A5075031456- Statistical Methods in Clinical Trials
- Optimal Experimental Design Methods
- Biosimilars and Bioanalytical Methods
- Hemodynamic Monitoring and Therapy
- Advanced Statistical Process Monitoring
- Reliability and Agreement in Measurement
- Health Systems, Economic Evaluations, Quality of Life
- Statistical Methods and Inference
- Multiple Myeloma Research and Treatments
- Gene expression and cancer classification
- Statistical Methods and Bayesian Inference
- Advanced Statistical Methods and Models
- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Spectroscopy and Chemometric Analyses
- Computational Drug Discovery Methods
- Multi-Criteria Decision Making
- Bayesian Methods and Mixture Models
- Cancer Treatment and Pharmacology
- Pesticide Residue Analysis and Safety
- Molecular Biology Techniques and Applications
- Statistical Distribution Estimation and Applications
- Cancer Immunotherapy and Biomarkers
- Peptidase Inhibition and Analysis
- Meta-analysis and systematic reviews
Incyte (United States)
2021-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2002-2021
Pennsylvania State University
2021
Penn State Milton S. Hershey Medical Center
2021
ASML (United States)
2021
Decision Sciences (United States)
2019-2020
Tris Pharma (United States)
2016
United States Military Academy
2002-2014
Teva Pharmaceuticals (United States)
2011
Merck (Japan)
2005
It is often necessary to compare two measurement methods in medicine and other experimental sciences. This problem covers a broad range of data. Many authors have explored ways assessing the agreement sets measurements. However, there has been relatively little attention determining sample size for designing an study. In this paper, method using interval approach concordance proposed calculate conducting The philosophy behind that satisfied when no more than pre-specified k discordances are...
The log-rank test is most powerful under proportional hazards (PH). In practice, non-PH patterns are often observed in clinical trials, such as immuno-oncology; therefore, alternative methods needed to restore the efficiency of statistical testing. Three categories testing were evaluated, including weighted tests, Kaplan-Meier curve-based tests (including and Restricted Mean Survival Time, RMST), combination Breslow test, Lee's combo MaxCombo test). Nine scenarios representing PH various...
Abstract It is often required to compare two measurements in medicine and other experimental sciences. This problem covers a broad range of data, examples can be found different industries. In this paper, new index on measuring agreement proposed, which similar Lin's concordance correlation coefficient but derived from criterion more conceptually appealing offers improvements. An example used demonstrate the benefit using index. Copyright © 2003 John Wiley & Sons, Ltd.
8021 Background: KEYNOTE-183 (NCT02576977) evaluated pom + low-dose dex (SOC) ± pembro in patients (pts) with RRMM. Methods: Pts were randomized 1:1 to (200 mg Q3W) SOC (4 [d 1-21] 40 1, 8, 15, 22]) every 28 d vs until progression (PD), unacceptable toxicity, withdrawal. Coprimary endpoints: PFS (2011 IMWG criteria), OS; secondary safety, ORR. On July 3, 2017 based on interim data presented the DMC, FDA halted KEYNOTE-183. Results: 249/300 pts enrolled (125, SOC; 124, SOC) median (range)...
Abstract Recently, the five‐parameter logistic (5PL) function has seen increased use as a model for bioassay dose‐response curves. The 5PL takes curve asymmetry into consideration to overcome some drawbacks of four‐parameter (4PL) function. These include biased estimates important parameters, poor characterization pharmacological pathways and mechanisms, inaccurate inference drug‐receptor interactions. However, currently used functional form does not have same practical useful parameter...
Time‐to‐event data are common in clinical trials to evaluate survival benefit of a new drug, biological product, or device. The commonly used parametric models including exponential, Weibull, Gompertz, log‐logistic, log‐normal, simply not flexible enough capture complex curves observed and medical research studies. On the other hand, nonparametric Kaplan Meier (KM) method is very successful on catching various shapes but lacks ability predicting future events such as time for certain number...
Abstract Background The data from immuno-oncology (IO) therapy trials often show delayed effects, cure rate, crossing hazards, or some mixture of these phenomena. Thus, the proportional hazards (PH) assumption is violated such that commonly used log-rank test can be very underpowered. In trials, conventional hazard ratio for describing treatment effect may not a good estimand due to lack an easily understandable interpretation. To overcome this challenge, restricted mean survival time (RMST)...
8010 Background: KEYNOTE-185 (NCT02579863) evaluated Rd ± pembro in patients (pts) with newly diagnosed, ASCT-ineligible MM. Methods: Pts were randomized 1:1 to (200 mg Q3W) + (len 25 [days (d) 1-21] 40 dex [weekly] every 28d) vs until progression (PD), unacceptable toxicity, or withdrawal. Randomization stratified by age ( < 75 ≥75 y), and disease stage (ISS I II III). Primary end point was PFS per 2011 IMWG; secondary points included OS safety. On July 3, 2017, based on interim data...
To develop a biosimilar product, it is essential to demonstrate the biosimilarity between proposed product and reference first in terms of quality stepwise approach that can then help inform extent safety efficacy data will be required establish biosimilarity. These comparability studies should have direct side-by-side comparisons test products. In this paper, we statistical method for unpaired head-to-head attribute comparisons. The uses plausibility interval derived from comparing against...
It is often necessary to compare two measurement methods in medicine and other experimental sciences. This problem covers a broad range of data with applications arising from many different fields. The Bland-Altman method has been favorite for concordance assessment. However, the approach creates interpretation when mixture fixed bias, proportional bias and/or error occurs. In this paper, an improved proposed handle more complicated scenarios practice. new includes Bland-Altman's as its...
"Rejoinder to Letter the Editor "The Hazards of Period Specific and Weighted Hazard Ratios"." Statistics in Biopharmaceutical Research, 12(4), pp. 520–521
Guanghan Frank Liu* & Jason J. Z. LiaoBiostatistics and Research Decision Sciences, Merck Co., Inc., North Wales, Pennsylvania, USA
To develop a biosimilar product, it is necessary to demonstrate biosimilarity between the proposed product and reference in terms of purity, potency, efficacy, safety. In this paper, clinical efficacy data required for establishing are considered.
Abstract Identifying the maximum tolerated dose (MTD) and recommending a Phase II for an investigational treatment is crucial in cancer drug development. A suboptimal often leads to failed late‐stage trial, while overly toxic causes harm patients. There very rich literature on trial designs dose‐finding oncology clinical trials. We propose novel hybrid design that maximizes merits minimizes limitations of existing designs. Building two designs: model‐assisted (the modified toxicity...
The reproducibility of a validated analytical method may require reassessment because various reasons, such as the transfer between laboratories or companies, changes in instruments software platforms (or both), critical reagents, among others. This paper is demonstration an assay bridging study evaluating reproducibility. approach simple but very informative and offers many advantages over existing approaches.
It is well known that outliers can have a significant effect on the conclusion of bioavailability/bioequivalence study. Existing approaches for outlier detection are ANOVA type based assumptions log-AUC, and they disconnected from pharmacokinetics (PK) literature. However, observations study correlated concentrations, not AUCs. Thus, estimate AUC related variance may be accurate because exclusion correlation nature. In this paper, predicted concentrations functional linear model which takes...
In medical and other related sciences, clinical or experimental measurements usually serve as a basis for diagnostic, prognostic, therapeutic, performance evaluations. Examples can be assessing the reliability of multiple raters (or measurement methods), suitability tumor evaluation using local laboratory central in randomized trial (RCT), validating surrogate endpoints study, determining that important outcome are interchangeable among evaluators an RCT. Any elegant study design cannot...
With dramatic increased spending on biologics and approaching patent expirations for existing biological products, there is a need to consolidate thinking the regulatory approval pathway of biosimilars. However, have much greater complexity by nature. The traditional paradigm currently used generic chemical drugs, where bioequivalence focus, cannot be extrapolated biologics. In biosimilars scenario, comparability pharmacokinetic pharmacodynamic parameters, efficacy safety from clinical...