Development of a standardised set of metrics for monitoring site performance in multicentre randomised trials: a Delphi study

Background: Despite the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) encouraging the use of risk-based monitoring for trials in 2013, there remains a lack of evidence-based guidelines on how to monitor. We surveyed the academic United Kingdom Clinical Research Collaboration (UKCRC) registered clinical trials units (CTUs) to find out their policy on monitoring of phase III randomised clinical trials of an investigational medicinal product (CTIMPs). Methods: An online survey of monitoring policy with sections on the CTU, central monitoring and on-site monitoring was sent to all 50 UKCRC registered CTUs in November 2018. Descriptive data analysis and tabulations are reported using the total number answering each question. Results: A total of 43/50 (86%) of CTUs responded with 38 conducting phase III randomised CTIMP trials. Of these 38 CTUs, 34 finished the survey. Most CTUs (36/37, 97%) use a central monitoring process to guide, target or supplement site visits. More than half (19/36, 53%) of CTUs do not use an automated monitoring report when centrally monitoring trials and all units use trial team knowledge to make a final decision on whether an on-site visit is required. A total of 31/34 (91%) CTUs used triggers to decide whether or not to conduct an on-site monitoring visit. On-site, a mixture of source data verification and checking of processes was carried out. The CTUs overwhelmingly (27/34, 79%) selected optimising central monitoring as their most pressing concern. Conclusion: The survey showed a wide variation in phase III randomised CTIMP trial monitoring practices by academic clinical trials units within a single research-active country. We urgently need to develop evidence-based regulator-agreed guidance for CTUs on best practice for both central and on-site monitoring and to develop tools for all CTUs to use.

Section: Discussionmentioning

confidence: 99%

Monitoring in practice – How are UK academic clinical trials monitored? A survey

Love

Yorke-Edwards

Lensen

et al. 2020

“…More recently, there has been a shift toward increased remote monitoring conducted by the trial sponsor or coordinating trials unit or both [3]. Central checks can be carried out on electronic records, consent forms and overall performance of participating sites [3], highlighted by the recent development of metrics in this area [4]. Although this may reduce the number or duration of visits, central monitoring has its own limitations, including access to the source data and reliance on sites maintaining data collection records.…”

Section: Introductionmentioning

confidence: 99%

An evaluation of risk-based monitoring in pragmatic trials in UK Clinical Trials Units

Beever

Swaby

2019

Background Good Clinical Practice guidelines issued in 2016 encourage risk-based approaches to monitoring clinical trials. This study compared current risk assessment and monitoring approaches in UK Clinical Trials Units (CTUs) with the published guidance and makes recommendations for risk-based monitoring in pragmatic trials. Methods An online survey of UK Clinical Research Collaboration registered CTUs was administered via email invitation. Forty-nine units were invited, and 23 responded. Respondents were also invited to share copies of risk assessment templates. Results Most CTUs reported using remote combined with on-site monitoring. All reported undertaking a risk assessment for Clinical Trials of Investigational Medicinal Products (CTIMPs) and 21 units did so for non-CTIMPs. Most CTIMP risk assessments used MHRA (Medicines and Healthcare products Regulatory Agency) classifications, although some also employed staff judgement. Almost all units based their monitoring on perceived risk level; this number was higher for CTIMPs (n = 22) than for non-CTIMPs (n = 19). In most cases, monitoring plans were produced. More CTUs revisited risk assessments during trials in CTIMPs (n = 21) than in non-CTIMPs (n = 18). Small numbers of units reviewed the monitoring approach always (n = 4) or sometimes (n = 9) and few used the reflection to guide future monitoring. Conclusions A high proportion of UK CTUs are using risk-based monitoring in the UK, as recommended by guidelines, for both CTIMPs and non-CTIMPs. This has the potential to make trials more efficient and reduce costs. However, there appears to be a lack of reflection on the value of these revised approaches. There may be a benefit in CTUs collaborating nationally to improve processes for reflection and making changes during the life course of a trial.

“…Secondly, investigator meetings can be held for a variety of reasons and we have not attempted to explore the potential effects of holding a meeting on other parameters, such as data collection and staff involvement and empowerment, simply due to the data being unavailable in this retrospective study. Finally, factors that could influence site recruitment, such as site engagement and prior research experience, were not explored, since this data was not available retrospectively, though we recognise that a site's performance is multi-faceted [17] and could influence recruitment rates.…”

Section: Discussionmentioning

confidence: 99%

Do investigator meetings improve recruitment rates in clinical trials? A retrospective before-and-after study of data from nine multi-centre clinical trials

Mitchell

Godolphin

Meakin

et al. 2020

Background: Poor recruitment in clinical trials is well-documented. In large, multi-centre trials, communication between the coordinating centre and trial sites is essential. A commonly used communication tool is the hosting of an investigator/collaborator meeting, which offers an opportunity for sites to retrain and receive trial updates, learn from each other, share best practice and troubleshoot issues. Anecdotally, there is a perception that recruitment rates may increase after holding such a meeting. The aim of this before-and-after study was to examine any changes in recruitment after an investigator meeting. Methods: We conducted a retrospective study of nine trials at the Nottingham Clinical Trials Unit (NCTU) that were open to recruitment between 2014 and 2018. In the 8 weeks prior to the date of the investigator meeting, 82 sites (across nine trials) were open to recruitment; 60 of which attended the meeting, 22 who did not. Using meeting attendance data available in Trial Master Files (TMF) and recruitment data from randomisation datasets, we examined recruitment rates in the 8 weeks prior to and following the date of the investigator meeting. Results: For the 82 sites included, 284 participants were recruited in the 8 weeks prior to the meeting, with a further 300 participants recruited in the 8 weeks post meeting. This gives a mean change in weekly recruitment of 0.073 (− 0.129, 0.275) per site, demonstrating no statistically significant increase in recruitment after the investigator meeting. For the 60 attending sites, recruitment increased from 254 participants prior to the meeting to 271 post meeting, giving a 0.100 (− 0.160, 0.360) mean change in weekly recruitment per site, providing no evidence that recruitment rates increase following an investigator meeting. Conclusion: There is no statistical evidence to conclude that holding an investigator meeting increases recruitment in the 8 weeks following the meeting. Thus, if the meeting has been held in the belief that it will have a positive impact upon recruitment, trialists may wish to consider other evidence-based strategies known to increase recruitment rates. However, since there are a variety of reasons why an investigator meeting may be held, trialists should continue to consider this as a communication strategy with sites.