Impact of COVID ‐19 Restrictions on Estimating Causal Effects: Fluoroquinolones and Tendon Rupture

Abstract

ABSTRACT Purpose The COVID‐19 pandemic disrupted healthcare services, potentially affecting causal effect estimation using real‐world data. As a case study, we replicated a cohort study using Clinical Practice Research Datalink Aurum to evaluate whether pandemic‐related disruptions influenced the measured association between fluoroquinolone use and tendon rupture. Methods We included adults initiating fluoroquinolones/cephalosporins during 1 January 2006–31 March 2023. Four analyses compared treatment effect estimates using different periods for exposure and outcome ascertainment: pre‐pandemic only, pre‐pandemic exposure with follow‐up extending through the pandemic, all available data and post‐pandemic only. We estimated hazard ratios (HRs) for tendon rupture using Cox regression. Results Among 891 968 fluoroquinolone users and 895 229 cephalosporin users, fluoroquinolone users had more comorbidities than cephalosporin users in the pre‐pandemic period but fewer in the post‐pandemic period. Pre‐pandemic analysis showed an increased risk of tendon rupture associated with fluoroquinolones (Propensity score weighted [PSW]‐HR: 1.94; 95% CI: 1.46–2.59), consistent with previous evidence. Estimates using all available data were similar for the overall study period (PSW‐HR: 1.91; 95% CI: 1.46–2.51) and the pre‐pandemic period (PSW‐HR: 1.96; 95% CI: 1.47–2.61) but were less precise during/post‐pandemic period (PSW‐HR: 1.57; 95% CI: 0.72–3.41) with no evidence of a period‐treatment interaction (PSW‐HR: 0.80; 95% CI: 0.35–1.84). Post‐pandemic analysis showed very few events among cephalosporin users but not fluoroquinolone users with a larger but imprecise estimate (PSW‐HR: 3.32; 95% CI: 0.62–17.72). Conclusion In this case study, there was no clear evidence that pandemic‐related healthcare disruptions materially altered causal estimates, albeit with limited power to detect differences between before and during/post‐pandemic effects. Studies using real‐world data across the pandemic should routinely examine temporal changes in baseline characteristics and outcome incidence.