2. Myeloma UK Clinical Trial Network (CTN)
Aims
Efficiently deliver a portfolio of early phase trials
Allow patients to access novel treatments
Reflect UK clinical practice
Enable a transition from phase I → phase II → phase III
Current portfolio
3 trials open
3 trials closed to recruitment
3 trials in set-up/design
2 trials completed
Who we are – coordinating centre for MUK CTN. Aims of the network are:…
We have an expanding team and a steady stream of trial...

3. Previous monitoring strategy
Risk assessment performed at the beginning of the trial
Monitoring plan written – pre-determined number of site visits
More patients = more site visits
Major issues eg Serious Breach = a site visit
Risk assessment carried out during set-up looked at patient safety and data quality risks as well as other issues such as IMP logistics and potential impediments to recruitment.
The central and site monitoring covered by the monitoring plan was mainly concerned with ensuring patient safety and data integrity and dictated a certain number of visits per site. There were really only a couple of triggers for additional visits - a high number of patients at a site or major issues namely a serious breach. However, as the trials we manage are all phase I and phase II, and therefore inherently higher risk than later phase trials, site visits and thorough in-house data checking are always necessary.
Restrictions of previous strategy:
- Common issues such as protocol violation and CRF compliance/quality were not consistently monitored and taken into account for monitoring
Information sharing between TM/DM and monitoring staff was limited

4. Risk-based monitoring
Inspiration
MRC/DH/MHRA Joint Project - ‘Risk-adapted Approaches to the Management of Clinical Trials of Investigational Medicinal Products’
CRUK Drug Development Office - Risk Assessment Tool
How to implement in the Myeloma UK trials?
Risk-based approaches to trial management and monitoring are not new. When we decided to update our monitoring strategy for the Myeloma UK trials, we were taking inspiration from a few sources, including the….. And the risk assessment tool developed, and generously shared by, the CRUK drug development office. However, we found that this tool didn’t quite fit our portfolio so we had to work out how best to implement a similar approach that worked for us. :

5. Implementation Which parameters do we want to monitor?
What issues occur on our trials?
What data do we already collect that could be utilised?
What new data do we need to collect?
What will we do with the information generated?
Who will keep the tool updated?
The questions we asked ourselves were:
We decided to carry

6. Our risk-based monitoring tool
Low (1)
Medium (2)
High (4)
Number of protocol violations
no violations
1 violation
2 or more violations
Number of Serious breaches
no serious breaches -
serious breach occurred
Other issues on monitoring log
no issues
1-3 issues
more than 3 issues
CRF compliance %
90% or higher
70-90%
less than 70%
Average days to return data
less than 3 days
3-10 days
more than 10 days
SAE reporting
within timelines
1 SAE outside of timelines
multiple SAEs outside timelines
Total data queries out
>10 data queries out
10-30 data queries out
> 30 data queries out
Key personnel change
no changes to key personnel
changes to Lead Research Nurse or other key team member in the last 6 months
change to PI in past 6 months, or high staff turnover in past 6 months
Recruitment % vs plan
recruitment >80% of plan
recruitment % of plan
recruitment greater than 110% of plan
Site visit/SDV outcome - data
No issues/no visit
Some issues seen
Serious issues seen
Site outcome- pharmacy
Before the trial starts, we will score the risk of the trial based on a number of factors such as the novelty of the IMPs involved, known clinical safety issues, complexity of the protocol and patient population – I won’t show an example of this here. This is used to inform the monitoring plan ie the standard number of site visits and level of central montoring required.
We have then developed a tool to allow us to assess the performance of sites on an ongoing basis throughout the life of the trial, looking at a number of parameters and allowing us to allocate a score depending on whether they fall into the low, medium or high risk category. The parameters that we look at are shown here:
Briefly describe parameters used to assess sites monthly.

7. Our risk-based monitoring tool
We then have a monthly snapshot comparing all sites and highlighting key issues and this is useful at meetings.

8. Our risk-based monitoring tool
Site data updated monthly by trial coordinator
Monitor adds information from site visits
Used by all members of team
Used to help decide when additional ‘targeted’ or ‘triggered’ visits are required
How this works in practice….
As time goes on and we have more experience with the tool we may be able to set specific thresholds to determine when extra visits are required but we are currently using the objective measures in the tool combined with a certain degree of subjectivity to determine when what we call targeted and triggered visits are required. Targeted visits are like a first warning and triggered visits are the next step up – triggered visits are notified to the sponsor and would be carried in response to individual serious incidents or perhaps repeated violations despite a previous targeted visit and remedial action being put in place.
I think the tool will like always be used with some subjectivity and that flexibility is necessary to allow us to act as we think appropriate, as long as this is clearly justified.
In the future, hope that a similar approach will be adopted by other teams at the CTRU.