Unplanned, uncontrolled, and unblinded experiments pose tremendous analytical challenges when treated as retrospective studies,1,2 but on those occasions when biases are successfully controlled,3,4 results can be informative and thought provoking. In this issue of JAMA, Castellani et al5 present their analysis of one such natural experiment, comparing the incidence of cystic fibrosis (CF) from adjacent regions in northern Italy that used different approaches to carrier detection. Screening of newborns for CF was performed throughout the entire region during the study period (1993-2007).6 In the western region near Verona, Alto-Adige, selective testing for CF carrier status was the practice, with detection efforts concentrating on relatives of patients confirmed to have CF and couples planning in vitro fertilization procedures. In contrast, in the eastern region near the University of Padua, Veneto, a more general program of screening for CF carrier status was offered.
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