Changing clinical practice in rare diseases through innovative trial designs: the CAPTIVATE node
Lead Research Organisation:
University of Birmingham
Department Name: Institute of Cancer and Genomic Sciences
Abstract
What we will do:
We will create a group of researchers that will develop better ways to test new medicines for people with rare diseases in clinical trials. We want to find ways that need as few people to take part as possible, that are quicker and that provide all the information needed for the authorities to approve a new medicine to be prescribed to people with rare diseases from one single trial. The group of researchers will be called 'the CAPTIVATE node' and people living with rare conditions will contribute to the research.
Why we are doing this:
People with rare diseases expect to receive treatments which have been approved for use in the NHS based on evidence from trials. 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. It is also hard to expect people to take a 'dummy' medicine (placebo) as part of randomised controlled trials. There is another method called Bayesian clinical trials (named after a scientist called Thomas Bayes). This method may be useful in trials in rare diseases because it is more flexible. The method allows us to learn about medicines being tested in the trial by analysing results from one patient at a time rather than waiting to the end of the trial. This can help reduce the number of people needed to take part. The method also allows us to look at any information that already exists about the medicine being tested. We can use this when we study the results of the trial.
How we will do it:
We will develop ways to test medicines in a single trial (a 'one-stop-study') that collects all the data needed for approval in one go. We will explore how best to include the information about a medicine that is already known. This way, 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. 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. There may be information from studies in adults that can also be useful and included in trials for children, and we will investigate this. We will try to find some alternatives to the traditional 'randomised controlled trial' such as using information from people affected by rare diseases instead of asking them to take a placebo.
How we will involve patients and the public:
We will work with Genetic Alliance UK, Alstrom Syndrome UK and other patient support groups to ensure the voice of people living with rare conditions (PLWRC) is included in the overall direction of the research. There will be patient partners invited to our regular project management meetings and we will set up an PLWRC advisory group that will provide guidance at the start and during the research.
Explaining our work:
The CAPTIVATE node will bring together the UK's leading trial experts with hospital researchers experienced in rare diseases, industry partners, policy makers and patient partners, to develop and discuss clinical trial designs that could speed up the approval of medicines for use in rare diseases. This network of experts will develop new designs and guidelines that we believe will improve the health of people living with rare diseases.
We will create a group of researchers that will develop better ways to test new medicines for people with rare diseases in clinical trials. We want to find ways that need as few people to take part as possible, that are quicker and that provide all the information needed for the authorities to approve a new medicine to be prescribed to people with rare diseases from one single trial. The group of researchers will be called 'the CAPTIVATE node' and people living with rare conditions will contribute to the research.
Why we are doing this:
People with rare diseases expect to receive treatments which have been approved for use in the NHS based on evidence from trials. 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. It is also hard to expect people to take a 'dummy' medicine (placebo) as part of randomised controlled trials. There is another method called Bayesian clinical trials (named after a scientist called Thomas Bayes). This method may be useful in trials in rare diseases because it is more flexible. The method allows us to learn about medicines being tested in the trial by analysing results from one patient at a time rather than waiting to the end of the trial. This can help reduce the number of people needed to take part. The method also allows us to look at any information that already exists about the medicine being tested. We can use this when we study the results of the trial.
How we will do it:
We will develop ways to test medicines in a single trial (a 'one-stop-study') that collects all the data needed for approval in one go. We will explore how best to include the information about a medicine that is already known. This way, 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. 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. There may be information from studies in adults that can also be useful and included in trials for children, and we will investigate this. We will try to find some alternatives to the traditional 'randomised controlled trial' such as using information from people affected by rare diseases instead of asking them to take a placebo.
How we will involve patients and the public:
We will work with Genetic Alliance UK, Alstrom Syndrome UK and other patient support groups to ensure the voice of people living with rare conditions (PLWRC) is included in the overall direction of the research. There will be patient partners invited to our regular project management meetings and we will set up an PLWRC advisory group that will provide guidance at the start and during the research.
Explaining our work:
The CAPTIVATE node will bring together the UK's leading trial experts with hospital researchers experienced in rare diseases, industry partners, policy makers and patient partners, to develop and discuss clinical trial designs that could speed up the approval of medicines for use in rare diseases. This network of experts will develop new designs and guidelines that we believe will improve the health of people living with rare diseases.
Technical Summary
The CAPTIVATE node aims to develop innovative clinical trial designs that enable the efficient evaluation of treatments for rare diseases with limited numbers of participants such that the designs and data are acceptable to regulators and policy makers. Running multiple sequential phases of clinical trials is not feasible in rare diseases, particularly in those that are ultra-rare, so our vision is to develop designs that form a single pivotal trial (a 'one-stop-study') that encompasses all phases of clinical trials. In addition, randomised controlled trials, which are expected when aiming to generate practice-changing evidence, may not be feasible in this setting so we will explore alternative options.
We envisage a variety of different designs (particularly adaptive, single-arm, n-of-1, platform, basket and umbrella) will underpin the methodology required, together with the use of Bayesian approaches and observational data. Implementing a Bayesian approach for trials in rare diseases provides a valuable opportunity to incorporate external data into the appraisal of treatments through the use of priors, thereby reducing the number of participants needed in the trial. We will explore how best to develop and incorporate priors such that trial results would be acceptable to all stakeholders. Bayesian methods maximise the utility of each patient in the trial and enable decisions to be made using small sample sizes but, as with frequentist designs, error rates will increase as sample size decreases. We will explore how low the sample size could go to provide evidence that would still be acceptable for approval and investigate the use of n-of-1 designs for ultra-rare diseases.
We will bring together leading trial methodologists with clinical researchers, industry partners, regulators, policy makers and people living with rare conditions to develop and discuss trial designs that could deliver the level of evidence required for licensing and approval in this setting.
We envisage a variety of different designs (particularly adaptive, single-arm, n-of-1, platform, basket and umbrella) will underpin the methodology required, together with the use of Bayesian approaches and observational data. Implementing a Bayesian approach for trials in rare diseases provides a valuable opportunity to incorporate external data into the appraisal of treatments through the use of priors, thereby reducing the number of participants needed in the trial. We will explore how best to develop and incorporate priors such that trial results would be acceptable to all stakeholders. Bayesian methods maximise the utility of each patient in the trial and enable decisions to be made using small sample sizes but, as with frequentist designs, error rates will increase as sample size decreases. We will explore how low the sample size could go to provide evidence that would still be acceptable for approval and investigate the use of n-of-1 designs for ultra-rare diseases.
We will bring together leading trial methodologists with clinical researchers, industry partners, regulators, policy makers and people living with rare conditions to develop and discuss trial designs that could deliver the level of evidence required for licensing and approval in this setting.