Towards clinical data-driven eligibility criteria optimization for interventional COVID-19 clinical trials

Abstract

Objective: This research aims to evaluate the impact of eligibility criteria on recruitment and observable clinical outcomes of COVID-19 clinical trials using electronic health record (EHR) data.

Materials and methods: On June 18, 2020, we identified frequently used eligibility criteria from all the interventional COVID-19 trials in ClinicalTrials.gov (n = 288), including age, pregnancy, oxygen saturation, alanine/aspartate aminotransferase, platelets, and estimated glomerular filtration rate. We applied the frequently used criteria to the EHR data of COVID-19 patients in Columbia University Irving Medical Center (CUIMC) (March 2020-June 2020) and evaluated their impact on patient accrual and the occurrence of a composite endpoint of mechanical ventilation, tracheostomy, and in-hospital death.

Results: There were 3251 patients diagnosed with COVID-19 from the CUIMC EHR included in the analysis. The median follow-up period was 10 days (interquartile range 4-28 days). The composite events occurred in 18.1% (n = 587) of the COVID-19 cohort during the follow-up. In a hypothetical trial with common eligibility criteria, 33.6% (690/2051) were eligible among patients with evaluable data and 22.2% (153/690) had the composite event.

Discussion: By adjusting the thresholds of common eligibility criteria based on the characteristics of COVID-19 patients, we could observe more composite events from fewer patients.

Conclusions: This research demonstrated the potential of using the EHR data of COVID-19 patients to inform the selection of eligibility criteria and their thresholds, supporting data-driven optimization of participant selection towards improved statistical power of COVID-19 trials.

Keywords: COVID-19, criteria optimization; clinical trial; eligibility criteria; real-world data.

Figure 1.

Proportion of eligible trials according to value of (A) eGFR, (B) AST/ALT, (C) oxygen saturation, and (D) platelets. The ULN of AST and ALT were 37 U/L and 50 U/L, respectively. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; eGFR, estimated glomerular filtration rate; ULN, upper limit of normal.

Figure 2.

Cumulative incidence of mechanical ventilation, tracheostomy, or in-hospital death by (A-B) different age groups, (C) different renal functions, and (D) oxygen saturation. Abbreviation: eGFR, estimated glomerular filtration rate.

Figure 3.

Cumulative incidence of mechanical ventilation, tracheostomy, or in-hospital death by eligibility to a hypothetical clinical trial using common eligibility criteria. Inclusion criteria for this hypothetical trial are as follows: 1) Age ≥ 18; 2) eGFR ≥ 30 mL/min/1.73m²; 3) AST/ALT ≤ 5 times the ULN; 4) not pregnant; 5) Oxygen saturation at room air ≤ 93% or requirement of supplemental oxygen; and 6) platelets ≥ 50 x10/μL. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; eGFR, estimated glomerular filtration rate; ULN, upper limit of normal.