Greedy caliper propensity score matching can yield variable estimates of the treatment-outcome association-A simulation study.

PURPOSE: Greedy caliper propensity score (PS) matching is dependent on randomness, which can ultimately affect causal estimates. We sought to investigate the variation introduced by this randomness. METHODS: Based on a literature search to define the simulation parameters, we simulated 36 cohorts of different sizes, treatment prevalence, outcome prevalence, treatment-outcome-association. We performed 1:1 caliper and nearest neighbor (NN) caliper PS-matching and repeated this 1000 times in the same cohort, before calculating the treatment-outcome association. RESULTS: Repeating caliper and NN caliper matching in the same cohort yielded large variations in effect estimates, in all 36 scenarios, with both types of matching. The largest variation was found in smaller cohorts, where the odds ratio (OR) ranged from 0.53 to 10.00 (IQR of ORs: 1.11-1.67). The 95% confidence interval was not consistently overlapping a neutral association after repeating the matching with both algorithms. We confirmed these findings in a noninterventional example study. CONCLUSION: Caliper PS-matching can yield highly variable estimates of the treatment-outcome association if the analysis is repeated.

Eliminated patient fee and changes in dispensing patterns of asthma medication in children-An interrupted time series analysis.

In 2016, all prescription drugs included in the reimbursement system in Sweden were made available for children (age 0-17 years) without any patient fees. Our aim was to estimate the association between this intervention and the dispensing patterns of asthma medications among children. Dispensing data on asthma medications for all children living in Stockholm County during 2014-2017 were selected to include two years before (January 2014-December 2015) and after (January 2016-December 2017) the intervention. In an uncontrolled before and after study, the measures of utilization were as follows: the proportion of children with at least one dispensed asthma medication (prevalence); the number of children initiated on treatment after an 18-month drug-free period (incidence); the number of defined daily doses (DDDs) dispensed per child; and the number of children with at least two prescriptions with controller medication (inhaled corticosteroid or leukotriene receptor antagonist) dispensed during 18 months (persistence). In an interrupted time series (ITS) analysis, all measures were included except for persistence. Socio-economic status was defined using Mosaic data. The prevalence increased after the intervention (from 11.9% to 13.0%). However, the ITS analysis showed a positive trend already before the intervention, and consequently, the increase was not attributable to the intervention. For incidence, similar patterns were observed. There was an increase in dispensed volumes related to the intervention, 46.3 DDDs/child/month before and 51.1 after the intervention (P-value 0.01). The proportion of children with persistent asthma medication increased from 46.0% to 51.9% in children with low socio-economic status. In conclusion, the intervention was only modestly associated with changes in the dispensing patterns of asthma medication, with the volume dispensed per child increasing slightly, particularly in children with low socio-economic status.

Effects of policy interventions on the introduction of novel oral anticoagulants in Stockholm: an interrupted time series analysis.

AIMS: The aim of the present study was to assess the effect of policy interventions - i.e. reimbursement decisions, guidelines and regional recommendations - on the prescribing of oral anticoagulant treatment in patients with atrial fibrillation (AF). METHODS: Interrupted time series analyses were carried out using monthly data on all patients with a recorded diagnosis of AF newly initiated (switchers and anticoagulant-naïve patients alike) on warfarin, dabigatran, rivaroxaban or apixaban in the Stockholm region from April 2011 until February 2016. RESULTS: A total of 34 165 initiations in 27 942 patients were included. The publication of the European Guidelines was associated with an increase in novel oral anticoagulant (NOAC) initiations of 12.5% [95% confidence interval (CI) 7.3, 17.7] after 5 months. The choice between the different NOACs was mainly associated with changes in the regional recommendations, with apixaban initiations increasing by 19.5% (95% CI 16.3, 22.7) 5 months after the drug was recommended as a first-line alternative to warfarin. Dabigatran received a second-line recommendation but initiations decreased by -9.5% (95% CI -12.6, -6.4), and initiations of rivaroxaban, which had no specific recommendation, decreased by -9.2% (95% CI -12.7, -5.7). A steady decrease in warfarin and increase in NOAC initiations was seen throughout the study period and from November 2015, AF patients were more likely to receive apixaban than any other anticoagulant, while less than 20% of the initiations were with warfarin. CONCLUSIONS: After reimbursement and inclusion in the European guidelines, the NOACs started gaining in popularity, while changes in regional recommendations were associated with the biggest change in prescribers' choice between the different NOACs.