CaPPtain's Blog: John Burn, June 2018

Welcome to the CaPPtain's blog.  I'm feeling in Churchillian mood; we have now consented 1305 people in the UK to take part in CaPP3.  Our four international partners are all now recruiting.  Finland have 63, Australia have 81, Israel have 2 and Pamplona in Spain have just started and have randomised 4 people.  This gives us a grand total of 1455 recruits.  To paraphrase Winston, as we approach our minimum target of 1500, is that this is not the end, nor is it the beginning of the end but it is perhaps, the end of the beginning!

Please pass on our thanks to all the people who have agreed to test the three aspirin doses.  Thanks also to the recruiters too numerous to name here, to the Trial Steering Committee and the Data Monitoring Committee, to my co-investigators and our central office led by Gill Borthwick who are constantly at work to keep the wheels on the trial.  We expect to pass the first recruitment milestone in the autumn with 1500 international recruits. But will ask to be allowed to keep recruiting in the UK until the end of 2018, when hopefully we will have the 1500 UK recruits.  A major reason for this is that our drop-out rate has been higher than expected.  In CAPP2 we had a 20% withdrawal, but in CaPP3 we are running at 26% withdrawal before the two year follow up.  The design change to allow us to invite people to remain on their respective doses in the open phase will, to some extent, make up for the loss of power, but it would be good to think about what factors are influencing people to withdraw. 

The famous "confetti" produced by the blister packed aspirin in the blinded phase is often discussed on the Lynch Syndrome Facebook page, but we can't do anything about that as it's part of the original design.  The size of the packets is also an issue we can't change.  We are open to suggestions from any and all of the CaPP community on how we can help to keep people in the study and taking their tablets at least until the 2 year mark.  It would be a great shame if we went to all this trouble only to be criticised for lacking the statistical power to decide which is the best dose.  It is worth reminding ourselves, that this is a once in a lifetime opportunity to get a meaningful answer which will influence the use of aspirin to prevent cancer for many years to come.  If you are talking with a participant who is thinking of stopping, please talk through with them their reasons, especially if in relation to an adverse event.  It may be that a short break to allow for external issues to be resolved will allow the participant to restart. We realise that some participants find it difficult taking pills every day, or often don't remember to take their evening dose. Discuss with them ways of remembering to take their pills, or suggest that they are taken once a day.   This is vital to being able to make best use of the data we collect in coming years.

It is also important to be clear that we can continue to collect information even if a person doesn't want to continue taking the tablets.  We think that taking aspirin for even a short time may have a useful effect, but we can only prove this if we retain the ability to follow up people who have been randomised.  For the reader unfamiliar with the way trials are analysed, great importance is attached to an analysis called "Intention to Treat". This means we have to look at all the data and include all the people who started the trial.  If we lose access to the medical data, the whole trial is weakened.

But let's end on a positive note.  We are doing the biggest genetically targeted therapeutic prevention randomised trial ever attempted and we are going to make our ambitious recruitment target.  We are keeping the issue of aspirin as a cheap practical means of cancer prevention in the consciousness of clinicians and regulators.  Cancer Research UK have awarded a £5million Catalyst grant to a research consortium led by Professor Jack Cuzick, of which we are a key member. This will allow us to dig deeper into the mechanism of aspirin effect and explore ways to minimise adverse effects and target aspirin prevention more effectively.

Thank you all again for your hard work and support.

John Burn

June 2018