Hidden Ethical Conflicts: The Need for Progress in Evidence-based Medicine - A Living Review

BACKGROUND AND INTRODUCTION. Randomized Controlled Trials (RCTs) are fundamental in Evidence-based Medicine. However, their importance is limited by the experimental design, patient selection, and the lack of real-world effectiveness. This commentary supports these statements and highlights the scientific and ethical contributions of Pragmatic Controlled Trials (PCTs) as a method of assessing Real-World Effectiveness (RWE). METHODS AND RESULTS. Four strategies were used to solve these tasks. We use the questions of Cochrane and Bredford-Hill "Can it work? Does it work? Is it worth it?" to design a three-dimensional strategy for the evaluation of health services. The "Form Follows Function (FFF)" rule supported both the definition of three care conditions (RCT, PCT, Care as usual, CAU) and four steps that support the construction of precise study questions. Fourth, specific objective criteria such as form, function, and thresholds were discussed to replace the assigned levels of scientific evidence.  The 3-dimensional strategy describes the proof of principle (RCTs), real-world effectiveness (PCTs) and subjective benefits by means of Complete Economic Analyses (CEAs). The FFF rule identifies scientific inconsistencies, e.g. the conflict between "efficacy" and "efficacy", the loss of information in the step-by-step development of scientific questions and replaces missing criteria to confirm the validity of the hierarchy of levels of evidence. CONCLUSIONS. Scientists need to uncover hidden forms of bias that cause avoidable societal burdens. The examples in this review include suggestions for possible corrections that provide a new ethical and moral basis for medical, economic, legal, and policy decisions. A "Living Review" can initiate the transformation of the healthcare system, increase its efficiency and develop new concepts for the necessary cooperation between the healthcare industry and health care.