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. Studies 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 resulting from flawed studies. In this article we discuss the major design flaws 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 randomized trials, is associated with a serious flaw. Retrospective preterm birth studies give misleading and inconclusive results to the question of safety because of the use of incomplete cohorts. The inadequately sized prospective studies in the current literature lack the power to detect important clinical differences.
Rosen
L J
LJ
School of Public Health, Ein Karem Campus, and the Department of Statistics, Hebrew University, Jerusalem, Israel. lrosen@vms.huji.ac.il
Zucker
D
D
Oppenheimer-Gazit
V
V
Yagel
S
S
D002543:Cerebral Hemorrhage / Q000139:chemically induced; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects / Q000627:therapeutic use; D016239:MEDLINE; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy; D012189:Retrospective Studies; D012312:Ritodrine / Q000009:adverse effects / Q000627:therapeutic use; D015149:Tocolytic Agents / Q000009:adverse effects* / Q000627:therapeutic use*
D015149:Tocolytic Agents; D012312:Ritodrine; D007213:Indomethacin