The great tocolytic debate: Some pitfalls in the study of safety

The controversy surrounding the use of tocolytic agents has been raging for decades. Tocolytic drugs play a pivotal role in the prevention of preterm birth, which is the major cause of neonatal morbidity and mortality. Studie s on the efficacy and safety of these drugs are of the utmost importance to many disciplines within the medical community. Unfortunately many clinical decisions regarding tocolytic agents are based on incorrect information re sulting from flawed studies. In this article we discuss the major design fl aws common to many studies of tocolytic safety and in so doing explain some of the conflicting evidence regarding safety. Each of the two major types of study designs, preterm birth retrospective studies and prospective rando mized trials, is associated with a serious flaw. Retrospective preterm birt h studies give misleading and inconclusive results to the question of safet y because of the use of incomplete cohorts. The inadequately sized prospect ive studies in the current literature lack the power to detect important cl inical differences.