- What is the effectiveness and comparative effectiveness of strategies (e.g., programs) to improve retention in medications for addiction treatment (MAT) among nonpregnant adults with opioid use disorder (OUD)?
- What are the harms of retention strategies for MAT?
- Does the effectiveness of the MAT retention strategy vary by patient characteristics (age, gender, socioeconomic status, geographic region, polysubstance use)?
Because this is a rapid review, strategic adjustments will be made to streamline traditional systematic review processes in order to deliver an evidence product in the allotted time. We will follow adjustments and streamlining processes proposed by the US Agency for Healthcare Research and Quality Evidence-based Practice Center Program.1-4 Examples of adjustments include narrowly focusing questions, limiting the number of databases searched and/or modifying search strategies, using a single reviewer and/or abstractor with a second to provide verification, and restricting to studies published in the English language.
We will search PubMed and the Cochrane Library for systematic reviews that address the research questions. If evidence gaps are identified, we will conduct follow-up searches of PubMed for primary studies.
- Systematic reviews: PubMed and the Cochrane Library to be searched from 2009 onwards. We will conduct ad hoc searches of additional databases as needed.
- Primary studies (if needed): PubMed. Search date will be based on evidence gaps.
Types of Studies To Be Included
We will assess systematic reviews based upon predefined inclusion criteria. Primary studies published in the last 10 years from included reviews, and any studies identified in subsequent searches, will be evaluated to see if these are applicable to our key questions. Because this review is being used to inform US decision-making, inclusion will be limited to studies published in English and conducted in countries classified as "very high human development" according to the United Nations Human Development Index.5
- Systematic reviews:
- Include: Reviews of reviews, systematic reviews, or rapid reviews. Reviews must search more than one database, pre-define their inclusion criteria, and conduct an assessment of study quality.
- Exclude: Narrative reviews, editorials or commentaries.
- Primary studies:
- Include: Randomized controlled trials, and cohort or other observational studies that address key gaps in the trial evidence.
- Exclude: Editorials, commentaries, or case series.
Condition or Domain Being Studied
Opioid use disorder (OUD) is an important public health issue. It is estimated that 2.1 million Americans 12 years or older met diagnostic criteria for OUD in 2017.6 Furthermore, in the U.S., 47,600 people died from an opioid overdose in 2017.7 In addition to overdose deaths, OUD is associated with markedly increased rates of comorbid conditions, including human immunodeficiency virus (HIV) and hepatitis C infections, and other substance use disorders.8
MAT currently refers to the three U.S. Food and Drug Administration approved medications for OUD- methadone, buprenorphine, and extended-release naltrexone.9 Prior systematic reviews of treatment studies have established that MAT significantly improves the outcomes of treatment for OUD.10,11 While strong evidence exists for the benefits of MAT, retention in MAT programs is highly variable, from 19% to 94% at 3 months.12 This rapid review, nominated by the Office of the Assistant Secretary for Health (OASH), Center for Drug Evaluation and Research at the U.S. Food and Drug Administration (FDA), the Office of the Assistant Secretary for Mental Health and Substance Use for the Substance Abuse and Mental Health Administration (SAMHSA), the Division of Unintentional Injury Prevention in the National Center for Injury Prevention and Control at the Centers for Disease Control and Prevention (CDC), the Office of the Assistant Secretary for Planning and Evaluation (ASPE), the National Institute on Drug Abuse (NIDA) at the National Institutes of Health (NIH), and the Health Resources and Services Administration (HRSA), will assist the US Department of Health and Human Services in US research, practice, and policy decision-making around strategies to improve MAT retention.
- Include: nonpregnant adults with OUD who are involved in MAT (buprenorphine, methadone, or naltrexone)
- Exclude: special populations (e.g., palliative care/end-of-life, HIV, children, incarcerated)
Any strategy (or adjunct to MAT) that impacts the retention of patients receiving MAT, such as:
- Pharmacologic aspects (e.g., choice of medication, formulation [extended release], dosage of medication, duration)
- Psychosocial adjuncts (e.g. counseling, Cognitive Behavioral Therapy [CBT], peer support, 12-step programs, mindfulness therapy)
- Contingency management
- Care coordination supports (e.g., peer recovery coach and navigators, care managers, hub and spoke models)
- Financial support (e.g. MAT medication/program reimbursement)
- Social services/logistic support (e.g., housing, transportation, daycare)
- Informational technology (IT) support (e.g., self-management apps)
Usual care, any above strategy
Out-of-hospital (community or outpatient)
- Treatment retention rates
- Functioning (e.g., physical and social)
Data Extraction (Selection and Coding)
Abstract and title review, full text review, and abstraction will be performed by one reviewer. A second reviewer will verify a 25% sample of articles and abstracted data. Disagreements will be resolved through discussion among the review team.
Data extraction categories will include author, year, country, study design, PICOs, and results.
Risk of Bias (Quality) Assessment
Study quality will be assessed either by extracting systematic reviews' quality assessments, or by using a risk of bias tool based on criteria developed by the U.S. Preventive Services Task Force.13
Strategy for Data Synthesis
Data will be compiled into evidence tables and synthesized narratively. We will not conduct a meta-analysis or do a formal process to grade the strength of evidence.
Analysis of Subgroups or Subsets
As data are available and time allows, we will examine whether the effectiveness of the MAT retention strategies vary by patient characteristics (age, gender, socioeconomic status, geographic region, type or severity of opioid disorder).
External Peer Review
The protocol will be posted publicly. At least one content expert and one methodological expert will review the draft report. Potential Peer Reviewers must disclose any financial conflicts of interest greater than $5,000 and any other relevant business or professional conflicts of interest. Invited Peer Reviewers may not have any financial conflict of interest greater than $5,000. As time and situation allows we would also like to provide time for public comment on the rapid review at draft stage.
EPC Team Disclosures
EPC core team members must disclose any financial conflicts of interest greater than $1,000 and any other relevant business or professional conflicts of interest. Related financial conflicts of interest that cumulatively total greater than $1,000 will usually disqualify EPC core team investigators.
Role of the Funder
This project was funded under Contract No. HHSA290201700003C from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services. The AHRQ Task Order Officer reviewed contract deliverables for adherence to contract requirements and quality. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
This protocol will be registered in the international prospective register of systematic reviews (PROSPERO).
- Hartling L, Guise JM, Kato E, et al. EPC Methods: An Exploration of Methods and Context for the Production of Rapid Reviews. AHRQ Comparative Effectiveness Reviews. 2015. PMID: 25654160.
- Hartling L, Guise JM, Hempel S, et al. EPC Methods: AHRQ End-User Perspectives of Rapid Reviews. AHRQ Methods for Effective Health Care. 2016. PMID: 27195347.
- Hartling L, Guise J-M, Hempel S, et al. Fit for purpose: perspectives on rapid reviews from end-user interviews. Systematic Reviews. 2017 February 17;6(1):32. doi: https://doi.org/10.1186/s13643-017-0425-7.
- Gilbert J, Veazie S, Joines K, et al. Patient Navigation Models for Lung Cancer. Rapid Evidence Product. Rockville, MD: Agency for Healthcare Research and Quality; 2018.
- United Nations Development Programme. Human Development Indices and Indicators: 2018 Statistical Update. 2018.
- Center for Behavioral Health Statistics and Quality. 2017 National Survey on Drug Use and Health: Detailed Tables 2018.
- Scholl L, Seth P, Kariisa M, et al. Drug and Opioid-Involved Overdose Deaths - United States, 2013- 2017. Morbidity and Mortality Weekly Report. 2019. 67(Nos. 51 & 52):1419-27.
- Van Handel MM, Rose CE, Hallisey EJ, et al. County-Level Vulnerability Assessment for Rapid Dissemination of HIV or HCV Infections Among Persons Who Inject Drugs, United States. J Acquir Immune Defic Syndr. 2016. Nov 1;73(3):323-31. doi: 10.1097/qai.0000000000001098. PMID: 27763996.
- Volkow ND, Jones EB, Einstein EB, et al. Prevention and Treatment of Opioid Misuse and Addiction: A Review. JAMA Psychiatry. 2019. 76(2):208-16. doi: 10.1001/jamapsychiatry.2018.3126.
- Ma J, Bao YP, Wang RJ, et al. Effects of medication-assisted treatment on mortality among opioids users: a systematic review and meta-analysis. Molecular Psychiatry. 2018 Jun 22;22:22. doi: https://dx.doi.org/10.1038/s41380-018-0094-5. PMID: 29934549.
- Sordo L, Barrio G, Bravo MJ, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017 Apr 26;357:j1550. doi: https://dx.doi.org/10.1136/bmj.j1550. PMID: 28446428.
- Timko C, Schultz NR, Cucciare MA, et al. Retention in medication-assisted treatment for opiate dependence: A systematic review. J Addict Dis. 2016.35(1):22-35. doi: 10.1080/10550887.2016.1100960. PMID: 26467975.
- Harris RP, Helfand M, Woolf SH, et al. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med. 2001. Apr;20(3 Suppl):21-35. PMID: 11306229.