Title : Suggestions for potential updates of the three domains of evidence-based medicine: Critical appraisal, systematic reviews, and clinical guidelines

Suggestions for potential updates of the three domains of Evidence-Based Medicine: Critical Appraisal, Systematic Reviews, and Clinical Guidelines.

Background/Aim: Randomized controlled trials (RCTs) are foundational in evidence-based medicine but are often limited by their reliance on controlled conditions and highly selective patient populations, which may not reflect real-world healthcare outcomes. This commentary summarizes the evidence supporting these assumptions and highlights the value of pragmatic controlled trials (PCTs) as a complementary method for evaluating real-world effectiveness (RWE). Methods/Design. We take different approaches to test the limited trust in RCTs. According to Sir A. Cochrane and Sir A. Bredford-Hill three questions need to be answered before implementing an innovation in healthcare “Can it work? Does it Work? Is it worth it?”. Simultaneously the recommendation of the American architects and designers "Form Follows Function (FFF)" is considered when analyzing the congruence of formal and functional criteria of epidemiological tools. The validity of "evidence-based" statements (e.g. the hierarchy of the different levels of evidence) is supported by naming concrete methods (e.g. RCT or PCT and the consideration of thresholds in PCTs but not RCTs) rather than the levels of evidence awarded. With the description of the methods used it turns out to be possible to check the correspondence of form and function. The FFF rule cannot be applied to levels of evidence. Results. The answers to the three Cochrane-Hill questions led to a three-dimensional evaluation strategy for health services. It includes the Proof of Principle (PoP) using RCTs, the description of Real-World Effectiveness (RWE) using Pragmatic Controlled Trials (PCTs), and of the Value (VAL) using Complete Economic Analyses (CEAs). The PCT is based on the description of endpoint-specific risk profiles (ESRPs), which are analyzed using Bayesian statistics. This method is suitable for the undistorted analysis of results generated under everyday conditions (Care as Usual, CAU). PCTs enable comprehensive assessment of healthcare interventions under everyday conditions, bridging the gap between experimental efficacy and practical applicability. In addition, PCT is supplemented by various other methods (e.g. the role of "perceived safety" and the application of thresholds). Discussion /Conclusions. The detection of RWE describes results that are observed under everyday conditions and are therefore clinically important. This epidemiological data lays the foundation for new ethical justifications and new medical, economic, legal and political decisions. Health care can be controlled according to new aspects and thus more efficiently than before.

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