Maternal Opioid Treatment: Human Experimental Research (MOTHER)—approach, issues and lessons learned

Abstract

Aims The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current – and single most comprehensive – research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine. Methods The MOTHER study design is outlined, and its basic features are presented. Conclusions At least seven important lessons have been learned from the MOTHER study: (1) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (2) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment goals, patient populations, and hospital practices that in turn differentially impact recruitment rates, treatment compliance, and attrition; (3) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (4) staff turnover needs to be addressed with a proactive focus on both hiring and training; (5) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (6) timely tracking of data in a multi-site trial is both demanding and unforgiving; and, (7) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results.

Neonatal outcomes and their relationship to maternal buprenorphine dose during pregnancy

“…MOTHER (Jones et al, 2012a, 2010) was a double-blind, double-dummy, flexible-dosing, parallel-group randomized clinical trial comparing outcomes for pregnant women with opioid use disorders and their neonates receiving either buprenorphine or methadone pharmacotherapy provided in the context of comprehensive care. Study findings showed that, on average, neonates in the buprenorphine condition compared to neonates in the methadone condition required significantly less morphine to treat NAS, has a shorter NAS treatment course, and spent significantly less time in the hospital.…”

Behavioral effects of perinatal opioid exposure

“…The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project found both methadone and buprenorphine to be important parts of a comprehensive treatment approach (Jones et al, 2012a(Jones et al, , 2012b. Many studies examining neonatal outcomes among pregnant heroin users treated with methadone have reported improvements in birth weight (Strauss et al, 1974;Kandall et al, 1975).…”

“…Therefore, it is difficult to assess these effects in clinical cohorts, which are beset with problems such as difficulties in documenting use patterns (Jones et al, 2012a). Thus, animal studies are required.…”

Management of psychotropic drugs during pregnancy

“…123 130 131 Four RCTs (n=271) have compared maternal and neonatal outcomes significant adverse maternal or neonatal outcomes; however, given the paucity of data on the safety and efficacy of this product when used in pregnancy, clinicians are usually advised to recommend that women switch from the combination to buprenorphine when they become pregnant. 139 140 Naltrexone Although preclinical data suggest no change in rodent maternal health or congenital malformations, data on naltrexone use in pregnant humans is lacking.…”