Study factors associated with the incompletion of clinical trials that include pediatric patients: a retrospective analysis of the European Clinical Trials Database and a lesson from the European region

Abstract

Background Incomplete clinical trials for pediatric drug development result in a lack of adequate scientific evidence for providing appropriate medication to pediatric populations; this is especially true for Japan. Thus, using the European Clinical Trials Database (EudraCT), this study aimed to identify the factors related to the study design and administration that lead to incompletion of clinical trials that included pediatric patients. Methods We focused on clinical trials that included patients under the age of 18 registered in the database, named as the European Clinical Trials Database between January 1, 2014, and December 31, 2018. Two groups of trials were identified: “all cases completed” and “not all cases completed,” reflecting whether they were completed in all participating countries/regions or not. To identify the factors of the occurrence of “not all cases completed,” a logistic regression analysis was performed to calculate the odds ratios and 95% confidence intervals. In total, 142 clinical trials (95 “all cases completed” and 47 “not all cases completed”) were analyzed. Results The logistic regression analysis showed the number of countries in which a clinical trial was conducted to be the only significant factor (odds ratio: 1.3; 95% confidence interval: 1.1-1.5); this was identified as the primary factor for the occurrence of “not all cases completed” in the clinical trials that included pediatric patients. Conclusion Our findings suggest that the feasibility of clinical trials that include pediatric patients, such as whether the countries in which the trial is to be conducted are suitable, must be considered prior to the trial.

Development and performance of the c4c national clinical trial networks for optimizing pediatric trial facilitation

“…In 2021, an analysis by Tanemura et al from the European Clinical Trials Database (EudraCT) suggested that incomplete pediatric trials are primarily associated with the phase of trial design, feasibility, and country eligibility. Low recruitment rate was related to the selection of sites and/or countries with lack of infrastructure and difficult communication (5). These factors led to insufficient scientific evidence for labeling and/or adjusting clinical use of drugs, resulting in a persistently high off-label drug use in children (6,7).…”

“…Furthermore, the utility of site identification summaries, a strategy set up by the BPCRN and piloted by BPCRN and Pedmed-NL, was found to be beneficial for sponsors through direct communication and coherence with potential site selection. Conducting high-quality clinical trial feasibilities and setting expectations, especially in a pediatric setting, has been shown as a key investment to ensure successful trial execution (5,18,20). To date, there are no published or publically available metrics to compare a site identification process within a research network setting.…”

Analysis of research topics and trends in investigator-initiated research/trials (IIRs/IITs): A topic modeling study

“…IST primarily focuses on obtaining drug approval from regulatory authorities, whereas IIRs/IITs aim to explore scientific value and address specific clinical questions, [ 1 ] including rare diseases, comparative diagnostics or treatments, novel uses for approved drugs, new indications, or innovative administration methods. [ 2 , 3 ] Clinical studies can employ noninterventional (prospective or retrospective) or interventional research methods. One key advantage of IIRs/IITs is its origin from real clinical problems encountered in daily practice, allowing investigators to have greater autonomy and a closer connection to practical aspects of medicine.…”