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. 2014 Apr 16:15:127.
doi: 10.1186/1745-6215-15-127.

Risk-proportionate clinical trial monitoring: an example approach from a non-commercial trials unit

Catrin Tudur Smith  1 , Paula Williamson, Ashley Jones, Alan Smyth, Simon Langton Hewer, Carrol Gamble
Affiliations

Risk-proportionate clinical trial monitoring: an example approach from a non-commercial trials unit

Catrin Tudur Smith et al. Trials. .

Abstract

Background: Some level of monitoring is usually required during a clinical trial to protect the rights and safety of trial participants and to safeguard the quality and reliability of trial results. Although there is increasing support for the use of risk-proportionate approaches to achieve these aims, the variety of methods and lack of an empirical evidence base can present challenges for clinical trial practitioners.

Methods: This paper describes the monitoring methods and procedures that are utilised by a non-commercial clinical trials unit which coordinates a range of clinical trials across a variety of clinical areas with different associated risks.

Results: Monitoring activities and approaches should be selected to be proportionate to the risks identified within a trial. A risk-proportionate approach to monitoring is described giving details of methods that may be considered by clinical trial practitioners during the development of a trial monitoring plan. An example risk assessment and corresponding monitoring plan for a low risk (type A in the Medicines and Healthcare Products Regulatory Agency (MHRA) classification system) pediatric trial is provided for illustration.

Conclusion: We present ideas for developing a monitoring plan for a clinical trial of an investigational medicinal product based on our experience. Alternative approaches may be relevant or preferable in other settings based on inherent risk.

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Figures

Figure 1
Figure 1
Risk proportionate approach to monitoring at CTRC.
Figure 2
Figure 2
Overall recruitment graph.
Figure 3
Figure 3
Example of acceptability threshold graph for missing primary outcome data.
Figure 4
Figure 4
Example graphical approaches(hypothetical data)for comparing serious adverse events (SAEs).(a) percentage participants with at least one SAE, (b) discrepancy in SAE event, (c) SAE rate at site 1.
See this image and copyright information in PMC

References

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    1. Effective and Efficient Monitoring as a Component of Quality. [ http://ctti-clinicaltrials.org/what-we-do/study-conduct/monitoring]
    1. MRC/DH/MHRA Joint Project. Risk-adapted Approaches to the Management of Clinical Trials of Investigational Medicinal Products. 2011. http://www.mhra.gov.uk/home/groups/l-ctu/documents/websiteresources/con1....
    1. Food and Drug Administration. Guidance for Industry Oversight of Clinical Investigations — A Risk-Based Approach to Monitoring. 2013. [ http://www.fda.gov/downloads/Drugs/…/Guidances/UCM269919.pdf Accessed 19/12/2013]

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