Randomized clinical trials are the gold standard for evaluating the efficacy of therapies or comparing one therapy with another.1 When applied in adequately powered trials, randomization eliminates selection and other forms of bias, generates groups under study that are alike in all important aspects (except for the intervention received), and avoids confounding by measured and unmeasured confounding variables. By design, randomized clinical trials have high internal validity, with the ability to determine cause-effect relationships. Randomized controlled clinical trials are considered the highest level of evidence for guideline generation and the fundamental basis of most regulatory agency approvals for drug therapies.1 However, by virtue of their inclusion and exclusion criteria and participation by volunteers providing informed consent, randomized clinical trials generally include patients who are adherent to therapy, monitoring, and follow-up and may not be entirely representative of the general patient population.2,3 It is also well recognized that higher-risk patients, older patients, women, and patients in racial/ethnic minority groups are underrepresented in randomized clinical trials.2,3 These differences may influence whether the efficacy and safety demonstrated in randomized clinical trials will completely translate into clinical effectiveness and safety when the same therapy is applied in clinical practice (generalizablility and external validity).1-3
Fonarow GC. Randomization—There Is No Substitute. JAMA Cardiol. 2016;1(6):633–635. doi:10.1001/jamacardio.2016.1792
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