Reconciling the results of randomized clinical trials (RCTs) and observational studies remains a substantial challenge for clinical medicine. There are numerous examples of studies showing that therapies seemed effective, or perhaps conferred risk, when investigated by observational methods that were later contradicted by evidence from RCTs, and vice versa. A number of reasons may account for why these 2 types of research studies may arrive at dissimilar findings. These include selection bias, confounding, statistical power, and differential adherence and follow-up. Another critical difference is generalizability. Randomized clinical trials tend to evaluate interventions under ideal conditions among highly selected populations, whereas observational studies examine effects in “real world” settings.
Ross JS. Randomized Clinical Trials and Observational Studies Are More Often Alike Than Unlike. JAMA Intern Med. 2014;174(10):1557. doi:10.1001/jamainternmed.2014.3366