Cost-effectiveness of diacetylmorphine versus methadone for chronic opioid dependence refractory to treatment

Background:

Although diacetylmorphine has been proven to be more effective than methadone maintenance treatment for opioid dependence, its direct costs are higher. We compared the cost-effectiveness of diacetylmorphine and methadone maintenance treatment for chronic opioid dependence refractory to treatment.

Methods:

We constructed a semi-Markov cohort model using data from the North American Opiate Medication Initiative trial, supplemented with administrative data for the province of British Columbia and other published data, to capture the chronic, recurrent nature of opioid dependence. We calculated incremental cost-effectiveness ratios to compare diacetylmorphine and methadone over 1-, 5-, 10-year and lifetime horizons.

Results:

Diacetylmorphine was found to be a dominant strategy over methadone maintenance treatment in each of the time horizons. Over a lifetime horizon, our model showed that people receiving methadone gained 7.46 discounted quality-adjusted life-years (QALYs) on average (95% credibility interval CI] 6.91–8.01) and generated a societal cost of $1.14 million (95% CI $736 800–$1.78 million). Those who received diacetylmorphine gained 7.92 discounted QALYs on average (95% CI 7.32–8.53) and generated a societal cost of $1.10 million (95% CI $724 100–$1.71 million). Cost savings in the diacetylmorphine cohort were realized primarily because of reductions in the costs related to criminal activity. Probabilistic sensitivity analysis showed that the probability of diacetylmorphine being cost-effective at a willingness-to-pay threshold of $0 per QALY gained was 76%; the probability was 95% at a threshold of $100 000 per QALY gained. Results were confirmed over a range of sensitivity analyses.

Interpretation:

Using mathematical modelling to extrapolate results from the North American Opiate Medication Initiative, we found that diacetylmorphine may be more effective and less costly than methadone among people with chronic opioid dependence refractory to treatment.Opioid substitution with methadone is the most common treatment of opioid dependence.^1–3 Participation in a methadone maintenance treatment program has been associated with decreases in illicit drug use,⁴ criminality⁵ and mortality.^6,7 However, longitudinal studies have shown that most people who receive opioid substitution treatment are unable to abstain from illicit drug use for sustained periods, either switching from treatment to regular opioid use or continuing to use opioids while in treatment.^8–13 An estimated 15%–25% of the most marginalized methadone clients do not benefit from treatment in terms of sustained abstention from the use of illicit opioids.¹⁴The North American Opiate Medication Initiative was a randomized controlled trial that compared supervised, medically prescribed injectable diacetylmorphine and optimized methadone maintenance treatment in people with long-standing opioid dependence and multiple failed treatment attempts with methadone or other forms of treatment.¹⁵ The trial was conducted in two Canadian cities (Vancouver, British Columbia; and Montréal, Quebec). Both treatment protocols included a comprehensive range of psychosocial services (e.g., addiction counselling, relapse prevention, case management, and individual and group interventions) and primary care services (e.g., testing for blood-borne diseases, provision of HIV treatment, and treatment of acute and chronic physical and mental health complications of substance use) in keeping with Health Canada best practices.¹⁶ The results of the trial confirmed findings of prior studies showing diacetylmorphine to be more effective than methadone maintenance treatment in retaining opioid-dependent patients in treatment^15,17–20 and improving health and social functioning.^19,21,22 Diacetylmorphine treatment has been proposed to reach a specific population of people with opioid dependence refractory to treatment who are at high risk of adverse health consequences and engagement in criminal activities to acquire the illicit drugs.For guiding policy-makers, the North American Opiate Medication Initiative alone does not address all the important considerations for decision-making. In addition to political challenges associated with the therapy,²³ there remains concern over the direct cost of diacetylmorphine over the long term, because it can be as much as 10 times greater than conventional methadone maintenance treatment.²¹ The North American Opiate Medication Initiative was only one year in duration, but a policy to introduce diacetylmorphine might have both positive and negative longer-term implications.We extrapolated outcomes from the North American Opiate Medication Initiative to estimate the long-term cost-effectiveness of diacetylmorphine versus methadone maintenance treatment for chronic, refractory opioid dependence.