The use of historical controls in breast cancer. An assessment in three consecutive trials

To evaluate the effectiveness of a new therapy some authors suggest the use of a retrospective control group, especially in cancer trials. In this article, by means of data collected in three consecutive randomized clinical trials on breast cancer performed at the Istituto Nazionale Tumori of Milan, the risks of a practice involving use of data from one trial as "historical controls" for the next one were investigated. The comparability between the baseline characteristics of different groups has been examined by resorting to univariate as well as multivariate statistical methods. The results of the final evaluation of the relative effectiveness of the treatments under study have also been investigated, using both randomized concurrent and historical controls. Although the eligibility criteria did not change, some differences between groups of consecutive trials were observed. The results attained by using historical control data, after adjusting for the differential composition in the baseline characteristics, made evident a biased conclusion in favor of the new treatment tested, which, in a historically controlled study, is always the last one. These results appear to be in agreement with those published by Sacks, Chalmers, and Smith (Am J Med 72:233-240, 1982).