Co-enrollment of critically ill patients into multiple studies: patterns, predictors and consequences

Abstract

IntroductionResearch on co-enrollment practices and their impact are limited in the ICU setting. The objectives of this study were: 1) to describe patterns and predictors of co-enrollment of patients in a thromboprophylaxis trial, and 2) to examine the consequences of co-enrollment on clinical and trial outcomes.MethodsIn an observational analysis of an international thromboprophylaxis trial in 67 ICUs, we examined the co-enrollment of critically ill medical-surgical patients into more than one study, and examined the clinical and trial outcomes among co-enrolled and non-co-enrolled patients.ResultsAmong 3,746 patients enrolled in PROTECT (Prophylaxis for ThromboEmbolism in Critical Care Trial), 713 (19.0%) were co-enrolled in at least one other study (53.6% in a randomized trial, 37.0% in an observational study and 9.4% in both). Six factors independently associated with co-enrollment (all P < 0.001) were illness severity (odds ratio (OR) 1.35, 95% confidence interval (CI) 1.19 to 1.53 for each 10-point Acute Physiology and Chronic Health Evaluation (APACHE) II score increase), substitute decision-makers providing consent, rather than patients (OR 3.31, 2.03 to 5.41), experience of persons inviting consent (OR 2.67, 1.74 to 4.11 for persons with > 10 years' experience compared to persons with none), center size (all ORs > 10 for ICUs with > 15 beds), affiliation with trials groups (OR 5.59, 3.49 to 8.95), and main trial rather than pilot phase (all ORs > 8 for recruitment year beyond the pilot). Co-enrollment did not influence clinical or trial outcomes or risk of adverse events.ConclusionsCo-enrollment was strongly associated with features of the patients, research personnel, setting and study. Co-enrollment had no impact on trial results, and appeared safe, acceptable and feasible. Transparent reporting, scholarly discourse, ethical analysis and further research are needed on the complex topic of co-enrollment during critical illness.

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial—PROSPECT: protocol for a feasibility randomized pilot trial

“…It is therefore essential to carefully record and monitor enrolment practices and make improvements where possible. We have successfully conducted other international trials [38–42] and are interested to evaluate co-enrolment across participating centers and countries [43]. When thoughtfully approached, co-enrolment has not been found to impact on trial results [43, 44], and thus, ways to maximize safe co-enrolment opportunities will be explored in this trial.…”

Enrollment of Neonates in More Than One Clinical Trial

“…9,10 In addition to concerns about statistical power, increased risk of adverse events (AEs), and the interpretation of study results, there may be a problem with outcome ascertainment bias. 11 Thus, whether to allow co-enrollment in 41 clinical trial requires a careful assessment of the potential impact on the study results, interactions between the interventions, subject safety, and the scientific validity of the clinical trials. [12][13][14][15]…”

“…Allowing coenrollment, when scientifically appropriate, respects the role of parents in deciding for their neonate and may result in a more representative population of those neonates who would receive the 2 interventions in clinical practice. 7,9,11 There are no data to indicate that it may be too stressful and thus unethical to approach parents about co-enrollment in multiple studies. 10 One study showed that most mothers of neonates were willing to participate in 41 study.…”

Clinical Trial Design in Acute Lung Injury—Issues and Controversies

“…In an era where the incidence, 17 mortality, 18 and management options for ALI are changing, rapid patient accrual is an important goal. Trialists, therefore, strive to implement their studies across national borders, to coenroll patients across trials where appropriate, 19 and to include the broadest case mix supported by current clinical practice and expectations for net benefit.…”