Scientific and political challenges in North America's first randomized controlled trial of heroin-assisted treatment for severe heroin addiction: rationale and design of the NAOMI study

Clin Trials. 2009 Jun;6(3):261-71. doi: 10.1177/1740774509105222.

Abstract

Background: Heroin addiction is a chronic relapsing disease, best treated with opioid-agonist substitution therapy such as methadone maintenance. However, a subset of the most severely affected individuals do not benefit sufficiently from this treatment. The North American Opiate Medication Initiative (NAOMI) is a randomized clinical trial (RCT) to evaluate the hypothesis that pharmaceutical-grade heroin, diacetylmorphine (DAM) is more effective in retaining patients and improving their outcomes than Methadone Maintenance Treatment (MMT) among those with chronic, refractory injection opioid dependence.

Purpose/methods: The study aimed at randomizing 253 participants to two intervention arms: (1) MMT alone or (2) injectable opioids (DAM or hydromorphone) plus adjunctive MMT if deemed appropriate. The planned study duration was 3 years, with a 1-year intake period, 1 year of treatment, and an additional year of follow-up. The NAOMI trial was initiated in March 2005 at two Canadian sites (Vancouver and Montreal). This was the first multicenter RCT in North America to compare the relative efficacy of these different therapeutic strategies. We discuss the rationale behind the NAOMI study design, as well as the scientific and political issues and methodological challenges arising from the conduct of a trial that involves the prescription of a controlled substance to individuals with dependence on that substance.

Limitations: Restrictive entry criteria led to the exclusion of many otherwise eligible participants, slowing recruitment into the study. Inability to offer DAM treatment beyond 12 months led to artificial boundary effects in the trial.

Conclusions: Addiction treatment research navigates between science and politics, and evidence-based medicine is many times confronted by moral beliefs. Political considerations influence study design to a further degree than in RCTs treating less-stigmatized disorders with more-reputable medications.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / therapeutic use*
  • Dose-Response Relationship, Drug
  • Endpoint Determination
  • Heroin / administration & dosage
  • Heroin / therapeutic use*
  • Heroin Dependence / drug therapy*
  • Humans
  • Methadone / therapeutic use
  • North America
  • Politics*
  • Research Design
  • Treatment Outcome

Substances

  • Analgesics, Opioid
  • Heroin
  • Methadone

Grants and funding