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

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. Electronic supplementary material The online version of this article (10.1186/s13063-019-3619-6) contains supplementary material, which is available to authorized users.


How many current CTIMP studies does your unit coordinate?
Mark only one oval.  Does the risk assessment and monitoring process differ between the two? Mark only one oval.

Yes
Skip to question 9.

Section 1: General information
Which of the following does your CTU use? Mark only one oval.
Only on-site monitoring Mostly on-site monitoring with some remote On-site and remote monitoring in equal proportion Mostly remote monitoring with some on-site Only remote monitoring 7.
Who makes the decision on the level of monitoring required? (I.e. in terms of content, rather than approval of processes / documentation) Mark only one oval.
Skip to question 12. Other: Skip to question 13.

11.
Section 2: Initial risk assessment Do you undertake a risk assessment for your studies? Mark only one oval.

Yes -All
Skip to question 20.

Yes -Most
Skip to question 20.

Yes -Some
Skip to question 20.

No
Skip to question 31.

12.
Section 2: Initial risk assessment Do you undertake a risk assessment for your CTIMP studies? Mark only one oval.

Yes -All
Yes -Most

Non-CTIMP studies?
Mark only one oval.

Yes -All
Yes -Most

Section 2: Initial risk assessment
If you do not undertake risk assessments for either CTIMPs, non-CTIMPs or both, please leave the relevant questions blank.

Does the risk assessment for the CTIMP study use the MHRA categorisations (A/B/C)?
Mark only one oval.

Does the risk assessment assess and categorise each individual risk, or the risk of the CTIMP study as a whole?
Tick all that apply.

Individual risks
Whole study 16.

Non-CTIMP?
Tick all that apply.

Individual risks
Whole study 17.

How is such assessment undertaken for a CTIMP? (If other, please specify)
Mark only one oval.

Using numerical scores
Using staff judgement

Non-CTIMP?
Mark only one oval.

Using numerical scores
Using staff judgement

Using both
Other:

19.
Skip to question 23. Does the risk assessment assess and categorise each individual risk, or the risk of the study as a whole? Tick all that apply.

Individual risks
Whole study

21.
How is such assessment undertaken? (If other, please specify) Mark only one oval.

Using numerical scores
Using staff judgement

Using both
Other:

Section 2: Initial risk assessment
Does the risk assessment tool indicate specific monitoring approaches to be used to mitigate the risks identified for a CTIMP study? Mark only one oval.

Non-CTIMP?
Mark only one oval.

Is the type of monitoring used dependent on the level of risk of the CTIMP study?
Mark only one oval.

Non-CTIMP?
Mark only one oval.
An Evaluation of Risk Based Monitoring in Pragmatic Trials 5 of 10 Section 2: Initial risk assessment Does the risk assessment tool indicate specific monitoring approaches to be used to mitigate the risks identified? Mark only one oval.

Is the type of monitoring used dependent on the level of risk of the study?
Mark only one oval.

Yes
No

Section 3: Monitoring approaches and adapting to identified risks Do you produce a monitoring plan for your CTIMP studies?
Mark only one oval.

Yes -All
Yes -Most

Non-CTIMPs?
Mark only one oval.

Yes -All
Skip to question 32.

Yes -Most
Skip to question 32.

Yes -Some
Skip to question 32.

No
Skip to question 32.

Section 3: Monitoring approaches and adapting to identified risks risks Is the risk assessment revisited throughout the course of the CTIMP study?
Mark only one oval.

Yes
No N/A (no risk assessment is undertaken) 32.

Non-CTIMP study?
Mark only one oval.

Yes
Skip to question 35.

No
Skip to question 35.
N/A (no risk assessment is undertaken) Skip to question 35.

Section 3: Monitoring approaches and adapting to identified risks
Is the risk assessment revisited throughout the course of the study? Mark only one oval.

Yes
Skip to question 39.

No
Skip to question 41.

N/A (no risk assessment is undertaken)
Skip to question 41.

Section 3: Monitoring approaches and adapting to identified risks
How often is the risk assessment revisited for a CTIMP? Tick all that apply.
At a fixed timepoint (e.g. yearly) Routinely after each protocol amendment In reaction to a specific issue / event N/A 35.

Non-CTIMP?
Tick all that apply.
At a fixed timepoint (e.g. yearly) Routinely after each protocol amendment In reaction to a specific issue / event N/A 36.

An Evaluation of Risk Based Monitoring in Pragmatic Trials
Is this reassessment used to adapt the initially agreed monitoring approaches for a CTIMP? Mark only one oval.

Yes
No N/A 37.

Non-CTIMP?
Mark only one oval.

Yes
No N/A

Section 3: Monitoring approaches and adapting to identified risks
How often is the risk assessment revisited? Tick all that apply.
At a fixed timepoint (e.g. yearly) Routinely after each protocol amendment In reaction to a specific issue / event 39.

Is this reassessment used to adapt the initially agreed monitoring approaches?
Mark only one oval.