Planning and evaluating clinical trials with composite time-to-first-event endpoints in a competing risk framework

2013 ◽  
Vol 32 (21) ◽  
pp. 3595-3608 ◽  
Author(s):  
G. Rauch ◽  
J. Beyersmann
Keyword(s):  
Clinical Trials ◽  
Competing Risk ◽  
Risk Framework

scholarly journals Competing risk and heterogeneity of treatment effect in clinical trials

Trials ◽  
2008 ◽  
Vol 9 (1) ◽  
Author(s):  
David M Kent ◽  
Alawi Alsheikh-Ali ◽  
Rodney A Hayward
Keyword(s):  
Clinical Trials ◽  
Treatment Effect ◽  
Competing Risk ◽  
Heterogeneity Of Treatment Effect

Risk Assessment Tool for Distant Recurrence After Platinum-Based Concurrent Chemoradiation in Patients With Locally Advanced Cervical Cancer: A Korean Gynecologic Oncology Group Study

2012 ◽  
Vol 30 (19) ◽  
pp. 2369-2374 ◽  
Author(s):  
Sokbom Kang ◽  
Byung-Ho Nam ◽  
Jeong-Yeol Park ◽  
Sang-Soo Seo ◽  
Sang-Young Ryu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Clinical Trials ◽  
Fdg Pet ◽  
Locally Advanced ◽  
Distant Recurrence ◽  
Competing Risk ◽  
Advanced Cervical Cancer ◽  
Concordance Index ◽  
Good Discrimination ◽  
Locally Advanced Cervical Cancer

Purpose Our study aimed to develop a model to predict distant recurrence in locally advanced cervical cancer, which can be used to select high-risk patients in enriched clinical trials. Patients and Methods Our study was a retrospective analysis of a multi-institutional cohort of patients treated between 2001 and 2009. According to the order of data submission, data from three institutions were allocated to a model development cohort (n = 434), and data from the remaining two institutions were allocated to an external validation cohort (n = 115). Patient information including [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) data and clinical outcome was modeled using competing risk regression analysis to predict 5-year cumulative incidence of distant recurrence. Results The competing risk analysis revealed that the following four parameters were significantly associated with distant recurrence: pelvic and para-aortic nodal positivity on FDG-PET, nonsquamous cell histology, and pretreatment serum squamous cell carcinoma antigen levels. This four-parameter model showed good discrimination and calibration, with a bootstrap-adjusted concordance index of 0.70. Also, the validation set showed good discrimination with a bootstrap-adjusted concordance index of 0.73. A user-friendly Web-based nomogram predicting 5-year probability of distant recurrence was developed. Conclusion We have developed a robust model to predict the risk of distant recurrence in patients with locally advanced cervical cancer. Further, we discussed how the selective enrichment of the patient population could facilitate clinical trials of systemic chemotherapy in locally advanced cervical cancer.

scholarly journals Admission Rothman Index, Aspirin, and Intermediate Dose Anticoagulation Effects on Outcomes in COVID-19: A Multi-Site Propensity Matched Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 23-24
Author(s):  
George Goshua ◽  
Yiwen Liu ◽  
Matthew L. Meizlish ◽  
Rebecca Fine ◽  
Kejal Amin ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Clinical Trials ◽  
Research Funding ◽  
Hospitalized Patients ◽  
Competing Risk ◽  
Hospital Death ◽  
Prophylactic Dose ◽  
Anti Platelet Therapy ◽  
Multivariable Regression ◽  
Intermediate Dose

Introduction: Venous thromboembolism and in-situ small vessel thrombosis are increased in hospitalized patients with COVID-19 in several patient cohorts. Endotheliopathy and activation of both platelets and coagulation predict critical illness and death. For these reasons the use of anti-platelet agents and increased-intensity anticoagulation in the care of hospitalized patients with COVID-19 is under intense study in several clinical trials. We sought to examine the impact of aspirin and anticoagulation on hospitalization outcomes. Methods: We examined outcomes in a large multi-site cohort of consecutive, hospitalized, COVID-19 laboratory confirmed patients under a risk-stratified treatment algorithm from March 13 through June 18, with a focus on efficacy of aspirin and/or increased-intensity anticoagulation. Out of 4150 identified hospitalized patients with COVID-19, we created 3 study cohorts. The overall cohort (2785 patients) excluded pediatric patients, those with incomplete electronic data, and those with multiple admissions. The aspirin (1956 patients) and anticoagulation (1623 patients) cohorts were nested within the overall cohort; the former excluded patients on any home anti-platelet therapy or those who received non-aspirin anti-platelet therapy in the hospital, while the latter excluded patients who did not receive prophylactic or intermediate dose anticoagulation in the hospital. The primary outcome was in-hospital death. Secondary outcomes were time-to-death with a competing risk (time-to-hospital-discharge), escalation to ICU, length-of-stay and use of mechanical ventilation. Variables examined included age, gender, BMI, race, Rothman Index (RI), D-dimer (DD) and patient co-morbidities including cardiovascular disease, chronic kidney disease, and prior VTE. The aspirin and anticoagulation cohorts underwent propensity score (PS) matching utilizing variables found to be significant in multivariable regression modeling in the overall cohort with 638 and 386 patients, respectively. Results: Univariate followed by multivariable regression modeling in the 2785 patient overall cohort established a novel role for RI, and independent roles for age, BMI, and maximum DD, in predicting severity of illness. In all cohorts the 50th and lower percentile of admission RI was predictive of mortality in multivariable modeling (i.e. aspirin: 3rd and 4th admission RI quartiles with HR = 0.18 for both, p<0.001 for both). In PS matched patients, aspirin was associated with a significant decrease in mortality (OR 0.65 [0.42, 0.98], p=0.044) and a significant increase in mechanical ventilation (OR 1.49 [1.03, 2.18], p=0.037) and ICU status (OR = 1.45 [1.06, 1.98], p=0.021). In PS matched patients in the anticoagulation cohort, intermediate versus prophylactic dose anticoagulation was associated with a marginal decrease in mortality (OR 0.60, p=0.053). In the aspirin cohort examining in-hospital death and discharge as competing risks, the use of aspirin was associated with decreased mortality (p=0.042) and had no effect on discharge (p=0.31). In the anticoagulation cohort a similar competing risk model showed the use of intermediate rather than prophylactic anticoagulation decreased mortality (p=0.046) and had no effect on discharge (p = 0.21). Conclusion: We show in a large cohort of consecutively hospitalized patients with COVID-19 treated under a risk-stratified algorithm the prognostic utility of the admission RI in assessing outcomes in hospitalized patients with COVID-19 and a potential benefit of aspirin therapy on in-hospital death from COVID-19. A potential albeit marginal benefit of intermediate dose anticoagulation over prophylactic dose anticoagulation merits further study with results of clinical trials awaited. Figure Disclosures Neuberg: Pharmacyclics: Research Funding; Madrigak Pharmaceuticals: Current equity holder in publicly-traded company; Celgene: Research Funding.

Another Look at the Relationship between Cohabitation and Marriage – The Use of Crude and Net Probabilities

2017 ◽  
Vol 136 (1) ◽  
pp. 66-73
Author(s):  
Paraskevi Peristera ◽  
Gebrenegus Ghilagaber
Keyword(s):  
Family Dynamics ◽  
Family Formation ◽  
Competing Risk ◽  
Theoretical Relationship ◽  
Risk Framework ◽  
Permanent Replacement ◽  
The Relationship

In this paper we propose an approach based on the theoretical relationship between crude and net probabilities of marriage in a competing-risk framework. Analyses based on family dynamics among Swedish men born 1936-1964 show that the probabilities of marriage increase if cohabitation was eliminated (and that probabilities of cohabitation increase if marriage was eliminated). Further, the gains in net probabilities increase at the prime ages of family formation (20-28) but are less significant at other ages. Such results support (at least for the data at hand) the argument that informal cohabitation serves as a prelude to marriage rather than a permanent replacement to it.

An original model to predict Intensive Care Unit length-of stay after cardiac surgery in a competing risk framework

2013 ◽  
Vol 168 (1) ◽  
pp. 219-225 ◽  
Author(s):  
Fabio Barili ◽  
Nicoletta Barzaghi ◽  
Faisal H. Cheema ◽  
Antonio Capo ◽  
Jeffrey Jiang ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Cardiac Surgery ◽  
Intensive Care ◽  
Length Of Stay ◽  
Unit Length ◽  
Original Model ◽  
Intensive Care Unit Length ◽  
Competing Risk ◽  
Risk Framework

Localization of Gallium-67 in Peritoneal Cells by Electron Microscopic Autoradiography

1973 ◽  
Vol 31 ◽  
pp. 404-405
Author(s):  
D. C. Swartzendruber ◽  
Norma L. Idoyaga-Vargas
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Tumor Tissue ◽  
Soft Tissue Tumors ◽  
Clinical Usefulness ◽  
Electron Microscopic ◽  
Normal Cells ◽  
Electron Microscopic Autoradiography ◽  
Peritoneal Cells ◽  
Gallium 67

The radionuclide gallium-67 (67Ga) localizes preferentially but not specifically in many human and experimental soft-tissue tumors. Because of this localization, 67Ga is used in clinical trials to detect humar. cancers by external scintiscanning methods. However, the fact that 67Ga does not localize specifically in tumors requires for its eventual clinical usefulness a fuller understanding of the mechanisms that control its deposition in both malignant and normal cells. We have previously reported that 67Ga localizes in lysosomal-like bodies, notably, although not exclusively, in macrophages of the spocytaneous AKR thymoma. Further studies on the uptake of 67Ga by macrophages are needed to determine whether there are factors related to malignancy that might alter the localization of 67Ga in these cells and thus provide clues to discovering the mechanism of 67Ga localization in tumor tissue.

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