The Use of the Target Trial Approach in Kidney Disease: A Methodological Systematic Review Protocol

Abstract Background Patients with kidney disease and failure have often been excluded from randomized trials leaving practitioners with limited data to navigate their decision-making at critical stages of patient’s lives. The concept of target trial emulation has recently been introduced and implemented in Nephrology to address critical questions in the comparative effectiveness and safety of interventions during kidney failure. However, the reach, validity, and application of trial emulation in nephrology remains unknown and warrants systematic investigation. This methodological systematic review protocol aims to describe the methodology for assessing the available evidence regarding emulated target trials for studying outcomes in patients with kidney disease. Methods This protocol is developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. MEDLINE, Embase, and reference lists will be searched up until 1st July 2023 to identify all studies in kidney disease patients that use target trial emulation as the primary approach for analysis. Two authors (AA, PK) will select articles based on title and abstract and then full text, with a third reviewer settling disagreements (JP). Prespecified variables will be extracted, and risk of bias assessed using prespecified data forms to determine, how robust the target trial design, emulation and answer is. Discussion The aim of this methodological systematic review is to understand the extent to which the target trial approach is being used in kidney disease, and to make recommendations for improving its use in nephrology. Methodological systematic review registration OSF, https://osf.io/z4y29 (under embargo currently).