Refine
Year of publication
- 2021 (2) (remove)
Document Type
- Article (2)
Language
- English (2)
Has Fulltext
- yes (2)
Is part of the Bibliography
- no (2)
Keywords
- Diabetes mellitus (1)
- Diabetic wound healing (1)
- E-cadherin (1)
- Entscheidungsfindung (1)
- Fraktionierung (1)
- ICH-GCP (1)
- Klinisches Experiment (1)
- Mechanism (1)
- Mitigation plan (1)
- Piper crocatum Ruiz & Pav (1)
Institute
- Fakultät III - Medien, Information und Design (2) (remove)
Improving Risk Assessment in Clinical Trials: Toward a Systematic Risk-Based Monitoring Approach
(2021)
Regulatory authorities have encouraged the usage of a risk-based monitoring (RBM) system in clinical trials before trial initiation for detection of potential risks and inclusion of a mitigation plan in the monitoring strategy. Several RBM tools were developed after the International Council for Harmonization gave sponsors the flexibility to initiate an approach to enhance quality management in a clinical trial. However, various studies have demonstrated the need for improvement of the available RBM tools as each does not provide a comprehensive overview of the characteristics, focus, and application. This research lays out a rationale for a risk methodology assessment (RMA) within the RBM system. The core purpose of RMA is to deliver a scientifically based evaluation and decision of any potential risk in a clinical trial. Thereby, a monitoring plan can be developed to elude prior identified risk outcome. To demonstrate RMA’s theoretical approach in practice, a Shiny web application (R Foundation for Statistical Computing) was designed to describe the assessment process of risk analysis and visualization tools that eventually aid in focusing monitoring activities. RMA focuses on the identification of an individual risk and visualizes its weight on the trial. The scoring algorithm of the presented approach computes the assessment of the individual risk in a radar plot and computes the overall score of the trial. Moreover, RMA’s novelty lies in its ability to decrease biased decision making during risk assessment by categorizing risk influence and detectability; a characteristic pivotal to serve RBM in assessing risks, and in contributing to a better understanding in the monitoring technique necessary for developing a functional monitoring plan. Future research should focus on validating the power of RMAs to demonstrate its efficiency. This would facilitate the process of characterizing the strengths and weaknesses of RMA in practice.
Introduction: Piper crocatum Ruiz & Pav (P. crocatum) has been reported to accelerate the diabetic wound healing process empirically. Some studies showed the benefits of P. crocatum in treating various diseases but its mechanisms in diabetic wound healing have never been reported. In the present study we investigated the diabetic wound healing activity of the active fraction of P. crocatum on wounded hyperglycemia fibroblasts (wHFs).
Methods: Bioassay-guided fractionation was performed to get the most active fraction. The selected active fraction was applied to wHFs within 72 h incubation. Mimicking a diabetic condition was done using basal glucose media containing an additional 17 mMol/L D-glucose. A wound was simulated via the scratch assay. The collagen deposition was measured using Picro-Sirius Red and wound closure was measured using scratch wound assay. Underlying mechanisms through p53, aSMA, SOD1 and Ecadherin were measured using western blotting.
Results: We reported that FIV is the most active fraction of P. crocatum. We confirmed that FIV\(7.81 mg/ml, 15.62 mg/ml, 31.25 mg/ml, 62.5 mg/ml, and 125 mg/ml) induced the collagen deposition and wound closure of wHFs. Furthermore, FIV treatment (7.81 mg/ml, 15.62 mg/ml, 31.25 mg/ml) down-regulated the protein expression level of p53 and up-regulated the protein expression levels of aSMA, E-cadherin, and SOD1.
Discussion/conclusions: Our findings suggest that ameliorating collagen deposition and wound closure through protein regulation of p53, aSMA, E-cadherin, and SOD1 are some of the mechanisms by which FIV of P. crocatum is involved in diabetic wound healing therapy.