Purpose: The Reduction by Dutasteride of Prostate Cancer Events (REDUCE) prostate cancer risk reduction study randomly assigned 8,231 men to dutasteride or placebo for 4 years. Protocol-mandated biopsies were obtained after 2 and 4 years. After the discovery of three cases of biopsy sample misidentification in the first 2 years, all protocol-mandated biopsy samples were DNA tested to verify biopsy identity.
Methods: Biopsy and blood DNA profiling was performed retrospectively for the year 2 scheduled biopsies and prospectively for the year 4 scheduled biopsies. Toward the end of year 2, multiple changes were made to improve sample handling and chain of custody.
Results: Of the 6,458 year 2 and 4,777 year 4 biopsies, 26 biopsies reflecting 13 sample handling errors at year 2 (0.4%) and one biopsy reflecting one sample handling error at year 4 (0.02%) were confirmed to be mismatched to the patient for whom they were originally submitted. Of 6,733 reference blood samples profiled, 31 (0.5%) were found to be mismatched to the patient's verified identity profile. Sample identification errors occurred at local research sites and central laboratories.
Conclusion: Biopsy misidentification is a potential problem in clinical laboratories and clinical trials. Until now, biopsy misidentification has not been studied in the setting of a large, multinational clinical trial. In the REDUCE study, process improvement initiatives halfway through the trial dramatically reduced biopsy mismatches. The potential for biopsy mismatches in clinical trials and clinical practice is an under-recognized problem that requires rigorous attention to details of chain of custody and consideration of more widespread DNA identity testing.