Bridging the Gap Between Observational Studies and Randomized Clinical Trials

Abstract

In his landmark 1985 article in The New England Journal of Medicine, “Statistical concepts fundamental to investigations” ( 1 Moses L.E. Statistical concepts fundamental to investigations. N Engl J Med. 1985; 312: 890-897 Crossref PubMed Scopus (44) Google Scholar ), Lincoln Moses, the founder of the Division of Biostatistics at Stanford University, compares randomized controlled trials and observational studies in their ability to influence health policy. To illustrate, he discusses 2 groups of experiments: the polio vaccine randomized clinical trial (RCT) and a series of 7 large-scale observational studies exploring the association between smoking and lung cancer, all published in 1954. He notes that in the Surgeon General’s 1964 report Smoking and Health, a consensus was finally reached that smoking elevated the risk of lung cancer by 10-fold. He explains that it took 10 years to reach this conclusion because “For each study indicating an adverse effect of smoking it was possible to suggest some possible biases that were not controlled, thus casting doubt on the indicated effect.” By contrast, the randomized, double-blind, placebo-controlled polio vaccine trial definitively demonstrated a 2.5-fold risk reduction, much smaller than the increased risk associated with smoking and lung cancer. Nevertheless, the results of the polio vaccine trial were accepted and put into practice within a year whereas it took at least a decade for a consensus to be reached regarding smoking and lung cancer. SEE CORRESPONDING ARTICLE ON PAGE 1127 SEE CORRESPONDING ARTICLE ON PAGE 1127 Emulating a Target Trial of Dynamic Treatment Strategies for Major Depressive Disorder Using Data From the STAR∗D Randomized TrialBiological PsychiatryVol. 93Issue 12PreviewClinical guidelines recommend adding a second drug for patients with major depressive disorder who have a partial response and switching antidepressants for those who show no response or intolerance. This guidelines-based strategy was compared with other strategies for the management of unresponsive depression. Full-Text PDF