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: (i) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (ii) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment, patient populations and hospital practices that, in turn, differentially impact recruitment rates, treatment compliance and attrition; (iii) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (iv) staff turnover needs to be addressed with a proactive focus on both hiring and training; (v) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (vi) timely tracking of data in a multi-site trial is both demanding and unforgiving; and (vii) 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.

Trial registration: ClinicalTrials.gov NCT00271219.

Conflict of interest statement

Declaration of Interest

All MOTHER grants are from the National Institute on Drug Abuse (NIDA) unless noted otherwise: Brown University, R01DA015778; Johns Hopkins University, R01DA015764; Medical University of Vienna, R01DA018417; Thomas Jefferson University, R01DA015738; University of Toronto, R01DA015741; University of Vermont, R01DA018410 and M01RR109; Vanderbilt University, R01DA017513 and M01RR00095, and Wayne State University, R01DA15832.

Reckitt Benckiser Healthcare, Hull, UK supplied buprenorphine tablets (and the associated placebo) via NIDA. Neither Reckitt Benckiser nor NIDA had any involvement in study design, data collection, analysis, interpretation, or manuscript preparation.

H.J. discloses that she has received reimbursement for time and travel from Reckitt Benckiser.

G.F. discloses that she has received financial support and honoraria for presentations from Reckitt Benckiser, as well as financial support and honoraria for presentations from Schering Plough.

P.S. discloses that he has received an unrestricted educational grant from Schering Canada to provide a single training program on buprenorphine substitution treatment in 2000. His hospital receives funds from the Government of Ontario to develop and provide a training program of which he is the course director for all Ontario physicians who wish to treat opioid dependence including in pregnant women. However, buprenorphine alone (Subutex®) is not available in Canada. All other authors declare no competing financial interests. No contractual constraints on publishing have been imposed by any agency from which an author has received funding.

KEO’G discloses that he has received reimbursement for time from Reckitt Benckiser.

The clinical trial was registered with ClinicalTrials.gov (Identifier: NCT00271219; Title: RCT Comparing Methadone and Buprenorphine in Pregnant Women).

© 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.