The overarching goal of this award is to prepare the applicant for an independent, sustained program of research that incorporates psychosocial, behavioral, and clinical concepts and methods to understand and design interventions to guide clinical translation of uncertain and reclassified genomic variants. Variants of uncertain significance (VUS) introduce uncertainty and can confuse clinical decision making for patients and providers. VUS are also frequently reclassified, especially in racial/ethnic minority populations, and can inform clinical decision making. However, insufficient evidence around the influences and outcomes of uncertain and reclassified variants presents a challenge for more diffuse clinical translation of these genetic variants. Such understanding is particularly important in clinical oncology, as identification of mutation carriers can significantly alter cancer prevention, screening, surgery recommendations, and treatment. The K99 phase is designed to augment the candidate's prior research experience though coursework, apprenticeships and directed readings with specific training in: 1) clinical health informatics, 2) psychometrics and survey methodology, and, 3) advanced qualitative methods. The proposed research will collect patient reported and electronic medical record data from six healthcare systems that provide clinical genetic services to a racially/ethnically diverse patient population.
Aim 1 (K99 phase) surveys a national sample of oncology providers to understand their practices related to variant reclassification and recontact.
Aim 2 (K99 phase) interviews patients to identify dimensions of reclassification associated psychosocial well-being.
Aim 3 (R00 phase) uses data from aim 2 and existing literature to develop and pilot an instrument to measure genomic uncertainty in patients.
Aim 4 (R00 phase) evaluates the clinical utility of variant reclassification. This work will generate evidence to inform institutional and professional practice around variant reclassification. Taken together, the findings from this study will contextualize, and provide tools for a future longitudinal study to determine the behavioral, psychosocial, and clinical consequences of receiving uncertain genetic test results. This project is a critical building block for the applicant's long-term research goal to develop and test interventions (at the levels of provider, patient and healthcare system) to facilitate the clinical translation of genomics into diverse health systems and into underserved populations. The proposed award will provide training, mentorship and research experience that will serve as the foundation for the applicant's career as an independently funded clinical investigator dedicating to improving health outcomes in translational genomics for underrepresented minority populations.
As genomic sequence data are being produced faster and at lower cost, the most significant challenge in clinical genetic testing today is accurate variant classification and communication of that information to patients which is being adversely affected by variants of unknown significance (VUS), which comprise of a substantial percentage of all genetic variants in clinical oncology. VUS along with other confirmed variants are being reclassified with increasing availability of more ethnically diverse reference data, yet there is a lack of understanding on how practicing clinicians, and patients are impacted by and manage these variants. To provide empirical data to fill this critical knowledge gap and potentially inform patient care, I will conduct a national survey of oncology providers about how their variant reclassification related practices, develop a tool for measuring patient reported uncertainty in genomics, and evaluate the clinical utility of VUS reclassification among cancer patients and at-risk individuals.