CaPPtain's Blog

  • CaPPtain's Blog: John Burn, December 2017

    posted on Wednesday, 3rd January 2018

    Not tagged.

    Happy CaPPmas

    Having spent the last three days at the wedding of our post doc Harsh Sheth in Ahmedabad, India, Tim Bishop and I are sat with our wives Julia and Linda, about to head west for 6 hours to do a little sightseeing in the Rann of Kutch, a vast salt desert.  What better time to write a CaPPtain's blog. 

    The last site agreement amendment to our modified trial design has been received, at long last and we have survived yet another audit.  I never cease to be amazed by the care and diligence of Gill, Donna, Lynne and Lynn in the CaPP office.  We owe them a debt of thanks for their cheerful forebearance as they respond to our over-engineered clinical trial processes.  Gill has now been given honorary status in our Trial Unit in Newcastle, which will ease communications. 

    The BIG news is that we have passed the 1300 mark when all recruits in the UK, Finland and Australia are combined.  Our absolute minimum target from the power analysis is 1500 so we are on course to reach that milestone in 2018.  Ideally, we will get to 1500 based on UK recruits alone so that data gathered in our international parallel studies becomes the icing on top rather than being a crucial ingredient of the cake, statistically speaking. (I hope that analogy translates into Finnish and Hebrew).

    On a wider front, the aspirin story remains as convincing as ever.  We have put forward a submission to the NICE consultation that aspirin be recognised as an acceptable treatment to be prescribed for people with Lynch syndrome.  This relies heavily on the result from the 5 year data in CAPP2.  Tim and I will soon distribute the paper based on the 10 year follow up analysis of CAPP2.  Apologies for the slow progress.  I spoke about aspirin at a variety of meetings during the year including a session at AACR (American Association for Cancer Research) organised by Andy Chan.  Andy and I were invited along with other aspirinologists to speak at a meeting in Berlin organised by the International Aspirin Foundation to mark the 120th anniversary of its approval for manufacture in Leverkusen.  It didn't hit the street as an analgesic until 1899 as the factory was too busy making the new cough medicine to replace opium which they had decided to call heroin…  It was selling like hot cakes. 

    Speaking of cakes, lunch beckons.  As ever, we are very grateful for the efforts of all our CaPP community.  Please keep recruiting and keep the data flowing into MACRO, the database.  I look forward to being able to announce by next December that we have reached the end of the beginning.


    With festive greetings - John & the CaPP3 Team


  • Captain's Blog: John Burn, January 2017

    posted on Thursday, 9th February 2017

    Not tagged.

    Captain's Blog: John Burn, January 2017

    A lot has happened since my last message. On the positive side, we are getting close to the magic 1000 recruits and after long negotiations; we are finally open in Finland. Negotiations are almost complete in Tel Aviv (site visit photo above) and Melbourne to allow recruitment to start there too. Our target is to recruit another thousand people with Lynch syndrome by the end of 2018. Our earliest recruits are now finishing their first two years of randomised aspirin and are about to be seen in clinic to transition to the open phase of the study. After much debate, we have changed our plan for the next phase. Instead of asking everyone to take a cardio aspirin, we are asking that people stay on the dose they have been taking for the previous two years. The reason for this is two-fold; first, we are forced to go "open label" because putting the aspirin in packets where no-one knows their dose is great for the science but very, very expensive. By switching to open label after two years we can keep the costs down but continue to keep in touch, while we wait to see what effect the aspirin is having on the risk of cancer. The second part is the decision to ask people to stay on the same dose. This is all about POWER - not the sort Mr Trump is after, but statistical power. Basically, the more people who try a treatment and the longer they do it, the more chance there is of getting a reliable result. We worked out the size of the study based on the results of CAPP2. Over the last few years we have collected more information and we have read about the results of other aspirin research. We are now convinced that we will be better able, to decide the best dose if people can stay on the same dose for longer. We don't expect it to make much difference in terms of side effects, but it will be important if the people on the bigger dose have fewer cancers. If they do, then we can recommend the bigger dose to everyone for the years to come. If the number of cancers is the same in all three groups, then we can opt safely for the smallest dose, which will have the fewest side effects over a lifetime.

    This begs the question, why did we need the "blind phase"? There are two main reasons; the first is that people are more convinced by trials where the people taking part are blinded to the dose they are taking. This mainly affects side effect reporting. We need to know if there is a difference in side effects, like indigestion. We are very suggestible, so if we know we are on the bigger dose we might experience more discomfort. The second reason is about doctors. For years, doctors have been told that aspirin causes many side effects. This was mainly in older people and often involved doses much higher than the ones used in CaPP3, but the effect has been that doctors are not keen to prescribe aspirin, especially in doses higher than the cardio aspirin. We have helped with a study of GP opinions, which confirms that many are unwilling to prescribe doses above 100mg. We need to be absolutely sure we are making a difference if we are going to change their minds. A disadvantage of everyone knowing the dose is that we can't rely on the polyp counts so much in case knowing the dose influenced the decision to report a polyp. The good news is that we are not relying on polyp counts, as we are focussing on cancers as a clear endpoint. Knowing how much aspirin someone is taking will not affect a decision to diagnose a cancer.

    Getting these changes through all the bureaucracy around clinical trials has taken several months. The next step is to clear with the hospitals that it's OK to give people their second phase "open label" aspirin as a routine prescription. Meanwhile, the packs of blister packed aspirin are coming to the end of their shelf life in April 2018, so we have asked Bayer for some more tablets and Cancer Research UK for an extra grant to allow us to pack another 4000 boxes. That will see us through to the end of the last recruits "blind phase" in 2020.

    We are happy to come and talk to you about the CaPP3 amendment and give you a study update. Some visits have already been organised.

Latest News