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Exposure Adjusted Incidence Rate and Event Rate in Clinical Trials with Treatment Crossover

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Abstract

Exposure adjusted incidence rate (EAIR) and exposure adjusted event rate (EAER) are two commonly used measures for adverse event risk in clinical trials. However, in clinical trials with treatment crossover, classical EAIR and EAER should be adapted before being used due to the presence of within subject correlation. In this paper, we review the definition and motivation of EAIR and EAER, discuss how we can use mixed-effect models and generalized estimating equations to adapt EAIR and EAER to the treatment crossover case, and evaluate the proposed methods on synthetic trial data. We aim to combine both theory and practicality – while presenting sufficient theoretical motivation and justification, we also provide the SAS code for the proposed methods and discuss the practical issues one might encounter when applying them.

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Acknowledgement

This manuscript was sponsored by AbbVie. AbbVie contributed to the design, research, and interpretation of data, writing, reviewing, and approving the content. Yunxia Sui, Yihan Li, and Xin Wang are employees of AbbVie Inc. Ruofei Zhao was a summer intern at AbbVie and a graduate student at the University of Michigan when he contributed to the research and the writing of this manuscript. All authors may own AbbVie stock.

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Authors and Affiliations

  1. AbbVie Inc, North Chicago, USA

    Yunxia Sui, Yihan Li & Xin Wang

  2. Department of Statistics, University of Michigan, Ann Arbor, USA

    Ruofei Zhao

Authors
  1. Yunxia Sui
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  2. Ruofei Zhao
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  3. Yihan Li
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  4. Xin Wang
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Corresponding author

Correspondence to Yunxia Sui.

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Sui, Y., Zhao, R., Li, Y. et al. Exposure Adjusted Incidence Rate and Event Rate in Clinical Trials with Treatment Crossover. Stat Biosci 14, 66–78 (2022). https://doi.org/10.1007/s12561-021-09314-6

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  • DOI: https://doi.org/10.1007/s12561-021-09314-6

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