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Negative controls and how to use them: a guidance paper
Sophie H Bots1, Anna Schultze2, Romin Pajouheshnia3
1Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Abstract:
Negative controls have gained traction as a useful tool for causal research to address confounding and bias. However, general guidance on how to select and apply negative controls and how to report and interpret their findings is lacking. This paper lays out the key steps of conducting a negative-control analysis and provides all relevant background information, important feasibility and validity considerations, and practical suggestions for the implementation and interpretation of each step. This includes a convenient overview of all methods, complete with their rationale, key considerations, and illustrative examples, and practical checklists that both researchers and reviewers can use to facilitate the complete and rigorous reporting of negative-control analyses.
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