The Efficiency of a Weighted Log-Rank Test under a Percent Error Misspecification Model for the Log Hazard Ratio

Biometrics ◽  
1992 ◽  
Vol 48 (3) ◽  
pp. 893 ◽  
Author(s):  
David M. Zucker
Keyword(s):  
Hazard Ratio ◽  
Rank Test ◽  
Percent Error ◽  
Log Rank Test

CDKN2A or CDKN2B homozygous deletion with high-immune infiltration as a favorable prognostic factor for lung adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20543-e20543
Author(s):  
Benxu Tan ◽  
Yonghong Chen ◽  
Lei Xia ◽  
Xian Yu ◽  
Yusheng Huang ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Lung Adenocarcinoma ◽  
Homozygous Deletion ◽  
Hazard Ratio ◽  
Gene Set Enrichment Analysis ◽  
Rank Test ◽  
Immune Infiltration ◽  
Log Rank Test ◽  
Significant Difference ◽  
Wild Group

e20543 Background: CDKN2A and CDKN2B both acted as tumor suppressor genes by regulating the cell cycle, which in humans were located at chromosome 9, band p21.3. The frequencies of homozygous deletion (HomDel) in CDKN2A and CDKN2B in lung adenocarcinoma (LUAD) were 12.5% and 12.1%, respectively. However, the genomic, immunogenomic features and impact on the prognosis of LUAD patients with CDKN2A/B HomDel were still unclear. Methods: The cohort of this study was from The Cancer Genome Atlas (TCGA). A total of 508 LUAD patients, including 99 CDKN2A/B HomDel (homdel) and 509 CDKN2A/B wild (wild). This study explored the difference of genomic and immunogenomic landscape between homdel and wild by analysis of whole-exome sequencing (WES) and RNA sequencing data. Results: The most frequently mutated genes were TP53, TTN, MUC16, and CSMD3. Their frequencies in homdel and wild are 46% and 48%, 43% and 46%, 35% and 41%, 33% and 38%, respectively. There was no significant difference of tumor mutational burden (TMB) between homdel and wild (median TMB, 133 in homdel vs 177 in wild; Wilcoxon test, p = 0.11), and clinical characteristics including age, gender, smoking history, and tumor stage were not significantly different between homdel and wild. Homdel had a shorter overall survival (OS) than wild (Log-rank test, p = 0.04, Hazard Ratio: 0.7, 95% CI: 0.49-1.02), but there was no significant difference in progression-free survival (PFS) (Log-rank test, p = 0.05, Hazard Ratio: 0.73, 95% CI: 0.51-1.04). We used single sample gene set enrichment analysis (ssGSEA) to calculate the enrichment score (ES) of 25 immune-related pathways such as antigen presentation and T cell-mediated immunity, and then used the consensus clustering algorithm (ConsensusClusterPlus) to cluster homdel and wild respectively, and both clustered into low and high immune infiltration groups. For the high immune infiltration and low immune infiltration in homdel and wild, high immune infiltration had a longer OS (Log-rank test, p = 0.009, Hazard Ratio: 2.19, 95% CI: 1.22-3.94) and PFS (Log-rank test, p = 0.044, Hazard Ratio: 1.8, 95% CI: 1.01-3.2) than low immune infiltration in homdel. However, there was no significant heterogeneity between high and immune infiltration in terms of PFS (Log-rank test, p = 0.28, Hazard Ratio: 1.21, 95% CI: 0.87-1.68) and OS (Log-rank test, p = 0.96, Hazard Ratio: 1.01, 95% CI: 0.71-1.44) in the wild group, the wild group had longer OS than homdel group with low immune infiltration (Log-rank test, p = 0.003, Hazard Ratio: 0.5, 95% CI: 0.29-0.88), while had the same OS with homdel with high immune infiltration, irrespective of immune infiltration. And so was PFS (Log-rank test, p = 0.005, Hazard Ratio: 0.48, 95% CI: 0.27-0.82). Conclusions: CDKN2A/B homdel was an unfavorable prognostic factor for LUAD, but which with high immune infiltration might improve patient survival time.

P2609H2FPEF score as a prognostic value in HFpEF patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Sueta ◽  
T Nishihara ◽  
E Yamamoto ◽  
K Tsujita
Keyword(s):  
Confidence Interval ◽  
Cardiovascular Events ◽  
Left Ventricular ◽  
Hazard Ratio ◽  
Left Ventricular Ejection ◽  
Rank Test ◽  
Characteristic Analysis ◽  
Simple Method ◽  
Log Rank Test ◽  
Cerebrovascular Events

Abstract Background The H2FPEF score is recognized as a simple method to diagnose heart failure (HF) with preserved left ventricular ejection fraction (HFpEF). Purpose We investigated the value of the H2FPEF score in predicting subsequent cardiovascular events in HFpEF patients. Methods This study was a retrospective, single-center, observational study. We calculated the H2FPEF scores for 404 consecutive HFpEF patients. Subjects were subdivided into low- (0–3), intermediate- (4–6), and high-score (7–9) groups and followed for 50-months. The primary and secondary endpoints were composite cardiovascular/ cerebrovascular events (cardiovascular death, non-fatal myocardial infarction, unstable angina pectoris, hospitalization for HF decompensation and non-fatal stroke) occurrence and HF-related events (hospitalization for HF decompensation) occurrence at 50-months, respectively. Results Kaplan–Meier analyses demonstrated a significantly higher incidence of cardiovascular/cerebrovascular events in proportion to a higher H2FPEF score (log-rank test, P=0.005). The HF-related event rate was higher in proportion to the H2FPEF score (log-rank test, P<0.001). Multivariate Cox hazard analyses identified the H2FPEF score (per 1 point) as an independent predictor of cardiovascular and HF-related events (Table, hazard ratio, 1.179; 95% confidence interval, 1.066–1.305; P=0.001 and hazard ratio, 1.288; 95% confidence interval, 1.134–1.463; P=0.001, respectively). Receiver operating characteristic analysis showed that the H2FPEF significantly predicted cardiovascular events (Figure A, AUC 0.626, 95% CI 0.557–0.693; P<0.001) and HF-related events (Figure B, AUC 0.680, 95% CI 0.600–0.759; P<0.001). The cutoff H2FPEF score was 5.5 for the identification of cardiovascular and HF-related events. Conclusion The H2FPEF score is a potentially useful marker for the prediction of cardiovascular and HF-related events in HFpEF patients.

scholarly journals Prognostic value of CD34 expression status in patients with myxofibrosarcomas and undifferentiated pleomorphic sarcomas

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshiya Sugiura ◽  
Rikuo Machinami ◽  
Seiichi Matsumoto ◽  
Hiroaki Kanda ◽  
Keisuke Ae ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Confidence Interval ◽  
Prognostic Value ◽  
Cox Model ◽  
Hazard Ratio ◽  
Rank Test ◽  
Log Rank Test ◽  
Cd34 Expression ◽  
Expression Status

AbstractIt is controversial whether patients with myxofibrosarcomas (MFSs) have better prognoses than those with undifferentiated pleomorphic sarcomas (UPSs). No useful prognostic factors have been established to date. We therefore aimed to evaluate the prognostic value of CD34 expression status in 192 patients with MFSs and UPSs. Using the log-rank test, we showed that patients with MFSs had a significantly better overall survival than did those with UPSs when defining the former as having a > 10% myxoid component (p = 0.03), but not when defining it as having a > 50% myxoid component (p = 0.1). Under the definition of MFSs as > 10% myxoid component, the log-rank test revealed that the diagnosis of the UPS and the CD34 loss (p < 0.001) were significant adverse predictors of overall survival. As per the Cox model, the CD34 loss remained an independent prognostic factor (hazard ratio = 3.327; 95% confidence interval 1.334–8.295), while the diagnosis of the UPS was a nonsignificant confounding factor (hazard ratio = 1.084; 95% confidence interval 0.679–1.727). In conclusion, CD34 expression status is a useful prognostic factor in patients with MFS and UPS, and it should be incorporated into grading systems that are used to predict outcomes.

Dementia and the Risk of Periodontitis: A Population-Based Cohort Study

2021 ◽  
pp. 002203452110372
Author(s):  
K.S. Ma ◽  
H. Hasturk ◽  
I. Carreras ◽  
A. Dedeoglu ◽  
J.J. Veeravalli ◽  
...  
Keyword(s):  
Cohort Study ◽  
Relative Risk ◽  
Propensity Score ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Rank Test ◽  
Confounding Factors ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Log Rank Test

Dementia and Alzheimer’s disease (AD) are proposed to be comorbid with periodontitis (PD). It is unclear whether PD is associated with dementia and AD independent of confounding factors. We aimed at identifying the relationship between the longitudinal risk of developing PD in a cohort of patients with dementia and AD who did not show any signs of PD at baseline. In this retrospective cohort study, 8,640 patients with dementia without prior PD were recruited, and 8,640 individuals without dementia history were selected as propensity score–matched controls. A Cox proportional hazard model was developed to estimate the risk of developing PD over 10 y. Cumulative probability was derived to assess the time-dependent effect of dementia on PD. Of the 8,640 patients, a sensitivity test was conducted on 606 patients with AD-associated dementia and 606 non-AD propensity score–matched controls to identify the impact of AD-associated dementia on the risk for PD. Subgroup analyses on age stratification were included. Overall 2,670 patients with dementia developed PD. The relative risk of PD in these patients was significantly higher than in the nondementia group (1.825, 95% CI = 1.715 to 1.942). Cox proportional hazard models showed that patients with dementia were more likely to have PD than individuals without dementia (adjusted hazard ratio = 1.915, 95% CI = 1.766 to 2.077, P < 0.0001, log-rank test P < 0.0001). The risk of PD in patients with dementia was age dependent ( P values for all ages <0.0001); younger patients with dementia were more likely to develop PD. The findings persisted for patients with AD: the relative risk (1.531, 95% CI = 1.209 to 1.939) and adjusted hazard ratio (1.667, 95% CI = 1.244 to 2.232; log-rank test P = 0.0004) of PD in patients with AD were significantly higher than the non-AD cohort. Our findings demonstrated that dementia and AD were associated with a higher risk of PD dependent of age and independent of systemic confounding factors.

Decrease of Mortality during Deferiprone Treatments: Results from A Large Randomised Cohort of Thalassemia Major Patients Under the Auspices of the Italian Society for Thalassemia and Hemoglobinopathies

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3885-3885 ◽  
Author(s):  
Aurelio Maggio ◽  
Angela Vitrano ◽  
Marcello Capra ◽  
Liana Cuccia ◽  
Francesco Gagliardotto ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cox Regression ◽  
Thalassemia Major ◽  
Randomised Clinical Trial ◽  
Hazard Ratio ◽  
Rank Test ◽  
Cardiac Damage ◽  
Treatment Groups ◽  
Log Rank Test

Abstract Prognosis of thalassemia major patients has dramatically improved in the past two decades. Previous papers, including retrospective and prospective non-randomised clinical trials, suggested that mortality, due mainly to cardiac damage, was less or completely absent in patients treated with DFP alone or with associated chelation treatment. For this reason, the main aim of this study was to evaluate whether the addition of deferiprone treatment was also associated with a mortality decrease among a large randomised cohort of thalassemia major patients. Survival analysis was performed among 264 thalassemia major patients assessed for eligibility from 09/30/2000 to 01/31/2008, during a long-term multicentre randomised clinical trial. The reported chelation therapies included sequential DFP-DFO, associated DFP and DFO, DFP and DFO interventions. The survival curves were compared by gender and treatment groups using the long-rank test. Cox regression models were used to explore association between risk for death among treatments and survival time. All statistical analyses were performed by STATA 9.2. All these patients performed DFO before the date of randomisation. One death was due to a graft versus host disease (GVHD) in a patient underwent bone marrow transplantation and this patient was censored at the time of transplant. The improved survival for sequential DFP-DFO, DFP-alone, and associated DFP-DFO treated patients versus DFO-treated was statistically significant (log-rank test, χ2= 18.64; p≤0.01). In fact, no deaths were reported during DFP-alone and DFP-DFO associated treatments along a 564.5 person-years period of observation. Only one death was reported during DFP-DFO sequential treatment in a patient who had experienced 1-year before an episode of heart failure. All other ten deaths were among patients under DFO treatment. The hazard ratio for death of DFO treatment versus other treatments was 27.78 (p= 0.002). The main factors correlated with increased hazard ratio for death were cirrhosis, arrhythmia, previous episode of heart failure, diabetes, hypogonadism, hypothyroidism. No correlation between serum ferritin levels and hazard ratio for death was found. These results confirm as deferiprone alone or in addition to deferoxamine intervention is able to reduce mortality in thalassemia major patients probably because of its specific cardioprotective effect occurring independently from body iron overloading

Statin Use Significantly Improves Overall Survival in High-Grade Endometrial Cancer

2016 ◽  
Vol 26 (9) ◽  
pp. 1642-1649 ◽  
Author(s):  
Christine H. Feng ◽  
Charlie M. Miller ◽  
Meaghan E. Tenney ◽  
Nita K. Lee ◽  
S. Diane Yamada ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Endometrial Cancer ◽  
High Risk ◽  
Confidence Interval ◽  
Hazard Ratio ◽  
Rank Test ◽  
Log Rank Test ◽  
Definitive Therapy ◽  
Statin Use

ObjectivePreclinical data and recent epidemiological studies suggest that statins have antiproliferative and antimetastatic effects in various cancer cells, and reduce cancer mortality and recurrence. We study the effect of statin use on survival outcomes and recurrence rates in patients with endometrial cancer with high-risk histology.Materials and MethodsAll patients receiving definitive therapy for high-risk endometrial cancer from 1995 to 2014 were retrospectively reviewed. Health characteristics at baseline were collected, and statin use was determined from medical records. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards regression models were used for univariate and multivariate analysis to determine independent factors associated with OS and PFS.ResultsA total of 199 patients were included in the study, of which 76 were hyperlipidemic and 50 used statins. The median follow-up time was 31 months from time of diagnosis. Hyperlipidemic patients who used statins had improved OS compared with hyperlipidemic patients not using statins (hazard ratio, 0.42; 95% confidence interval, 0.20–0.87;P= 0.02). Statin use was also associated with improved PFS (hazard ratio, 0.47; 95% confidence interval, 0.23–0.95;P= 0.04) on multivariate analysis. Hyperlipidemic patients who used statins had borderline improved freedom from local failure compared with hyperlipidemic cases not using statins (P= 0.08, log-rank test). Statin use was not found to be associated with improved cancer-specific mortality.ConclusionsStatin use is independently associated with significant improvements in PFS for the overall group and PFS and OS in the hyperlipidemic group.

Stem Cell Mobilization With Plerixafor + G-CSF In Comparison To Cyclophosphamide + G-CSF and Time-To-Progression After Autologous Stem Cell Transplantation For Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3354-3354
Author(s):  
Alfred L. Garfall ◽  
Andrew Dougherty ◽  
Dan T. Vogl ◽  
Brendan M Weiss ◽  
Adam D Cohen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Maintenance Therapy ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Rank Test ◽  
Hematopoietic Stem ◽  
Log Rank Test ◽  
Induction Regimen ◽  
Cell Mobilization

Abstract Background G-CSF in combination with either cyclophosphamide (G-Cy) or plerixafor (G-P) safely mobilizes hematopoietic stem cells of adequate quality and quantity for auto-SCT in patients with multiple myeloma. Few studies have examined the impact of mobilization regimen on post-transplant disease control, particularly since the availability of plerixafor. Methods We retrospectively compared time-to-progression (TTP) after single melphalan-conditioned (140-200 mg/m2) auto-SCT in a single-institution cohort in which stem cells were mobilized with either cyclophosphamide 3 gm/m2 + G-CSF 10 mcg/kg/day x 10-14 days (G-Cy, n=93) or G-CSF 10 mcg/kg/day x 5-9 days with addition of plerixafor 240 mcg/kg/day starting on day 5 (G-P, n=55). Choice of mobilization regimen was according to physician preference. All patients had symptomatic multiple myeloma and had completed induction therapy with a regimen containing bortezomib and/or lenalidomide/thalidomide. Transplants conducted from January 2010 to May 2013, when commercially-available plerixafor was first used at our institution, were included in the analysis. Patients receiving tandem or salvage transplants and patients receiving investigational therapies in conjunction with transplant were excluded. Maintenance therapy was prescribed at the discretion of the treating physician. Progression was scored according to IMWG criteria. Results The G-Cy and G-P cohorts were well matched for age, gender, and baseline multiple myeloma prognostic factors (see table). Cytogenetic data and beta-2-microglobulin measurements were not consistently available at baseline. Patients receiving G-P were more likely to have a >60 day interval between mobilization and transplant (P<0.0001) and >1 year interval between diagnosis and transplant (P=0.05). At time of transplant, hemoglobin was lower in the G-Cy group (P=0.0003), and platelet count was lower in the G-P group (P=0.035). Renal function at time of transplant was similar between the two groups. Patients in the G-P group were more likely to have received dose-reduced melphalan (<200 mg/m2) (p=0.03). The G-P group had higher ALC at day +15, which has been reported previously as a favorable prognostic factor for progression-free and overall survival. Median follow-up was 22 months. TTP was significantly different in the two groups (p=0.0095, log-rank test); median TTP was 25 months in the G-Cy group vs. 13 months in the G-P group (see figure). The difference in TTP remained significant when patients were excluded from the analysis who were transplanted more than 1 year after diagnosis (median TTP 26 vs. 13 months, P=0.0136 by log-rank test) or who were transplanted more than 60 days after mobilization (TTP 25 vs 13 months, P=0.0017 by log-rank test). Other variables that were significantly correlated with inferior TTP included IgA isotype (p=0.022) and receipt of >1 induction regimen (p=0.0077). In a univariate Cox regression, mobilization with G-P was associated with a hazard ratio of 2.1 (95% CI 1.2-3.9, p=0.011) for progression. In a multivariate Cox regression incorporating presence of IgA isotype, receipt of >1 induction regimen, mobilization regimen, age at transplant, time from diagnosis to transplant, time from mobilization to transplant, receipt of reduced melphalan dose, creatinine/hemoglobin/platelet count at time of transplant, ALC on day +15, and receipt of maintenance therapy, the association between G-P and inferior TTP was preserved (hazard ratio 2.8, 95% CI 1.3-6.0, p=0.007). The only other statistically significant variable was receipt of >1 induction regimen (hazard ratio 2.3, 95% CI 1.3-4.4, p=0.008). Receipt of maintenance therapy had a protective effect that approached statistical significance (hazard ratio 0.58, 95% CI 0.33-1.03, P=0.065). There were no significant differences in overall survival between the G-Cy and G-P groups. Conclusion Hematopoietic stem cell mobilization with G-P was associated with significantly shorter post-transplant TTP compared to G-Cy in this single-institution cohort of multiple myeloma patients. We cannot conclude whether this association is due to effects of the mobilization regimen or confounding variables not accounted for in our analysis. This association warrants examination in a larger, multi-institution cohort. Disclosures: Stadtmauer: Sanofi: Consultancy.

Safety and efficacy of bevacizumab biosimilar in glioma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14541-e14541
Author(s):  
Gunjesh Kumar Singh ◽  
Hollis D'souza ◽  
Sujay Srinivas ◽  
Dilip Harindran Vallathol ◽  
Mounika Boppana ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Cox Regression ◽  
Low Cost ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Recurrent Glioma ◽  
Rank Test ◽  
P Value ◽  
Cox Regression Analysis ◽  
Log Rank Test

e14541 Background: Anti-VEGF antibody Bevacizumab (Avastin: Roche Pharma AG) is the recommended drug for recurrent glioma. Multiple low-cost bio-similars of this drug are now available however their clinical efficacy has never been compared against the original molecule. The aim of the current analysis is to compare the overall survival (OS) between recurrent glioma patients with bio-similar and innovator molecule. Methods: Adult recurrent glioma patients treated with bevacizumab from 1st July 2015 to 30th July 2019 were identified from the Neuro-Medical Oncology database. These patients were either offered Avastin or Bevacizumab biosimilar (BevaciRel: Reliance Life sciences or Bryta: Zydus Oncosciences) depending upon the financial affordability. The primary endpoint of the study was OS. It was defined as the time in months from the start of bevacizumab to death. Progression-free survival (PFS) was defined as the time in months from the start of bevacizumab to progression or death. The time to event variables was estimated using Kaplan Meier method. The median with its 95% confidence interval (CI) was calculated using Brookmeyer and Crowley method. The estimates were compared between the original and bio-similar bevacizumab cohort using the log-rank test. The hazard ratio was calculated using COX regression analysis. Results: There were 82 patients, out of which 57 received innovator and 25 received bio-similar bevacizumab. At median follow up of 26 months, 76 patients had an event for progression. The median PFS was 3.66 (95% CI 2.08 to 5.25) and 3.3 months (95% CI 2.38 to 4.21) in innovator and bio-similar arm respectively (Log-rank test P-value = 0.072). The hazard ratio for progression was 0.61 (95% CI 0.35 to 1.05; P-value = 0.075). At the time of data cutoff, there were 69 deaths. The median OS was 5.53 (95% CI, 5.07 to 5.99) vs 7.33 months (95% CI, 5.63 to 9.03) in innovator and bio-similar arm respectively (Log-rank test P-value = 0.51). The hazard ratio for death was 1.21 (95% CI, 0.67 to 2.17; p-value = 0.51). Conclusions: In the brain tumor patients, both innovator and bio-similar bevacizumab seem to have similar clinical efficacy.

Characteristics and outcomes of Embolic Stroke of Undetermined Source according to stroke severity

2020 ◽  
Vol 15 (8) ◽  
pp. 866-871
Author(s):  
Ioannis Leventis ◽  
Kalliopi Perlepe ◽  
Dimitrios Sagris ◽  
Gaia Sirimarco ◽  
Davide Strambo ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Rank Test ◽  
Stroke Recurrence ◽  
Cumulative Probability ◽  
Stroke Severity ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Product Limit

Background and aims Patients with embolic strokes of undetermined source (ESUS) usually present with mild symptoms. We aimed to compare the baseline characteristics between mild and severe ESUS, identify predictors for severe ESUS, and assess outcomes of patients with severe ESUS. Methods In the AF-ESUS (AF-ESUS) dataset, we stratified ESUS severity using the median National Institutes of Health Stroke Scale (NIHSS) score on admission as cut-off. We performed multivariable stepwise regression analyses to identify independent predictors of severe ESUS and to assess the association between ESUS severity and stroke recurrence, death, and new incident atrial fibrillation (AF) on follow-up. The 10-year cumulative probabilities of outcome incidence were estimated by the Kaplan–Meier product limit method. Results In 772 patients (median NIHSS: 6 (interquartile range: 3–12)), 414 (53.6%) patients had severe ESUS (i.e. NIHSS ≥6). Female sex was the only independent predictor for severe ESUS (odds ratio: 1.72 (1.27–2.33)). The rates of recurrence (3.3%/year vs. 3.4%/year, adjusted-hazard ratio: 1.09 (0.73–1.62)) and new incident AF (13.5% vs. 17.0%, adjusted odds ratio: 0.67 (0.44–1.03)) were similar between severe and mild ESUS, but mortality was higher (5.4%/year vs. 3.7%/year, adjusted-hazard ratio: 1.51 (1.05–2.16)) in severe ESUS. The 10-year cumulative probability for stroke recurrence was similar between severe and mild ESUS (38.1% (29.2–48.6) vs. 36.6% (27.8–47.0), log-rank test: 0.01, p = 0.920). The 10-year cumulative probability of death was higher in patients with severe ESUS compared with mild ESUS (40.5% (32.5–50.0) vs. 34.0% (26.0–43.6) respectively; log-rank test: 4.54, p = 0.033). Conclusions Women have more severe ESUS compared with men. Patients with severe ESUS have similar rates of stroke recurrence and new incident AF, but higher mortality compared with mild ESUS.

scholarly journals A modified weighted log-rank test for confirmatory trials with a high proportion of treatment switching

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259178
Author(s):  
José L. Jiménez ◽  
Julia Niewczas ◽  
Alexander Bore ◽  
Carl-Fredrik Burman
Keyword(s):  
Statistical Power ◽  
Experimental Treatment ◽  
Hazard Ratio ◽  
Rank Test ◽  
Control Group ◽  
Potential Hazard ◽  
Intention To Treat ◽  
Treatment Switching ◽  
Log Rank Test ◽  
The Impact

In confirmatory cancer clinical trials, overall survival (OS) is normally a primary endpoint in the intention-to-treat (ITT) analysis under regulatory standards. After the tumor progresses, it is common that patients allocated to the control group switch to the experimental treatment, or another drug in the same class. Such treatment switching may dilute the relative efficacy of the new drug compared to the control group, leading to lower statistical power. It would be possible to decrease the estimation bias by shortening the follow-up period but this may lead to a loss of information and power. Instead we propose a modified weighted log-rank test (mWLR) that aims at balancing these factors by down-weighting events occurring when many patients have switched treatment. As the weighting should be pre-specified and the impact of treatment switching is unknown, we predict the hazard ratio function and use it to compute the weights of the mWLR. The method may incorporate information from previous trials regarding the potential hazard ratio function over time. We are motivated by the RECORD-1 trial of everolimus against placebo in patients with metastatic renal-cell carcinoma where almost 80% of the patients in the placebo group received everolimus after disease progression. Extensive simulations show that the new test gives considerably higher efficiency than the standard log-rank test in realistic scenarios.

Sign in / Sign up

Export Citation Format

Share Document