Empirically contrasting urine drug screening-based opioid use disorder treatment outcome definitions.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 9304118 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1360-0443 (Electronic) Linking ISSN: 09652140 NLM ISO Abbreviation: Addiction Subsets: MEDLINE

Publication: Oxford : Wiley-Blackwell
Original Publication: Abingdon, Oxfordshire, UK : Carfax Pub. Co., c1993-

Opioid-Related Disorders*/urine ; Opioid-Related Disorders*/drug therapy ; Substance Abuse Detection*/methods; Humans ; Treatment Outcome ; Opiate Substitution Treatment ; Cluster Analysis ; Outcome Assessment, Health Care

Background and Aims: A lack of consensus on the optimal outcome measures to assess opioid use disorder (OUD) treatment efficacy and their precise definition and computation has hampered the pooling of research data for evidence synthesis and meta-analyses. This study aimed to empirically contrast multiple clinical trial definitions of treatment success by applying them to the same dataset.
Methods: Data analysis used a suite of functions, developed as a software package for the R language, to operationalize 61 treatment outcome definitions based on urine drug screening (UDS) results. Outcome definitions were derived from clinical trials that are among the most influential in the OUD treatment field. Outcome functions were applied to a harmonized dataset from three large-scale National Drug Abuse Treatment Clinical Trials Network (CTN) studies, which tested various medication for OUD (MOUD) options (n = 2492). Hierarchical clustering was employed to empirically contrast outcome definitions.
Results: The optimal number of clusters identified was three. Cluster 1, comprising eight definitions focused on detecting opioid-positive UDS, did not include missing UDS in outcome calculations, potentially resulting in inflated rates of treatment success. Cluster 2, with the highest variability, included 10 definitions characterized by strict criteria for treatment success, relying heavily on UDS results from either a brief period or a single study visit. The 43 definitions in Cluster 3 represented a diverse range of outcomes, conceptualized as measuring abstinence, use reduction and relapse. These definitions potentially offer more balanced measures of treatment success or failure, as they avoid the extreme methodologies characteristic of Clusters 1 and 2.
Conclusions: Clinical trials using urine drug screening (UDS) for objective substance use assessment in outcome definitions should consider (1) incorporating missing UDS data in outcome computation and (2) avoiding over-reliance on UDS data confined to a short time frame or the occurrence of a single positive urine test following a period of abstinence.
(© 2024 Society for the Study of Addiction.)

Han B. Key Substance Use and Mental Health Indicators in the United States: Results from the 2019 National Survey on Drug Use and Health [Internet]. SAMHSA; 2020 [cited 2022 Nov 22] p. 114. Report No.: PEP20‐07‐01‐001. Available from: https://www.samhsa.gov/data/sites/default/files/reports/rpt29393/2019NSDUHFFRPDFWHTML/2019NSDUHFFR1PDFW090120.pdf.
Blanco C, Iza M, Schwartz RP, Rafful C, Wang S, Olfson M. Probability and predictors of treatment‐seeking for prescription opioid use disorders: A national study. Drug Alcohol Depend. 2013 Jul;131(1–2):143–148. https://doi.org/10.1016/j.drugalcdep.2012.12.013.
Ahmad F, Cisewski J, Rossen L, Sutton P. Provisional Drug Overdose Death Counts [Internet]. National Center for Health Statistics; 2022 Sep [cited 2022 Sep 28]. Available from: https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm.
Tai B, Dobbins R, Blackeney Q, Liu D, Moran L. The NIDA clinical trials network: Evolving, expanding, and addressing the opioid epidemic. Addict Sci Clin Pract [Internet]. 2021 May [cited 2022 Sep 9];16(1):28. https://doi.org/10.1186/s13722-021-00238-6.
Donovan DM, Bigelow GE, Brigham GS, Carroll KM, Cohen AJ, Gardin JG, et al. Primary outcome indices in illicit drug dependence treatment research: systematic approach to selection and measurement of drug use end‐points in clinical trials. Addiction [Internet]. 2012 [cited 2022 Nov 22;107(4):694–708. https://doi.org/10.1111/j.1360-0443.2011.03473.x.
Roll JM, Petry NM, Stitzer ML, Brecht ML, Peirce JM, McCann MJ, et al. Contingency management for the treatment of methamphetamine use disorders. Am J Psychiatry. 2006 Nov [cited 2022 Nov 22];163(11):1993–1999. https://doi.org/10.1176/ajp.2006.163.11.1993.
Hughes JR, Keely JP, Niaura RS, Ossip‐Klein DJ, Richmond RL, Swan GE. Measures of abstinence in clinical trials: Issues and recommendations. N&TR. 2003 Feb;5(1):13–25. https://doi.org/10.1080/1462220031000070552.
Psychopharmacologic Drugs Advisory Committee. ; Notice of Meeting [Internet]. FDA White Oak Campus: Food; Drug Administration; 2013 [cited 2022 Nov 22]. Available from: https://www.federalregister.gov/documents/2013/02/27/2013-04536/psychopharmacologic-drugs-advisory-committee-notice-of-meeting.
Weiss RD, Rao V. The prescription opioid Addiction treatment study: what have we learned. Drug Alcohol Depend. 2017 Apr [cited 2022 Nov 22];173(Suppl 1):S48–S54. Available from: https://www.sciencedirect.com/science/article/pii/S0376871617300029, https://doi.org/10.1016/j.drugalcdep.2016.12.001.
Daley D, Wakim PG, Cohen AJ, Blazer D, Brigham GS, Donovan DM, et al. Clinical Trials Network (CTN) Treatment Effect & Assessment Measures (Team) Task Force Recommendations [Internet]. NIDA Clinical Trials Network; 2010 Apr [cited 2022 Nov 22] p. 20. Available from: http://ctndisseminationlibrary.org/PDF/522.pdf.
Kosten TR, Schottenfeld R, Ziedonis D, Falcioni J. Buprenorphine versus methadone maintenance for opioid dependence. J Nerv Ment Dis. 1993 Jun [cited 2022 Sep 15];181(6):358–364. https://doi.org/10.1097/00005053-199306000-00004.
Ling W, Charuvastra C, Collins JF, Batki S, Brown LS Jr, Kintaudi P, et al. Buprenorphine maintenance treatment of opiate dependence: A multicenter, randomized clinical trial. Addiction [Internet]. 1998 [cited 2022 Sep 15];93(4):475–486. https://doi.org/10.1046/j.1360-0443.1998.9344753.x.
Shufman EN, Porat S, Witztum E, Gandacu D, Bar‐Hamburger R, Ginath Y. The efficacy of naltrexone in preventing reabuse of heroin after detoxification. Biol Psychiatry [Internet]. 1994 Jun [cited 2022 Sep 15];35(12):935–945. Available from: https://www.sciencedirect.com/science/article/pii/0006322394912408, https://doi.org/10.1016/0006-3223(94)91240-8.
Schottenfeld RS, Chawarski MC, Mazlan M. Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: A randomised, double‐blind, placebo‐controlled trial. The Lancet [Internet].2008 Jun [cited 2022 Sep 15];371(9631):2192–2200. https://doi.org/10.1016/S0140-6736(08)60954-X.
Mokri A, Chawarski MC, Taherinakhost H, Schottenfeld RS. Medical treatments for opioid use disorder in Iran: A randomized, double‐blind placebo‐controlled comparison of buprenorphine/naloxone and naltrexone maintenance treatment. Addiction [Internet]. 2016 May [cited 2022 Sep 15];111(5):874–882. https://doi.org/10.1111/add.13259.
Schottenfeld RS, Chawarski MC, Pakes JR, Pantalon MV, Carroll KM, Kosten TR. Methadone versus buprenorphine with contingency management or performance feedback for cocaine and opioid dependence. Am J Psychiatry [Internet]. 2005 Feb [cited 2022 Sep 15];162(2):340–349. https://doi.org/10.1176/appi.ajp.162.2.340.
Lofwall MR, Walsh SL, Nunes EV, Bailey GL, Sigmon SC, Kampman KM, et al. Weekly and monthly subcutaneous buprenorphine depot formulations vs daily sublingual buprenorphine with naloxone for treatment of opioid use disorder: a randomized clinical trial. JAMA Intern Med [Internet]. 2018 Jun[cited 2022 Sep 15];178(6):764–773. https://doi.org/10.1001/jamainternmed.2018.1052.
Rosenthal RN, Lofwall MR, Kim S, Chen M, Beebe KL, Vocci FJ, et al. Effect of buprenorphine implants on illicit opioid use among abstinent adults with opioid dependence treated with sublingual buprenorphine: a randomized clinical trial. JAMA [Internet]. 2016 Jul [cited 2022 Sep 15];316(3):282–290. https://doi.org/10.1001/jama.2016.9382.
Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended‐release naltrexone for opioid dependence: A double‐blind, placebo‐controlled, multicentre randomised trial. The Lancet [Internet]. 2011 Apr [cited 2022 Sep 15];377(9776):1506–1513. https://doi.org/10.1016/S0140-6736(11)60358-9.
Lee JD, Friedmann PD, Kinlock TW, Nunes EV, Boney TY, Hoskinson RA, et al. Extended‐release naltrexone to prevent opioid relapse in criminal justice offenders. NEJM [Internet]. 2016 Mar [cited 2022 Sep 15];374(13):1232–1242. https://doi.org/10.1056/NEJMoa1505409.
Lee JD, Nunes EV, Novo P, Bachrach K, Bailey GL, Bhatt S, et al. Comparative effectiveness of extended‐release naltrexone versus buprenorphine‐naloxone for opioid relapse prevention (X:BOT): A multicentre, open‐label, randomised controlled trial. The Lancet [Internet]. 2018 Jan [cited 2022 Sep 15];391(10118):309–318. https://doi.org/10.1016/S0140-6736(17)32812-X.
Strain EC, Stitzer ML, Liebson IA, Bigelow GE. Buprenorphine versus methadone in the treatment of opioid dependence: self‐reports, urinalysis, and addiction severity index. J Clin Psychopharmacol [Internet]. 1996 Feb [cited 2022 Sep 15];16(1):58–67. https://doi.org/10.1097/00004714-199602000-00010.
Soyka M, Zingg C, Koller G, Kuefner H. Retention rate and substance use in methadone and buprenorphine maintenance therapy and predictors of outcome: results from a randomized study. IJNP [Internet]. 2008 Aug [cited 2022 Sep 15];11(5):641–653. https://doi.org/10.1017/S146114570700836X.
Woody GE, Poole SA, Subramaniam G, Dugosh K, Bogenschutz M, Abbott P, et al. Extended vs short‐term buprenorphine‐naloxone for treatment of opioid‐addicted youth: a randomized trial. JAMA. 2008 Nov [cited 2022 Sep 15];300(17):2003–2011. https://doi.org/10.1001/jama.2008.574.
Eissenberg T, Johnson RE, Bigelow GE, Walsh SL, Liebson IA, Strain EC, et al. Controlled opioid withdrawal evaluation during 72 h dose omission in buprenorphine‐maintained patients. Drug Alcohol Depend. 1997 Apr [cited 2022 Sep 15];45(1‐2):81–91. Available from: https://www.sciencedirect.com/science/article/pii/S0376871697013471.
Strang J, Metrebian N, Lintzeris N, Potts L, Carnwath T, Mayet S, et al. Supervised injectable heroin or injectable methadone versus optimised oral methadone as treatment for chronic heroin addicts in England after persistent failure in orthodox treatment (RIOTT): a randomised trial. The Lancet. 2010 May [cited 2022 Sep 15];375(9729):1885–1895. https://doi.org/10.1016/S0140-6736(10)60349-2.
Sobell LC, Sobell MB. Timeline follow‐back. In: Litten RZ, Allen JP, editorsMeasuring alcohol consumption: psychosocial and biochemical methods [Internet] Totowa, NJ: Humana Press; 1992 [cited 2022 Nov 23]. p. 41–72 https://doi.org/10.1007/978-1-4612-0357-5_3.
Karnik NS, Campbell CI, Curtis ME, Fiellin DA, Ghitza U, Hefner K, et al. Core outcomes set for research on the treatment of opioid use disorder (COS‐OUD): The National Institute on Drug Abuse Clinical Trials Network protocol for an e‐Delphi consensus study. Trials [Internet]. 2021 Jan [cited 2022 Nov 23];22(1):102. https://doi.org/10.1186/s13063-021-05051-9.
Carroll KM, Kiluk BD, Nich C, DeVito EE, Decker S, LaPaglia D, et al. Toward empirical identification of a clinically meaningful indicator of treatment outcome: features of candidate indicators and evaluation of sensitivity to treatment effects and relationship to one year follow up cocaine use outcomes. Drug Alcohol Depend. 2014 Apr [cited 2022 Nov 23];137:3–19. https://doi.org/10.1016/j.drugalcdep.2014.01.012.
McCann DJ, Ramey T, Skolnick P. Outcome measures in medication trials for substance use disorders. Curr Treat Options Psychiatry. 2015 Jun [cited 2022 Nov 23];2(2):113–121. https://doi.org/10.1007/s40501-015-0038-5.
Balise RR, Hu M‐C, Luo S, Calderon AR, Odom G, Brandt L, et al. The harmonization of "high stakes" clinical trial data: medication assisted treatment for opioid use disorder. PLOS Med.
Strain EC, Stitzer ML, Liebson IA, Bigelow GE. Dose‐response effects of methadone in the treatment of opioid dependence. Ann Intern Med. 1993 Jul [cited 2022 Sep 15];119(1):23–27. https://doi.org/10.7326/0003-4819-119-1-199307010-00004.
Strain EC, Stitzer ML, Liebson IA, Bigelow GE. Comparison of buprenorphine and methadone in the treatment of opioid dependence. Am J Psychiatry. 1994 Jul;151(7):1025–1030. https://doi.org/10.1176/ajp.151.7.1025.
Strain EC, Bigelow GE, Liebson IA, Stitzer ML. Moderate‐ vs high‐dose methadone in the treatment of opioid dependence a randomized trial. JAMA. 1999 Mar [cited 2022 Sep 15];281(11):1000–1005. https://doi.org/10.1001/jama.281.11.1000.
Johnson RE, Jaffe JH, Fudala PJ. A controlled trial of buprenorphine treatment for opioid dependence. JAMA. 1992 May [cited 2022 Sep 15];267(20):2750–2755. https://doi.org/10.1001/jama.1992.03480200058024.
Weiss RD, Potter JS, Fiellin DA, Byrne M, Connery HS, Dickinson W, et al. Adjunctive counseling during brief and extended buprenorphine‐naloxone treatment for prescription opioid dependence: a 2‐phase randomized controlled trial. Arch Gen Psychiatry. 2011 Dec [cited 2022 Sep 15];68(12):1238–1246. https://doi.org/10.1001/archgenpsychiatry.2011.121.
Zaks A, Fink M, Freedman AM. Levomethadyl in maintenance treatment of opiate dependence. JAMA. 1972 May [cited 2022 Sep 15];220(6):811–813. https://doi.org/10.1001/jama.1972.03200060039005.
Wolstein J, Gastpar M, Finkbeiner T, Heinrich C, Heitkamp R, Poehlke T, et al. A randomized, open‐label trial comparing methadone and levo‐alpha‐acetylmethadol (LAAM) in maintenance treatment of opioid Addiction. Pharmacopsychiatry. 2009 Jan [cited 2022 Sep 15];42(01):1–8. https://doi.org/10.1055/s-0028-1083818.
Tanum L, Solli KK, Latif ZH, Benth JŠ, Opheim A, Sharma‐Haase K, et al. Effectiveness of injectable extended‐release naltrexone vs daily buprenorphine‐naloxone for opioid dependence: a randomized clinical noninferiority trial. JAMA Psychiatry. 2017 Dec [cited 2022 Sep 15];74(12):1197–1205. https://doi.org/10.1001/jamapsychiatry.2017.3206.
Strang J, Kelleher M, Mayet S, Day E, Hellier J, Byford S, et al. Extended‐release naltrexone versus standard oral naltrexone versus placebo for opioid use disorder: the NEAT three‐arm RCT. Health Technolo Assess. 2019 Feb [cited 2022 Sep 15];23(3):1–72. https://doi.org/10.3310/hta23030.
Preston KL, Umbricht A, Epstein DH. Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance. Arch Gen Psychiatry [Internet]. 2000 Apr [cited 2022 Sep 15];57(4):395–404. https://doi.org/10.1001/archpsyc.57.4.395.
Petitjean S, Stohler R, Déglon JJ, Livoti S, Waldvogel D, Uehlinger C, et al. Double‐blind randomized trial of buprenorphine and methadone in opiate dependence. Drug Alcohol Depend. 2001 Mar [cited 2022 Sep 15];62(1):97–104. https://doi.org/10.1016/S0376-8716(00)00163-0.
Pani PP, Maremmani I, Pirastu R, Tagliamonte A, Gessa GL. Buprenorphine: A controlled clinical trial in the treatment of opioid dependence. Drug Alcohol Depend. 2000 Jul [cited 2022 Sep 15];60(1):39–50. https://doi.org/10.1016/S0376-8716(00)80006-X.
Mattick RP, Ali R, White JM, O'Brien S, Wolk S, Danz C. Buprenorphine versus methadone maintenance therapy: A randomized double‐blind trial with 405 opioid‐dependent patients. Addiction [Internet]. 2003 Mar [cited 2022 Sep 15];98(4):441–452. https://doi.org/10.1046/j.1360-0443.2003.00335.x.
Ling W, Charuvastra VC, Kaim SC, Klett CJ. Methadyl acetate and methadone as maintenance treatments for heroin addicts: a veterans administration cooperative study. Arch Gen Psychiatry. 1976 Jun [cited 2022 Sep 15];33(6):709–720. https://doi.org/10.1001/archpsyc.1976.01770060043007.
Ling W, Casadonte P, Bigelow G, Kampman KM, Patkar A, Bailey GL, et al. Buprenorphine implants for treatment of opioid dependence: A randomized controlled trial. JAMA. 2010 Oct [cited 2022 Sep 15];304(14):1576–1583. https://doi.org/10.1001/jama.2010.1427.
Jaffe JH, Senay EC, Schuster CR, Renault PR, Smith B, DiMenza S. Methadyl acetate vs methadone: A double‐blind study in heroin users. JAMA. 1972 Oct [cited 2022 Sep 15];222(4):437–442. https://doi.org/10.1001/jama.1972.03210040013004.
Haight BR, Learned SM, Laffont CM, Fudala PJ, Zhao Y, Garofalo AS, et al. Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: A multicentre, randomised, double‐blind, placebo‐controlled, phase 3 trial. The Lancet. 2019 Feb [cited 2022 Sep 15];393(10173):778–790. https://doi.org/10.1016/S0140-6736(18)32259-1.
Fudala PJ, Bridge TP, Herbert S, Williford WO, Chiang CN, Jones K, et al. Office‐based treatment of opiate addiction with a sublingual‐tablet formulation of buprenorphine and naloxone. NEJM. 2003 Sep [cited 2022 Sep 15];349(10):949–958. https://doi.org/10.1056/NEJMoa022164.
Fiellin DA, Pantalon MV, Chawarski MC, Moore BA, Sullivan LE, O'Connor PG, et al. Counseling plus buprenorphine–naloxone maintenance therapy for opioid dependence. NEJM. 2006 Jul [cited 2022 Sep 15];355(4):365–374. https://doi.org/10.1056/NEJMoa055255.
Eissenberg T, Bigelow GE, Strain EC, Walsh SL, Brooner RK, Stitzer ML, et al. Dose‐related efficacy of Levomethadyl acetate for treatment of opioid dependence: a randomized clinical trial. JAMA. 1997 Jun [cited 2022 Sep 15];277(24):1945–1951. https://doi.org/10.1001/jama.1997.03540480045037.
Comer SD, Sullivan MA, Yu E, Rothenberg JL, Kleber HD, Kampman K, et al. Injectable, sustained‐release naltrexone for the treatment of opioid dependence: a randomized, placebo‐controlled trial. Arch Gen Psychiatry. 2006 Feb [cited 2022 Sep 15];63(2):210–218. https://doi.org/10.1001/archpsyc.63.2.210.
Schwartz RP, Highfield DA, Jaffe JH, Brady JV, Butler CB, Rouse CO, et al. A randomized controlled trial of interim methadone maintenance. Arch Gen Psychiatry [Internet]. 2006 Jan [cited 2022 Sep 15];63(1):102. https://doi.org/10.1001/archpsyc.63.1.102.
Luo SX, Feaster DJ, Liu Y, Balise RR, Hu MC, Bouzoubaa L, et al. Individual level risk prediction of return‐to‐use during opioid use disorder treatment. JAMA Psychiatry. 2024 [cited 2024 Jan 03];81(1):45–56. https://doi.org/10.1001/jamapsychiatry.2023.3596.
Krupitsky EM, Zvartau EE, Masalov DV, Tsoi MV, Burakov AM, Egorova VY, et al. Naltrexone for heroin dependence treatment in St. Petersburg, Russia. J Subst Abuse Treat [Internet]. 2004 Jun [cited 2022 Sep 15];26(4):285–294. Available from: https://www.sciencedirect.com/science/article/pii/S0740547204000078.
Krupitsky EM, Zvartau EE, Masalov DV, Tsoy MV, Burakov AM, Egorova VY, et al. Naltrexone with or without fluoxetine for preventing relapse to heroin addiction in St. Petersburg, Russia. J Subst Abuse Treat. 2006 Dec [cited 2022 Sep 15];31(4):319–328. https://doi.org/10.1016/j.jsat.2006.05.005.
Biondi BE, Zheng X, Frank CA, Petrakis I, Springer SA. A literature review examining primary outcomes of medication treatment studies for opioid use disorder: what outcome should be used to measure opioid treatment success? Am J Addict [Internet]. 2020 Apr [cited 2022 Sep 15];29(4):249–267. https://doi.org/10.1111/ajad.13051.
Dennis BB, Sanger N, Bawor M, Naji L, Plater C, Worster A, et al. A call for consensus in defining efficacy in clinical trials for opioid addiction: combined results from a systematic review and qualitative study in patients receiving pharmacological assisted therapy for opioid use disorder. Trials [Internet]. 2020 Jan [cited 2022 Sep 15];21(1):30. https://doi.org/10.1186/s13063-019-3995-y.
Luo SX, Feaster DJ. Individual Level Predictive Modeling of Opioid Use Disorder Treatment Outcome [Internet]. NIDA Clinical Trials Network; [cited 2022 Dec 16]. Report No.: CTN‐0094. Available from: http://ctndisseminationlibrary.org/protocols/ctn0094.htm.
Saxon AJ, Ling W, Hillhouse M, Thomas C, Hasson A, Ang A, et al. Buprenorphine/naloxone and methadone effects on laboratory indices of liver health: a randomized trial. Drug Alcohol Depend. 2013 Feb [cited 2022 Sep 15]. 128(1‐2):71–76. https://doi.org/10.1016/j.drugalcdep.2012.08.002.
Balise R, Odom G, Calderon A. public.ctn0094data: Deidentified Data from CTN‐0094 [Internet]. 2023 [cited 2023 Aug 16]. Available from: https://cran.r-project.org/web/packages/public.ctn0094data/index.html.
Odom G, Brandt L, Balise R, Bouzoubaa L. CTNote: CTN Outcomes, Treatments, and Endpoints [Internet]. 2022 [cited 2022 Oct 13]. Available from: https://CRAN.R-project.org/package=CTNote.
Odom JG, Brandt L, Castro C, Luo SX, Feaster DJ, Balise RR. Capturing Drug Use Patterns at a Glance: An n‐Ary Word Sufficient Statistic for Repeated Univariate Categorical Values. PLOS ONE [Internet]. 2023 Sep [cited 2023 Sep 15];18(9):e0291248. https://doi.org/10.1371/journal.pone.0291248.
Efron B, Tibshirani RJ. An introduction to the bootstrap New York: Chapman; Hall/CRC; 1994.
Bridges CC. Hierarchical cluster analysis. Psychological Reports [Internet]. 1966 Jun [cited 2022 Sep 15];18(3):851–854. https://doi.org/10.2466/pr0.1966.18.3.851.
MacQueen JB. Some methods for classification and analysis of multivariate observations, [internet]. Western management Science Inst Univ of California Los Angeles; 1966 Mar [cited 2022 Sep 15]. Available from: https://apps.dtic.mil/sti/citations/AD0632526.
Little RJ, D'Agostino R, Cohen ML, Dickersin K, Emerson SS, Farrar JT, et al. The prevention and treatment of missing data in clinical trials. NEJM. 2012 Oct [cited 2022 Nov 23];367(14):1355–1360. https://doi.org/10.1056/NEJMsr1203730.
McPherson S, Barbosa‐Leiker C, Burns GL, Howell D, Roll JM. Missing data in substance abuse treatment research: current methods and modern approaches. Ex Clin Psychopharmacol. 2012;20:243–250. https://doi.org/10.1037/a0027146.
McPherson S, Barbosa‐Leiker C, McDonell M, Howell D, Roll JM. Longitudinal missing data strategies for substance use clinical trials using generalized estimating equations: An example with a buprenorphine trial. Hum Psychopharmacol: Clinical and Experimental. 2013 [cited 2022 Nov 23];28(5):506–515. https://doi.org/10.1002/hup.2339.
King C, Englander H, Priest KC, Korthuis PT, McPherson S. Addressing missing data in substance use research: A review and data justice‐based approach. J Addict Med. 2020 Dec [cited 2022 Nov 23];14(6):454–456. Available from: https://journals.lww.com/journaladdictionmedicine/Abstract/2020/12000/Addressing_Missing_Data_in_Substance_Use_Research_4.aspx.
Reproducibility and Replicability in Science [Internet] Washington, D.C.: National Academies Press; 2019 [cited 2022 Dec 16]. Available from: https://www.nap.edu/catalog/25303.

UG1DA013035-17 United States DA NIDA NIH HHS; FIU-RCMI Pilot AWD000000009108 United States MD NIMHD NIH HHS; UG1DA013035-17 United States DA NIDA NIH HHS; FIU-RCMI Pilot AWD000000009108 United States MD NIMHD NIH HHS

Keywords: abstinence; clinical trial; opioid use disorder; outcome; relapse; treatment; urine drug screen

ClinicalTrials.gov NCT00315341; NCT00316277; NCT02032433

Date Created: 20240415 Date Completed: 20240606 Latest Revision: 20240626

20240626

10.1111/add.16494

38616571