Lessons Learned from Alzheimer Disease: Clinical Trials with Negative Outcomes
Clinical and Translational Science,Volume 11, Issue 2, Page 147-152, March 2018. (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - August 2, 2017 Category: Biomedical Science Source Type: research
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Clinical and Translational Science, Ahead of Print. (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - August 2, 2017 Category: Biomedical Science Source Type: research
Patient Decisions to Receive Secondary Pharmacogenomic Findings and Development of a Multidisciplinary Practice Model to Integrate Results Into Patient Care
Whole exome sequencing (WES) has the potential of identifying secondary findings that are predictive of poor pharmacotherapy outcomes. The purpose of this study was to investigate patients’ wishes regarding the reporting of secondary pharmacogenomic findings. WES results (n = 106 patients) were retrospectively reviewed to determine the number of patients electing to receive secondary pharmacogenomic results. Phenotypes were assigned based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The percent of patients with a predicted phenotype associated with a gene‐based CPIC dosing recommendation wa...
Source: Clinical and Translational Science - July 27, 2017 Category: Biomedical Science Authors: J. Kevin Hicks, Amy Shealy, Allison Schreiber, Marissa Coleridge, Ryan Noss, Marvin Natowicz, Rocio Moran, Timothy Moss, Angelika Erwin, Charis Eng Tags: ARTICLE Source Type: research
Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis
Given the recognition that disease‐modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient‐level longitudinal data of 672 subjects with early‐stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP‐1347 Trial (PRECEPT) clinical trial were utilized in a linear mix...
Source: Clinical and Translational Science - July 27, 2017 Category: Biomedical Science Authors: Daniela J. Conrado, Timothy Nicholas, Kuenhi Tsai, Sreeraj Macha, Vikram Sinha, Julie Stone, Brian Corrigan, Massimo Bani, Pierandrea Muglia, Ian A. Watson, Volker D. Kern, Elena Sheveleva, Kenneth Marek, Diane T. Stephenson, Klaus Romero, Tags: ARTICLE Source Type: research
Issue Information
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - July 11, 2017 Category: Biomedical Science Tags: ISSUE INFORMATION Source Type: research
Identification of OAT1/OAT3 as Contributors to Cisplatin Toxicity
Cisplatin is among the most widely used anticancer drugs and known to cause a dose‐limiting nephrotoxicity, which is partially dependent on the renal uptake carrier OCT2. We here report a previously unrecognized, OCT2‐independent pathway of cisplatin‐induced renal injury that is mediated by the organic anion transporters OAT1 and OAT3. Using transporter‐deficient mouse models, we found that this mechanism regulates renal uptake of a mercapturic acid metabolite of cisplatin that acts as a precursor of a potent nephrotoxin. The function of these two transport systems can be simultaneously inhibited by the tyrosine ki...
Source: Clinical and Translational Science - July 8, 2017 Category: Biomedical Science Authors: S Hu, AF Leblanc, AA Gibson, KW Hong, JY Kim, LJ Janke, L Li, A Vasilyeva, DB Finkelstein, JA Sprowl, DH Sweet, E Schlatter, G Ciarimboli, JHM Schellens, SD Baker, N Pabla, A Sparreboom Tags: ARTICLE Source Type: research
High ‐Performance Liquid Chromatography Method for Rich Pharmacokinetic Sampling Schemes in Translational Rat Toxicity Models With Vancomycin
We describe: (i) a vancomycin high‐performance liquid chromatography (HPLC) method for rat plasma and kidney tissue homogenate; (ii) a rat pharmacokinetic (PK) study to demonstrate utility; and (iii) a catheter retention study to enable future preclinical studies. Rat plasma and pup kidney tissue homogenate were analyzed via HPLC for vancomycin concentrations ranging from 3–75 and 15.1–75.5 μg/mL, respectively, using a Kinetex Biphenyl column and gradient elution of water with 0.1% formic acid: acetonitrile (70:30 v/v). Sprague‐Dawley rats (n = 10) receiving 150 mg/kg of vancomycin intraperitoneally had plasma sam...
Source: Clinical and Translational Science - July 4, 2017 Category: Biomedical Science Authors: MD Joshi, JN O'Donnell, N Venkatesan, J Chang, H Nguyen, NJ Rhodes, G Pais, RL Chapman, B Griffin, MH Scheetz Tags: ARTICLE Source Type: research
Current Status and Open Issues Concerning Global Clinical Trials (GCTs) in Japan and East Asia
When global clinical trials are carried out, it is important to consider the influence of racial and ethnic differences on the outcome. From this viewpoint, global clinical trials in East Asia, where racial differences are estimated to be small, are now attracting close attention. Under such circumstances, we conducted a survey using the data registered with ClinicalTrial.gov to investigate the status of participation of East Asian countries in global clinical trials and differences in the regions selected for drug development between Japanese enterprises and non‐Japanese enterprises. This survey revealed that about 90% ...
Source: Clinical and Translational Science - July 4, 2017 Category: Biomedical Science Authors: Koichi Miyazaki, Yasunori Sato, Hideki Hanaoka, Yoshiaki Uyama Tags: ARTICLE Source Type: research
The Burden of the “False‐Negatives” in Clinical Development: Analyses of Current and Alternative Scenarios and Corrective Measures
The “false‐negatives” of clinical development are the effective treatments wrongly determined ineffective. Statistical errors leading to “false‐negatives” are larger than those leading to “false‐positives,” especially in typically underpowered early‐phase trials. In addition, “false‐negatives” are usually eliminated from further testing, thereby limiting the information available on them. We simulated the impact of early‐phase power on economic productivity in three developmental scenarios. Scenario 1, representing the current status quo, assumed 50% statistical power at phase II and 90% at phas...
Source: Clinical and Translational Science - July 4, 2017 Category: Biomedical Science Authors: T Burt, KS Button, HHZ Thom, RJ Noveck, MR Munaf ò Tags: ARTICLE Source Type: research
Does Secretory Clearance Follow Glomerular Filtration Rate in Chronic Kidney Diseases? Reconsidering the Intact Nephron Hypothesis
In conclusion, dosing adjustments in CKD require refinement; in addition to GFR, biomarkers of tubular function are needed for secreted drugs. (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - July 4, 2017 Category: Biomedical Science Authors: A Chapron, DD Shen, BR Kestenbaum, C Robinson ‐Cohen, J Himmelfarb, CK Yeung Tags: ARTICLE Source Type: research
Progress in rare diseases research 2010 –2016: an IRDiRC perspective
This article is protected by copyright. All rights reserved (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - July 1, 2017 Category: Biomedical Science Authors: Hugh JS Dawkins, Ruxandra Draghia ‐Akli, Paul Lasko, Lilian PL Lau, Anneliene H Jonker, Christine M Cutillo, Ana Rath, Kym M Boycott, Gareth Baynam, Hanns Lochmüller, Petra Kaufmann, Yann Le Cam, Virginie Hivert, Christopher P Austin, Tags: REVIEW Source Type: research
The Role of Public –Private Partnerships in Catalyzing the Critical Path
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - July 1, 2017 Category: Biomedical Science Authors: Kimberly E. Maxfield, ShaAvhr ée Buckman‐Garner, Ameeta Parekh Tags: REVIEW Source Type: research
Lessons Learned from Alzheimer Disease: Clinical Trials with Negative Outcomes
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - July 1, 2017 Category: Biomedical Science Authors: Jeffrey Cummings Tags: REVIEW Source Type: research
Lost in Translation: No Effect of a High ‐Profile Publication on the Concomitant Use of Interacting Drugs
We examined prepublication and postpublication dispensing trends using Poisson regression. ACEI + potassium‐sparing diuretic use did not differ postpublication vs. prepublication (P = 0.11). Digoxin + clarithromycin use decreased minimally postpublication vs. prepublication (relative rate = 0.9996: 95% confidence interval [CI] = 0.9993–0.9998). Glyburide + cotrimoxazole use increased minimally postpublication vs. prepublication (relative rate = 1.0220; 95% CI = 1.0187–1.0254). Therefore, the high‐profile DDI publication had minimal to no measurable effect in reducing the concomitant use of the interacting drugs stu...
Source: Clinical and Translational Science - July 1, 2017 Category: Biomedical Science Authors: Emily K Acton, Charles E Leonard, Warren B Bilker, Shobha Phansalkar, Sean Hennessy Tags: BRIEF REPORT Source Type: research
