The impact of eligibility criteria on enrollment in ICU sepsis clinical trials

Introduction

Although clinical trials of novel mediator-targeted compounds in sepsis employ similar entry criteria, exclusion criteria are variable. We evaluated the impact of variability in such criteria on recruitment of patients into one of three multi-center studies.

Method

We have previously developed a screen log for monitoring eligibility and enrollment of patients into multiple clinical trials. All patients admitted to the Medical-Surgical Intensive Care Unit of a large Canadian University affiliated teaching hospital were screened for study eligibility into one of three multi-center sepsis trials. The screen log defines patients who meet inclusion criteria as eligible. Reasons for non-enrollment are divided as follows: 1, study specific exclusion criteria; 2, hopeless prognosis; and 3, enrolled in another trial. Truly eligible patients were those who did not meet above criteria 1–3 and were not enrolled because informed consent could not be obtained or because the window of eligibility was missed by study personnel. Recruitment efficiency was calculated as the proportion of patients enrolled of those who were truly eligible.

Results

During the 23-month period of screening, 559 patients were admitted with sepsis or presumed sepsis. The inclusion criteria were met for 273/559 (48.8%) patients in least one of these three sepsis studies. Only 37/559 (6.6%) were enrolled into a sepsis trial. The Table contains the number of eligible, excluded (with reasons for exclusion) and enrolled patients screened for entry into the three trials.

Conclusion

Within an institution that actively participates in sepsis clinical trials, only a minority of patients with sepsis are treated in the context of a trial. The impact of study-specific exclusion criteria is to create very different study populations. Such differences may account in part for the discordant results seen in Phase II and Phase III trials and raise important questions regarding the external validity of conclusions from trials with low inclusion or recruitment efficiencies.

Table 1