Accepted for/Published in: JMIR Research Protocols
Date Submitted: Jul 21, 2026
Date Accepted: Sep 30, 2026
Risk of Bias Assessment of Target Trial Emulation (TTE) studies at Regulatory and Policy Decision Points along the Medical Product Lifecycle: Protocol for a Scoping Review and Stakeholder Survey
ABSTRACT
Background:
Target trial emulation (TTE) studies are increasingly important for regulatory decision‑making and health technology assessments (HTAs) but current risk of bias (RoB) tools are not specifically tailored to assess biases central to TTEs—such as immortal time bias, misaligned eligibility criteria, and prevalent user bias. RoB assessment for TTEs remains thus difficult, and it is unclear which tools and adaptations researchers currently use or how well they work.
Objective:
To provide a systematic overview of the RoB tools specifically developed, used, adapted or evaluated for TTE studies and to assess the perceived importance and feasibility of assessing the RoB in TTE studies by HTA assessors, regulators, systematic reviewers and methods experts.
Methods:
This is a protocol for a scoping review and online survey among systematic reviewers, methods experts, European HTA organisations, and regulators. A systematic literature search for published and grey literature was conducted in five electronic databases (including PubMed, Scopus, and Web of Science), by reference list checking, and on relevant websites (e.g. Cochrane, HTA and regulatory agencies). Throughout the study screening for eligibility, data extraction, and data analysis using qualitative content analysis will be done in duplicate. We will collect data on the name, description, and feasibility of RoB tools used, adapted and developed for TTE studies as well as the RoB assessment results and the RoB sources relevant for TTE studies.
Results:
The systematic literature search was conducted in May and June 2026. As of June 30th 2026 seventy-eight articles are included for data extraction. The survey will be conducted in August 2026.
Conclusions:
We will provide an overview of the type, feasibility and assessment results of RoB tools currently used, adapted or developed for TTE studies as well as the RoB sources considered relevant for TTE studies by HTA assessors, regulators, systematic reviewers and methods experts.
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