DAT-Emulating target trials with big data to strengthen the evidence base for the clinical management of opioid use disorder

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ABSTRACT DAT18-06 In 2016, following a dramatic increase in opioid-related overdose deaths, the province of British Columbia (BC), Canada declared a public health emergency. BC reported 1,510 illicit drug overdose deaths in 2018, a rate of 31.0 per 100,000, placing it 10th among US states, equal to Rhode Island (31.0), behind West Virginia (57.8), Ohio (46.3) and Pennsylvania (44.3) but ahead of New Jersey (30.0), Michigan (27.8) and Florida (25.1). While the four-fold increase in overdose deaths observed since 2012 is largely attributable to the contamination of fentanyl and other synthetic opioids in the illicit drug supply, many decedents had sought treatment in the past and experienced relapses. Opioid agonist treatment (OAT) is among the most effective tools available to combat the epidemic. However, OAT uptake and retention is sub-optimal in BC and internationally, compromised largely by social and structural factors but also deviations from evidence-based standards of care and fragmented care, particularly for those with concurrent disorders. Furthermore, a number of aspects of Canadian and US clinical guidelines for the management of opioid use disorder (OUD) are based on limited and low-quality evidence. Even basic evidence on the comparative effectiveness of available treatment options overall and for key populations in the fentanyl era is lacking. This proposal aims to apply cutting-edge methods for causal inference in emulating a series of ‘target trials’ in three immediate aims: (1) to determine the comparative effectiveness of methadone versus buprenorphine/naloxone for different patient subgroups presenting for OAT; (2) to determine the impact of urine drug screening – a ubiquitous and non-evidence- based element of OUD care – on OAT retention and mortality; and (3) to determine the complementary effects of OAT on uptake and adherence to directing-acting antivirals for people with opioid use disorder (PWOUD) with concurrent Hepatitis C Virus. The ‘target trial’ framework channels counterfactual theory in providing a flexible basis for comparing the effects of treatment and clinical management strategies on either an intent-to-treat or per-protocol basis. We have identified a number of additional questions related to the clinical management of PWOUD where guidelines are supported by weaker empirical evidence and will endeavor to answer as many of these questions as possible, prioritizing analysis using a common framework focused on methodological rigor and