Table 3.

Potential sources of bias and how addressed in the RWE study (adapted from Reference 30)

Methodological challenge	Strategy to reduce bias	How addressed in this study
Temporality in administrative data	Use of cohort study design ensures exposure precedes outcome	Applied a cohort design with start follow‐up for outcomes at first prescription of either weekly exenatide or basal insulin
Time‐varying hazards and treatment duration effects	New‐user cohort design	Both weekly exenatide and basal insulin users were naïve initiators of injectable diabetes therapy
Exposure risk window definition	Clear biologic hypothesis	Time‐frame of RCT (6 months) and RWE study (12 months) represent similar short‐term timeframe
Time‐varying exposures	Consider both ITT and as‐treated analyses	Both RCT and RWE study used ITT analysis
Confounding	Choose appropriate comparison group Apply appropriate methods	Both RCT and RWE study used active comparison group Use of propensity score improves comparability of groups in RWE study