The challenge of recruitment in clinical trials in Canada: an analysis of trial registry data

BACKGROUND AND OBJECTIVES: Clinical trials that have low enrollment risk being underpowered for answering the intended research question and wasting the resources invested. We aimed to quantify the extent of unsuccessful recruitment among clinical trials in Canada and examine associations between design-related factors and success. METHODS: We searched ClinicalTrials.gov for interventional trials with at least one site in Canada and were marked "completed," "suspended," or "terminated." We restricted the study sample to trials with start dates between January 2017 and December 2021 that met the inclusion criteria. We divided the estimated enrollment count retrieved from the registration version submitted prior to the start of the trial by the actual enrollment count in the latest registration version. We explored associations between design-related factors and enrollment. RESULTS: Of 2213 trials that met inclusion, 681 (31%) were unsuccessful in recruiting at least 85% of their estimated enrollment count. Proportionally, more federally and other publicly funded trials were unsuccessful compared to privately funded trials. Regression models showed that trials with larger intended sample sizes and follow-up durations of 1-year or more were associated with lower odds of recruitment success. Trials with more than two arms were more likely to recruit successfully than single-arm trials. Trials with active and/or placebo comparators were more likely to recruit successfully compared to trials without these comparators. CONCLUSION: Recruitment challenges are a pervasive issue in Canadian trials, especially among federally/publicly funded trials. The findings underscore a need for recruitment optimization to mitigate research waste and better uphold ethical obligations to patients. PLAIN LANGUAGE SUMMARY: This study analyzed over 2200 clinical trials in Canada to explore how many met their recruitment goals. Nearly one-third (31%) of these trials failed to recruit within 85% of their goal. The analysis also revealed that trials funded by the government or public organizations struggled with recruitment more than those funded by private companies. There were differences in what kinds of trials were more likely to fall short: trials that aimed for higher recruitment goals and trials that planned to follow participants for a year or longer. This study highlighted a need to focus on better recruitment strategies.