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Randomized controlled trials in very preterm infants: does inclusion in the study result in any long-term benefit?
Christoph M Rüegger1, Andrea Kraus, Brigitte Koller
1Division of Neonatology, University Hospital Zurich, Zurich, Switzerland.
Insights
Very preterm infants in clinical trials had similar neurodevelopmental outcomes to eligible non-participants. This study compared randomized placebo infants to non-randomized infants, finding equivalent long-term results.
Area of Science:
- Neonatal Research
- Clinical Trial Methodology
- Developmental Pediatrics
Background:
- Debate exists on whether clinical trial participants have different outcomes than non-participants.
- Ensuring generalizability of randomized controlled trial (RCT) findings is crucial in clinical research.
Purpose of the Study:
- To compare neurodevelopmental outcomes of very preterm infants in a placebo group of an RCT with those of eligible infants who were not randomized (eligible NR).
- To assess the equivalence of neurodevelopmental outcomes between randomized and non-randomized very preterm infants.
Main Methods:
- Retrospective comparison of 72 infants randomized to placebo versus 108 eligible NR infants in an erythropoietin RCT.
- Primary outcomes: Mental (MDI) and Psychomotor (PDI) Developmental Indices using Bayley Scales II at 24 months corrected age.
- Equivalence defined as mean difference confidence intervals within a ±5-point margin.
Main Results:
- Groups were balanced on perinatal variables, though trial participants had higher socioeconomic status.
- Mean MDI difference (eligible NR vs. placebo) was -2.1 points; PDI difference was -0.8 points.
- Adjusted MDI difference was -0.5 points, indicating equivalence.
Conclusions:
- Participation in this RCT was associated with equivalent long-term neurodevelopmental outcomes for very preterm infants compared to non-participants.
- Findings support the generalizability of RCT results in very preterm infant populations.
Background:
Since the introduction of randomized controlled trials (RCT) in clinical research, there has been discussion of whether enrolled patients have worse or better outcomes than comparable non-participants.
Objective:
To investigate whether very preterm infants randomized to a placebo group in an RCT have equivalent neurodevelopmental outcomes to infants who were eligible but not randomized (eligible NR).
Methods:
In the course of an RCT investigating the neuroprotective effect of early high-dose erythropoietin on the neurodevelopment of very preterm infants, the outcome data of 72 infants randomized to placebo were retrospectively compared with those of 108 eligible NR infants. Our primary outcome measures were the mental (MDI) and psychomotor (PDI) developmental indices of the Bayley Scales of Infant Development II at 24 months of corrected age. The outcomes of the two groups were considered equivalent if the confidence intervals (CIs) of their mean differences fitted within our ±5-point margin of equivalence.
Results:
Except for a higher socioeconomic status of the trial participants, both groups were balanced for most perinatal variables. The mean difference (90% CI) between the eligible NR and the placebo group was -2.1 (-6.1 and 1.9) points for the MDI and -0.8 (-4.2 and 2.5) points for the PDI. After adjusting for the socioeconomic status, maternal age and child age at follow-up, the mean difference for the MDI was -0.5 (-4.3 and 3.4) points.
Conclusions:
Our results indicate that the participation of very preterm infants in an RCT is associated with equivalent long-term outcomes compared to non-participating infants.
