Improving The Basics: Why Do We Do Clinical Trial Monitoring?

Whilst working from home over the last two years I have had the pleasure of being part of a topic group within the Trial Conduct Working Group of the Trial Methodology Research Partnership looking at Data Monitoring & Quality led by Sharon Love.  One of the things this group has done is come together across virtual space from eight different trials units in the UK, one clinical department in London and the Trial Methodology Research Network in Ireland to ask ourselves what sounds like a very simple question: What is the purpose of clinical trial monitoring. We recognised that despite working with the same regulations and guidance, in application to our CTU processes and systems as well as to individual trials, we all interpreted it slightly differently.

Why is variation a problem?

Variation that is due to the particular needs or risks of a study is entirely warranted, but we discuss waste a lot in relation to clinical research and therefore we need to make sure that all the activities we undertake fulfil their purpose, add value to the quality of the study and minimise the burden on participants and health services.  In the UK this latter has become even greater a priority given the pressures on the NHS left by COVID and the effort to deliver COVID research.  In order to reduce ‘bad’ variation it is important we collectively understand why we do clinical trial monitoring and the best methods to undertake that.

What did we do?

We reviewed all guidance that the CTUs referred to in making decisions about planning monitoring, including the regulators in the UK, US and EU as well as UK national and international guidelines. Each was reviewed by multiple people and then brought together as a group.  We distilled this into a set of principles which were then shared with a broader group to see if they made sense to others.

What did we conclude?

The five principles reasons for monitoring that we produced were:

• Keeping participants safe and respecting their rights
• Having data we can trust
• Making sure the trial was run as it was meant to be
• Improving the way the trial is run
• Preventing problems before they happen

We then linked each of these to examples of what this might mean in practice and these can be seen in a recently published paper in Trials.

Reflections

Often in monitoring we can get very focussed on detection of mistakes and fraud, what these principles reflect for me is that we often neglect the focus on quality improvement through the course of a trial AND then being able to sum up that learning to feed into the next trial. We are all getting better at doing that within our CTUs, but increasing sharing across CTUs is also vital to all take those quality improvement steps forwards, especially as trials themselves are changing so much.

My second reflection would be that our next focus needs to be on how we approach risk adaptation across the sector.  I recently read this interesting systematic review from Katharina Klatte that pulled together all the evidence for different forms of monitoring and it is clear that risk adaptation is the approach we need to build on.

As a CTU Director this kind of work is essential for us to move forward in trial efficiency and we do need to question ourselves regularly about if we are doing things a certain way because that is ‘how they are done’.