Background Immortal time bias is a spurious or exaggerated protective association that commonly arises in naive analyses of observational data. It occurs when people receive the intervention because they survive, rather than survive because they received the intervention. Studies in conditions with substantial early mortality, such as acute severe infections, are particularly vulnerable. The bias can be avoided by fitting the intervention as a time-varying exposure. Methods We developed IMMORTOOL, an R package accessible via a user-friendly web interface. This tool will estimate the potential for immortal time bias using empiric or assumed data on the distributions of time to intervention and time to event. Assumptions are that no other biases are present and that the intervention does not impact the outcome. The tool was benchmarked using studies presenting both naive analyses and analyses with the intervention fit as a time-varying exposure. We applied IMMORTOOL to a set of influential observational studies that used naive analyses when estimating the impact of polyclonal intravenous immunoglobulin (IVIG) on survival in streptococcal toxic shock syndrome (STSS). Results IMMORTOOL demonstrated that published estimates suggesting a survival advantage from giving IVIG in STSS are explained, at least in part, by immortal time bias. Conclusions IMMORTOOL can quantify the potential for immortal time bias in observational analyses. This may help readers interrogate published studies. We do not advocate IMMORTOOL being used to justify naive analyses where the intervention could be fit as a time-varying exposure. To what extent giving IVIG in STSS improves survival remains uncertain.

TP was an author on the IVIG in STSS systematic review that we cite. Beyond this, the authors have no relevant conflicts of interest to declare.

TAY is an NIHR Clinical Lecturer, funded by the National Institute for Health and Care Research. TP is a Clinical Research Career Development Fellow, funded by the Wellcome Trust (222098/Z/20/Z). PJD was supported by a fellowship from the UK Medical Research Council (MR/P022081/1). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health and Care Research, or the Department of Health and Social Care.

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The study used ONLY openly available human data that were originally located in the cited publications.

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We have made IMMORTOOL available as an R package, with a ShinyApp interface, so readers can undertake their own analyses. The underlying code, including code to reproduce all results reported in this paper, are available at https://github.com/petedodd/IMMORTOOL. Online access to the Shiny interface is available at https://petedodd.github.io/IMMORTOOL-live/. Note, in some browsers, the interface will take a few minutes to load.

https://github.com/petedodd/IMMORTOOL

https://petedodd.github.io/IMMORTOOL-live