TY - JOUR

T1 - Improving Risk Assessment in Clinical Trials

T2 - Toward a Systematic Risk-Based Monitoring Approach

AU - Fneish, Firas

AU - Schaarschmidt, Frank

AU - Fortwengel, Gerhard

N1 - Funding Information: The authors thank the journal for its editorial support and the anonymous referees for their numerous constructive comments toward improving our manuscript. The shinyapp was coded using R software (R Foundation for Statistical Computing) and is platform independent; specifically, an interactive hypertext markup language document is produced using Rmarkdown runtime shiny. The Rmarkdown shiny syntax is deployed to shinyapps server in which it preserves the functionality of the code. The syntax is available on Github at https://github.com/firasfneish/Risk-Methodology-Assessment. Project home page: https://firasfneish.shinyapps.io/Risk_Based_Monitoring_Methodology/, F. Fneish designed and conceptualized the methodology of the tool, programmed the shinyapp, and drafted the manuscript for intellectual content. F. Schaarschmidt, critically reviewed the manuscript. G. Fortwengel designed and conceptualized the methodology of the tool and critically reviewed the manuscript. The authors approved the final version of the manuscript. None.

PY - 2021/8/28

Y1 - 2021/8/28

N2 - Regulatory authorities have encouraged the usage of a 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.

AB - Regulatory authorities have encouraged the usage of a 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.

KW - Clinical trials

KW - ICH-GCP

KW - Mitigation plan

KW - Risk methodology assessment

KW - Risk-based monitoring

UR - http://www.scopus.com/inward/record.url?scp=85116079618&partnerID=8YFLogxK

U2 - 10.1016/j.curtheres.2021.100643

DO - 10.1016/j.curtheres.2021.100643

M3 - Article

AN - SCOPUS:85116079618

VL - 95

JO - Current Therapeutic Research - Clinical and Experimental

JF - Current Therapeutic Research - Clinical and Experimental

SN - 0011-393X

M1 - 100643

ER -