Challenges in preparing and implementing a clinical trial at field level in an Ebola emergency: A case study in Guinea, West Africa

During the large Ebola outbreak that affected West Africa in 2014 and 2015, studies were launched to evaluate potential treatments for the disease. A clinical trial to evaluate the effectiveness of the antiviral drug favipiravir was conducted in Guinea. This paper describes the main challenges of the implementation of the trial in the Ebola treatment center of Guéckédou. Following the principles of the Good Clinical Research Practices, we explored the aspects of the community's communication and engagement, ethical conduct, trial protocol compliance, informed consent of participants, ongoing benefit/risk assessment, record keeping, confidentiality of patients and study data, and roles and responsibilities of the actors involved. We concluded that several challenges have to be addressed to successfully implement a clinical trial during an international medical emergency but that the potential for collaboration between research teams and humanitarian organizations needs to be highlighted.status: publishe

Challenges in preparing and implementing a clinical trial at field level in an Ebola emergency: A case study in Guinea, West Africa.

During the large Ebola outbreak that affected West Africa in 2014 and 2015, studies were launched to evaluate potential treatments for the disease. A clinical trial to evaluate the effectiveness of the antiviral drug favipiravir was conducted in Guinea. This paper describes the main challenges of the implementation of the trial in the Ebola treatment center of Guéckédou. Following the principles of the Good Clinical Research Practices, we explored the aspects of the community's communication and engagement, ethical conduct, trial protocol compliance, informed consent of participants, ongoing benefit/risk assessment, record keeping, confidentiality of patients and study data, and roles and responsibilities of the actors involved. We concluded that several challenges have to be addressed to successfully implement a clinical trial during an international medical emergency but that the potential for collaboration between research teams and humanitarian organizations needs to be highlighted

TEM-1 Backbone Dynamics—Insights from Combined Molecular Dynamics and Nuclear Magnetic Resonance

Dynamic properties of class A β-lactamase TEM-1 are investigated from molecular dynamics (MD) simulations. Comparison of MD-derived order parameters with those obtained from model-free analysis of nuclear magnetic resonance (NMR) relaxation data shows high agreement for N-H moieties within α- and β-secondary structures, but significant deviation for those in loops. This was expected, because motions slower than the protein global tumbling often take place in loop regions. As previously shown using NMR, TEM-1 is a highly ordered protein. Motions are observed within the Ω loop that could, upon substrate binding, stabilize E166 in a catalytically efficient position as the cavity between the protein core and the Ω loop is partially filled. The rigidity of active site residues is consistent with the enzyme high turnover number. MD data are also shown to be useful during the model selection step of model-free analysis: local N-H motions observed over the course of the trajectories help assess whether a peptide plan undergoes low or high amplitude motions on one or more timescales. This joint use of MD and NMR provides a better description of protein dynamics than would be possible using either technique alone

Key recommendations for a trial implementation in an Ebola outbreak.

<p>Key recommendations for a trial implementation in an Ebola outbreak.</p