scholarly journals Validation of the Smooth Test of Goodness-of-Fit for Proportional Hazards in Cancer Survival Studies

Author(s):  
Bernard Omolo ◽  
Collins Odhiambo ◽  
John Odhiambo
2012 ◽  
Vol 29 (2) ◽  
pp. 419-446 ◽  
Author(s):  
Anil K. Bera ◽  
Aurobindo Ghosh ◽  
Zhijie Xiao

The two-sample version of the celebrated Pearson goodness-of-fit problem has been a topic of extensive research, and several tests like the Kolmogorov-Smirnov and Cramér-von Mises have been suggested. Although these tests perform fairly well as omnibus tests for comparing two probability density functions (PDFs), they may have poor power against specific departures such as in location, scale, skewness, and kurtosis. We propose a new test for the equality of two PDFs based on a modified version of the Neyman smooth test using empirical distribution functions minimizing size distortion in finite samples. The suggested test can detect the specific directions of departure from the null hypothesis. Specifically, it can identify deviations in the directions of mean, variance, skewness, or tail behavior. In a finite sample, the actual probability of type-I error depends on the relative sizes of the two samples. We propose two different approaches to deal with this problem and show that, under appropriate conditions, the proposed tests are asymptotically distributed as chi-squared. We also study the finite sample size and power properties of our proposed test. As an application of our procedure, we compare the age distributions of employees with small employers in New York and Pennsylvania with group insurance before and after the enactment of the “community rating” legislation in New York. It has been conventional wisdom that if community rating is enforced (where the group health insurance premium does not depend on age or any other physical characteristics of the insured), then the insurance market will collapse, since only older or less healthy patients would prefer group insurance. We find that there are significant changes in the age distribution in the population in New York owing mainly to a shift in location and scale.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18012-e18012
Author(s):  
Karthik Ramakrishnan ◽  
Ali Mojebi ◽  
Dieter Ayers ◽  
Diana Romana Chirovsky ◽  
Rebekah Borse ◽  
...  

e18012 Background: In the KEYNOTE-048 trial, pembrolizumab as monotherapy (P) and in combination with platinum+5FU chemotherapy (P+C) versus cetuximab+platinum+5FU (EXTREME regimen) significantly improved overall survival (OS) in the combined positive score (CPS) ≥1 (hazard ratio: 0.74; 95% confidence interval: 0.61-0.90) and total (0.72; 0.60-0.87) R/M HNSCC populations, respectively, and was approved by the FDA in these patient populations. While the EXTREME regimen is considered standard of care in 1L R/M HNSCC, other systemic treatment options including cetuximab+platinum+docetaxel (TPEx regimen), platinum+paclitaxel/taxane (Pt+T), and platinum+5FU (Pt+F) are also commonly used. Due to lack of head-to-head comparisons with pembrolizumab, an NMA was conducted to estimate the comparative efficacy of P and P+C versus these interventions in 1L R/M HNSCC. Methods: A systematic literature review (SLR) was conducted on November 13, 2019 to identify randomized controlled trials for the relavant interventions. Data were extracted for the OS and progression-free survival (PFS) outcomes. NMA analyses were conducted for the total population and for the CPS ≥1 and CPS ≥20 subgroups in a Bayesian framework using proportional hazards (base case) and time-varying (sensitivity analysis) treatment-effect models. The deviance information criterion was used to compare the goodness-of-fit of the alternative survival models. Results: The SLR identified 28 trials, of which six trials matched the trial eligibility criteria of KEYNOTE-048 and were included in the NMA. Results from the fixed-effects NMA for P and P+C are summarized in table below for the FDA indicated population. Improvement in OS was noted for P and P+C versus EXTREME, Pt+T, and Pt+F, and a trend in improved OS versus TPEx was observed. The sensitivity analysis showed improved OS over time across all comparisons. PFS was improved with P and P+C versus Pt+F and comparable versus other interventions. These results were generally consistent for P and P+C in the CPS (CPS ≥1 or CPS ≥20) patient subgroups. Additionally, NMA results versus EXTREME were consistent with the KEYNOTE-048 trial results. Conclusions: Pembrolizumab (P or P+C), showed improved OS and comparable PFS outcomes versus alternative 1L R/M HNSCC interventions, consistent with the efficacy results versus EXTREME observed in the KEYNOTE-048 trial. [Table: see text]


2020 ◽  
Vol 49 (4) ◽  
pp. 1366-1377 ◽  
Author(s):  
Xiaoyan Wang ◽  
Rohit P Ojha ◽  
Sonia Partap ◽  
Kimberly J Johnson

Abstract Background Differences in access, delivery and utilisation of health care may impact childhood and adolescent cancer survival. We evaluated whether insurance coverage impacts survival among US children and adolescents with cancer diagnoses, overall and by age group, and explored potential mechanisms. Methods Data from 58 421 children (aged ≤14 years) and adolescents (15–19 years), diagnosed with cancer from 2004 to 2010, were obtained from the National Cancer Database. We examined associations between insurance status at initial diagnosis or treatment and diagnosis stage; any treatment received; and mortality using logistic regression, Cox proportional hazards (PH) regression, restricted mean survival time (RMST) and mediation analyses. Results Relative to privately insured individuals, the hazard of death (all-cause) was increased and survival months were decreased in those with Medicaid [hazard ratio (HR) = 1.27, 95% confidence interval (CI): 1.22 to 1.33; and −1.73 months, 95% CI: −2.07 to −1.38] and no insurance (HR = 1.32, 95% CI: 1.20 to 1.46; and −2.13 months, 95% CI: −2.91 to −1.34). The HR for Medicaid vs. private insurance was larger (pinteraction <0.001) in adolescents (HR = 1.52, 95% CI: 1.41 to 1.64) than children (HR = 1.16, 95% CI: 1.10 to 1.23). Despite statistical evidence violation of the PH assumption, RMST results supported all interpretations. Earlier diagnosis for staged cancers in the Medicaid and uninsured populations accounted for an estimated 13% and 19% of the survival deficit, respectively, vs. the privately insured population. Any treatment received did not account for insurance-associated survival differences in children and adolescents with cancer. Conclusions Children and adolescents without private insurance had a higher risk of death and shorter survival within 5 years following cancer diagnosis. Additional research is needed to understand underlying mechanisms.


2020 ◽  
Vol 59 (11) ◽  
pp. 1266-1274 ◽  
Author(s):  
Frida E. Lundberg ◽  
Therese M.-L. Andersson ◽  
Mats Lambe ◽  
Gerda Engholm ◽  
Lina Steinrud Mørch ◽  
...  

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