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

Trials

Carrol Gamble²  Simon Langton Hewer³  Alan Smyth¹  Ashley Jones²  Paula Williamson²  Catrin Tudur Smith² 

[1] Division of Child Health, Obstetrics & Gynaecology, E Floor East Block, Queens Medical Centre, Derby Road, Nottingham NG7 2UH, UK;Clinical Trials Research Centre, Department of Biostatistics, and North West Hub for Trials Methodology Research, University of Liverpool, 1st floor Duncan Building, Daulby Street, Liverpool L69 3GA, UK;Department of Paediatric CF and Respiratory Medicine, Bristol Royal Hospital for Children, Upper Maudlin Street, Bristol BS2 8BJ, UK

关键词: Quality assurance;    Risk proportionate;    On-site monitoring;    Central monitoring;    Monitoring;   

Others  :  806882
DOI  :  10.1186/1745-6215-15-127

 received in 2013-04-12, accepted in 2014-03-21,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Tudur Smith et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice E6(R1). 1996. [http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/Step4/E6_R1__Guideline.pdf webcite]
• [2]Baigent C, Harrell FE, Buyse M, Emberson JR, Altman DG: Ensuring trial validity by data quality assurance and diversification of monitoring methods. Clin Trials 2008, 5:49-55.
• [3]Effective and Efficient Monitoring as a Component of Quality. [http://ctti-clinicaltrials.org/what-we-do/study-conduct/monitoring webcite]
• [4]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/con111784.pdf webcite
• [5]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 webcite Accessed 19/12/2013]
• [6]European Medicines Agency: Reflection paper on risk based quality management in clinical trials. 2013. [http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/11/WC500155491.pdf webcite]
• [7]Morrison BW, Cochran CJ, White JG, Harley J, Kleppinger CF, Liu A, Mitchel JT, Nickerson DF, Zacharias CR, Kramer JM, Neaton JD: Monitoring the quality of conduct of clinical trials: a survey of current practices. Clin Trials 2011, 8:342-349.
• [8]Tudur Smith C, Stocken D, Dunn J, Cox T, Ghaneh P, Cunningham D, Neoptolemos JP: The value of source data verification in a cancer clinical trial. Plos One 2012, 7:e51623.
• [9]Bakobaki JM, Rauchenberger M, Joffe N, McCormack S, Stenning S, Meredith S: The potential for central monitoring techniques to replace on-site monitoring: findings from an international multi-centre clinical trial. Clin Trials 2012, 9:257-264.
• [10]Prospective cluster-randomized investigation into strategies adapted on a study-specific basis for on-site monitoring in conjunction with additional quality assurance measures. [http://www.adamon.de/ADAMON_EN/Home.aspx webcite]
• [11]Journot V, Pignon JP, Gaultier C, Daurat V, Bouxin-Metro A, Giraudeau B, Preux PM, Treluyer JM, Chevret S, Plattner V, Thalamas C, Clisant S, Ravaud P, Chene G: Validation of a risk-assessment scale and a risk-adapted monitoring plan for academic clinical research studies--the Pre-Optimon study. Contemp Clin Trials 2011, 32:16-24. [Research Support, Non-US Gov't]
• [12]Buyse MGS, Evans S, Geller NL, Ranstam J, Scherrer B, Lesaffre E, Murray G, Edler L, Hutton J, Colton T, Lachenbruch P, Verma BL: The role of biostatistics in the prevention, detection and treatment of fraud in clinical trials. Stat Med 1999, 18:3435-3451.
• [13]Clinical Trials Toolkit: Work stream 6: Pharmacovigilance. 2012. [http://www.ct-toolkit.ac.uk/__data/assets/pdf_file/0010/35956/joint-project-pharmacovigilance.pdf webcite]
• [14]Gamble C, Wolf A, Sinha I, Spowart C, Williamson PR: The role of systematic reviews in pharmacovigilance planning and clinical trials authorisation application: example from the SLEEPS trial. Plos One 2013, 8:e51787.