How I have helped clients recently with reviewing patients in screening for inclusion/exclusion biomarkers
Diving into recent patient screenings for inclusion/exclusion biomarker criteria revealed a tapestry of intriguing cases:
🧬 Genomic Puzzle: Spotting Lesion Discrepancies
Multiple genomics reports for one patient had seemingly little similarity. We identified that the reports were from different lesions. The primary, and largest, lesion harbored the mutation in the inclusion criteria, whereas the remaining smaller lesions did not have this mutation detected. As the majority of the disease harbored the mutation, the patient was enrolled in the trial.
🔍 Client's Archival Journey: A Comprehensive Detour
A client was enrolling patients from archival reports, which include multiple assay types. One screening patient had a genomic report that was not from a comprehensive test. This report identified the inclusion mutation but the test did not include the genes in the exclusion criteria. Discussions with the site resulted in the patient having a fast turnaround comprehensive ctDNA test, which included the genes in the exclusion criteria, before enrollment in the trial.
📅 Time-Traveling Genomics: A Costly Oversight In the annals of patient history
An archival patient genomic report was performed recently, but the sample was collected more than 8 years ago. It was recommended by us to perform a ctDNA test on this patient before enrollment as genomics may have changed whilst on interim treatments, but due to trial logistics, this was not possible. After enrollment, a confirmatory baseline test on a freshly collected biopsy showed the patient did not have the mutation which unfortunately resulted in a waste of time for the trial and the patient.
🧬 Archival Report Mirage: Exclusion Gene Hotspots
A test on an archival report for a screening patient looked like it included the gene to be tested to meet exclusion criteria. Unfortunately this test only included hotspots for that gene, so the patient was considered not eligible for enrollment (unless they had another test that included the full gene).
🔄 Hereditary Hurdle: Inclusion Mutation Unveiled as Familial
A mutation that fell within inclusion criteria was identified in a patient’s tumor at screening. Recommended subsequent testing showed the variant was hereditary, and both the patient and sponsor decided not to enroll in the trial.
👣 Footnote Mirage:
A site referred a patient for screening with a mutation in the footnotes. Usually these variants are of uncertain significance and not to be used for clinical decision making. However, upon independent review we identified that the additional supporting literature on this variant had changed its classification to likely pathogenic. The patient was enrolled on the trial.
Each screening encounter, a unique narrative in the chronicles of clinical trials.
