A systematic review of 120 studies focusing on neonatal clinical trials within U.S. neonatal intensive care units (NICUs) reveals that a significant proportion of eligible infants are not included in trial results, raising concerns about the representativeness and generalizability of findings. The study, published in JAMA Network Open, highlights that only 44.4% of eligible infants were included in reported trial results.
The analysis of these trials, conducted between 2017 and 2022, showed that out of 26,854 eligible infants, only 11,924 were represented in the reported outcomes. The reasons for non-inclusion were categorized as modifiable, potentially modifiable, or non-modifiable. Parents declining to participate (29.8%) and parents never being approached (9.3%) were the predominant reasons for non-inclusion.
Key Reasons for Non-Inclusion
The study identified several key reasons for the non-inclusion of eligible infants:
- Parental Declination: Approximately 29.8% of eligible infants were not included because parents declined to participate.
- Lack of Approach: 9.3% of eligible infants were not included because their parents were never approached about the trial.
- Study Logistics: Modifiable factors related to study logistics, such as failure to collect data on enrolled infants, accounted for 3.2% of non-inclusions.
- Other Reasons: Other modifiable reasons, including loss to follow-up or unaccounted eligible participants, accounted for 7.1%.
- Non-Modifiable Reasons: Clinical changes or death accounted for only 3.2% of non-inclusions.
Adherence to CONSORT Guidelines
The researchers assessed adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines, which aim to improve the quality of reporting on clinical trials. The review found that only 55.0% of the included articles provided complete reporting on the numbers of infants screened, eligible, allocated to an intervention, and included in the analysis, along with reasons for non-inclusion of all eligible infants.
Implications for Future Trials
The study emphasizes the need for improved documentation on the flow of eligible infants through neonatal clinical trials. According to the researchers, improved adherence to standardized reporting may clarify which potential participants are being missed, improving understanding of the generalizability of research findings. Furthermore, understanding why parents decline to participate in neonatal research trials and why some are never approached about research may help increase overall participation.
Elliott M. Weiss, MD, MSME, Treuman Katz Center for Pediatric Bioethics and Palliative Care, Seattle Children’s Hospital & Research Institute, corresponding author of the study, stated that, "Clear, transparent, and complete reporting of which patients are and are not included in trial results is essential for assessing the validity and generalizability of findings and for promoting health equity."
The study also found that trials of surgical interventions, those without dedicated funding, those that took place at 5 or fewer sites, or those that enrolled for more than 28 months had higher proportions of eligible infants included in reported results.
Recommendations
The authors recommend that future iterations of CONSORT guidelines offer standard categories for reporting reasons for non-inclusion. They also suggest that future work aimed at increasing trial participation should focus on understanding why parents decline or are not approached for consent. Finally, the findings illustrate that participant accrual in neonatal trials is a slow process, which trialists should account for as they design future studies.
