Enrollment in randomized trial does not change clinical outcomes for preemies

NEW YORK (Reuters Health) - In-hospital outcomes of extremely preterm infants do not differ according to whether they enroll in a randomized controlled trial (RCT), according to a retrospective analysis.

"Our results were very similar to results of similar studies performed in adults and older children," Dr. Elizabeth E. Foglia from University of Pennsylvania, Philadelphia, told Reuters Health by email. "However, it was important to perform this study specifically in preterm infants, who represent a unique and vulnerable patient population."

Dr. Foglia and colleagues compared in-hospital outcomes between 3795 extremely premature infants enrolled in RCTs and 1594 extremely premature infants who were eligible but not enrolled in RCTs conducted by the National Institute of Child Health and Human Development Neonatal Research Network (NRN).

The primary outcome was a composite of death, bronchopulmonary dysplasia, severe brain injury, or severe retinopathy of prematurity. Secondary outcomes included culture-proven late-onset sepsis, necrotizing enterocolitis, and the individual components of the primary outcome.

The primary outcome occurred in 68% of the enrolled group versus 69% of the eligible but not enrolled group, according to the June 16 JAMA report.

The two groups did not differ in any of the secondary outcomes, and the primary outcome did not differ between groups when analyzed by individual trial.

"Consenting to enroll an infant in a RCT is a very personal decision for families," Dr. Foglia said. "Parents who consider enrolling their infant in a trial should take many factors into consideration, most particularly the potential risks and benefits associated with that specific trial."

"I do not believe that we should uniformly reference findings from this study during trial enrollment discussions with parents or in informed consent documents," she said. "However, if parents are concerned that trial participation in and of itself is dangerous for preterm babies, these findings may provide reassurance."

"Neonatology is a relatively young field, and many therapies that are commonly used in preterm and sick infants have never been tested," Dr. Foglia added. "The only way we can know with confidence that a given therapy works in our patients is by performing well-designed and appropriately regulated RCTs. These findings demonstrate that the practice of performing RCTs in extremely preterm infants is not detrimental to trial participants' outcomes."

Dr. Dominic Wilkinson, neonatologist at John Radcliffe Hospital, Oxford, UK, told Reuters Health by email, "This study is really helpful. Many parents of sick children and babies are asked whether they would be happy for their child to be in a research study. Often parents would like to help, but they are worried about the risks involved. But it is now very clear that taking part in trials does not put patients at risk."

Dr. John D. Lantos, from Children's Mercy Hospital, Kansas City, Missouri, offered Reuters Health three comments by email: "1) These findings apply to clinical studies that have been well-designed, have been reviewed by IRBs (institutional review boards) and/or scientific committees to ensure that the studies are rigorous, and that have appropriate measures in place to monitor safety and efficacy. 2) It would be unethical not to give this information to patients (or parents) who are trying to decide whether or not to enroll. 3) Current federal regulations do not require that patients be given this information. They should."

Dr. Neena Modi, professor of neonatal medicine at Imperial College London, UK, told Reuters Health by email, "A major weakness of this analysis is that only babies that had outcomes recorded in the Neonatal Research Network Low Birth Weight registry were included; a robust test of inclusion benefit would be to compare outcomes of enrolled versus all nonenrolled but eligible infants in the relevant geographically defined population."

"I am also saddened that in the 14-year period covered they identified only six RCTs for inclusion," Dr. Modi said. "Babies require evidence-based health care, and it is truly shocking that given the myriad uncertainties that clinicians have to contend with every day such a small number of RCTs have been conducted."

SOURCE: http://bit.ly/1ff60Rn

JAMA 2015.

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