Analysis of Rates of Completion, Delays, and Participant Recruitment in Randomized Clinical Trials in Surgery

Abstract

ImportanceDiscontinuation and nonpublication are established sources of avoidable waste among surgical trials, but rates of delayed completion and recruiting shortfalls remain unclear.ObjectivesTo examine the rate of delayed completion, incomplete enrollment, and discontinuation among randomized clinical trials in surgical populations and the duration of delays and extent of recruiting shortfalls among these trials.Design, Setting, and ParticipantsThis cross-sectional study examined randomized clinical trials in surgical populations registered on ClinicalTrials.gov between January 1, 2010, and December 31, 2014. Analysis was conducted between October 27, 2021, and June 30, 2022.Main Outcomes and MeasuresThe main outcomes were the percentages of trials completed on time or with full enrollment. Delays and recruiting shortfalls were identified by comparing projected enrollment and study timeframes prespecified at the time of registration with the actual study duration and enrollment reported on completion or discontinuation. Absolute and relative differences between planned and actual trial conduct were presented for discontinued trials and those completed with delays or recruiting shortfalls.ResultsIn total, 2542 randomized clinical trials in surgical populations were included in the study sample, of which 370 (14.6%; 95% CI, 13.2%-15.9%) were completed both on time and with full enrollment. Approximately 1 in 5 trials (20.4%; 95% CI, 18.9%-22.0%) were completed within their planned timeframe, and 1166 trials (45.9%; 95% CI, 43.9%-47.8%) met their prespecified enrollment target. The median delay among completed trials was 12.2 months (IQR, 5.1-24.3 months) or 66.7% (IQR, 30.1%-135.8%) longer than planned. Among completed trials that did not meet their prespecified enrollment target, the median recruiting shortfall was equivalent to 31.0% (IQR, 12.7%-55.5%) of the planned study sample. A total of 546 trials (21.5%; 95% CI, 19.9%-23.1%) were discontinued. The median time to discontinuation was 26.4 months (IQR, 15.2-45.7 months), and the median recruiting shortfall among discontinued trials was equivalent to 92.7% (IQR, 65.0%-100.0%) of the trial’s prespecified enrollment target.Conclusions and RelevanceThis cross-sectional study found that delayed completion, recruiting shortfalls, and untimely discontinuation were common among surgical trials. These findings highlight the importance of ensuring that investigators and funders do not overestimate the feasibility of planned trials.

Randomized controlled trials in lung cancer surgery: How are we doing?

“… 10 , 19 , 20 Another study that grouped surgical RCTs as a whole found a completion rate of 78.5% of the 2542 included trials, which is a stark contrast to our finding and further highlights the scope of the problem. 9 A majority of the trials we examined were open-label and single-center, falling short of the true gold standard of a blinded multicenter RCT, further supporting the need to improve on current processes.…”

“…Within the group of “unknown” status studies, the median time from trial initiation to date of data extraction in April 2023 was 7.7 years, which suggests that these 17 studies have likely been abandoned or discontinued as a prior study using the ClinicalTrials.gov database demonstrated that the median time to study discontinuation is 2.2 years. 9 …”

“…In addition, the most common reason that RCTs were discontinued was secondary to accrual issues. A cross-sectional study by Shadbolt and colleagues 9 found that of 2542 surgical RCTs performed in 2010 to 2014, only 45.9% met their prespecified enrollment target, and those that did not met their target were shy by approximately 31% of the planned study sample. This is highly concerning because power analyses done during RCT design specify a minimum number of subjects to avoid a type II error, and approximately half of trials do not meet this benchmark.…”

Plastic Surgery Clinical Trials: A Systematic Review of Characteristics, Research Themes, and Predictors of Publication and Discontinuation

“…An estimated 47% of CTs are completed, 27% are in various recruitment stages, 11% have been discontinued, and 15% have unknown statuses. Given CT discontinuation rates of 8.5%-22.7% in medicine 24,25 and 21.5% in surgery, 26 the 11% rate in PRS CTs indicates a comparatively higher completion rate. Half (50.8%) of CT phases are labeled "not applicable" due to nonconventional structures.…”

Influences on clinical trial participation: Enhancing recruitment through a gender lens - A scoping review

“…However, conducting a successful clinical trial can be challenging [ 2 ]. A key contributor to clinical trial failure is low participant recruitment rates [ 3 , 4 ]; up to 35% of clinical trials are discontinued because of difficulties recruiting participants [ 5 ] and only 17% of randomised clinical trials in surgery reach target sample sizes within the planned timeframe [ 4 ]. Additionally, one third of completed clinical trials are at risk of being underpowered as pre-specified recruitment targets are not attained, jeopardising the trustworthiness of trial findings [ 4 , 6 ].…”