OBJECTIVE: This study leverages the rich diversity of the All of Us Research Program (All of Us)'s dataset to devise a predictive model for cardiovascular disease (CVD) in breast cancer (BC) survivors. Central to this endeavor is the creation of a robust data integration pipeline that synthesizes electronic health records (EHRs), patient surveys, and genomic data, while upholding fairness across demographic variables. MATERIALS AND METHODS: We have developed a universal data wrangling pipeline to process and merge heterogeneous data sources of the All of Us dataset, address missingness and variance in data, and align disparate data modalities into a coherent framework for analysis. Utilizing a composite feature set including EHR, lifestyle, and social determinants of health (SDoH) data, we then employed Adaptive Lasso and Random Forest regression models to predict 6 CVD outcomes. The models were evaluated using the c-index and time-dependent Area Under the Receiver Operating Characteristic Curve over a 10-year period. RESULTS: The Adaptive Lasso model showed consistent performance across most CVD outcomes, while the Random Forest model excelled particularly in predicting outcomes like transient ischemic attack when incorporating the full multi-model feature set. Feature importance analysis revealed age and previous coronary events as dominant predictors across CVD outcomes, with SDoH clustering labels highlighting the nuanced impact of social factors. DISCUSSION: The development of both Cox-based predictive model and Random Forest Regression model represents the extensive application of the All of Us, in integrating EHR and patient surveys to enhance precision medicine. And the inclusion of SDoH clustering labels revealed the significant impact of sociobehavioral factors on patient outcomes, emphasizing the importance of comprehensive health determinants in predictive models. Despite these advancements, limitations include the exclusion of genetic data, broad categorization of CVD conditions, and the need for fairness analyses to ensure equitable model performance across diverse populations. Future work should refine clinical and social variable measurements, incorporate advanced imputation techniques, and explore additional predictive algorithms to enhance model precision and fairness. CONCLUSION: This study demonstrates the liability of the All of Us's diverse dataset in developing a multi-modality predictive model for CVD in BC survivors risk stratification in oncological survivorship. The data integration pipeline and subsequent predictive models establish a methodological foundation for future research into personalized healthcare.

Many data sources, including tracking social behavior to election polling to testing studies for understanding disease spread, are subject to sampling bias whose implications are not fully yet understood. In this paper we study estimation of a given feature (such as disease, or behavior at social media platforms) from biased samples, treating non-respondent individuals as missing data. Prevalence of the feature among sampled individuals has an upward bias under the assumption of individuals’ willingness to be sampled. This can be viewed as a regression model with symptoms as covariates and the feature as outcome. It is assumed that the outcome is unknown at the time of sampling, and therefore the missingness mechanism only depends on the covariates. We show that data, in spite of this, is missing at random only when the sizes of symptom classes in the population are known; otherwise data is missing not at random. With an information theoretic viewpoint, we show that sampling bias corresponds to external information due to individuals in the population knowing their covariates, and we quantify this external information by active information. The reduction in prevalence, when sampling bias is adjusted for, similarly translates into active information due to bias correction, with opposite sign to active information due to testing bias. We develop unified results that show that prevalence and active information estimates are asymptotically normal under all missing data mechanisms, when testing errors are absent and present respectively. The asymptotic behavior of the estimators is illustrated through simulations.