Comparison of Survivorship by the Logrank Test: Criticisms and Alternatives

Ecology ◽  
1991 ◽  
Vol 72 (6) ◽  
pp. 2290-2293 ◽  
Author(s):  
Michael J. Hutchings ◽  
Karen D. Booth ◽  
Stephen Waite
Keyword(s):  
Logrank Test

scholarly journals Factors Affecting the Control of Chronic Rhinosinusitis With Nasal Polyps: A Comparison in Patients With or Without NERD

2021 ◽  
Vol 12 ◽  
pp. 215265672110038
Author(s):  
Markus Jukka Lilja ◽  
Anni Koskinen ◽  
Paula Virkkula ◽  
Seija Inkeri Vento ◽  
Jyri Myller ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Female Gender ◽  
Sinus Surgery ◽  
Logrank Test ◽  
Free Survival ◽  
Factors Affecting ◽  
Advanced Therapy ◽  
And Gender

Objectives The aim was to compare the control of chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS), in patients with/without nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). Study Desing: A retrospective hospital-based sample of CRSwNP patients with/without NERD with follow-up. Setting Tertiary rhinology centers. Methods Electronic patient record data from 116 CRSwNP patients (46 with NERD and 70 without NERD) undergoing ESS during 2001–17 were studied. Mean follow-up time was 9.9 years (range 1.1–15.3). Endpoints reflecting uncontrolled CRSwNP were revision ESS, and need for rescue/advanced therapy (e.g. antibiotics, oral corticosteroids and/or biological therapy) during follow-up. NERD was variable of interest and gender, age, asthma, allergic rhinitis (AR), smoking, Lund-Mackay (LM) score of sinus computed tomography scans previous ESS and baseline total ethmoidectomy were used as covariates. Results Twenty-one (49.7%) NERD patients and 18 (25.7%) non-NERD patients underwent revision ESS within a mean ± SD of 4.3 ± 2.8 and 3.7 ± 2.6 years, respectively (p = .013, by Logrank test). In Cox´s regression models, NERD, female gender, young age, asthma, AR, previous ESS, and lack of total ethmoidectomy were associated with revision-ESS. In adjusted model, only the total ethmoidectomy predicted revision-free survival. In adjusted logistic regression model, there was an insignificant trend that NERD and LM score were associated with the need for rescue/advanced therapy in the follow-up. Conclusions Patients with NERD had higher risk of uncontrolled CRSwNP than patient group without NERD, as measured by revision ESS and/or need for rescue/advanced therapy in the follow-up. In addition, baseline total ethmoidectomy was associated with revision-free survival.

scholarly journals A global logrank test for adaptive treatment strategies based on observational studies

2013 ◽  
Vol 33 (5) ◽  
pp. 760-771 ◽  
Author(s):  
Zhiguo Li ◽  
Marcia Valenstein ◽  
Paul Pfeiffer ◽  
Dara Ganoczy
Keyword(s):  
Observational Studies ◽  
Treatment Strategies ◽  
Logrank Test ◽  
Adaptive Treatment ◽  
Adaptive Treatment Strategies

scholarly journals A SAS macro for a clustered logrank test

2011 ◽  
Vol 104 (2) ◽  
pp. 266-270 ◽  
Author(s):  
Margaret R. Stedman ◽  
David R. Gagnon ◽  
Robert A. Lew ◽  
Sin-Ho Jung ◽  
Elena Losina ◽  
...  
Keyword(s):  
Logrank Test ◽  
Sas Macro

Abstract W P113: Prolonged Use of Clopidogrel and Aspirin and Stroke Risk in Intracranial Stenosis in SAMMPRIS

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Christine Holmstedt ◽  
Michael J Lynn ◽  
Tanya N Turan ◽  
Colin P Derdeyn ◽  
David Fiorella ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Statistical Power ◽  
Intracranial Stenosis ◽  
Antithrombotic Agent ◽  
Logrank Test ◽  
Major Hemorrhage ◽  
Exact Test ◽  
Lipid Disorder ◽  
Primary Endpoints ◽  
Event Rates

Background: In the SAMMPRIS trial, the use of combination aspirin and clopidogrel for 90 days after enrollment could be one reason that the outcome of patients in the medical arm was better than expected. The SAMMPRIS protocol required stopping clopidogrel after 90 days unless the patient had a non-neurological indication for continued use. We sought to compare outcomes in patients on vs. off clopidogrel beyond 90 days. Methods: For patients who did not have a primary endpoint within 90 days after enrollment (n = 397), we compared baseline features (t and Fisher’s exact tests), survival curves for the primary endpoint beyond 90 days after enrollment (the logrank test), and major hemorrhages (Fisher’s exact test) in patients on vs. off clopidogrel in the medical arm and stenting arms. Results: In the medical and stenting groups combined, baseline factors that were significantly (p<0.05) different between those on vs. off clopidogrel beyond 90 days (all higher in on clopidogrel group) were: age, diabetes, lipid disorder, coronary disease, SBP, and on antithrombotic agent at qualifying event. The table shows the primary endpoints and major hemorrhages in patients on vs. off clopidogrel in both treatment groups. Conclusion: This analysis, which was underpowered to detect even very large differences in event rates, suggests that prolonged use of clopidogrel plus aspirin may lower the risk of stroke in medically treated patients with intracranial stenosis, but increase the risk of major hemorrhage. Further studies with higher statistical power are needed to test this hypothesis.

Impact of IGF-I and CYP19 Gene Polymorphisms on the Survival of Patients With Metastatic Prostate Cancer

2006 ◽  
Vol 24 (13) ◽  
pp. 1982-1989 ◽  
Author(s):  
Norihiko Tsuchiya ◽  
Lizhong Wang ◽  
Hiroyoshi Suzuki ◽  
Takehiko Segawa ◽  
Hisami Fukuda ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Genetic Polymorphisms ◽  
Metastatic Prostate Cancer ◽  
Genetic Factors ◽  
Response To Treatment ◽  
Logrank Test ◽  
Ca Repeat ◽  
Igf I

Purpose The prognosis of metastatic prostate cancer significantly differs among individuals. While various clinical and biochemical prognostic factors for survival have been suggested, the progression and response to treatment of those patients may also be defined by host genetic factors. In this study, we evaluated genetic polymorphisms as prognostic predictors of metastatic prostate cancer. Patients and Methods One hundred eleven prostate cancer patients with bone metastasis at the diagnosis were enrolled in this study. Thirteen genetic polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism or an automated sequencer with a genotyping software. Results Among the polymorphisms, the long allele (over 18 [CA] repeats) of insulin-like growth factor-I (IGF-I) and the long allele (over seven [TTTA] repeats) of cytochrome P450 (CYP) 19 were significantly associated with a worse cancer-specific survival (P = .016 and .025 by logrank test, respectively). The presence of the long allele of either the IGF-I or CYP19 polymorphisms was an independent risk factor for death (P = .019 or .026, respectively). Furthermore, the presence of the long allele of both the IGF-I and CYP19 polymorphisms was a stronger predictor for survival (P = .001). Conclusion The prognosis of metastatic prostate cancer patients is suggested to be influenced by intrinsic genetic factors. The IGF-I (CA) repeat and CYP19 (TTTA) repeat polymorphisms may be novel predictors in prostate cancer patients with bone metastasis at the diagnosis.

The Average Hazard Ratio – A Good Effect Measure for Time-to-event Endpoints when the Proportional Hazard Assumption is Violated?

2018 ◽  
Vol 57 (03) ◽  
pp. 089-100 ◽  
Author(s):  
Werner Brannath ◽  
Matthias Brückner ◽  
Meinhard Kieser ◽  
Geraldine Rauch
Keyword(s):  
Proportional Hazards ◽  
Weighting Function ◽  
Hazard Ratio ◽  
Group Differences ◽  
Proportional Hazard ◽  
Time To Event ◽  
Logrank Test ◽  
Proportional Hazard Assumption ◽  
Effect Measure ◽  
Average Hazard Ratio

Summary Background: In many clinical trial applications, the endpoint of interest corresponds to a time-to-event endpoint. In this case, group differences are usually expressed by the hazard ratio. Group differences are commonly assessed by the logrank test, which is optimal under the proportional hazard assumption. However, there are many situations in which this assumption is violated. Especially in applications were a full population and several subgroups or a composite time-to-first-event endpoint and several components are considered, the proportional hazard assumption usually does not simultaneously hold true for all test problems under investigation. As an alternative effect measure, Kalbfleisch and Prentice proposed the so-called ‘average hazard ratio’. The average hazard ratio is based on a flexible weighting function to modify the influence of time and has a meaningful interpretation even in the case of non-proportional hazards. Despite this favorable property, it is hardly ever used in practice, whereas the standard hazard ratio is commonly reported in clinical trials regardless of whether the proportional hazard assumption holds true or not. Objectives: There exist two main approaches to construct corresponding estimators and tests for the average hazard ratio where the first relies on weighted Cox regression and the second on a simple plug-in estimator. The aim of this work is to give a systematic comparison of these two approaches and the standard logrank test for different time-toevent settings with proportional and nonproportional hazards and to illustrate the pros and cons in application. Methods: We conduct a systematic comparative study based on Monte-Carlo simulations and by a real clinical trial example. Results: Our results suggest that the properties of the average hazard ratio depend on the underlying weighting function. The two approaches to construct estimators and related tests show very similar performance for adequately chosen weights. In general, the average hazard ratio defines a more valid effect measure than the standard hazard ratio under non-proportional hazards and the corresponding tests provide a power advantage over the common logrank test. Conclusions: As non-proportional hazards are often met in clinical practice and the average hazard ratio tests often outperform the common logrank test, this approach should be used more routinely in applications.

CASPAR (Alliance A031902): A randomized, phase III trial of enzalutamide (ENZ) with rucaparib (RUCA)/placebo (PBO) as a novel therapy in first-line metastatic castration-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS181-TPS181
Author(s):  
Arpit Rao ◽  
Charles J. Ryan ◽  
David James VanderWeele ◽  
Glenn Heller ◽  
Lionel D Lewis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiographic Progression ◽  
Synthetic Lethality ◽  
Short Form ◽  
Parp Inhibitor ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Dna Breaks ◽  
Phase 3 ◽  
Logrank Test

TPS181 Background: Treatment with novel antiandrogens (NAA) and androgen deprivation therapy prolongs life in men with mCRPC but approximately 40% patients (pts) have radiographic progression within the first year. Inhibition of androgen receptor signaling results in increased double-strand DNA breaks and genomic instability. NAA+PARP inhibitor (PARPi) combinations have shown induction of synthetic lethality by this mechanism in multiple preclinical studies. Homologous recombination repair (HRR) gene aberrations do not appear to be necessary for this synergy and an NAA+PARPi combination has shown improved radiographic progression-free survival (rPFS) in HRR-wild-type pts compared with NAA alone. Methods: CASPAR (A031902) is a randomized phase 3 study in which 984 pts will be randomized on a 1:1 basis to ENZ plus RUCA/PBO. A PK substudy will precede the phase 3 portion and enroll 6-18 pts to various doses of ENZ plus RUCA to establish safety and evaluate any clinically-significant drug-drug interactions (S-DDI). Treatment will be continued until disease progression and cross-over is not allowed. Co-primary endpoints are rPFS and overall survival (OS). The OS analysis will be undertaken as a primary endpoint if the rPFS endpoint is met. For a one-sided logrank test with a type 1 error rate equal to 0.025, the study has 90% power to detect a hazard ratio (HR) of 0.71 in rPFS (median rPFS of 15 and 21 months in control and combination arms, respectively), and 80% power to detect an HR of 0.80 in OS (median OS of 32 and 40 months, respectively). Key secondary endpoints are rPFS and OS in pts with vs without pathogenic BRCA1, BRCA2, or PALB2 mutations; and differences in adverse events and quality of life (QOL) outcomes between the treatment arms. QOL assessments include Functional Assessment of Cancer Therapy–Prostate (FACT-P), Brief Pain Inventory Short Form (BPI-SF), and EQ-5D-5L. A key correlative endpoint is the concordance between tissue and plasma ctDNA-based HRR testing. Key eligibility criteria are age ≥ 18 years, ECOG PS 0-2, biopsy-proven prostate adenocarcinoma, progressive (PSA or radiographic) disease per Prostate Cancer Working Group 3 guidelines, measurable or non-measurable disease per RECIST 1.1, no prior treatment for mCRPC (prior abiraterone, darolutamide, or apalutamide in non-mCRPC setting is allowed), no significant uncontrolled comorbidity, and no medications with S-DDI with ENZ/RUCA. HRR gene aberration is not required for enrollment. All pts will undergo next-generation targeted-exome sequencing from archival tumor tissue (new biopsy only required if no archival tissue available). CASPAR is available for participation to all US-NCTN sites starting in October 2020 with a projected enrollment of 3 years. Support: U10CA180821, U10CA180882; acknowledgments.alliancefound.org. Clinical trial information: NCT04455750.

Abstract T MP35: Frequency, Risk Factors, and Impact of Coexistent Small Vessel Disease in the SAMMPRIS Trial

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Hyung-Min Kwon ◽  
Michael J Lynn ◽  
Tanya N Turan ◽  
Colin P Derdeyn ◽  
David Fiorella ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Stroke Recurrence ◽  
Logrank Test ◽  
Exact Test ◽  
Vessel Disease ◽  
Atherosclerotic Stenosis ◽  
The Impact

Background: Intracranial atherosclerotic stenosis (ICAS) and small vessel disease (SVD) may coexist. We investigated the frequency and risk factors for SVD in SAMMPRIS patients and the impact of SVD on stroke recurrence in the medical arm of the trial. Methods: Of 451 patients enrolled in SAMMPRIS, 313 had baseline brain MRIs read centrally for SVD. SVD was defined by any of the following: old lacunar infarction, Fazekas score of 2-3 for white matter hyperintensities, or microbleeds. We compared risk factors in patients with vs. without SVD using Fisher’s exact test (for percentages), independent groups t test (for means) or Wilcoxon rank sum test (for medians), and compared the survival curves of patients with vs. without SVD in the medical arm for ischemic stroke in the territory of the stenotic artery and any ischemic stroke using the logrank test. Results: Of the 313 patients, 161 (51.4%) had SVD on the baseline MRI. Variables that were significantly (p<0.05) higher in patients with SVD were age, diabetes, lipid disorder, baseline SBP, coronary disease, and old infarct in the territory. The Kaplan-Meier curves in the figure show that patients with SVD were at significantly higher risk of any ischemic stroke (p = 0.048) but not stroke in the territory (p = 0.10) compared with patients without SVD. Conclusion: SVD in patients with ICAS is common, especially in patients who are older, diabetic, hyperlipidemic, and have higher SBP. Patients with ICAS and coexistent SVD are at higher risk of any ischemic stroke but may not be at higher risk for stroke in the territory.

NACRE: A randomized study comparing short course radiotherapy with radiochemotherapy for locally advanced rectal cancers in the elderly—Preliminary results.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 4-4
Author(s):  
Eric FRANCOIS ◽  
Mandy Pernot ◽  
Philippe Ronchin ◽  
Elodie Nouhaud ◽  
Isabelle Martel Lafay ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Locally Advanced ◽  
The Elderly ◽  
R0 Resection ◽  
Resection Rate ◽  
Logrank Test ◽  
Delayed Surgery ◽  
Short Course ◽  
Short Course Radiotherapy

4 Background: Neoadjuvant therapy followed by total mesorectal surgery is the standard of care for locally advanced rectal carcinoma (RC). In the elderly, often underrepresented in clinical trials, but who represent a very large number of patients, therapeutic proposals are not based on high levels of evidence. The NACRE study investigated the role of short course radiotherapy with delayed surgery in this population. Methods: The PRODIGE 42-GERICO 12 NACRE is a multicenter randomized clinical trial aimed at comparing Arm A preop radiochemotherapy (RCT) (50 Gy, 2Gy/fraction [fr]; 25 fr + capecitabine) and delayed surgery and Arm B short course radiotherapy (25 gy, 5Gy/fr, 5fr) and delayed surgery. Eligible patients (pts) had cT3 or cT4 (or cT2 of the very low rectum), M0 rectal adenocarcinomas <12 cm from the anal verge, age ≥75years, and WHO PS ≤2. Randomization was stratified by center, T (T2/T3-T4) stage and Age (≤80 or >80 years). Two primary end-points will be analyzed according to the hierarchical sequential procedure: firstly R0 resection rate (non-inferiority test with a 8% non-inferiority margin), secondly preservation of autonomy using IADL score (superiority test with 15% absolute difference margin); secondary end-point will be survival and toxicity. We present here the results for R0 resection, survival and toxicities. Results: 29 sites randomized 101 patients from 01/2016 to 08/2019, 59 were males (58.4%), median age was 80 years (range 75-91). Pts characteristics were well balanced. 14% of pts in arm A did not receive all of the planned neoadjuvant treatment compared to 0% in arm B. The R0 resection rate in arm B (86.0% [IC95% 73-94%]) was not-inferior to the R0 resection rate in arm A (89.8% [ic95% 77-97%]), p=0.04 (non inferiority test). With a median follow-up of 15.8 months (CI95%: 14.8-26.0), the 6 months death rate was 10.0% (CI95%: 3.0-22.0) in arm A and 3.92% (CI95%: 0 -13.0) in arm B. There is a significant difference in overall survival between the two arm in favor of arm B (p=0.04, LogRank test), and there is a trend in favor of arm B for specific survival (p=0.06 LogRank test). Disease free survival is not statistically different (p=0.9). 13 serious adverse events were observed in arm A during preoperative phase, 7 in arm B, 16 and 10 respectively during the post-operative phase. Conclusions: These preliminary results show that short course radiotherapy with delayed surgery is associated with better compliance than radiochemotherapy in elderly patients and could give an advantage in overall survival. This regimen may be preferred in elderly patients. Clinical trial information: NCT02551237.

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