Progress of therapy in acute leukemia 1948-1981: randomized versus nonrandomized clinical trials

This paper gives a review of selected clinical studies in acute leukemia over the last 33 years and addresses two questions: What advances in the practice of medicine have resulted from clinical trials, both randomized and nonrandomized? What generalizations can be made about clinical trials which have led to advances in treatment? The review demonstrates that nonrandomized studies have been the primary mechanism for establishing the efficacy of new therapies. Such studies have also been utilized to determine patient characteristics related to prognosis and some important concepts of treatment (e.g., independent action of some drugs). Randomized studies have tended to yield positive results concerning treatment differences when there were prior suggestions of activity from nonrandomized studies. Analyses of randomized studies have been made to determine patient features related to prognosis and concepts for the treatment of patients (e.g., independent action of some drugs and the importance of treating patients in a disease-free state).