Related Experiment Video
Updated: Jun 9, 2025
A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition
Published on: September 20, 2019
Eligible Infants Included in Neonatal Clinical Trials and Reasons for Noninclusion: A Systematic Review
Henna Shaikh1, Allison N J Lyle2, Ellie Oslin1,2
1Department of Pediatrics, University of Washington School of Medicine, Seattle.
Insights
Many eligible infants are not included in neonatal clinical trials, limiting research generalizability. Modifiable factors like parental consent and recruitment issues are key reasons for noninclusion, suggesting areas for improvement.
Area of Science:
- Neonatal research
- Clinical trial methodology
- Pediatric health outcomes
Background:
- Clinical trial results are limited to included participants, potentially biasing findings.
- Insufficient participation in neonatal trials can lead to trial failure and limit generalizability.
- Infants excluded from research may differ significantly from those included.
Purpose of the Study:
- To determine the proportion of eligible infants enrolled in neonatal clinical trials.
- To identify and categorize reasons for infant noninclusion in clinical trial results.
- To inform strategies for improving participation and generalizability in neonatal research.
Main Methods:
- Systematic search of Cochrane CENTRAL for full-length, peer-reviewed articles published between 2017-2022.
- Inclusion criteria: trials in US neonatal intensive care units, at least 20 human infants, English language.
- Screening by two independent researchers; data extraction on eligible vs. included infants and reasons for noninclusion.
Main Results:
- 120 articles met criteria; 91 reported on 26,854 eligible infants.
- Only 44.4% (11,924 infants) were included in reported results.
- Predominant reasons for noninclusion were parental refusal (29.8%) and not being approached (9.3%), both modifiable.
Conclusions:
- Significant proportion of eligible infants are excluded from neonatal trial results, impacting generalizability.
- Most noninclusion reasons are modifiable, highlighting the need for improved trial protocols and recruitment strategies.
- Enhanced documentation of infant flow and understanding parental decision-making are crucial for future neonatal research.
Importance:
Results of clinical trials can only represent included participants, and many neonatal trials fail due to insufficient participation. Infants not included in research may differ from those included in meaningful ways, biasing the sample and limiting the generalizability of findings.
Objective:
To describe the proportion of eligible infants included in neonatal clinical trials and the reasons for noninclusion.
Evidence Review:
A systematic search of Cochrane CENTRAL was performed by retrieving articles meeting the following inclusion criteria: full-length, peer-reviewed articles describing clinical trial results in at least 20 human infants from US neonatal intensive care units, published in English, and added to Cochrane CENTRAL between 2017 and 2022. Retrieved articles were screened for inclusion by 2 independent researchers.
Findings:
In total 120 articles met inclusion criteria and 91 of these (75.8%) reported the number of infants eligible for participation, which totaled 26 854 in aggregate. Drawing from these, an aggregate of 11 924 eligible infants (44.4%) were included in reported results. Among all eligible infants, most reasons for noninclusion in results were classified as modifiable or potentially modifiable by the research team. Parents declining to participate (8004 infants [29.8%]) or never being approached (2507 infants [9.3%]) were the 2 predominant reasons for noninclusion. Other modifiable reasons included factors related to study logistics, such as failure to appropriately collect data on enrolled infants (859 of 26 854 infants [3.2%]) and other reasons (1907 of 26 854 infants [7.1%]), such as loss to follow-up or eligible participants that were unaccounted for. Nonmodifiable reasons, including clinical change or death, accounted for a small proportion of eligible infants who were not included (858 of 26 854 infants [3.2%]).
Conclusions And Relevance:
This systematic review of reporting on eligible infants included and not included in neonatal clinical trials highlights the need for improved documentation on the flow of eligible infants through neonatal clinical trials and may also inform recruitment expectations for trialists designing future protocols. Improved adherence to standardized reporting may clarify which potential participants are being missed, improving understanding of the generalizability of research findings. Furthermore, these findings suggest that future work to understand why parents decline to participate in neonatal research trials and why some are never approached about research may help increase overall participation.
More Related Videos
Related Concept Videos
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
01:29Nursing Interventions II: Selecting and Classifying the Nursing Interventions