Choice of time period to identify confounders for propensity score matching, affected the estimate: a retrospective cohort study of drug effectiveness in asthmatic children

Objectives: To control for confounding by indication in comparative (drug) effectiveness studies, propensity score (PS) methods may be used. Since childhood diseases or outcomes often present as acute events, we compared the effect of using different look-back periods in electronic health-care data, to construct PSs. This was applied in our research on the effect of a combination of inhaled corticosteroids/long-acting beta-2 agonists (ICS + LABA), either as fixed combination or used as loose combination (2 separate inhaler devices) in the prevention of severe asthma exacerbations. Methods: We created a cohort of children (5–17 years) diagnosed with asthma from the Dutch Integrated Primary Care information database. Within this cohort, we identified new users of ICS + LABA, either as fixed combination or loose combination (2 separate inhaler devices). The outcome of interest was severe asthma exacerbations. PSs for type of treatment were created using comorbidity and drug use history in different time windows: 1 week, 1 month, 3 months, 1 year, and full history prior to the start of treatment. PSs were used for matching subjects in both exposure groups. Time to first asthma exacerbation was analyzed with Cox proportional hazard regression. The results were compared with published clinical trials. Results: Of 39,682 asthmatic children, 3,500 (8.8%) were new users of either ICS + LABA fixed (3,324 [95.0%]) or loose (176 [5.0%]). The crude hazard ratio (HR) for a severe asthma exacerbation, comparing ICS + LABA fixed to loose was 0.37 (95% confidence interval [CI]: 0.20–0.66). PS-matched HRs (1 week, 1 month, 3 month, 1 year, and full history) were 0.48 (95% CI: 0.22–1.04); 0.60 (95% CI: 0.26–1.38), 0.69 (95% CI: 0.31–1.57), 0.56 (CI: 0.25–1.24), and 0.58 (CI: 0.24–1.36), respectively. Conclusions: PS matching can be used to control for confounding in pediatric comparative (drug) effectiveness studies, the impact of different look-back periods to implement the PS is important. Controlling for confounders occurring in the 3 months preceding drug exposure may yield results comparable to clinical trial results.