Survival estimation in two-phase cohort studies with application to biomarkers evaluation

2016 ◽  
Vol 25 (6) ◽  
pp. 2895-2908 ◽  
Author(s):  
Paola Rebora ◽  
Maria Grazia Valsecchi
Keyword(s):  
Phase Ii ◽  
Lymphoblastic Leukemia ◽  
Sampling Strategy ◽  
Two Phase ◽  
Entire Cohort ◽  
Kaplan Meier ◽  
Phase Study ◽  
Survival Estimation ◽  
Predictive Role

Two-phase studies are attractive for their economy and efficiency in research settings where large cohorts are available for investigating the prognostic and predictive role of novel genetic and biological factors. In this type of study, information on novel factors is collected only in a convenient subcohort (phase II) drawn from the cohort (phase I) according to a given (optimal) sampling strategy. Estimation of survival in the subcohort needs to account for the design. The Kaplan–Meier method, based on counts of events and of subjects at risk in time, must be applied accounting, with suitable weights, for the sampling probabilities of the subjects in phase II, in order to recover the representativeness of the subcohort for the entire cohort. The authors derived a proper variance estimator of survival by linearization. The proposed method is applied in the context of a two-phase study on childhood acute lymphoblastic leukemia, which was planned in order to evaluate the role of genetic polymorphisms on treatment failure due to relapse. The method has shown satisfactory performance through simulations under different scenarios, including the case–control setting, and proved to be useful for describing results in the clinical example.

scholarly journals Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in Hepatocarcinogenesis

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jing Shen ◽  
Shuang Wang ◽  
Abby B. Siegel ◽  
Helen Remotti ◽  
Qiao Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Potential Role ◽  
Dna Hypermethylation ◽  
Two Phase ◽  
Genome Wide ◽  
Phase Study ◽  
A Genome ◽  
Genome Wide Expression ◽  
Inactive Chromatin

Background.Previous studies, including ours, have examined the regulation of microRNAs (miRNAs) by DNA methylation, but whether this regulation occurs at a genome-wide level in hepatocellular carcinoma (HCC) is unclear.Subjects/Methods.Using a two-phase study design, we conducted genome-wide screening for DNA methylation and miRNA expression to explore the potential role of methylation alterations in miRNAs regulation.Results.We found that expressions of 25 miRNAs were statistically significantly different between tumor and nontumor tissues and perfectly differentiated HCC tumor from nontumor. Six miRNAs were overexpressed, and 19 were repressed in tumors. Among 133 miRNAs with inverse correlations between methylation and expression, 8 miRNAs (6%) showed statistically significant differences in expression between tumor and nontumor tissues. Six miRNAs were validated in 56 additional paired HCC tissues, and significant inverse correlations were observed for miR-125b and miR-199a, which is consistent with the inactive chromatin pattern found in HepG2 cells.Conclusion.These data suggest that the expressions of miR-125b and miR-199a are dramatically regulated by DNA hypermethylation that plays a key role in hepatocarcinogenesis.

Acquisition and Extinction of a Runway Response under Odor-Intensified or -Minimized Conditions, Within-Subjects Trial Administration, and a One-Minute Intertrial Interval

1974 ◽  
Vol 38 (1) ◽  
pp. 119-129 ◽  
Author(s):  
Robert E. Prytula ◽  
James H. Payne
Keyword(s):  
Phase Ii ◽  
Intertrial Interval ◽  
Albino Rats ◽  
Two Phase ◽  
Phase Study ◽  
Within Subjects

A two-phase study was conducted during which 2 groups of albino rats received the same schedule of reward and nonreward, the same magnitude of reward and nonreward confinement, the same intertrial and intersubject intervals and the same trial order. The only difference was that one group of Ss was trained and extinguished under an odor-intensified condition, whereas the second group was trained and extinguished under an odor-reduced condition. In the goal segment Ss trained under an odor-intensified condition discriminated the schedule perfectly during acquisition and were less resistant to extinction than Ss trained under the odor-reduced condition. Following a 2-wk. interval, Phase II, the groups underwent acquisition and extinction again under reversed odor-conditions. The results were replicated within the study.

Predictive role of FAS for trabectedin in second lines of advanced soft tissue sarcoma (ASTS): A Spanish group for research on sarcoma (GEIS) study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11071-11071 ◽  
Author(s):  
Javier Martin Broto ◽  
David Marcilla ◽  
Rafael Ramos ◽  
David Silva Moura ◽  
Ramiro Alvarez ◽  
...  
Keyword(s):  
Selection Criteria ◽  
Unmet Need ◽  
Predictive Biomarkers ◽  
Rank Test ◽  
Second Line ◽  
Kaplan Meier ◽  
Diagnostic Time ◽  
Predictive Role ◽  
Set Up

11071 Background: There are currently several second-line options for the treatment of ASTS as gemcitabine combinations, trabectedin, pazopanib, eribulin or olaratumab plus doxorubicin in cases where anthracyclins are still possible. There is an unmet need for predictive biomarkers which hinders the rational selection of the best sequence in second line. We already published the prognostic value of FAS in first line of ASTS while this study analyzes its predictive role in different second line schemes. Methods: Most relevant selection criteria for this study were having received trabectedin in 2nd line or beyond for ASTS, progressive disease after at least one previous line for ASTS and signed CI. A TMA was set up for FAS staining (Cell Signaling) with blocks from diagnostic time. Two expert blinded pathologists reviewed and classified the cases as negative, weak or strong. Kaplan–Meier estimations were used for time-to-event variables and the log-rank test was used to compare groups. Results: A series of 198 patients accomplished selection criteria. Metastases at diagnosis occurred in 46 (24%) and median time to metastases was 18.8 months (CI 16,3; 21.3). Previous line to trabectedin consisted of gemcitabine combination 83 (42%), Doxorubicin-based 65 (33%) and others 50 (25%). Median PFS for previous and trabectedin lines were 3.5 (2.8-4.2) and 3.4 (2.8-4) months respectively. FAS positive entailed significantly better PFS for the previous trabectedin line: 4.1 (1.5-6.7) vs 3.0 (2.5-3.5) months, p = 0.01 whereas FAS positive was related with worse PFS for the trabectedin line 2.5 (2.2-2.8) vs 3.7 (2.7-4.8) months, p = 0.028. These results were more notorious for L-sarcoma cases: 7.0 (3.6-10.5) vs 4.3 (1.9-6.6) months, p = 0.017 in previous line and 2.4 (2.2-2.6) vs 6.5 (3.8-9.3) months, p < 0.001 in trabectedin. From trabectedin administration, FAS+ had significantly worse OS especially in L-sarcomas: 11.9 (5.2-18.7) vs 21.7 (12.7-30.8) months, p = 0.002. Conclusions: FAS showed predictive value in PFS and OS for trabectedin administration in ASTS. The different prognostic role of FAS across distinct lines and its relevance in L-sarcomas deserve further attention.

Prognostic Value of Microvessel Density in Hepatocellular Carcinoma Patients: A Meta-Analysis

2014 ◽  
Vol 29 (3) ◽  
pp. 279-287 ◽  
Author(s):  
Yanyan Li ◽  
Xuelei Ma ◽  
Jing Zhang ◽  
Xiaoxiao Liu ◽  
Lei Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Microvessel Density ◽  
Meta Analysis ◽  
Tumor Stage ◽  
Disease Recurrence ◽  
Prognostic Role ◽  
Kaplan Meier ◽  
Poorly Differentiated ◽  
Predictive Role

Introduction The identification of microvessel density (MVD) in patients suffering from different types of cancer has become a hot point as an emerging and promising biomarker. The aim of the present study is to clarify the prognostic relevance of MVD in hepatocellular carcinoma (HCC). Methods Relevant articles were screened in PubMed and EMBASE databases. Patients' clinical characteristics, overall survival (OS), disease/recurrence-free survival (DFS/RFS), and MVD levels were extracted for further analysis. The statistical analysis derived from the Kaplan—Meier survival curves was calculated indirectly with the methods developed by Parmar, Williamson, and Tierney. Multivariate Cox hazard regression analysis was used directly in Stata 11.0. The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to evaluate the prognostic role of MVD in HCC. Results Our online literature search identified 12 articles including a total of 1,138 HCC patients. Meta-analysis of all the included studies considering survival outcomes showed a positive correlation between poor prognosis and higher-MVD levels. The pooled HRs (and 95% CIs) for OS and DFS/RFS were respectively 2.08 [1.77-2.45] and 2.64 [2.12-3.29]. Subgroup analyses considering tumor stage (I-II/III-IV), tumor size (<5 cm/≥5 cm), differentiation (well/poor), or cirrhosis status (≥20%/<20%) were also conducted, and all the above analyses supported the prognostic role of MVD in HCC. Conclusion Our meta-analysis showed that the available evidence supports the proposition that MVD has a good predictive role in HCC, especially when the patients have late stage, large size, or poorly differentiated tumors.

scholarly journals Judging Expertise Through Communication Styles in Intercultural Collaboration

2019 ◽  
Vol 33 (2) ◽  
pp. 238-271 ◽  
Author(s):  
Y. Connie Yuan ◽  
Wang Liao ◽  
Natalya N. Bazarova
Keyword(s):  
Cultural Differences ◽  
Chinese Students ◽  
Communication Styles ◽  
Second Phase ◽  
Two Phase ◽  
Intercultural Collaboration ◽  
Phase Study ◽  
Expertise Recognition ◽  
Task Oriented

Recent research on expertise management calls for more attention to the role of communication in expertise recognition. Cultural differences in communication styles can complicate communication of expertise and consequently make expertise recognition more difficult in mixed-culture groups than in same-culture groups. This article reports results from a two-phase study (348 Chinese and non-Asian U.S. citizen [NAUSC] students in the first phase, and 24 four-person groups that consist of both NAUSC and Chinese students in the second phase) on the role of communication styles in intercultural collaboration. The results suggest that for both Chinese and NAUSC students, conversational control, tenseness, task-oriented communication, and confidence are important cues influencing expertise judgment, but perceived expertise and actual expertise may be unrelated to each other.

scholarly journals Effect of Pharmacists’ Interventions on the Appropriateness of Empiric Vancomycin Therapy in Oncology Patients with Febrile Neutropenia

2019 ◽  
Vol 26 (2) ◽  
pp. 53-59
Author(s):  
Nour Baghdady ◽  
Daniel Voit ◽  
Anne M. McDonell ◽  
David W. Kubiak
Keyword(s):  
Febrile Neutropenia ◽  
Phase I ◽  
Phase Ii ◽  
Vancomycin Therapy ◽  
Gram Positive ◽  
Oncology Patients ◽  
Two Phase ◽  
Pharmacy Intervention ◽  
Phase Study ◽  
Objective Evidence

The purpose of this observational study is to evaluate the effect of an active pharmacy intervention to facilitate timely discontinuation of empiric vancomycin therapy in oncology patients with febrile neutropenia who lack objective evidence of a Gram-positive infection. This was a two-phase study. Vancomycin use was evaluated retrospectively on all oncology patients with febrile neutropenia over four weeks (phase I). In a parallel four weeks a year later, vancomycin use in this patient population was evaluated prospectively (phase II). In the absence of evidence of Gram-positive infection after 72 hours of treatment initiation, the team was contacted by a pharmacist to encourage discontinuation. Usage was compared between both phases. Forty-three patients in phase I and 25 patients in phase II were treated with vancomycin with no evidence for Gram-positive infections. Pharmacists’ interventions were documented on 18 patients in phase II. Of these, 56% of interventions to discontinue vancomycin were accepted, but only 33.3% of patients had treatment stopped within 72 hours of initiation. Although not significant, a trend in more appropriate use of vancomycin in oncology patients with febrile neutropenia was observed. Pharmacist’s interventions might have played a role in this observation.

Consumer trust and distrust: retaining paper bills in online banking

2015 ◽  
Vol 33 (1) ◽  
pp. 5-22 ◽  
Author(s):  
Joanne McNeish
Keyword(s):  
Phase 1 ◽  
Customer Relationship ◽  
Mobile Banking ◽  
Two Phase ◽  
Content Type ◽  
Phase Study ◽  
Mixed Messages ◽  
Paper Documentation ◽  
Intention To Continue

Purpose – The purpose of this paper is to explore the role of paper bills and statements in online and mobile banking and how they may serve to support trust along with mitigating distrust for consumers when dealing with banks and billing firms. Design/methodology/approach – A two-phase study with 208 Canadian online bill payers. Phase 1 verified the comprehension of the measurement items being tested. In Phase 2, exploratory factor analysis was used to determine the factor structure. Regression analysis was used to identify the relationship of the factors with the intention to continuing receiving paper bills. Findings – Four factors for trust and distrust were identified in this study of which two (structural assurance and counted on to help) plus subjective norm predict the intention to continue receiving paper bills. Research limitations/implications – Trust and distrust are shown to co-exist in this study. Consumers feel vulnerable to the risks inherent in online financial interactions, but signal their willingness to trust by adopting online and mobile banking. Consumers mitigate the distrust they have in banks and billing firms by continuing to receive paper bills and statements. This study is limited to paper bills and statements. The role of other paper documents in customer relationship management is worthy of further exploration. Practical implications – This research investigates the role of financial documents in the consumer-firm relationship. This study suggests that paper bills are a communication method that supports consumers’ trust in the banks and billing firms and their adoption of online and mobile banking. Banks and billing firms’ continued emphasis on consumers’ giving up paper bills while insisting on original paper documentation in problem resolution situations, sends mixed messages to consumers, which heightens their distrust in these firms. Originality/value – This is the first study to suggest that paper bills and statements have a role in influencing trust or distrust of banks and billing firms.

scholarly journals Leadership characteristics that influence corporate efficiency

2020 ◽  
Author(s):  
Annamária Kazai Ónodi ◽  
Rita Répáczki
Keyword(s):  
Individual Characteristics ◽  
Management Skills ◽  
Leadership Qualities ◽  
Two Phase ◽  
Leadership Practice ◽  
Phase Study ◽  
Focus Analysis ◽  
Questionnaire Research ◽  
The Individual

Economic focus analysis alone cannot answer an organisation’s efficiency issues, as the soft attributes associated with management skills and leadership qualities are also important. According to transformational leadership theory (Bass–Avolio 1994, Bass 1990, Judge–Bono 2000, Bass–Bass 2008), there is a transformation between the manager and the subordinate, in which the two parties interact with and affect each other. A joint two-phase study was conducted to investigate the role of management in increasing corporate efficiency. As a first step, financial data of 1752 Hungarian manufacturing firms were analyzed. Companies were grouped according to their TFP (total factor productivity) (Juhász et al. 2020). As a second step, we linked a questionnaire survey to the preliminary TFP categorization. In our questionnaire research, we examined the individual characteristics, qualities, and specialties of leadership practices concerning the economic performance of the organizations. According to our findings, both the individual qualities of the leader and the characteristics of the leadership practice are decisive for the efficiency and results of the organization.

Effect of adjuvant (AD) radiotherapy (RT) on outcomes following pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PDA): A margin-stratified analysis.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 311-311
Author(s):  
Lee Mayer Ocuin ◽  
Jennifer Lee Miller ◽  
Mazen S Zenati ◽  
Jennifer Steve ◽  
Aatur D. Singhi ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Multivariate Regression Analysis ◽  
Entire Cohort ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Node Ratio ◽  
Definition Of ◽  
Stratified Analysis

311 Background: The role of RT following PD for PDA remains controversial due to ambiguity in the definition of R0/R1 margin status in existing clinical trials. Recent data suggest that increased margin clearance (MC) is associated with improved survival after PD for PDA, however the role of adjuvant radiotherapy (ADRT) in patients with known MC is undefined. We sought to analyze the influence of ADRT on outcomes of PD for PDA based on MC data. Methods: We retrospectively identified 326 patients with MC data (in mm) who underwent PD between 2002-2014. Recurrence-free (RFS) and overall survival (OS) was determined by Kaplan-Meier analysis. Hazard ratios (HR) were calculated by Cox multivariate regression analysis on significant variables. Results: Mean age was 68 yrs and 55% were male. Median follow-up was 21 mos (IQR 12-34 mos). ADRT was administered to 87 patients (27%). Median RFS and OS for the entire cohort was 14 mos and 25 mos. On univariate analysis, ADRT was not associated with improved median RFS (13 vs. 14 mos; p = NS) or OS (23 vs. 27 mos; p = NS), but increasing MC was associated with prolonged median RFS [10 (0mm) vs. 13 (0-1mm) vs. 23 mos ( > 1mm); p < 0.02 for all pairs] and OS [16 (0mm) vs. 23 (0-1mm) vs. 40 mos ( > 1mm); p < 0.01 for all pairs]. After controlling for sex, BMI, neoadjuvant therapy, LVI, PNI, lymph node ratio > 0.2, tumor size > 2.5cm, and adjuvant chemotherapy, increasing MC was independently associated with improved OS [HR 0.680; p = 0.034 (0-1mm); HR 0.451; p < 0.001 ( > 1mm), compared to 0mm]. Patients were subsequently stratified into 3 groups based on MC [0mm (n = 73); 0-1mm (n = 118); > 1mm (n = 135)]. ADRT was administered less frequently to patients with greater MC [0mm (n = 29; 41%); 0-1mm (n = 36; 31%); > 1mm (n = 22; 16%); p < 0.001]. Even when stratified by MC, ADRT was not associated with improved RFS [10 vs. 9 mos (0mm); 13 vs. 12 mos (0-1mm); 21 vs. 23 mos ( > 1mm); p = NS for all pairs] or OS [16 vs. 18 mos (0mm); 24 vs. 23 mos (0-1mm); 33 vs. 42 mos ( > 1mm); p = NS for all pairs]. Conclusions: ADRT is not associated with improved RFS or OS following PD for PDA regardless of MC. The use of RT following PD for PDA should be re-examined.

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