Study design and objectives

The prospective ORACLE observational research registry (October 2018 to March 2020) is a multicenter cohort assembled to evaluate the impact of an IC on physician decision-making when used in the clinical management of a recently identified PNs with Mayo SPN pCA ≤ 50% as compared to a historical control population from the same institutions. A total of 15 community and academic pulmonary practices covering a wide geographic area participated in the study and the institutional review boards at each site or centrally approved the study. Written consent was obtained from all eligible patients and patient follow-up was continued until all eligible patients had completed at least one year.

The primary objective of the ORACLE study was to show a statistically significant reduction in the proportion of benign PNs experiencing invasive procedures (biopsies or surgery) between a prospective group of patients managed by the IC test and a control group managed by usual care. Additionally, the secondary objective of the study was to show a statistically significant noninferiority of the proportion of surveilled PNs resulting in a malignant diagnosis, under management with the IC test as compared to a control group managed by usual care.

The sample size for the ORACLE study was powered based on the secondary objective due to larger patient numbers required over the primary objective. A power analysis indicated that with a noninferiority margin of 10% relative to management without the IC (control group), 453 patients per group would be necessary to reject the null hypothesis with 80% power and type 1 error α = 0.05, one-sided.