Patient Eligibility for Randomized Controlled Trials in Critical Care Medicine: An International Two-Center Observational Study*

Ivie, Ryan; Vail, Emily A.; Wunsch, Hannah; Goldklang, Monica; Fowler, Robert; Moitra, Vivek K.

doi:10.1097/ccm.0000000000002061

Cited by 12 publications

(12 citation statements)

References 39 publications

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“…This is also borne out by recruiters more commonly experiencing patients being incorrectly excluded from trials than incorrectly included. This links to the recognised problem of limited generalisability of trial results, observed across various trial settings 10,19,[37][38][39][40][41][42] and for at least the last few decades. 17,43 Although other factors may contribute towards limited generalisability (such as recruiter discomfort in approaching some eligible patients 44 or underlying problems with the feasibility of interventions 45 ), speci c exclusions in eligibility criteria are likely to play a large part.…”

Section: Discussionmentioning

confidence: 99%

Clinical Trial Recruiters’ Experiences Working With Trial Eligibility Criteria: Results of an Exploratory, Cross-sectional, Online Survey

Cragg

McMahon

Oughton

et al. 2021

Preprint

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BackgroundEligibility criteria are a fundamental element of clinical trial design, defining who can and who should not participate in a trial. Problems with the design or application of criteria are known to occur and pose risks to participants' safety and trial integrity, sometimes also negatively impacting on trial recruitment and generalisability. We conducted a short, exploratory survey to gather evidence on UK recruiters' experiences interpreting and applying eligibility criteria and their views on how criteria are communicated and developed.MethodsOur survey included topics informed by a wider programme of work at the Clinical Trials Research Unit, University of Leeds, on assuring eligibility criteria quality. Respondents were asked to answer based on all their trial experience, not only on experiences with our trials. The survey was disseminated to recruiters collaborating on trials run at our trials unit, and via other mailing lists and social media. The quantitative responses were descriptively analysed, with inductive analysis of free-text responses to identify themes.ResultsA total of 823 eligible respondents participated. 79% of respondents reported finding problems with eligibility criteria in some trials, and 9% in most trials. The main themes in the types of problems experienced were criteria clarity (67% of comments), feasibility (34%) and suitability (14%). 27% of those reporting some level of problem said these problems had led to patients being incorrectly included in trials; 40% said they had led to incorrect exclusions. Most respondents (56%) reported accessing eligibility criteria mainly in the trial protocol. Most respondents (74%) supported the idea that they might review eligibility criteria earlier in the protocol development process.ConclusionsOur survey corroborates other evidence about the existence of suboptimal trial eligibility criteria. Problems with clarity were the most often reported, but the number of comments on feasibility and suitability suggest some recruiters feel eligibility criteria and associated assessments can hinder recruitment to trials. Our proposal for more recruiter involvement in protocol development has strong support and some potential benefits, but questions remain about how best to implement this. We invite other trialists to consider our other suggestions for how to assure quality in trial eligibility criteria.

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Section: Discussionmentioning

confidence: 99%

Clinical Trial Recruiters’ Experiences Working With Trial Eligibility Criteria: Results of an Exploratory, Cross-sectional, Online Survey

Cragg

McMahon

Oughton

et al. 2021

Preprint

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“…All RCTs have inclusion and exclusion criteria, which serves to identify patients with the illness and specifically exclude patients who are either unlikely to benefit or have a greater likelihood of harm from the trial treatment [9,25]. The sepsis RCTs mainly differ in terms of their exclusion criteria (eTable-3) [26], with similar inclusion criteria [27]. Therefore, we do not suggest that these principles are completely ignored in published sepsis trials where, for example, patients with metastatic cancer and cirrhosis are frequently excluded presumably because of the high non-sepsis attributable mortality of critical illness in these subsets (eTable-3) (20).…”

Section: Discussionmentioning

confidence: 99%

Estimating attributable fraction of mortality from sepsis to inform clinical trials

Shankar-Hari

Harrison

Rowan

et al. 2018

Journal of Critical Care

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“…8 INSERM CIC 1432, Clinical Epidemiology, University of Burgundy, Dijon, France. 9 Medical-Surgical Intensive Care Unit, General Hospital Center, Saint Brieuc, France. 10 Medical-Surgical Intensive Care Unit, General Hospital Center, Le Mans, France.…”

Section: Supplementary Informationmentioning

confidence: 99%

Insights from patients screened but not randomised in the HYPERION trial

Lascarrou

Muller

Quenot

et al. 2021

Ann. Intensive Care

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Background Few data are available about outcomes of patients screened for, but not enrolled in, randomised clinical trials. Methods We retrospectively reviewed patients who had non-inclusion criteria for the HYPERION trial comparing 33 °C to 37 °C in patients comatose after cardiac arrest in non-shockable rhythm, due to any cause. A good neurological outcome was defined as a day-90 Cerebral Performance Category score of 1 or 2. Results Of the 1144 patients with non-inclusion criteria, 1130 had day-90 information and, among these, 158 (14%) had good functional outcomes, compared to 7.9% overall in the HYPERION trial (10.2% with and 5.7% without hypothermia). Considerable centre-to-centre variability was found in the proportion of non-included patients who received hypothermia (0% to 83.8%) and who had good day-90 functional outcomes (0% to 31.3%). The proportion of patients with a good day-90 functional outcome was significantly higher with than without hypothermia (18.5% vs. 11.9%, P = 0.003). Conclusion Our finding of better functional outcomes without than with inclusion in the HYPERION trial, despite most non-inclusion criteria being of adverse prognostic significance (e.g., long no-flow and low-flow times and haemodynamic instability), raises important questions about the choice of patient selection criteria and the applicability of trial results to everyday practice. At present, reserving hypothermia for patients without predictors of poor prognosis seems open to criticism.

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Patient Eligibility for Randomized Controlled Trials in Critical Care Medicine: An International Two-Center Observational Study*

Cited by 12 publications

References 39 publications

Clinical Trial Recruiters’ Experiences Working With Trial Eligibility Criteria: Results of an Exploratory, Cross-sectional, Online Survey

Clinical Trial Recruiters’ Experiences Working With Trial Eligibility Criteria: Results of an Exploratory, Cross-sectional, Online Survey

Estimating attributable fraction of mortality from sepsis to inform clinical trials

Insights from patients screened but not randomised in the HYPERION trial

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