Validation of the SOPHiA DDM HRD Solution as a Companion Diagnostic for PARPi Access in Australia.
In this multilaboratory validation study of 145 ovarian cancer samples, the SOPHiA DDM HRD Solution was compared with the regulatory-approved Myriad myChoice HRD assay to assess clinical comparability for class 3 in-house in vitro diagnostic medical device companion diagnostic use. BRCA (BRCA1 and BRCA2) mutation status showed 100% concordance, and genomic instability (GI) measurements demonstrated strong linear agreement, absence of bias, and high analytical precision. Receiver operating characteristic analysis suggested a threshold adjustment from 0 to -1.5, improving overall accuracy to 91.2% when combined with BRCA mutation status to assign homologous recombination deficiency (HRD) status. Approximately 6% of samples were excluded because of inconclusive results, whereas GI classification discordance was concentrated near the clinical threshold. Neither inconclusiveness nor discordance was associated with sample-related factors. These findings indicate that the SOPHiA HRD assay can provide results broadly interchangeable with Myriad myChoice, although caution is warranted when assigning HRD status to borderline GI values.