scholarly journals Missing Data in Clinical Studies: Issues and Methods

2012 ◽  
Vol 30 (26) ◽  
pp. 3297-3303 ◽  
Author(s):  
Joseph G. Ibrahim ◽  
Haitao Chu ◽  
Ming-Hui Chen
Keyword(s):  
Clinical Trial ◽  
Missing Data ◽  
Linear Models ◽  
Cox Regression ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Time To Event ◽  
Linear Mixed Effects ◽  
Covariate Data ◽  
Generalized Linear Mixed Effects

Missing data are a prevailing problem in any type of data analyses. A participant variable is considered missing if the value of the variable (outcome or covariate) for the participant is not observed. In this article, various issues in analyzing studies with missing data are discussed. Particularly, we focus on missing response and/or covariate data for studies with discrete, continuous, or time-to-event end points in which generalized linear models, models for longitudinal data such as generalized linear mixed effects models, or Cox regression models are used. We discuss various classifications of missing data that may arise in a study and demonstrate in several situations that the commonly used method of throwing out all participants with any missing data may lead to incorrect results and conclusions. The methods described are applied to data from an Eastern Cooperative Oncology Group phase II clinical trial of liver cancer and a phase III clinical trial of advanced non–small-cell lung cancer. Although the main area of application discussed here is cancer, the issues and methods we discuss apply to any type of study.

Predictors for response to cetuximab in a prospective clinical trial (E2303) of patients with head and neck squamous cell carcinoma (HNSCC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5576-5576 ◽  
Author(s):  
Amanda Psyrri ◽  
Ju-Whei Lee ◽  
Eirini Pectasides ◽  
Maria Vassilakopoulou ◽  
Barbara Burtness ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Cox Regression ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Disease Stage ◽  
Rank Test ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Event Time

5576 Background: Theidentification of resistance mechanisms to Epidermal Growth Factor Receptor (EGFR) inhibitors remains critical lack in the management of HNSCC. We sought to determine predictors for response to cetuximab in a phase II clinical trial. Methods: 63 patients (pts) with operable stage III/IV HNSCC participated in E2303, an Eastern Cooperative Oncology Group (ECOG) phase II trial of induction chemotherapy with weekly cetuximab, paclitaxel and carboplatin x 6 followed by chemoradiotherapy with the same regimen. A tissue microarray was constructed and EGFR, ERK1/2, Met, pAkt and STAT protein expression levels were assessed using AQUA. The objectives of analysis were to determine association of biomarkers with E2303 efficacy outcomes (best objective response (OR), overall survival (OS), progression-free survival (PFS), and event-free survival (EFS)). The logistic regression model was used to examine relationship between marker measurements (on a continuous scale) and OR. The univariate and multivariate Cox proportional hazards models were used to evaluate the relationship between markers and event-time distributions. Fisher’s exact test was used to evaluate differences in response rate between groups (high vs. low AQUA scores). Event-time distributions were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: Cytoplasmic ERK1/2 levels weresignificantly associated with PFS and OS (p=0.03 and 0.01, respectively). Nuclear ERK1/2 levels were significantly associated with OS (p=0.02) and tended towards significance for PFS (p=0.09). The multivariate Cox regression analysis shows that cytoplasmic and nuclear ERK1/2 are significantly associated with OS and PFS after controlling for primary site and disease stage, respectively There was no significant association between cytoplasmic or nuclear ERK1/2 status and OR (p-values 0.98 and 0.41, respectively).No association was found between expression of any of other biomarkers and outcome measures. Our data analysis was based on 35 pts with marker data available. Conclusions: Ras/MAPK/ERKpathway may be associated with resistance to cetuximab in HNSCC.

Phase III Clinical Trial of Thalidomide Plus Dexamethasone Compared With Dexamethasone Alone in Newly Diagnosed Multiple Myeloma: A Clinical Trial Coordinated by the Eastern Cooperative Oncology Group

2006 ◽  
Vol 24 (3) ◽  
pp. 431-436 ◽  
Author(s):  
S. Vincent Rajkumar ◽  
Emily Blood ◽  
David Vesole ◽  
Rafael Fonseca ◽  
Philip R. Greipp
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Response Rate ◽  
Eastern Cooperative Oncology Group ◽  
Response Rates ◽  
Incidence Rates ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Monoclonal Protein ◽  
Grade 3

Purpose To determine if thalidomide plus dexamethasone yields superior response rates compared with dexamethasone alone as induction therapy for newly diagnosed multiple myeloma. Patients and Methods Patients were randomly assigned to receive thalidomide plus dexamethasone or dexamethasone alone. Patients in arm A received thalidomide 200 mg orally for 4 weeks; dexamethasone was administered at a dose of 40 mg orally on days 1 to 4, 9 to 12, and 17 to 20. Cycles were repeated every 4 weeks. Patients in arm B received dexamethasone alone at the same schedule as in arm A. Results Two hundred seven patients were enrolled: 103 were randomly assigned to thalidomide plus dexamethasone and 104 were randomly assigned to dexamethasone alone; eight patients were ineligible. The response rate with thalidomide plus dexamethasone was significantly higher than with dexamethasone alone (63% v 41%, respectively; P = .0017). The response rate allowing for use of serum monoclonal protein levels when a measurable urine monoclonal protein was unavailable at follow-up was 72% v 50%, respectively. The incidence rates of grade 3 or higher deep vein thrombosis (DVT), rash, bradycardia, neuropathy, and any grade 4 to 5 toxicity in the first 4 months were significantly higher with thalidomide plus dexamethasone compared with dexamethasone alone (45% v 21%, respectively; P < .001). DVT was more frequent in arm A than in arm B (17% v 3%); grade 3 or higher peripheral neuropathy was also more frequent (7% v 4%, respectively). Conclusion Thalidomide plus dexamethasone demonstrates significantly superior response rates in newly diagnosed myeloma compared with dexamethasone alone. However, this must be balanced against the greater toxicity seen with the combination.

Introduction

2021 ◽  
pp. 1-8
Author(s):  
Andy Hector
Keyword(s):  
Generalized Linear Models ◽  
Linear Models ◽  
Linear Regression Analysis ◽  
Learning By Doing ◽  
Analysis Of Covariance ◽  
Mixed Effects Models ◽  
Linear Mixed Effects Models ◽  
Linear Mixed Effects ◽  
Normal Distributions ◽  
Generalized Linear Mixed Effects

This chapter sets out the aims of the book, the approach, what is covered in the book, and what is not. The chapter introduces the R and RStudio software packages. It also summarizes the changes made to the second edition of the book. The book starts by introducing several different variations of the basic linear-model analysis (analysis of variance, linear regression, analysis of covariance, etc.). The later part of the book covers generalized linear models (for data with non-normal distributions). The book ends by combining these two extensions into generalized linear mixed-effects models. To allow a learning-by-doing approach, the R code necessary to perform the basic analysis is embedded in the text along with the key output from R.

Real-world effectiveness of nab-paclitaxel plus carboplatin as first-line therapy for patients with advanced NSCLC: Results of the second interim analysis of the NEPTUN study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21611-e21611
Author(s):  
Tobias Nicolaas Dechow ◽  
Jorge Riera-Knorrenschild ◽  
Björn Hackanson ◽  
Ludwig Fischer von Weikersthal ◽  
Holger Schulz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Real World ◽  
Interim Analysis ◽  
Active Sites ◽  
Advanced Nsclc ◽  
Cox Regression ◽  
Small Cell Lung Carcinoma ◽  
Phase Iii ◽  
First Line ◽  
Cell Lung Carcinoma

e21611 Background: Collecting real-world evidence is required not only to evaluate effectiveness and safety in routine clinical practice, but to improve clinical cancer outcomes. Methods: NEPTUN is a prospective, multicenter, non-interventional study designed to evaluate effectiveness, safety and quality of life (QoL) of first-line nab-Paclitaxel plus carboplatin in patients (pts) with advanced or metastatic non-small cell lung carcinoma (NSCLC) in the real-world setting in Germany. The primary endpoint was 6-months progression free survival rate (PFSR). Descriptive statistics were used to analyze data. Results: Between August 2016 and June 2019, 408 pts were enrolled at 75 active sites, 373 pts started treatment according to label. The cut-off date for this interim analysis (07 Dec 2019) was after all pts were observed for at least 6 months. The 6-months PFSR was 40.8% (95% CI, 35.3-46.2), median PFS 5.2 months (95% CI, 4.5-5.7). Overall response rate was 41.5% (95% CI, 36.3-46.8) with a complete response documented in 6 pts (1.7%) and a partial response in 142 pts (39.8%). Disease control rate was 61.6% (95% CI, 56.4-66.7). Employing a multivariable cox regression model for PFS adjusted for ECOG, histology, age group, renal impairment, and smoking status, elderly patients and patients with squamous histology were identified as being of favorable risk (HR squamous vs. non-squamous histology 0.76 (95% CI, 0.58-1.01); HR for ≥70 vs. < 70 years of age 0.80 (95% CI, 0.59-1.08)). Median overall survival (OS) was 10.5 months (95% CI, 9.2-11.6) with 9.6 months (95% CI, 7.7-11.2) for non-squamous and 11.8 months (95% CI, 9.2-13.8) for squamous histology. 12-months OS rate was 43.1% (95% CI, 37.3-48.7). The most common treatment-emergent AEs (TEAEs) were anemia (26.5%), leukopenia (25.7%) and thrombocytopenia (16.6%). Polyneuropathy was documented for 11.3% of pts. 54.2% of pts developed TEAE grade 3/4 including leukopenia (10.2%), anemia (8.6%) and pneumonia (5.1%). 9.9% pts discontinued nab-paclitaxel due to nab-paclitaxel-related TEAEs. EQ-5D-5L visual analogue scale and FACT-L total score remained stable during therapy. Conclusions: nab-Paclitaxel plus carboplatin given first-line according to German SmPC in advanced NSCLC patients in a real-world clinical setting is an effective and safe therapy commonly applied. These results were similar to those reported in the phase iii clinical trial setting. QoL scores remained stable during first-line treatment. No new safety signals emerged. Clinical trial information: NCT02799862.

Utility of Interphase FISH To Stratify Patients into Cytogenetic Risk Categories at Diagnosis of AML in an ECOG Clinical Trial (E1900).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2377-2377
Author(s):  
Gail H. Vance ◽  
Haesook Kim ◽  
Gary Hicks ◽  
Athena Cherry ◽  
Rodney Higgins ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
P Value ◽  
Cell Transplant ◽  
Interphase Fish ◽  
Normal Fish ◽  
Normal Cytogenetics ◽  
Probe Set ◽  
Risk Categories

Abstract Background: Cytogenetic risk categories based on conventional chromosome studies are widely used in clinical practice to make treatment decisions for AML. We evaluated the efficacy of interphase FISH to detect chromosome anomalies in the workup of young (&lt;60 years) patients with AML. Methods: Study subjects were enrolled in E1900, a front-line Eastern Cooperative Oncology Group (ECOG) clinical trial for AML. This is an on-going Phase III clinical trial with Daunorubicin dose-intensification ± Gemtuzumab-Ozogamicin consolidation therapy prior to stem cell transplant. This trial opened December 2002; as of February 2005, 223 patients were enrolled. The protocol was designed to collect bone marrow for both cytogenetic and FISH studies at study entry (diagnosis). Cytogenetic studies were done by local laboratories with results reviewed centrally by the ECOG Cytogenetics Committee. Each case was classified as acceptable or unacceptable based on predefined ECOG cytogenetic criteria. FISH for each patient was performed in the ECOG FISH laboratory at Mayo Clinic and utilized eight probe sets to detect t(8;21), t(9;22), t(11;var), t(15;17), inv(16), +8, −5/5q, and −7/7q (Vysis, Downer Grove, IL). Results: 64 (29%) of 223 specimens had incomplete cytogenetic and/or FISH results. We analyzed the remaining 159 (71%) specimens with complete cytogenetic and FISH results. Results for each specimen were classified by probe set into one of the following categories: Normal cytogenetics and normal FISH; Abnormal cytogenetics and abnormal FISH for the anomaly the probe was designed to detect; Abnormal cytogenetics and abnormal FISH for an anomaly the probe was not primarily designed to detect; Normal cytogenetics and abnormal FISH; Abnormal cytogenetics and normal FISH; or Abnormal cytogenetics and abnormal FISH that further defined the karyotype. Figure 1: Results for 159 patients by category and FISH probe set: *t(8;21); t(9;22); t(11;var); t(15;17); inv(16); cen(8); del(5/5q); de(7/7q). Figure 1:. Results for 159 patients by category and FISH probe set: *t(8;21); t(9;22); t(11;var); t(15;17); inv(16); cen(8); del(5/5q); de(7/7q). The concordance rate between cytogenetic and FISH results ranged from 97 to 100% for all probe sets and kappa analysis for concordance had a p value of &lt;0.0001. Of the total 159 cases, discrepancies between FISH and cytogenetic results occurred in only 4 cases; two with normal cytogenetics and abnormal FISH and two with abnormal cytogenetics and normal FISH results. Conclusions: The high level of agreement between cytogenetics and FISH demonstrates the accuracy of a panel of 8 FISH probe sets for the detection of significant abnormalities in AML. The data from this investigation support the use of FISH as an adjunct in cases of failed cytogenetic analyses to increase the yield of useful cytogenetic results in large cooperative trials. Furthermore, because of the strong correlation between cytogenetics and FISH, our results demonstrate the potential of FISH as a follow-up study of minimal residual disease in ECOG trials.

scholarly journals Real-world benefit of nivolumab in a Canadian non-small-cell lung cancer cohort

2018 ◽  
Vol 25 (6) ◽  
Author(s):  
R. A. Juergens ◽  
C. Mariano ◽  
J. Jolivet ◽  
N. Finn ◽  
J. Rothenstein ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Real World ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Outcome Data ◽  
Phase Iii ◽  
Study Cohort ◽  
Duration Of Treatment

Background Nivolumab was the first immuno-oncology agent available for the treatment of lung cancer in Canada. In the present study, we evaluated the real-world benefit of nivolumab in Canadian patients with lung cancer.Methods Patients included in the cohort were identified from a registry of patients treated through expanded access to nivolumab before and after Health Canada approval. Demographics were collected from the application forms. Outcome data for the duration of treatment and survival were collected retrospectively.Results In contrast to the randomized clinical trial populations, our study cohort included patients who were older (median age: 66 years; range: 36–92 years) and who had an Eastern Cooperative Oncology Group performance status of 2 (8.9%). Despite the poorer-prognosis cohort, median overall survival was 12.0 months, which is comparable to the survival demonstrated in the randomized phase iii trials of nivolumab in lung cancer. Median time to treatment discontinuation was 3.45 months and was similar for all patient subgroups, including poorer-prognosis groups such as those with a performance status of 2, those 75 years of age and older, and those with brain metastases.Conclusions Nivolumab given in a real-world clinical setting was associated with results similar to those reported in the phase iii clinical trial setting.

Sign in / Sign up

Export Citation Format

Share Document