The Necessity of Randomized Clinical Trials

Abstract

Aims: The hierarchy of evidence-based medicine determines the inferential powers of different clinical research designs. We want to address the difficult question if observational evidence under some circumstances can validate intervention effects. Methodology: Assessment of previous argumentation aiming at a clear conclusion for future decision-making. Results: We present five arguments demonstrating the fundamental need of randomized clinical trials to sufficiently validate intervention effects. Furthermore, we argue that hindrances to the conduct of randomized clinical trials can be lessened through education, collaboration, infrastructure, and other measures. Our arguments validate why the randomized clinical trial should and must be the study design evaluating interventions. By choosing the randomized clinical trial as the primary study design, effective preventive, prognostic, diagnostic, and therapeutic interventions will reach more patients earlier. Conclusion: Clinical experience or observational studies should never be used as the sole basis for assessment of intervention effects-randomized clinical trials are always needed. Therefore, always randomize the first patient as Thomas C Chalmers suggested in 1977. Observational studies should primarily be used for quality control after treatments are included in clinical practice.

Evidence-based clinical practice: Overview of threats to the validity of evidence and how to minimise them

“…Results of RCTs are generally of higher level compared to results of controlled cohort (non-randomised) studies 13,14,41 . Deeks and colleagues conducted simulations comparing results from RCTs to those of controlled cohort studies (Fig.…”

“…Systematic reviews are based upon peer-reviewed protocols and folSystematic reviews are based upon peer-reviewed protocols and follow standardised methodologies. Figure 1 The hierarchy of clinical evidence of random errors (misleading results due to 'play of chance') [11][12][13][14][15][16] . We suggest possible solutions to the threats including establishment of national or transnational research infrastructures like ECRIN to improve clinical research and hereby reduce research waste [17][18][19][20][21][22][23][24][25] .…”

“…Evidence from a well-conducted systematic review of several RCTs with low risk of bias therefore generally represents a higher level of evidence compared to the results from a single RCT [11][12][13][14]29,30 . It also appears intuitively evident that inclusion of all available data from all RCTs with low risks of bias ever conducted, should be treated as a higher level of evidence compared to the data from one single RCT 13,30 .…”

“…It also appears intuitively evident that inclusion of all available data from all RCTs with low risks of bias ever conducted, should be treated as a higher level of evidence compared to the data from one single RCT 13,30 . As a relatively new approach, network metaanalyses allow comparing interventions that have never been tested head to head in RCTs 36 .…”

“…Provided the methodological quality of your study is good, the higher your study is in the hierarchy, the more likely you observe something close to the 'truth'. With better inferential powers, the higher the likelihood for improving patient outcomes when one translates the research findings into clinical practice (TRIP) 13 . All levels of the hierarchy may be threatened by systematic errors; design errors; and random errors 11,13,26 .…”