Publications
Department of Medicine faculty members published more than 3,600 peer-reviewed articles in 2024.
2015
2015
2015
2015
OBJECTIVE
To develop a method for profiling the collective populations targeted for recruitment by multiple clinical studies addressing the same medical condition using one eligibility feature each time.
METHODS
Using a previously published database COMPACT as the backend, we designed a scalable method for visual aggregate analysis of clinical trial eligibility features. This method consists of four modules for eligibility feature frequency analysis, query builder, distribution analysis, and visualization, respectively. This method is capable of analyzing (1) frequently used qualitative and quantitative features for recruiting subjects for a selected medical condition, (2) distribution of study enrollment on consecutive value points or value intervals of each quantitative feature, and (3) distribution of studies on the boundary values, permissible value ranges, and value range widths of each feature. All analysis results were visualized using Google Charts API. Five recruited potential users assessed the usefulness of this method for identifying common patterns in any selected eligibility feature for clinical trial participant selection.
RESULTS
We implemented this method as a Web-based analytical system called VITTA (Visual Analysis Tool of Clinical Study Target Populations). We illustrated the functionality of VITTA using two sample queries involving quantitative features BMI and HbA1c for conditions "hypertension" and "Type 2 diabetes", respectively. The recruited potential users rated the user-perceived usefulness of VITTA with an average score of 86.4/100.
CONCLUSIONS
We contributed a novel aggregate analysis method to enable the interrogation of common patterns in quantitative eligibility criteria and the collective target populations of multiple related clinical studies. A larger-scale study is warranted to formally assess the usefulness of VITTA among clinical investigators and sponsors in various therapeutic areas.
View on PubMed2015
PURPOSE
We determined the safety, pharmacokinetics, pharmacodynamics, and recommended phase II dose of MK-8776 (SCH 900776), a potent, selective checkpoint kinase 1 (Chk1) inhibitor, as monotherapy and in combination with gemcitabine in a first-in-human phase I clinical trial in patients with advanced solid tumor malignancies.
PATIENTS AND METHODS
Forty-three patients were treated by intravenous infusion with MK-8776 at seven dose levels ranging from 10 to 150 mg/m(2) as monotherapy and then in combination with gemcitabine 800 mg/m(2) (part A, n = 26) or gemcitabine 1,000 mg/m(2) (part B, n = 17). Forty percent of patients had three or more prior treatment regimens, and one third of patients had previously received gemcitabine.
RESULTS
As monotherapy, MK-8776 was well tolerated, with QTc prolongation (19%), nausea (16%), fatigue (14%), and constipation (14%) as the most frequent adverse effects. Combination therapy demonstrated a higher frequency of adverse effects, predominantly fatigue (63%), nausea (44%), decreased appetite (37%), thrombocytopenia (32%), and neutropenia (24%), as well as dose-related, transient QTc prolongation (17%). The median number of doses of MK-8776 administered was five doses, with relative dose-intensity of 0.96. Bioactivity was assessed by γ-H2AX ex vivo assay. Of 30 patients evaluable for response, two showed partial response, and 13 exhibited stable disease.
CONCLUSION
MK-8776 was well tolerated as monotherapy and in combination with gemcitabine. Early evidence of clinical efficacy was observed. The recommended phase II dose is MK-8776 200 mg plus gemcitabine 1,000 mg/m(2) on days 1 and 8 of a 21-day cycle.
View on PubMed2015
2015
2015
2015