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

Abstract

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.

Research monitoring practices in critical care research: a survey of current state and attitudes

“…We support the call by Love et al [ 24 ] to elevate the requirement for a clinical trial monitoring plan to the same status as a protocol and statistical analysis plan. Presently, there are limited resources and guidance documents to provide direction on the processes involved with developing a robust monitoring plan, including risk assessment and implementation of associated risk mitigation and monitoring strategies.…”

“…The survey was developed following a review of the literature. A limited number of surveys examining similar topics have been published [ 20 , 22 , 24 , 25 ]; we reviewed these surveys and included questions relevant to the ANZ critical care setting, and specifically, academic-led clinical trials. Additionally, we developed questions relevant to our setting, and particularly in response to the coronavirus disease-19 (COVID-19) pandemic and the impact it has had on undertaking monitoring.…”

What is the purpose of clinical trial monitoring?

“…As each group leading clinical trials has created their own monitoring strategy and language, there have been difficulties in communicating between groups [ 5 ]. Our principles clarifying the purpose of monitoring should improve communication and enable the monitoring community to start producing clear monitoring practical guidelines and to start sharing tools.…”

“…Clinical trial monitoring is a crucial part of trial conduct, improving the safety of the participants, the quality of the data and the trial integrity. Clinical trial monitoring is conducted by monitors, quality assurance teams and by trial managers [5]. Guidance on trial monitoring is spread amongst different sources within and between organisations, is often in technical language and does not describe Keeping participants safe and respecting their rights To ensure, enhance and protect participants' safety, wellbeing and rights.…”

“…Therefore, each clinical trial sponsor has taken this definition or the one in their own country's legislation (for example [3]), interpreted it and created their own monitoring activities. This has led to wide variation in practices, as noted in several surveys of monitoring approaches [4][5][6].…”