In the current study, 23.6% of the examined JCOG trials were completed within the planned accrual period. Shorter planned accrual periods and the stratification of the trial design by phase and randomization were significant risk factors for trial extensions, whereas considering the accrual pace of past trials when calculating the required accrual period was a significant factor in ensuring the trial was completed in a timely manner.

A previous study of adult phase III clinical trials conducted by the NCI-sponsored Clinical Trials Cooperative Group found that 27–31% of trials were terminated early because of poor accrual [2, 13]. Among trials supported by NCI-CTEP (n = 764), 81.5% (n = 623) failed to complete their target accrual within the planned period [14]. In the current study, 76.4% (152/199) of all included trials and 82.3% (121/147) of phase III trials did not complete accrual in a timely manner, and these findings are consistent with the trends reported by NCI-CTEP. Furthermore, 81.4% of JCOG trials were completed within twice the planned accrual period, consistent with the findings of Bennette et al. [4], where 81.6% of trials were not classified as poor accrual trials (defined as an accrual pace < 50% of the planned pace).

Approximately 5% of JCOG trials were terminated early because of poor accrual, which is a lower proportion than that reported by the NCI-sponsored Clinical Trials Cooperative Group (27–31%) [2, 13]. This may be attributed to the fact that the Data and Safety Monitoring Committee proposed a countermeasure for poor accrual and did not mandate termination because of poor accrual until recently. However, an early trial termination rule for trials with poor accrual was enforced by the JCOG in 2019 (Table 5). Additionally, over 20% of JCOG trials conducted between 2000 and 2018 would be subject to the termination rule.

The risk factor analysis showed that stratified trial designs (i.e., by randomization and phase) were a risk factor for poor accrual, and this finding was consistent with that reported by previous studies [4]. A phase-by-phase analysis showed that randomized phase III trials had a significantly higher risk of poor accrual than nonrandomized phase II trials. A key disadvantage of randomized trials compared with nonrandomized trials was that the former did not allow patients to choose their treatment, making obtaining consent difficult [15]. In the current study, nonrandomized phase III trials also showed a tendency toward poor accrual compared with nonrandomized phase II trials. As for the reason, in our study, a nonrandomized phase III trial design was often to be adopted in studies examining rare cancers, thereby making patient accrual challenging.

A shorter planned accrual period was another significant risk factor for trial extension, with underestimation of the planned accrual period being considered a possible cause. Extending the planned accrual period increases the chances of trial completion within the planned period. However, overestimating the planned accrual period may delay the publication of trial findings, potentially reducing its value, while underestimating it may make maintaining the necessary accrual pace challenging, thereby leading to trial extensions and an increase in associated costs. Therefore, exploring methods for accurately estimating the accrual pace is essential.

Planned accrual period estimation should be determined based on the study sample size, feasibility of the clinical trial group, and participating institutions. The current study findings suggest that the actual accrual pace of past trials conducted by the same group should also be considered when calculating the required accrual period. Discrepancies between the planned and actual accrual periods may result in increased associated costs and potential delays in treatment development, emphasizing the importance of minimizing this discrepancy. In the current study, this discrepancy was only 0.6 and 2.1 years in trials that considered and did not consider the accrual pace of past trials, respectively, and this trend was particularly noticeable in phase III trials. Therefore, this method may be considered useful as it minimizes the discrepancies between the planned and actual accrual periods.

In contrast, considering survey evaluations of the accrual pace at participating institutions did not improve the accuracy of estimating planned accrual periods. Furthermore, discrepancies between planned and actual accrual periods were observed regardless of whether survey evaluation of the accrual pace of participating institutions was considered or not. This could include the possibility that the survey was not clearly conducted, such as not indicating the eligibility criteria using those trials, borderline patients who would not be enrolled in the actual study may have been counted, and the differences in the quality of each answer of institutions.

The results of this study could be applied to future clinical trials as follows. First, proactive interventions may be necessary for monitoring enrollment progress, especially in randomized phase III trials. Specifically, this involves investigating reasons for poor accrual, monitoring enrollment progress at participant institutions, and conducting meetings with researchers and research groups. Additionally, employing electronic methods and offering incentives may boost patient accrual.

Second, it is recommended the method of consideration of the accrual pace of past trials. However, if similar trials have not been conducted within the community, it may be beneficial to use accrual pace data of clinical trials from clinical trial registration systems, conduct surveys with rigorous and detailed methods, or refer to registration records from trials in other communities. Further research is needed to assess whether these methods can be effective for patient accrual and to better understand the factors contributing to accrual rate overestimation.

The current study has several limitations. First, it was conducted in a single clinical trial group, which prevents generalization of the findings to wider groups. Second, the methods used for determining the planned accrual period could not be examined for trials that did not report this information in the study protocols, monitoring reports, or clinical study reports. Factors that were difficult to quantify in JCOG trials, as mentioned in the methods, were excluded. Third, this study did not examine the specific interventions being implemented. Finally, poor accrual can be partially addressed by modifying the eligibility criteria, but this study did not consider that approach.