Changing Clinical Practice Through Innovative Trial Designs


Lead Contact

Professor Lucinda Billingham

University of Birmingham


Dr Victoria Homer (Co-Director), University of Birmingham

Professor Pamela Kearns, University of Birmingham

Professor Timothy Barrett, University of Birmingham

Professor Simon Gates, University of Birmingham

Professor Steven Julious, University of Sheffield

Professor Carrol Gamble, University of Liverpool


The CAPTIVATE node will bring together the UK’s leading trial experts with hospital researchers experienced in rare diseases, industry partners, regulators, policy makers and patient partners, to develop better ways to test new medicines for people with rare diseases in clinical trials. People expect to receive treatments which have been approved for use in the NHS based on evidence from trials but it is hard to do trials in rare diseases because there may only be a few people affected with the disease who are able to take part. Often a clinical trial will require several phases, one after the other, but this is not feasible in rare diseases so we will develop ways to test medicines in a single trial (a ‘one-stop-study’) that collects all the evidence needed to approve the treatment in one go. We will explore how best to include the information about a medicine that is already known to ensure trial results are more likely to be accepted by healthcare professionals, people living with rare diseases and the authorities who set the rules for approving new medicines. One type of trial that is often used, called a “randomised controlled trial”, has participants assigned to two or more groups, where one of the groups receive whatever treatment would be considered as standard of care for that disease. This group is called the “control arm”.

We will look for alternatives to including a control arm in studies to reduce the number of participants needed. We will investigate alternative approaches to statistical analysis of the data from trials, such as those based on the Bayesian method, named after a scientist called Thomas Bayes, that may be useful in trials of rare diseases because they can be more flexible and may help to reduce the number of patients needed to take part.

We will work on trials in children, where it is so important to make sure medicines that work get to children with rare diseases quickly and explore how we can best test medicines in ultra-rare diseases.


The CAPTIVATE node aims to:
  • Develop designs that form a single pivotal trial (‘one-stop-study’), encompassing all phases of clinical trials and providing data that are acceptable to regulators and policy makers;
  • Determine the best way to include external information into trials of rare diseases to maximise the benefit of such data and minimise the number of patients required in the clinical trial;
  • Determine how small the sample size for a trial can be to still provide sufficient evidence to convince clinical and patient communities and that would be deemed robust enough for approval of experimental treatments by regulators and policy makers, with particular focus on n-of-1 trials.