Comparative Analysis of Instrumental Variables on the Assignment of Buprenorphine/Naloxone or Methadone for the Treatment of Opioid Use Disorder.

BACKGROUND: Instrumental variable (IV) analysis provides an alternative set of identification assumptions in the presence of uncontrolled confounding when attempting to estimate causal effects. Our objective was to evaluate the suitability of measures of prescriber preference and calendar time as potential IVs to evaluate the comparative effectiveness of buprenorphine/naloxone versus methadone for treatment of opioid use disorder (OUD). METHODS: Using linked population-level health administrative data, we constructed five IVs: prescribing preference at the individual, facility, and region levels (continuous and categorical variables), calendar time, and a binary prescriber's preference IV in analyzing the treatment assignment-treatment discontinuation association using both incident-user and prevalent-new-user designs. Using published guidelines, we assessed and compared each IV according to the four assumptions for IVs, employing both empirical assessment and content expertise. We evaluated the robustness of results using sensitivity analyses. RESULTS: The study sample included 35,904 incident users (43.3% on buprenorphine/naloxone) initiated on opioid agonist treatment by 1585 prescribers during the study period. While all candidate IVs were strong (A1) according to conventional criteria, by expert opinion, we found no evidence against assumptions of exclusion (A2), independence (A3), monotonicity (A4a), and homogeneity (A4b) for prescribing preference-based IV. Some criteria were violated for the calendar time-based IV. We determined that preference in provider-level prescribing, measured on a continuous scale, was the most suitable IV for comparative effectiveness of buprenorphine/naloxone and methadone for the treatment of OUD. CONCLUSIONS: Our results suggest that prescriber's preference measures are suitable IVs in comparative effectiveness studies of treatment for OUD.

COVID-19 vaccination mandates and vaccine uptake.

We evaluate the impact of government-mandated proof of vaccination requirements for access to public venues and non-essential businesses on COVID-19 vaccine uptake. We find that the announcement of a mandate is associated with a rapid and significant surge in new vaccinations (a more than 60% increase in weekly first doses), using the variation in the timing of these measures across Canadian provinces in a difference-in-differences approach. Time-series analysis for each province and for France, Italy and Germany corroborates this finding. Counterfactual simulations using our estimates suggest the following cumulative gains in the vaccination rate among the eligible population (age 12 and over) as of 31 October 2021: up to 5 percentage points (p.p.) (90% confidence interval, 3.9-5.8) for Canadian provinces, adding up to 979,000 (425,000-1,266,000) first doses in total for Canada (5 to 13 weeks after the provincial mandate announcements); 8 p.p. (4.3-11) for France (16 weeks post-announcement); 12 p.p. (5-15) for Italy (14 weeks post-announcement) and 4.7 p.p. (4.1-5.1) for Germany (11 weeks post-announcement).

The effect of a methadone reformulation on opioid agonist treatment outcomes: A population-based study in British Columbia, Canada, 2013-14.

INTRODUCTION: The province of British Columbia, Canada, changed the existing oral anhydrous methadone solution to a 10-times more concentrated pre-mixed solution, Methadose®, on February 1, 2014. We aimed to assess the immediate effects of the methadone reformulation on missed doses, days off methadone, changes in medication dosing and dispensations of opioids for pain, and hospitalizations and mortality among all people receiving treatment at or near the time of the change. METHODS: We conducted a population-based retrospective cohort study including all individuals receiving at least one methadone dispensation in the 12 months prior to the study period. We executed a difference-in-differences analysis by estimating a multivariate regression model to compare outcomes in the three months before and after the reformulation (November 1, 2013 to April 30, 2014) versus a time-lagged control cohort with similar characteristics observed during an equivalent nonoverlapping interval. We used daily individual-level linked health administrative data capturing missed doses, days off methadone, changes in methadone dosing, concurrent dispensations of opioids for pain, hospitalizations, and mortality. We stratified the cohorts into three subgroups: (i) those receiving OAT for ≥12 months; (ii) those receiving OAT for <12 months; and (iii) those not receiving OAT at the start of the study period. We conducted sensitivity analyses and placebo tests to assess the robustness of our results. RESULTS: Among the 16,339 individuals receiving methadone during the study period, the reformulation was associated with more instances of methadone dose increases (34.5% [95% Confidence Interval (CI): 27.4%, 41.5%]). For those retained in treatment ≥12 months prior to the study period (n = 7449), the reformulation was associated with more instances of methadone dose increases (50.2% [39.5%, 60.8%]) and dispensations of opioids for pain (62.2% [40.8%, 83.5%]), as well as an increase in missed doses (41.9% [29.1%, 54.7%]) and days off methadone (62.6% [39.7%, 85.4%]). We found no statistically significant change in risk of hospitalization or mortality. Sensitivity analyses supported our results. CONCLUSION: Our results reinforce the need expressed by people receiving methadone for greater client involvement in the planning and implementation of regulatory changes that may impact client care, especially those patients with a relatively long treatment history.

Face masks, public policies and slowing the spread of COVID-19: Evidence from Canada.

We estimate the impact of indoor face mask mandates and other non-pharmaceutical interventions (NPI) on COVID-19 case growth in Canada. Mask mandate introduction was staggered from mid-June to mid-August 2020 in the 34 public health regions in Ontario, Canada's largest province by population. Using this variation, we find that mask mandates are associated with a 22 percent weekly reduction in new COVID-19 cases, relative to the trend in absence of mandate. Province-level data provide corroborating evidence. We control for mobility behaviour using Google geo-location data and for lagged case totals and case growth as information variables. Our analysis of additional survey data shows that mask mandates led to an increase of about 27 percentage points in self-reported mask wearing in public. Counterfactual policy simulations suggest that adopting a nationwide mask mandate in June could have reduced the total number of diagnosed COVID-19 cases in Canada by over 50,000 over the period July-November 2020. Jointly, our results indicate that mandating mask wearing in indoor public places can be a powerful policy tool to slow the spread of COVID-19.

Supplier-induced demand for newborn treatment: evidence from Japan.

We estimate the degree of supplier-induced demand for newborn treatment by exploiting changes in reimbursement arising from the introduction of the partial prospective payment system (PPS) in Japan. Under the partial PPS, neonatal intensive care unit (NICU) utilization became relatively more profitable than other procedures, since it was excluded from prospective payments. We find that hospitals have responded to PPS adoption by increasing NICU utilization and by more frequently manipulating infants' reported birth weights which in large part determine their maximum allowable stay in the NICU. This induced demand substantially increases the reimbursements received by hospitals.