Beyond the Evidence: Why Do Clinical Guidelines and Recommendations Differ?

The development of clinical guidelines in health care has accelerated in the last decade. In medicine and dentistry, guidelines are increasingly used to standardise care, support clinical decision-making, promote evidence-based practice, and hopefully benefit our patients. However, clinical guidelines have limitations, such as generalisation to standard clinical scenarios that may not fully reflect clinical reality. We write this letter with great appreciation for the substantial effort required to develop high-quality clinical guidelines. The purpose of this letter is to point out how differences in methodological frameworks and transparency in guideline development can lead to divergent recommendations in daily practice and potential confusion among clinicians and policy makers, even when based on similar evidence. The S3-level Clinical Practice Guideline for the Treatment of Pulpal and Apical Diseases issued by the European Society of Endodontology (ESE) (Duncan et al. 2023) makes a major contribution to the field of endodontology. It combines a rigorous evaluation of the literature with practical and clinically orientated recommendations, and its impact on education and daily practice is substantial. The reflections on the processes underlying its recommendations are therefore highly relevant for both clinicians and guideline developers. When comparing international endodontic guidelines, such as those of the ESE, American Association of Endodontists (AAE) (n.d.), and national societies including the Nederlandse Vereniging voor Endodontologie (NVvE) (2025), it becomes clear that most recommendations are based on a similar underlying body of evidence. Differences arise in the way recommendations are framed, the strength with which they are expressed, and the way uncertainty is managed. The following example highlights differences in recommendations between clinical guidelines concerning the activation of irrigation solutions during root canal treatment. The ESE guideline names sodium hypochlorite as the irrigant of choice, a recommendation supported by expert consensus and stakeholder discussion, rather than by comparative evidence of high certainty. Furthermore, the S3 guideline recommends not using adjunct irrigation activation in addition to traditionally administered irrigants based on low-certainty evidence and the absence of sufficiently robust or clinically decisive effects. In the Dutch guideline, the recommendation is to consider the use of ultrasonic activation, and not to use additional laser techniques. These divergent recommendations can be explained by the application of GRADE and Core GRADE (Meneses-Echavez et al. 2023; Moberg et al. 2018; Guyatt et al. 2025) that emphasise not only statistical significance, but also whether the effect is large, moderate, small, or trivial and whether it matters to patients. An effect that is not statistically significant may still be important if it is sufficiently large. According to GRADE and Core GRADE (Guyatt et al. 2025), the observed effect size (SMD −0.73) (Duncan et al. 2023) indicates a clinically important benefit, but imprecision and low evidence certainty limit confidence in its exact magnitude. The same evidence can be used in a different way using Core GRADE to make a deliberately cautious, explicitly conditional recommendation, reflecting this limited certainty and weighing the benefit against alternatives. Core GRADE focuses on the key judgements needed to synthesise comparative evidence and make recommendations for individual care (Meneses-Echavez et al. 2023), integrating effect estimates, benefits and harms, evidence quality and patients' values and preferences. Similar patterns of divergence can be seen in recommendations for the management of dental trauma. Variations in protocols, such as the use of intracanal medicaments after luxation injuries or splinting time, reflect the role of clinical judgement and professional norms in the absence of robust evidence. These differences emphasize that guideline development involves contextual and methodological choices beyond the underlying data. These reflections are presented in a spirit of constructive engagement and with full recognition of the substantial resources and expertise required to develop high-quality clinical guidelines. No framework is inherently superior, and all have flaws. We hope that explicitly acknowledging how methodological and contextual factors shape recommendations may support greater clarity, ease cross-national learning, and promote more effective implementation. The transparency of the processes by which evidence is translated into recommendations is at least as critical as the underlying evidence itself. Yours sincerely, Ellemieke S. Hin and Hagay Shemesh Planning, research and writing by both authors, Hin & Shemesh. Both authors are members of the guideline development group of the NVvE (Dutch Society for Endodontics). Prof.Dr. H. Shemesh also is a member of the S3 guideline development group of the ESE. The data that support the findings of this study are available from the corresponding author upon reasonable request.