March 2000

Do Sick Newborn Infants Benefit From Participation in Randomized Clinical Trials?

Schmidt B; Gillie P; Caco C; Roberts J; Roberts R.
J Pediatr   1999 Feb;134(2):151-5,

Commentary by Charles Coté, M.D.

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[ see abstract below ]

Schmidt et al examined the outcomes of sick newborn infants who participated in controlled clinical trials. I have long been an advocate of giving children the same benefits of drug development as adults and several previous commentaries have addressed this topic (cc-99feb-seri.shtml, cc-98may-ivani.shtml, cc-97jul-davis.shtml, in the AnesthesiaWeb Archives). What is unique about the Schmidt study is that it found that outcomes for neonates was better even for the placebo control group! This improved outcome may reflect the greater attention to detail that is required by any clinical trial, as well as other factors. The bottom line is that at least this is the beginning of developing a data base to demonstrate that clinical trials can be conducted safely and without harm even in premature infants. It would be wonderful if we could convince pharmaceutical manufacturers that proper studies of all new drugs should include trials in premature infants, if there will ever be a need to use the drug in that age group. This paper leads to two others that examined the use of opioids in the neonatal intensive care unit:

ABSTRACT Do sick newborn infants benefit from participation in a randomized clinical trial? Schmidt B; Gillie P; Caco C; Roberts J; Roberts R SOURCE: J Pediatr 1999 Feb;134(2):151-5 ABSTRACT: BACKGROUND: Adult participants in randomized controlled trials often have better outcomes than patients who are eligible but not enrolled. OBJECTIVE: To examine whether newborn infants who were allocated to placebo in an investigational drug trial had better outcomes than infants who were eligible but not randomized (eligible NR). STUDY DESIGN: During a randomized controlled trial of antithrombin therapy in premature infants with respiratory distress syndrome, data were collected prospectively on all 76 infants in the eligible NR group. Study outcomes were compared with those of all 61 infants who were randomized to placebo. The same exogenous surfactant was used in all patients. RESULTS: : In the placebo group the mean (SD) birth weight was 1201 (314) g, mean (SD) gestational age was 28.8 (2.3) weeks, and 51% were male. In infants in the eligible NR group, mean (SD) birth weight was 1141 (262) g, mean (SD) gestational age was 28.3 (2. 3) weeks, and 58% were male; 57% of infants in both groups had been exposed to steroids before birth. The median duration of mechanical ventilation was reduced from 6.2 days in the eligible NR group to 4. 8 days in the placebo group (P =.008). There was also a trend toward less frequent and less severe intraventricular hemorrhage in trial participants. CONCLUSIONS: These data are consistent with the hypothesis that sick newborn infants may benefit from participation in a randomized controlled trial.