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Randomized Controlled Trial
. 2024 Dec 27;25(1):851.
doi: 10.1186/s13063-024-08701-w.

Enrolment patterns in a randomized controlled trial of probiotics in critically ill patients: a retrospective analysis of the PROSPECT trial

Alyson Takaoka  1 , Jennie Johnstone  2 , François Lauzier  3 , Diane Heels-Ansdell  4 , Megan Davis  4 , Nicole Zytaruk  4 , Erick Duan  5 , Joanna Dionne  5 , Lois Saunders  4 , Yaseen M Arabi  6 , John Marshall  2 , Lehana Thabane  4 , France Clarke  4 , Lori Hand  4 , Marie-Helene Masse  7 , Bram Rochwerg  4 , Lauralyn McIntyre  8 , Martin Girard  9 , Andreas Freitag  4 , Tim Karachi  4 , Deborah J Cook  10 ; PROSPECT Investigators; Canadian Critical Care Trials Group
Collaborators, Affiliations
Randomized Controlled Trial

Enrolment patterns in a randomized controlled trial of probiotics in critically ill patients: a retrospective analysis of the PROSPECT trial

Alyson Takaoka et al. Trials. .

Abstract

Background: Understanding site-related factors that influence enrolment within multicenter randomized controlled trials (RCT) may help reduce trial delays and cost over-runs and prevent early trial discontinuation. In this analysis of PROSPECT (Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial), we describe patient enrolment patterns and examine factors influencing site-based monthly enrolment.

Design: Retrospective analysis of a multicenter RCT.

Methods: The PROSPECT multicenter RCT enrolled patients in the main trial from July 2015 to March 2019. We documented site characteristics and trial metrics including data from the methods center tracking documents, site-level data at trial initiation, screening logs submitted by research coordinators, and prospectively collected case report forms. In this retrospective analysis of trial data, we analyzed enrolment patterns across sites using negative binomial regression to explore the association between monthly enrolment rate accounting for number of ICU beds, site characteristics, and trial metrics.

Results: Overall, 41 sites enrolling 2365 patients in the PROSPECT main trial were analyzed. After accounting for number of beds in each ICU, site launch early in the trial was associated with higher monthly enrolment rates, but time to first enrolment and research coordinator experience was not. We observed considerable variability in the number of active screening months and enrolment rates across sites.

Conclusion: These findings highlight the complexity of recruitment dynamics in critical care RCTs and emphasize the need for tailored approaches to trial planning and execution.

Trial registration: PROSPECT (Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial): NCT02462590 (registered June 2, 2015).

Keywords: Critical illness; Enrolment; Randomized trial; Screening.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: We did not require ethical approval to carry out this pre-planned, post-hoc analysis since data included only site-level variables with no patient-level data or identifiers. Consent for publications: Not applicable. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
PROSPECT Timeline and Milestones. Timeline of the PROSPECT trial, including major milestones, beginning with pilot trial registration in June 2013 and completing with final manuscript published in July 2020. NOL = no objection letter; RCT = randomized controlled trial
Fig. 2
Fig. 2
Average monthly enrolment across centres. This figure depicts the average number of patients enrolled per recruiting site (red) and per open site (green) with the total number of open sites (blue) over the course of the trial
Fig. 3
Fig. 3
Cumulative patients enrolled. This figure depicts the cumulative number of patients enrolled by month in addition to the number of open sites over the course of the trial
Fig. 4
Fig. 4
Average Monthly Enrolment Per Site Per 15 ICU Beds. This figure depicts the average monthly enrolment per site indexed to 15 ICU beds in ascending order. The red line indicates the overall average monthly enrolment rate per 15 ICU beds across sites (1.2 patients/month)
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