A5008127215- Statistical Methods in Clinical Trials
- Cancer Immunotherapy and Biomarkers
- Health Systems, Economic Evaluations, Quality of Life
- Advanced Causal Inference Techniques
- Lung Cancer Treatments and Mutations
- Diabetes Treatment and Management
- Cancer Genomics and Diagnostics
- Lung Cancer Diagnosis and Treatment
- Statistical Methods and Inference
- Pharmacology and Obesity Treatment
- Diabetes Management and Research
- Lung Cancer Research Studies
- Colorectal Cancer Treatments and Studies
- Pancreatic and Hepatic Oncology Research
- Optimal Experimental Design Methods
- Metabolism, Diabetes, and Cancer
- Peptidase Inhibition and Analysis
- COVID-19 and healthcare impacts
- Biosimilars and Bioanalytical Methods
- Computational Drug Discovery Methods
- Economic and Financial Impacts of Cancer
- Esophageal Cancer Research and Treatment
- Ovarian cancer diagnosis and treatment
- PARP inhibition in cancer therapy
- Pancreatic function and diabetes
Merck & Co., Inc., Rahway, NJ, USA (United States)
2014-2023
Daiichi Sankyo (United States)
2023
Decision Sciences (United States)
2016-2021
Bausch Health (United States)
2014
Rutgers, The State University of New Jersey
2009-2010
Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased tumors express ligand (PD-L1).In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated NSCLC PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation the epidermal growth factor receptor gene or translocation anaplastic lymphoma kinase to receive either...
To assess the efficacy and safety of MK-0941, a glucokinase activator (GKA), when added to stable-dose insulin glargine in patients with type 2 diabetes.In this double-blind study, 587 taking (±metformin ≥1,500 mg/day) were randomized (1:1:1:1:1) MK-0941 10, 20, 30, or 40 mg matching placebo t.i.d. before meals (a.c.). This study included an initial 14-week, dose-ranging phase followed by 40-week treatment during which be uptitrated as tolerated (or placebo) a.c. The primary end point was...
105 Background: Pembro plus pemetrexed and carboplatin resulted in superior objective response rate (ORR), progression-free survival (PFS) overall (OS) for untreated pts with non-sq NSCLC. is active sq NSCLC, so combining chemo a rational next step. Methods: KEYNOTE-407 (NCT02775435) randomized, placebo-controlled, global study of 560 metastatic NSCLC ECOG 0-1. Pts were stratified by type taxane, PD-L1 (TPS <1% vs ≥1%), site (East Asia other). Investigators chose taxane. randomized 1:1 to...
BackgroundIn KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes based on PD-L1 expression archival newly collected tumor samples using recently updated data.Patients and methodsPD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) or samples. Patients received 2 10 mg/kg Q3W 75 mg/m2 for 24...
–The COVID-19 pandemic has had and continues to have major impacts on planned ongoing clinical trials. Its effects trial data create multiple potential statistical issues. The scale of impact is unprecedented, but when viewed individually, many the issues are well defined feasible address. A number strategies recommendations put forward assess address related estimands, missing data, validity modifications analysis methods, need for additional analyses, ability meet objectives overall...
Abstract A randomized trial allows estimation of the causal effect an intervention compared to a control in overall population and subpopulations defined by baseline characteristics. Often, however, clinical questions also arise regarding treatment patients, which would experience or disease related events post‐randomization. Events that occur after initiation potentially affect interpretation existence measurements are called intercurrent ICH E9(R1) guideline. If event is consequence...
The present study was conducted to evaluate the efficacy, safety and tolerability of sitagliptin added ongoing metformin therapy in Chinese patients with type 2 diabetes (T2DM) who failed achieve adequate glycemic control monotherapy. After a titration/stabilization period 2-week, single-blind, placebo run-in period, 395 T2DM aged 25-77 years (baseline HbA1c 8.5%) were randomized (1:1) double-blind or 100 mg q.d. open-label (1000 1700 mg/day) for 24 weeks. Significant (P < 0.001) changes...
9000 Background: In KEYNOTE-024 (NCT02142738), pembrolizumab (pembro) was superior to chemotherapy (chemo) as first-line (1L) therapy for advanced NSCLC with PD-L1 TPS ≥50% and no sensitizing EGFR mutations or ALK translocations. After a median follow-up of 11.2 mo, HR 0.50 PFS by independent central radiologic review ( P< 0.001) 0.60 OS P= 0.005). Here we present PFS2 updated OS. Methods: 305 pts were randomly assigned pembro 200 mg Q3W (n = 154) investigator (INV)-choice...
To evaluate the efficacy and safety of taranabant in overweight obese patients with type 2 diabetes mellitus (T2DM).This was a multicenter, double-blind, randomized, placebo-controlled study T2DM (ages > or = 18 < 75 years) BMI 27 kg/m(2) 43 HbA1c =7.0 10.0%, who were either not on an antihyperglycaemic agent stable dose metformin (> 1500 mg/day). After 2-week placebo run-in, randomized to (N 156) 0.5-mg 155), 1-mg 157), 2-mg 155) once daily for 52 weeks. Primary endpoints changes from...
COVID-19 outbreak has rapidly evolved into a global pandemic. The impact of on patient journeys in oncology represents new risk to interpretation trial results and its broad applicability for future clinical practice. We identify key intercurrent events that may occur due trials with focus time-to-event endpoints discuss considerations pertaining the other estimand attributes introduced ICH E9 addendum. propose strategies handle related events, depending their relationship malignancy...
Abstract The purpose of this note is to raise awareness the complexity practice involving dichotomization. It well known that regular regression models are effective tools for analyzing Gaussian‐type response variables, and researchers often told it a ‘bad idea’ dichotomization if continuous measurements available. We demonstrate through special cases, however, there another side story variable contaminated. Although causes loss information, can also reduce input contamination. If reduction...
Abstract Background Type 2 diabetes mellitus (T2DM) treatment generally requires multiple antihyperglycemic agents. When diet, exercise, and with sulfonylurea metformin do not achieve glycemic goals, several options are available. The present study evaluated the efficacy tolerability of sitagliptin 100 mg/day added to therapy metformin. Methods Patients HbA1c ≥7.5% ≤10.5% while on a were randomized 1 : or placebo for 24 weeks. At Week 24, patients in group switched pioglitazone 30 both...
Oncology drug developers sometimes decide to initiate Phase III randomized confirmatory trials at risk after significant preliminary anti-tumor activities are observed in small I/II single arm studies. There two clear challenges. First, these investigational drugs may have a greater benefit biomarker enriched population. But the limited data from can hardly provide much-needed information for selecting cutpoint or prioritizing hypothesis testing. Second, seldom any insight on how treatment...
An addendum of the ICH E9 guideline on Statistical Principles for Clinical Trials was released in November 2019 introducing estimand framework. This new framework aims to align trial objectives and statistical analyses by requiring a precise definition inferential quantity interest, that is, estimand. explicitly accounts intercurrent events, such as switching anticancer therapies analysis overall survival (OS), gold standard oncology. Traditionally, OS confirmatory studies is analyzed using...
9015 Background: In the phase III KEYNOTE-010 study (NCT01905657), pembrolizumab (pembro; MK-3475) provided superior OS over docetaxel (doce) in patients (pts) with previously treated, PD-L1–positive advanced NSCLC (P = 0.0008 for 2 mg/kg and P < 0.0001 10 total [tumor proportion score (TPS) ≥ 1%] population). We assessed outcomes when PD-L1 was further categorized as a TPS of 1%-24%, 25%-49%, 50%-74%, 75%. Methods: Pts progression after cycles platinum-doublet chemotherapy 1% by IHC (22C3...
9024 Background: KEYNOTE-010 (NCT01905657) showed that the anti–PD-1 antibody pembrolizumab (pembro; MK-3475) at doses of 2 and 10 mg/kg Q3W provided superior OS over docetaxel in patients (pts) with previously treated, PD-L1–positive advanced NSCLC: HR 0.71, P = 0.0008 for 0.61, < 0.0001 mg/kg. Efficacy was greatest co-primary, PD-L1 TPS ≥ 50% population: 0.54, 0.0002 0.50, 0.0001. In a post hoc analysis, we assessed efficacy pts 1%-49% enrolled KEYNOTE-010. Methods: Key eligibility...
In randomized clinical trials with survival outcome, there has been an increasing interest in subgroup identification based on baseline genomic, proteomic markers, or characteristics. Some of the existing methods identify subgroups that benefit substantially from experimental treatment by directly modeling outcomes effect. When goal is to find optimal for a given patient rather than finding right treatment, under individualized regime framework estimate rule would lead best expected outcome...