Comment on: Suissa and Azoulay. Metformin and the Risk of Cancer: Time-Related Biases in Observational Studies. Diabetes Care 2012;35:2665–2673

In a recent article in Diabetes Care , Suissa and Azoulay (1) concluded that the impressive results of the metformin-associated reduced cancer risk were due to many researchers failing to adjust for immortal time bias and not using time-dependent analysis of drug exposure. However, this conclusion is not justified since it remains controversial whether immortal time would introduce substantial bias.We used statins and their effect on cardiovascular disease (CVD) to illustrate how different analyses could yield different results in pharmacoepidemiological studies. In a time-fixed Cox model, statin use was associated with a hazard ratio (HR) of 0.66 (95% CI 0.50–0.88) for CVD, an effect size similar to that in randomized trials despite 48% of the total follow-up time in the statin users being immortal time (i.e., without drug exposure). Herein, immortal time …