Nonparametric procedures for comparing the performance of repeated markers used to predict a survival endpoint

This work considers methods for evaluating repeated markers to be used as a substitute for a clinical examination or to predict an outcome, in our case progression of breast cancer. We propose a definition of specificity and sensitivity for this setting and describe nonparametric estimators for these parameters. We then derive the theory required to obtain confidence intervals for the specificity and sensitivity of a marker and to define an asymptotically normal statistic for comparing the sensitivities of two markers at a fixed specificity. The theory allows for correlations introduced by the fact that markers may be obtained from the same patient at multiple visits and that both markers being compared may be obtained from the same patient. The work allows for an approach that complements the frequently used time dependent Cox model which, we believe, will facilitate clinical interpretation of marker data. We also present simulation results for comparing a weighted average of sensitivities across all specificities, instead of being restricted to one specificity

Generating Productive Dialogue between Consulting Statisticians and their Clients in the Pharmaceutical and Medical Research Settings

Due to the ever-increasing complexity of scientific technologies and resulting data, consulting statisticians are becoming more involved in the design, conduct, and analysis of biomedical research. This requires extensive collaboration between the consulting statistician and nonstatisticians, such as researchers, clinicians, and corporate executives. Consequently, a successful consulting career is becoming ever more dependent on the statistician's ability to effectively communicate with nonstatisticians. This is especially true when more complex, nontraditional analytical methods are required. In this paper, we examine the collaboration between statisticians and nonstatisticians from three different professional perspectives. Integrating these perspectives, we discuss ways to help the consulting statistician generate productive dialogue with clients. Finally, we examine how universities can better prepare students for careers in statistical consulting by incorporating more communication-based elements into their curriculum and by offering students ample opportunities to collaborate with nonstatisticians. Overall, we designed this exercise to help the consulting statistician generate dialogue with clients that results in more productive collaborations and a more satisfying work experience

Effectiveness and Safety of Direct Oral Anticoagulants Among Patients with Non-valvular Atrial Fibrillation and Multimorbidity

Introduction In the USA, there is a steady rise of atrial fibrillation due to the aging population with increased morbidity. This study evaluated the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among elderly patients with non-valvular atrial fibrillation (NVAF) and multimorbidity prescribed direct oral anticoagulants (DOACs). Methods Using the CMS Medicare database, a retrospective observational study of adult patients with NVAF and multimorbidity who initiated apixaban, dabigatran, or rivaroxaban from January 1, 2012 to December 31, 2017 was conducted. High multimorbidity was classified as having ≥ 6 comorbidities. Cox proportional hazard models were used to evaluate the hazard ratios of S/SE and MB among three 1:1 propensity score matched DOAC cohorts. All-cause healthcare costs were estimated using generalized linear models. Results Overall 36% of the NVAF study population had high multimorbidity, forming three propensity score matched (PSM) cohorts: 12,511 apixaban-dabigatran, 60,287 apixaban-rivaroxaban, and 12,567 dabigatran-rivaroxaban patients. Apixaban was associated with a lower risk of stroke/SE and MB when compared with dabigatran and rivaroxaban. Dabigatran had a lower risk of stroke/SE and a similar risk of MB when compared with rivaroxaban. Compared to rivaroxaban, apixaban patients incurred lower all-cause healthcare costs, and dabigatran patients incurred similar all-cause healthcare costs. Compared to dabigatran, apixaban patients incurred similar all-cause healthcare costs. Conclusion Patients with NVAF and ≥ 6 comorbid conditions had significantly different risks for stroke/SE and MB when comparing DOACs to DOACs, and different healthcare expenses. This study\u27s results may be useful for evaluating the risk–benefit ratio of DOAC use in patients with NVAF and multimorbidity

Effectiveness and Safety of Apixaban Versus Warfarin Among Older Patients with Venous Thromboembolism with Different Demographics and Socioeconomic Status

Introduction Impact of demographics and socioeconomic status (SES) on anticoagulant treatment outcomes among patients with venous thromboembolism (VTE) is not well understood. This study evaluated risks of recurrent VTE, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among older patients with VTE initiating apixaban or warfarin stratified by demographics and SES. Methods Adult patients (≥ 65 years) who initiated apixaban or warfarin after a VTE event were selected from the US CMS Medicare database (September 2014–December 2017). Stabilized inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Patients were stratified by age, gender, race, and SES. For each subgroup, Cox proportional hazard models were used to evaluate if there was a significant interaction (p \u3c 0.10) between treatment and subgroup for recurrent VTE, MB, and CRNMB. Results In total, 22,135 apixaban and 45,840 warfarin patients with VTE were included. Post-IPTW, patient characteristics were balanced between treatment cohorts. In older patients, apixaban treatment was associated with significantly lower risks of recurrent VTE (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.52–0.79), MB (HR 0.65; 95% CI 0.57–0.75), and CRNMB (HR 0.79; 95% CI 0.75–0.85) versus warfarin. When stratified by demographics and SES, higher incidence rates of recurrent VTE, MB, and CRNMB were observed for black vs white patients and patients with lower vs higher SES. Comparison of apixaban with warfarin by different demographic and SES subgroups showed generally consistent results as the overall analysis. For most subgroups, no significant interaction was observed between treatment and subgroup strata for recurrent VTE, MB, and CRNMB. Conclusion Among older patients with VTE initiating apixaban or warfarin, higher rates of recurrent VTE and bleeding were observed in black patients and patients with lower SES. Apixaban had a lower risk of recurrent VTE, MB, and CRNMB compared to warfarin. Analyses of demographic and SES subgroups showed consistent findings

Effectiveness and safety of apixaban vs warfarin among venous thromboembolism patients at high-risk of bleeding

This study evaluated effectiveness and safety of apixaban versus warfarin among venous thromboembolism patients at high-risk of bleeding (defined as having at least one of the following bleeding risk factors: ≥75 years; used antiplatelet, NSAIDs, or corticosteroids; had prior gastrointestinal bleeding or gastrointestinal-related conditions; late stage chronic kidney disease). Adult venous thromboembolism patients initiating apixaban or warfarin with ≥1 bleeding risk factor were identified from Medicare and four commercial claims databases in the United States. To balance characteristics between apixaban and warfarin patients, stabilized inverse probability treatment weighting was conducted. Cox proportional hazards models were used to estimate the risk of recurrent venous thromboembolism, major bleeding, and clinically relevant non-major bleeding. In total, 88,281 patients were identified. After inverse probability treatment weighting, the baseline patient characteristics were well-balanced between the two cohorts. Among venous thromboembolism patients at high-risk of bleeding, apixaban was associated with significantly lower risk of recurrent venous thromboembolism, major bleeding and clinically relevant non-major bleeding. No significant interactions were observed between treatment and number of risk factors on major bleeding and clinically relevant non-major bleeding or between treatment and type of bleeding risk factors on any of the outcomes. In conclusion, apixaban was associated with significantly lower risk of recurrent venous thromboembolism and bleeding among venous thromboembolism patients at high-risk of bleeding. Effects were generally consistent across subgroups of patients with different number or type of bleeding risk factors

Effectiveness and Safety of Apixaban vs Warfarin in Patients with Venous Thromboembolism with Risk Factors for Bleeding or for Recurrences

Introduction Patients at increased risk of bleeding and recurrent VTE who develop venous thromboembolism (VTE) present challenges for clinical management. This study evaluated the effectiveness and safety of apixaban vs warfarin in patients with VTE who have risk factors for bleeding or recurrences. Methods Adult patients with VTE initiating apixaban or warfarin were identified from five claims databases. Stabilized inverse probability treatment weighting (IPTW) was used to balance characteristics between cohorts for the main analysis. Subgroup interaction analyses were conducted to evaluate treatment effects among patients with and without each of the conditions that increased the risk of bleeding (thrombocytopenia and history of bleed) or recurrent VTE (thrombophilia, chronic liver disease, and immune-mediated disorders). Results A total of 94,333 warfarin and 60,786 apixaban patients with VTE met selection criteria. After IPTW, all patient characteristics were balanced between cohorts. Apixaban (vs warfarin) patients were at lower risk of recurrent VTE (HR [95% confidence interval (CI) 0.72 [0.67–0.78]), major bleeding (MB) (HR [95% CI] 0.70 [0.64–0.76]), and clinically relevant non-major (CRNM) bleeding (HR [95% CI] 0.83 [0.80–0.86]). Subgroup analyses showed generally consistent findings with the overall analysis. For most subgroup analyses, there were no significant interactions between treatment and subgroup strata on VTE, MB and CRNM bleeding. Conclusion Patients with prescription fills for apixaban had lower risk of recurrent VTE, MB, and CRNM bleeding compared with warfarin patients. Treatment effects of apixaban vs warfarin were generally consistent across subgroups of patients at increased risk of bleeding/recurrences

Oral anticoagulant underutilization among elderly patients with atrial fibrillation: insights from the United States Medicare database

Background Oral anticoagulants (OACs) mitigate stroke risk in patients with atrial fibrillation (AF). The study aim was to analyze prevalence and predictors of OAC underutilization. Methods Newly diagnosed AF patients with a CHA2DS2-VASc score ≥ 2 were identified from the US CMS Database (January 1, 2013–December 31, 2017). Patients were stratified based on having an OAC prescription versus not and the OAC prescription group was stratified by direct OAC (DOACs) versus warfarin. Multivariable logistic regression models were used to examine predictors of OAC underutilization. Results Among 1,204,507 identified AF patients, 617,611 patients (51.3%) were not prescribed an OAC during follow-up (mean: 2.4 years), and 586,896 patients (48.7%) were prescribed an OAC during this period (DOAC: 388,629 [66.2%]; warfarin: 198,267 [33.8%]). Age ≥ 85 years (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.55–0.56), female sex (OR 0.96, 95% CI 0.95–0.96), Black race (OR 0.78, 95% CI 0.77–0.79) and comorbidities such as gastrointestinal (GI; OR 0.43, 95% CI 0.41–0.44) and intracranial bleeding (OR 0.29, 95% CI 0.28–0.31) were associated with lower utilization of OACs. Furthermore, age ≥ 85 years (OR 0.92, 95% CI 0.91–0.94), Black race (OR 0.78, 95% CI 0.76–0.80), ischemic stroke (OR 0.77, 95% CI 0.75–0.80), GI bleeding (OR 0.73, 95% CI 0.68–0.77), and intracranial bleeding (OR 0.72, 95% CI 0.65–0.80) predicted lower use of DOACs versus warfarin. Conclusions Although OAC therapy prescription is the standard of care for stroke prevention in AF patients, its overall utilization is still low among Medicare patients ≥ 65 years old, with specific patient characteristics that predict underutilization