BMC Med. 2026 Apr 24. doi: 10.1186/s12916-026-04831-x. Online ahead of print.
ABSTRACT
BACKGROUND: Transparency in randomized controlled trials (RCTs) has substantially improved in recent years, notably through trial registration and public availability of protocols and statistical analysis plans (SAPs). However, the reporting of protocol and SAPs modifications remains insufficiently standardized. As a result, even when these documents are publicly available, it is often challenging and time-consuming to identify what changes were made, why they were implemented, and whether they may affect the trustworthiness of the trial results.
ARGUMENTS: In this paper, we advocate for the development of a consensus-based framework for protocol modifications in RCTs. This need arises from the inherent tension between the necessity and the risks of protocol modifications. On the one hand, such modifications are often essential to address unforeseen operational, scientific, or ethical challenges. On the other hand, they may introduce bias and undermine confidence in trial findings, particularly when changes are data-driven or insufficiently justified. Although major transparency initiatives have strengthened trial reporting, important gaps persist. We review empirical evidence demonstrating the prevalence and nature of such modifications and discuss their potential implications for the validity, interpretation, and credibility of trial findings. Furthermore, readers, reviewers, and decision-makers face substantial challenges in identifying, understanding, and evaluating the potential impact of protocol changes. In the absence of standardized reporting, key information remains dispersed across multiple documents, placing an unreasonable burden on stakeholders to identify, interpret, and assess protocol modifications and their implications for the credibility of trial results.
CONCLUSIONS: Standardized and transparent reporting of protocol modifications is essential to ensure that their nature, timing, and rationale can be clearly understood and critically evaluated. We therefore advocate for the development of a consensus-based reporting framework, informed by a Delphi process, to improve transparency, facilitate critical appraisal, and strengthen confidence in RCT findings.
PMID:42032663 | DOI:10.1186/s12916-026-04831-x
