI (econom$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$ OR budget$) OR (expenditure$ not energy) OR (value NEAR/2 money)) OR (AB (econom$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$ OR budget$) OR (expenditure$ not energy) OR (value NEAR/2 money)) NOT ((TI (metabolic N2 cost) OR ((energy or oxygen) N2 (cost OR expenditure))) OR (AB (metabolic N2 cost) OR ((energy or oxygen) N2 (cost OR expenditure)))) 145 813
Combined sets:
5. 1 AND 2 1 700
6. 3 AND 5 49
Final result
7. 4 AND 6 2

Embase via embase.com 25 August 2021

Economical evaluations of opiate substitution treatment
The final search result, usually found at the end of the documentation, forms the list of abstracts.

/de = Term from the EMTREE controlled vocabulary; /exp = Includes terms found below this term in the EMTREE hierarchy; /mj = Major Topic; :ab = Abstract; :au = Author; :ti = Article Title; :ti,ab = Title or abstract; * = Truncation; ' ' = Citation Marks; searches for an exact phrase; NEAR/n = Requests terms that are within 'n' words of each other in either direction; NEXT/n = Requests terms that are within 'n' words of each other in the order specified
Search terms Items found
Population: Opioid dependence
1. 'narcotic dependence'/exp OR 'withdrawal syndrome'/exp OR 'substance abuse'/exp OR ((Opioid OR heroin OR opiate OR substance) NEAR/2 (use OR abuse OR misuse OR dependen*)):ti,ab,kw 192 248
Intervention: Opioid substitution treatment
2. 'methadone'/exp OR 'opiate substitution treatment'/exp OR 'buprenorphine'/exp OR (methadone or buprenorphine or methadose or Subutex OR ((substitution OR maintenance) NEAR/1 (treatment* OR therap*))):ti,ab,kw 90 757
Study types: Systematic reviews
3. ‘Systematic review’/exp OR ‘meta-analysis’/exp OR ((Systematic* NEAR/3 review*) OR ‘Meta-analysis’):ti,ab,kw 525 509
Health economic aspects
4. ((“Health Economics”/de OR “Economic Evaluation”/exp OR “Pharmacoeconomics”/exp) OR ((econom$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$) OR (expenditure$ not energy) OR (value NEAR/2 money) OR budget$):ti,ab) NOT (('editorial'/it OR 'letter'/it OR 'note'/it) OR ((metabolic NEAR/2 cost) OR ((energy or oxygen) NEAR/2 (cost OR expenditure))):ti,ab) 1 142 619
Combined sets
5. 1 AND 2 22 014
6. 3 AND 5 771
7. 4 AND 6 93
Final result
8. limit 7 to yr="2007 -Current" 73

Medline via OvidSP 24 August 2021

conomical evaluations of opiate substitution treatment
The final search result, usually found at the end of the documentation, forms the list of abstracts.

ab. = Abstract; .ab,ti. = Abstract or title; .af. = All fields; Exp = Term from the Medline controlled vocabulary, including terms found below this term in the MeSH hierarchy; .sh. = Term from the Medline controlled vocabulary; .ti. = Title; / = Term from the Medline controlled vocabulary, but does not include terms found below this term in the MeSH hierarchy; * = Focus (if found in front of a MeSH-term); * or $ = Truncation (if found at the end of a free text term); .mp = Text, heading word, subject area node, title; “ “ = Citation Marks; searches for an exact phrase; ADJn = Positional operator that lets you retrieve records that contain your terms (in any order) within a specified number (n) of words of each other.

1. http://www.crd.york.ac.uk/crdweb/searchstrategies.asp
  Items found
Population: Opioid dependence
1. Substance-Related disorder/ 99162
2. substance withdrawal syndrome/ 21803
3. exp Substance Abuse, Intravenous/ 15878
4. exp Drug overdose/ 12664
5. exp Opioid-Related Disorders/ 29448
6. ((Opioid or heroin or opiate or substance) adj2 (use? or abuse or misuse or dependen*)).ti,ab,kw  
7. 1 or 2 or 3 or 4 or 5 or 6 206245
Intervention: Opioid substitution treatment
8. exp methadone/ 12866
9. exp opiate substitution treatment/ 3684
10. exp buprenorphine/ 6024
11. (methadone or buprenorphine or methadose or subutex or ((substitution or maintenance) adj1 (treatment* or therap*))).ti,ab,kw 42194
12. 8 or 9 or 10 or 11 46124
Study types: Systematic review
13. (Systematic Review or Meta-Analysis).pt. or Cochrane Database Syst Rev.ja. or ((systematic adj3 review) or "meta analys*" or metaanalys*).ti,ab 349905
Health economic aspects (filter: NHS EED1)
14. (economics/ OR exp "costs and cost analysis"/ OR economics, dental/ OR exp "economics, hospital"/ OR economics, medical/ OR economics, nursing/ OR economics, pharmaceutical/ OR (economic$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$).ti,ab. OR (expenditure$ not energy).ti,ab OR (value adj1 money).ti,ab. OR budget$.ti,ab.) NOT (((energy or oxygen) adj cost).ti,ab. OR (metabolic adj cost).ti,ab. OR ((energy or oxygen) adj expenditure).ti,ab. NOT (letter.pt or historical article.pt.)  
Combined sets
15. 7 and 12 16424
16. 15 and 14 973
17. 16 and 13 37
Limits: from 2007
18. limit 17 to yr="2007 -Current" 30
Final result
19.   30

Scopus via Elsevier 25 August 2021

Economical evaluations of opiate substitution treatment
The final search result, usually found at the end of the documentation, forms the list of abstracts.

TITLE-ABS-KEY = Title or abstract or keywords; ALL = All fields; PRE/n = "precedes by". The first term in the search must precede the second by a specified number of terms (n).; W/n = "Within". The terms in the search must be within a specified number of terms (n) in any order.; * = Truncation; “ “ = Citation Marks; searches for an exact phrase; LIMIT-TO (SRCTYPE, "j" = Limit to source type journal; LIMIT-TO (DOCTYPE, "ar" = Limit to document type article; LIMIT-TO (DOCTYPE, "re" = Limit to document type review
Search terms Items found
Population: Opioid dependence
1. TITLE-ABS-KEY ( “Substance-Related disorder” OR “withdrawal syndrome” OR OUD OR “Narcotic-Related disorders” OR “Drug overdose” OR “Opioid-Related Disorders” OR ((Opioid OR heroin OR opiate OR substance) W/2 (use OR abuse OR misuse OR dependen*))) 235 060
Intervention: Opioid substitution treatment
2. TITLE-ABS-KEY ( methadone OR buprenorphine OR methadose OR subutex OR temgesic OR ( ( substitution OR maintenance ) W/1 ( treatment* OR therap* ) ) ) 104 192
Health economic aspects /economic aspects
3. TITLE-ABS-KEY ( "health economics" OR "health-care cost" OR pharmacoeconomics OR cost OR costs OR costly OR costing OR price OR prices OR pricing OR budget* OR pharmaeconomic* OR "resource allocation" OR "cost utility" OR "cost benefit" OR "cost effectiveness" OR "cost analysis" OR icer OR economic* OR "economic evaluation" OR "economic analysis" OR "quality adjusted life" OR qaly OR "willingness to pay" OR "willingness to accept" OR "willing to pay" ) 5 402 264
Study types: systematic reviews
4. TITLE-ABS-KEY ( cochrane OR ( ( systematic W/3 review ) OR "meta analys*" OR metaanalys* ) ) 544 938
Combined sets
5. 1 AND 2 23 646
6. 5 AND 3 2 056
7. 6 AND 4 125
Limits: From 2007
8. 7 AND ( LIMIT-TO ( PUBYEAR , 2021 ) OR LIMIT-TO ( PUBYEAR , 2020 ) OR LIMIT-TO ( PUBYEAR , 2019 ) OR LIMIT-TO ( PUBYEAR , 2018 ) OR LIMIT-TO ( PUBYEAR , 2017 ) OR LIMIT-TO ( PUBYEAR , 2016 ) OR LIMIT-TO ( PUBYEAR , 2015 ) OR LIMIT-TO ( PUBYEAR , 2014 ) OR LIMIT-TO ( PUBYEAR , 2013 ) OR LIMIT-TO ( PUBYEAR , 2012 ) OR LIMIT-TO ( PUBYEAR , 2011 ) OR LIMIT-TO ( PUBYEAR , 2010 ) OR LIMIT-TO ( PUBYEAR , 2009 ) OR LIMIT-TO ( PUBYEAR , 2008 ) OR LIMIT-TO ( PUBYEAR , 2007 ) ) 99
Final result
9.   99
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