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Practical implementation of frailty models in Mendelian risk prediction.

ABSTRACT: There are numerous statistical models used to identify individuals at high risk of cancer due to inherited mutations. Mendelian models predict future risk of cancer by using family history with estimated cancer penetrances (age- and sex-specific risk of cancer given the genotype of the mutations) and mutation prevalences. However, there is often residual risk heterogeneity across families even after accounting for the mutations in the model, due to environmental or unobserved genetic risk factors. We aim to improve Mendelian risk prediction by incorporating a frailty model that contains a family-specific frailty vector, impacting the cancer hazard function, to account for this heterogeneity. We use a discrete uniform population frailty distribution and implement a marginalized approach that averages each family's risk predictions over the family's frailty distribution. We apply the proposed approach to improve breast cancer prediction in BRCAPRO, a Mendelian model that accounts for inherited mutations in the BRCA1 and BRCA2 genes to predict breast and ovarian cancer. We evaluate the proposed model's performance in simulations and real data from the Cancer Genetics Network and show improvements in model calibration and discrimination. We also discuss alternative approaches for incorporating frailties and their strengths and limitations.

SUBMITTER: Huang T

PROVIDER: S-EPMC7895423 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSuicide risk prediction models derived from electronic health records (EHR) are a novel innovation in suicide prevention but there is little evidence to guide their implementation.MethodsIn this qualitative study, 30 clinicians and 10 health care administrators were interviewed from one health system anticipating implementation of an automated EHR-derived suicide risk prediction model and two health systems piloting different implementation approaches. Site-tailored interview guides focused on respondents' expectations for and experiences with suicide risk prediction models in clinical practice, and suggestions for improving implementation. Interview prompts and content analysis were guided by Consolidated Framework for Implementation Research (CFIR) constructs.ResultsAdministrators and clinicians found use of the suicide risk prediction model and the two implementation approaches acceptable. Clinicians desired opportunities for early buy-in, implementation decision-making, and feedback. They wanted to better understand how this manner of risk identification enhanced existing suicide prevention efforts. They also wanted additional training to understand how the model determined risk, particularly after patients they expected to see identified by the model were not flagged at-risk and patients they did not expect to see identified were. Clinicians were concerned about having enough suicide prevention resources for potentially increased demand and about their personal liability; they wanted clear procedures for situations when they could not reach patients or when patients remained at-risk over a sustained period. Suggestions for making risk model workflows more efficient and less burdensome included consolidating suicide risk information in a dedicated module in the EHR and populating risk assessment scores and text in clinical notes.ConclusionHealth systems considering suicide risk model implementation should engage clinicians early in the process to ensure they understand how risk models estimate risk and add value to existing workflows, clarify clinician role expectations, and summarize risk information in a convenient place in the EHR to support high-quality patient care.

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Practical implementation of frailty models in Mendelian risk prediction.

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