Stephen L. George

Journal article J Biopharm Stat · 2018 Featured Publication In the era of precision medicine, drugs are increasingly developed to target subgroups of patients with certain biomarkers. In large all-comer trials using a biomarker stratified design, the cost of treating and following patients for clinical outcomes may ... Full text Open Access Link to item Cite

Validation of Progression-Free Survival as a Surrogate Endpoint for Overall Survival in Malignant Mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials.

Journal article Oncologist · February 2017 Featured Publication PURPOSE: The aim of this study was to investigate whether progression-free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in malignant mesothelioma. MATERIALS AND METHODS: Individual data were collected from 15 Cancer and L ... Full text Link to item Cite

Prevalence of data fraud.

Journal article Int J Clin Oncol · December 2016 Featured Publication Full text Link to item Cite

Design and analysis of phase II cancer clinical trials

Book · August 19, 2016 Featured Publication Full text Cite

Time-dependent classification accuracy curve under marker-dependent sampling.

Journal article Biom J · July 2016 Featured Publication Evaluating the classification accuracy of a candidate biomarker signaling the onset of disease or disease status is essential for medical decision making. A good biomarker would accurately identify the patients who are likely to progress or die at a partic ... Full text Link to item Cite

Research misconduct and data fraud in clinical trials: prevalence and causal factors.

Journal article Int J Clin Oncol · February 2016 Featured Publication The disclosure of cases of research misconduct in clinical trials, conventionally defined as fabrication, falsification or plagiarism, has been a disturbingly common phenomenon in recent years. Such cases can potentially harm patients enrolled on the trial ... Full text Link to item Cite

A Multi-state Model for Designing Clinical Trials for Testing Overall Survival Allowing for Crossover after Progression.

Journal article Stat Biopharm Res · 2016 Featured Publication In designing a clinical trial for comparing two or more treatments with respect to overall survival (OS), a proportional hazards assumption is commonly made. However, in many cancer clinical trials, patients pass through various disease states prior to dea ... Full text Link to item Cite

Research methods for clinical trials in personalized medicine: A systematic review

Book section · January 1, 2014 Featured Publication Full text Cite

ROC curve estimation under test-result-dependent sampling.

Journal article Biostatistics · January 2013 Featured Publication The receiver operating characteristic (ROC) curve is often used to evaluate the performance of a biomarker measured on continuous scale to predict the disease status or a clinical condition. Motivated by the need for novel study designs with better estimat ... Full text Link to item Cite

Individual patient data meta-analysis of randomized trials evaluating IL-2 monotherapy as remission maintenance therapy in acute myeloid leukemia.

Journal article Blood · June 30, 2011 Featured Publication IL-2 is a natural, T cell-derived cytokine that stimulates the cytotoxic functions of T and natural killer cells. IL-2 monotherapy has been evaluated in several randomized clinical trials (RCTs) for remission maintenance in patients with acute myeloid leuk ... Full text Link to item Cite

Multiple testing of treatment-effect-modifying biomarkers in a randomized clinical trial with a survival endpoint.

Journal article Stat Med · June 15, 2011 Featured Publication The recent revolution in genomics and the advent of targeted therapies have increased interest in biomarker-defined subgroups of patients who respond to therapy or exhibit specific toxicities. Such biomarker-defined subgroups are also being investigated fo ... Full text Link to item Cite

Multiple testing for gene sets from microarray experiments.

Journal article BMC Bioinformatics · May 26, 2011 Featured Publication BACKGROUND: A key objective in many microarray association studies is the identification of individual genes associated with clinical outcome. It is often of additional interest to identify sets of genes, known a priori to have similar biologic function, a ... Full text Open Access Link to item Cite

Clinical trials data collection: when less is more.

Journal article J Clin Oncol · December 1, 2010 Featured Publication Full text Link to item Cite

Robust test method for time-course microarray experiments.

Journal article BMC Bioinformatics · July 22, 2010 Featured Publication BACKGROUND: In a time-course microarray experiment, the expression level for each gene is observed across a number of time-points in order to characterize the temporal trajectories of the gene-expression profiles. For many of these experiments, the scienti ... Full text Open Access Link to item Cite

permGPU: Using graphics processing units in RNA microarray association studies.

Journal article BMC Bioinformatics · June 16, 2010 Featured Publication BACKGROUND: Many analyses of microarray association studies involve permutation, bootstrap resampling and cross-validation, that are ideally formulated as embarrassingly parallel computing problems. Given that these analyses are computationally intensive, ... Full text Open Access Link to item Cite

A permutation-based multiple testing method for time-course microarray experiments.

Journal article BMC Bioinformatics · October 15, 2009 Featured Publication BACKGROUND: Time-course microarray experiments are widely used to study the temporal profiles of gene expression. Storey et al. (2005) developed a method for analyzing time-course microarray studies that can be applied to discovering genes whose expression ... Full text Link to item Cite

Flexible Phase I Clinical Trials: Allowing for Nonbinary Toxicity Response and Removal of Other Common Limitations.

Journal article Stat Biopharm Res · August 1, 2009 Featured Publication Phase I clinical trials are often subject to severe limitations. The most important one is that they typically allow only for binary response-toxic (1) or nontoxic (0)-rather than a range of responses from 0 to 1. They also may not allow a new patient to b ... Full text Link to item Cite

Sample size calculation for microarray experiments with blocked one-way design.

Journal article BMC Bioinformatics · May 28, 2009 Featured Publication BACKGROUND: One of the main objectives of microarray analysis is to identify differentially expressed genes for different types of cells or treatments. Many statistical methods have been proposed to assess the treatment effects in microarray experiments. R ... Full text Link to item Cite

Between-arm comparisons in randomized Phase II trials.

Journal article J Biopharm Stat · 2009 Featured Publication In a Phase II trial, we may randomize patients to multiple arms of experimental therapies and evaluate their efficacy to determine if any of them is worthy of a large scale Phase III trial. Usually the primary objective of such a study is to identify exper ... Full text Link to item Cite

Low-dose interleukin-2 immunotherapy does not improve outcome of patients age 60 years and older with acute myeloid leukemia in first complete remission: Cancer and Leukemia Group B Study 9720.

Journal article J Clin Oncol · October 20, 2008 Featured Publication PURPOSE: Cancer and Leukemia Group B (CALGB) 9720 evaluated subcutaneous low-dose recombinant interleukin-2 (rIL-2) maintenance immunotherapy as a strategy for prolonging remission in older patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: ... Full text Link to item Cite

Tomorrow's cancer treatments today: the first 50 years of the Cancer and Leukemia Group B.

Journal article Semin Oncol · October 2008 Featured Publication Members of the Cancer and Leukemia Group B (CALGB) have been striving to improve cancer therapies for more than 50 years. The organization began in the mid 1950s as a multi-institutional collaboration between investigators at the National Cancer Institute, ... Full text Link to item Cite

Statistical issues in translational cancer research.

Journal article Clin Cancer Res · October 1, 2008 Featured Publication The explosion of knowledge about the basic biological processes and the genetics of cancer has led to increasing optimism that this knowledge can be put to practical clinical use in the near future. Indeed, important examples of translational approaches ca ... Full text Link to item Cite

Statistical challenges in preprocessing in microarray experiments in cancer.

Journal article Clin Cancer Res · October 1, 2008 Featured Publication Many clinical studies incorporate genomic experiments to investigate the potential associations between high-dimensional molecular data and clinical outcome. A critical first step in the statistical analyses of these experiments is that the molecular data ... Full text Link to item Cite

Overcoming challenges in designing and implementing a phase II randomized controlled trial using a presurgical model to test a dietary intervention in prostate cancer.

Journal article Clin Trials · 2008 Featured Publication BACKGROUND: The time between the diagnosis of cancer and a planned definitive surgical procedure offers a strong and direct approach for assessing the impact of interventions (including lifestyle interventions) on the biology of the target tissue and the t ... Full text Link to item Cite

Randomized clinical trial design for assessing noninferiority when superiority is expected.

Journal article J Clin Oncol · November 1, 2007 Featured Publication The randomized clinical trial (RCT) is the gold standard for definitive evaluation of new therapies. RCTs designed to show that the therapeutic efficacy of a new therapy is not unacceptably inferior to that of standard therapy are called noninferiority tri ... Full text Link to item Cite

Response rate as an endpoint in clinical trials.

Journal article J Natl Cancer Inst · January 17, 2007 Featured Publication Full text Link to item Cite

Controversies in the early reporting of a clinical trial in early breast cancer

Journal article · December 1, 2006 Featured Publication The role of adjuvant chemotherapy in the treatment of breast cancer has been the subject of intense research activity in recent years. It is now generally accepted that some types of adjuvant therapy have a positive effect on disease-free and overall survi ... Full text Cite

Processes to activate phase III clinical trials in a Cooperative Oncology Group: the Case of Cancer and Leukemia Group B.

Journal article J Clin Oncol · October 1, 2006 Featured Publication PURPOSE: National Cancer Institute-sponsored cooperative oncology groups are major sponsors of phase III clinical trials, yet the time and steps required to design and activate such studies has not been well studied. We examine the processes and document t ... Full text Link to item Cite

P-value calculation for multistage phase II cancer clinical trials.

Journal article J Biopharm Stat · 2006 Featured Publication Due to ethical and practical issues, clinical trials are conducted in multiple stages, but the reported p-values often fail to reflect the design aspect of the trials. We investigate some approaches to p-value calculation in analyzing multi-stage Phase II ... Full text Link to item Cite

A multiple testing procedure to associate gene expression levels with survival.

Journal article Stat Med · October 30, 2005 Featured Publication In many microarray studies the primary objective is to identify, from a large panel of genes, those which are prognostic markers of a censored survival endpoint such as time to disease recurrence or death. Often, these genes are considered prognostic in th ... Full text Link to item Cite

Sample size calculation for simulation-based multiple-testing procedures.

Journal article J Biopharm Stat · 2005 Featured Publication In this article, we present a simple method to calculate sample size and power for a simulation-based multiple testing procedure which gives a sharper critical value than the standard Bonferroni method. The method is especially useful when several highly c ... Full text Link to item Cite

A general formulation for a one-sided group sequential design.

Journal article Clin Trials · 2005 Featured Publication BACKGROUND: A major contribution to the statistical literature on group sequential designs was provided by Pampallona and Tsiatis who developed closed form functions that can be used to iteratively calculate the boundary points of a family of popular group ... Full text Link to item Cite

Strength of accumulating evidence and data monitoring committee decision making.

Journal article Stat Med · September 15, 2004 Featured Publication The data monitoring committee (DMC) is a vital component of a randomized clinical trial. Its responsibilities include stopping the trial early for extreme results. The decision to stop the trial must be based on a careful synthesis of statistical methodolo ... Full text Link to item Cite

Managing accrual in cooperative group clinical trials.

Journal article J Clin Oncol · August 1, 2004 Featured Publication Full text Link to item Cite

Fulfillment of the uncertainty principle in cancer clinical trials.

Journal article J Clin Oncol · July 15, 2004 Featured Publication 6003 Background: For randomized controlled trials to be ethical, the relative benefits of the study treatments must be uncertain. Therefore, the prior probability that either treatment is actually better should not be too high. Concerns about violation of ... Link to item Cite

Fulfillment of the uncertainty principle in cancer clinical trials.

Conference JOURNAL OF CLINICAL ONCOLOGY · July 15, 2004 Featured Publication Link to item Cite

Satisfaction of the uncertainty principle in cancer clinical trials: retrospective cohort analysis.

Journal article BMJ · June 19, 2004 Featured Publication OBJECTIVE: To assess whether publicly funded adult cancer trials satisfy the uncertainty principle, which states that physicians should enroll a patient in a trial only if they are substantially uncertain which of the treatments in the trial is most approp ... Full text Link to item Cite

Should statisticians reporting to data monitoring committees be independent of the trial sponsor and leadership?

Journal article Stat Med · May 30, 2004 Featured Publication It has long been a fundamental principle of clinical trials that interim comparative data should be kept confidential, with such data accessible only to a small number of individuals responsible for its analysis and monitoring. The rationale for keeping in ... Full text Link to item Cite

Admissible two-stage designs for phase II cancer clinical trials.

Journal article Stat Med · February 28, 2004 Featured Publication In a typical two-stage design for a phase II cancer clinical trial for efficacy screening of cytotoxic agents, a fixed number of patients are initially enrolled and treated. The trial may be terminated for lack of efficacy if the observed number of tumour ... Full text Link to item Cite

Data monitoring and large apparent treatment effects.

Journal article Control Clin Trials · February 2004 Featured Publication Full text Link to item Cite

The Society for Clinical Trials supports United States legislation mandating trials registration. Position paper.

Journal article Clin Trials · 2004 Featured Publication The official position of the Society for Clinical Trials is to support legislation in the United States and internationally that mandates registration of all controlled clinicals trials at or before enrollment of the first participant. The major trial spon ... Full text Link to item Cite

Selection bias, phase II trials, and the FDA accelerated approval process.

Journal article J Natl Cancer Inst · September 17, 2003 Featured Publication Full text Link to item Cite

Admissible two-stage designs for phase II cancer clinical trials

Conference CONTROLLED CLINICAL TRIALS · June 2003 Featured Publication Link to item Cite

The long-term clinical course of patients with cutaneous melanoma.

Journal article Cancer · September 15, 2002 Featured Publication BACKGROUND: The clinical course of cutaneous melanoma is associated with pathologic and clinical factors, such as thickness, ulceration, and location of tumor and gender of the patient. The authors used a parametric survival model that incorporated a cured ... Full text Link to item Cite

Detecting treatment-by-centre interaction in multi-centre clinical trials.

Journal article Stat Med · January 30, 2001 Featured Publication This paper considers several permutation tests for treatment-by-centre interaction in multi-centre clinical trials in which the endpoint is survival time subject to censoring. Some of the tests are based on existing tests and some are new. To evaluate and ... Full text Link to item Cite

Fraud in medical research: an international survey of biostatisticians. ISCB Subcommittee on Fraud.

Journal article Control Clin Trials · October 2000 Featured Publication The characteristics of scientific fraud and its impact on medical research are in general not well known. However, the interest in the phenomenon has increased steadily during the last decade. Biostatisticians routinely work closely with physicians and sci ... Full text Link to item Cite

The role of biostatistics in the prevention, detection and treatment of fraud in clinical trials.

Journal article Stat Med · December 30, 1999 Featured Publication Recent cases of fraud in clinical trials have attracted considerable media attention, but relatively little reaction from the biostatistical community. In this paper we argue that biostatisticians should be involved in preventing fraud (as well as unintent ... Full text Link to item Cite

Data monitoring committees and interim monitoring guidelines.

Journal article Control Clin Trials · October 1999 Featured Publication Most large randomized clinical trials have a data monitoring committee that periodically examines efficacy and safety results. A typical data monitoring committee meets every 6 months, but the interim monitoring guidelines for many trials specify formal an ... Full text Link to item Cite

Statistical reviewing policies of medical journals: caveat lector?

Journal article J Gen Intern Med · November 1998 Featured Publication OBJECTIVE: To describe the current policies regarding statistical review of clinical research in biomedical journals. DESIGN: Cross-sectional survey. PARTICIPANTS: Editors of biomedical journals that publish original clinical research. MEASUREMENTS: Genera ... Full text Link to item Cite

Guidelines for quality assurance in multicenter trials: a position paper.

Journal article Control Clin Trials · October 1998 Featured Publication In the wake of reports of falsified data in one of the trials of the National Surgical Adjuvant Project for Breast and Bowel Cancer supported by the National Cancer Institute, clinical trials came under close scrutiny by the public, the press, and Congress ... Full text Link to item Cite

Reducing patient eligibility criteria in cancer clinical trials.

Journal article J Clin Oncol · April 1996 Featured Publication PURPOSE: To discuss patient eligibility criteria in phase III cancer clinical trials in the larger setting of the complexity of these trials, to review the various reasons for imposing restrictive eligibility requirements, to discuss the problems caused by ... Full text Link to item Cite

Design of marker studies

Conference AMERICAN STATISTICAL ASSOCIATION 1996 PROCEEDINGS OF THE BIOMETRICS SECTION · 1996 Featured Publication Link to item Cite

Free-riding and the prisoner's dilemma: problems in funding economic analyses of phase III cancer clinical trials.

Journal article J Clin Oncol · September 1995 Featured Publication PURPOSE: Both economic and clinical data on new agents are important to policy-makers who approve pharmaceuticals for widespread use. Randomized clinical trials have been used to evaluate both clinical results and total medical costs associated with new ag ... Full text Link to item Cite