Tool for Implementing TArget Trial emulatioN (TITAN): an open-access design assistant

BackgroundTarget trial emulation offers a structured framework to reduce bias in observational studies by emulating the design of a hypothetical target randomised controlled trial. Despite a growing interest for this framework, the implementation of target trial emulation is often inconsistent, with design flaws frequently introducing avoidable biases. ObjectiveTo develop a design assistant tool to provide structured guidance to researchers for planning and conducting target trial emulations. MethodsA multi-disciplinary steering committee defined the scope, content and structure of Tool for Implementing TArget Trial emulatioNs (TITAN). First, we reviewed the literature to identify concepts according to the steps of planning and designing a target trial emulation. Then, we developed the tool through an iterative process with two rounds of pilot testing and subsequent refinement by the steering committee. ResultsTITAN provides guidance to emulate a pragmatic two-arm trial assessing a pharmacological intervention. The tool is organized in two main sections. First, the users define the research question and the target trial. Then, they emulate the target trial using the available observational data. The tool provides warnings, in addition to suggestions, to minimize avoidable biases and major methodological errors; particularly focusing on the alignment of study time points (eligibility, treatment assignment, and start of follow-up) and related biases. The tools output is a synthesis that includes a summary of the target trial, design of its emulation, and possible biases and solutions. ConclusionsTITAN could help researchers ensure that observational studies follow the key principles of target trial emulation.