Reason and reality-identifying barriers to patient enrolment for clinical trials in invasive candidiasis.

OBJECTIVES

Enrolment of subjects to clinical trials investigating novel drugs for infectious diseases is an ongoing challenge. In this study, we evaluate factors associated with non-enrolment in treatment trials for invasive candidiasis.

METHODS

We conducted a retrospective review of pre-screening logs of patients that were assessed for enrolment in the three clinical trials ACTIVE (NCT00413218), APX001-201 (NCT03604705) and ReSTORE (NCT03667690), investigating novel drugs for invasive candidiasis between September 2007 and August 2021 to identify reasons for study ineligibility.

RESULTS

Two hundred and fifty-six patients with invasive candidiasis were identified for potential study participation with n = 154 for the ACTIVE trial, n = 89 for APX001-201 and n = 13 for ReSTORE. Half of the potential participants were unable or unwilling to consent. We further identified comorbid conditions such as hepatic or renal impairment [21 hepatic and renal cases (13.6%) in ACTIVE; 12 hepatic (13.5%) and 28 renal cases (31.5%) in APX], prior antifungal treatment [11 cases (7.1%) in ACTIVE; 16 (18.0%) in APX; 7 (38.5%) in ReSTORE] and the last positive culture obtained ≥96 h prior to dosing [1 case (0.6%) in ACTIVE; 7 (7.9%) in APX; 5 (38.5%) in ReSTORE] as relevant reasons for non-enrolment. We also identified criteria repetitively used in the analysed studies that did not contribute substantially to ineligibility rates. Ultimately, 254/256 patients (99.2%) were ineligible for enrolment in the respective trial.

CONCLUSIONS

This study identified barriers to enrolment in clinical trials assessing novel antifungal agents in invasive candidiasis. Identification of eligibility criteria associated with non-enrolment allows modification of future trial designs and may ultimately result in higher recruitment rates.