Counterpoint: Keeping the Demons at Bay When Handling Time-Varying Exposures-Beyond Avoiding Immortal Person-Time

The potential for immortal time bias is pervasive in epidemiologic studies with left truncation or time-varying exposures. Unlike other biases in epidemiologic research (e.g., measurement bias, confounding due to unmeasured factors, and selection based on unmeasured predictors of the outcome), immortal time bias can and should be avoided by the correct assignment of person-time during follow up. However, even when handing person-time correctly, allowing late entry into a study or into an exposure group can open the door to more insidious sources of bias, some of which we explore here. Clear articulation of the study question, including the treatment plans of interest, can provide navigation around these sources of bias and elucidate the assumptions needed for inference given the available data. Here, we use simulated data to illustrate the assumptions required under various approaches to estimate the effect of a time-varying treatment and describe how these assumptions relate to the assumptions necessary to estimate single sample rates and risks in settings with censoring and truncation.