TITAN

Tool objective

Target trial emulation is a method of designing observational analyses so that they explicitly emulate a hypothetical randomized trial (i.e. the target trial) that would answer the question at hand; it can be considered as an attempt to make causal inference with observational data.

The aim of this tool is to provide guidance for emulating a target trial assessing a pharmacological intervention, in order to avoid major errors and biases by design.

The tool aims to provide guidance to emulate a target trial that is:

• a pragmatic randomized controlled trial ;
• comparing two interventions (two-arm trial);
• assessing a pharmacological intervention; and
• assessing the initiation and/or adherence to an intervention.

The main characteristics of a pragmatic trial are:

• having less stringent eligibility criteria (broader population);
• having flexible intervention and comparator as it would be in clinical practice and
• measuring outcomes that are directly relevant to participants, funders, communities, and healthcare practitioners.

Sections

The tool is organized in two sections:

1. Definition of the target trial
2. Design of emulation using observational data

A supplementary section ‘Additional information’ provides additional details on target trial emulation and statistical considerations.

A series of statistical methods are proposed, however they are non-exhaustive, and the consultation of a statistician during the process of the target trial emulation is necessary.

A synthesis will be generated that includes a table illustrating the design elements and definitions of the target trial, modified target trial and the emulation, in addition to a summary of possible biases and proposed solutions.

Please note that emulating a target trial that involves dynamic treatment strategies, treatment discontinuation, switching, dose changes, multiple comparators or non-pharmacologic interventions requires an additional set of verification questions and considerations that are not addressed in the current version of the tool.

Notes:

• "Additional information": opens in a separate window, when clicked.
• "More info": provides details in a box on the same page, when clicked.
• Underlined dotted words: provide details in a pop-up, when hovering over it.

Learn more

If you want to know more about this tool, please refer to our preprint.

We are constantly working to improve the tool. If you have any feedback, suggestions, or technical issues, please contact us via titan@clinicalepidemio.fr or our contact form.