A5020047598- Statistical Methods in Clinical Trials
- Advanced Causal Inference Techniques
- Statistical Methods and Bayesian Inference
- HIV Research and Treatment
- Statistical Methods and Inference
- Optimal Experimental Design Methods
- Health Systems, Economic Evaluations, Quality of Life
- Genetic Associations and Epidemiology
- HIV/AIDS drug development and treatment
- Herpesvirus Infections and Treatments
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- Vaccine Coverage and Hesitancy
- Advanced Statistical Methods and Models
- Advanced Statistical Process Monitoring
- Bioinformatics and Genomic Networks
- Immune Cell Function and Interaction
- Hepatitis C virus research
- Computational Drug Discovery Methods
- Helicobacter pylori-related gastroenterology studies
- Genetic Mapping and Diversity in Plants and Animals
- Genetic and phenotypic traits in livestock
- Biosimilars and Bioanalytical Methods
- vaccines and immunoinformatics approaches
- COVID-19 Clinical Research Studies
Merck & Co., Inc., Rahway, NJ, USA (United States)
2014-2024
Decision Sciences (United States)
2006-2024
Graphic Era University
2024
Merck (Japan)
2000-2021
Gwynedd Mercy University
2017-2018
United States Military Academy
1997-2014
Office of AIDS Research
2011
University of Zurich
2010-2011
Institute of Social and Preventive Medicine
2010-2011
Zimmer Biomet (Switzerland)
2010-2011
The safety and immunogenicity of the MRK adenovirus type 5 human immunodeficiency virus 1 clade B gag/pol/nef vaccine, a replication-incompetent 5-vectored vaccine designed to elicit cell-mediated immunity against conserved proteins, was assessed in phase trial. Healthy adults not infected with were enrolled multicenter, dose-escalating, blind, placebo-controlled study evaluate 3-dose homologous prime-boost regimen trivalent containing from 3 x 10(6) 10(11) viral particles per 1-mL dose...
Abstract In randomized clinical trials, a pre‐treatment measurement is often taken at baseline, and post‐treatment effects are measured several time points post‐baseline, say t =1, …, T . At the end of trial, it interest to assess treatment effect based on mean change from baseline last point We consider statistical methods for (i) estimate 95 per cent confidence interval each group, (ii) p ‐value between‐group difference in baseline. The manner which responses used analysis influences both...
Several vaccine candidates to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or disease 2019 (COVID-19) have entered will soon enter large-scale, phase 3, placebo-controlled randomized clinical trials. To facilitate harmonized evaluation and comparison of the efficacy these vaccines, a general set endpoints is proposed, along with considerations guide selection primary on basis statistical reasoning. The plausibility that protection symptomatic...
Abstract Polygenic risk scores (PRS) have been successfully developed for the prediction of human diseases and complex traits in past years. For drug response randomized clinical trials, a common practice is to apply PRS built from disease genome-wide association study (GWAS) directly corresponding pharmacogenomics (PGx) setting. Here, we show that such an approach relies on stringent assumptions about prognostic predictive effects selected genetic variants. We propose shift PGx approaches...
Summary Fisher's exact test for comparing response proportions in a randomized experiment can be overly conservative when the group sizes are small or close to zero one. This is primarily because null distribution of statistic becomes too discrete, partial consequence inference being conditional on total number responders. Accordingly, unconditional procedures have gained popularity, premise that power will increase presumably less discrete. However, we caution researchers poor choice...
Clinical adverse experience (AE) data are routinely evaluated using between group P values for every AE encountered within each of several body systems. If the reported and interpreted without multiplicity considerations, there is a potential an excess false positive findings. Procedures based on confidence interval estimates treatment effects have same findings as value methods. Excess can needlessly complicate safety profile safe drug or vaccine. Accordingly, we propose novel method...
Human immunodeficiency virus type 1 (HIV-1)-specific cellular immunity contributes to the control of HIV-1 replication. HIV-1-infected volunteers who were receiving antiretroviral therapy given a replication-defective adenovirus 5 gag vaccine in randomized, blinded therapeutic vaccination study.
The Safety Planning, Evaluation and Reporting Team (SPERT) was formed in 2006 by the Pharmaceutical Research Manufacturers of America.SPERT's goal to propose a pharmaceutical industry standard for safety planning, data collection, evaluation, reporting, beginning with planning first-in-human studies continuing through post-product-approval period.SPERT's recommendations are based on our review relevant literature consensus reached discussions.An important recommendation is that sponsors...
The Step study was a randomized trial to determine whether an adenovirus type 5 (Ad5) vector vaccine, which elicits T cell immunity, can lead control of human immunodeficiency virus (HIV) replication in participants who became HIV-infected after vaccination.We evaluated the effect vaccine on trends HIV viral load, CD4+ counts, time initiation antiretroviral therapy (ART), and AIDS-free survival 87 male infected with during had median 24 months post-infection follow-up.There no overall mean...
In some randomized (drug versus placebo) clinical trials, the estimand of interest is between-treatment difference in population means a endpoint that free from confounding effects "rescue" medication (e.g., HbA1c change baseline at 24 weeks would be observed without rescue regardless whether or when assigned treatment was discontinued). such settings, missing data problem arises if patients prematurely discontinue trial initiate while trial, latter necessitating discarding post-rescue data....
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...
An effective vaccine for HIV is likely to require induction of T-cell-mediated immune responses, and the interferon-gamma (IFNgamma) enzyme-linked immunospot (ELISPOT) assay has become most commonly used measuring these responses in trials. We optimized validated ELISPOT using an empirical method establish positivity criteria that results a < or =1% false-positive rate. Using this assay, we detected broad range HIV-specific peptide pools overlapping 20mers, 15mers, 9mers study volunteers...
Extensive observational data suggest that herpes simplex virus type 2 (HSV-2) infection may facilitate HIV acquisition, increase viral load, and accelerate progression onward transmission. To explore these relationships, we examined the impact of preexisting HSV-2 in an international vaccine trial.We analyzed associations between prevalent HIV-1 acquisition among 1836 men who have sex with men. We used Cox proportional hazards regression models to estimate association both antiretroviral...
The genetic diversity of human immunodeficiency virus type 1 (HIV-1) raises the question whether vaccines that include a component to elicit antiviral T cell immunity based on single viral clade could provide cellular immune protection against divergent HIV-1 clades. Therefore, we quantified cross-clade reactivity, among unvaccinated individuals, anti-HIV-1 responses infecting relative other major circulating clades.Cellular clades A, B, and C were compared by standardized interferon- gamma...
Quantitative analysis of cell-mediated immune responses induced by candidate HIV vaccines requires robust procedures for collecting and processing human peripheral mononuclear blood cells (PBMCs). We evaluated several parameters in order to optimize a sample handling process that would be suitable multicenter clinical trial. Among the findings, systematic increases magnitude IFN-γ ELISpot were observed when time from collection PBMC freezing was reduced <12 h. By implementing these...
Vaccines inducing pathogen-specific cell-mediated immunity are being developed using attenuated adenoviral (Ad) vectors. We report the results of two independent Phase I trials similar replication-deficient Ad5 vaccines containing a near-consensus HIV-1 clade B gag transgene. Healthy HIV-uninfected adults were enrolled in separate, multicenter, dose-escalating, blinded, placebo-controlled studies to assess safety and immunogenicity three-dose homologous regimen MRKAd5 given on day 1, week 4,...
In many two‐period, two‐treatment (2 × 2) crossover trials, for each subject, a continuous response of interest is measured before and after administration the assigned treatment within period. The resulting data are typically used to test null hypothesis involving true difference in means. We show that power achieved by different statistical approaches greatly influenced (i) ‘structure’ variance–covariance matrix vector within‐subject responses (ii) how baseline (i.e., pre‐treatment)...
In October 2014, the Steering Committee of International Conference on Harmonization endorsed formation an expert working group to develop addendum E9 guideline ("Statistical Principles for Clinical Trials"). The will focus two topics involving randomized confirmatory clinical trials: estimands and sensitivity analyses. Both are motivated, in part, by need improve precision with which scientific questions interest formulated addressed trialists regulators, specifically context...
Abstract Background Randomized controlled clinical trials remain the gold standard for determining efficacy of new heart failure (HF) therapies; however, to account heterogeneity in risk primary endpoint(s) may dilute treatment efficacy. The novel 5-step stratified testing and amalgamation routine (5-STAR) methodology addresses these limitations using stratification based on treatment-independent associations between baseline covariates outcomes. We applied 5-STAR original VICTORIA database...