As a scientist doing research, you are generally taught to investigate one thing at a time. Identify a problem, review what’s already known and then test different things that impact on that problem to try and find a solution. That’s also how clinical trials have traditionally been designed for many years meaning new medicines have been taking an average of 12 years to reach clinical practice. (1)
But there is another way of conducting trials where scientists investigate multiple clinical questions at the same time. In Complex Innovative Design (CID) trials you can efficiently combine multiple research questions into a single study, as well as having the flexibility to add new, or stop existing, parts of the study whilst it’s ongoing. It’s a rapidly expanding method of research, and it has the potential to get new medicines to patients faster.
One of the earliest examples of a CID trial was the international PROFILE 1001 non-small cell lung cancer study designed to investigate crizotinib. As data started coming in, it was found that a subset of patients in whom the drug was working all had the same genetic change (known as the ALK fusion gene). The study was changed so more patients with this genetic change were recruited into the trial. This led to the medicine receiving approval from the EU in 2012 - only 5 years after the discovery of the fusion gene.
Knowledge and awareness of CID trials has increased over recent years, notably since Dame Tessa Jowell gave an emotional speech in the House of Lords, almost 2 years to the day, calling for the increased use of adaptive trials.
In early 2018, I was invited by the Experimental Cancer Medicine Centre (ECMC) to join a Working Group to look at how CID trials can work better for everyone. Alongside other members from regulatory agencies, pharmaceutical companies, Government, charities, Research Ethics Committees, universities, the NHS and patient groups, we set out to identify recommendations to navigate the hurdles often encountered when conducting CID trials.
It’s essential this work was done – the process of researching and developing new medicines is time-consuming, costly, and there is a high rate of failure. Anything we can do to improve this is a win for patients, the NHS and industry.
In brief, the ten recommendations published today are:
The Working Group is now calling on clinicians, funders, regulators and the pharmaceutical industry to get behind the recommendations and work together to rapidly implement them.
Progress is being made – following the publication of the Government’s Life Sciences Sector Deals (2,3), significant action has been taken over the last two years to strengthen the environment for clinical trials. Most recently, MHRA launched a survey in order to gather feedback on their advice and services, with a particular focus on novel designs, with a view to transform the services they offer in the future. But there is still much more to be done in order to “consolidate our world-leading position in delivering novel and innovative trials” – a commitment in Sector Deal 2.
The UK’s success in early science has been built on attracting investment and research activity from global pharmaceutical companies to our world-famous universities and research centres. The industry runs thousands of trials around the world at any one time (4) and invests significantly into UK R&D. At £4.5 billion a year (5), the industry invests far in excess of any other sector.
If we are to continue attracting international pharmaceutical companies, we must maintain and strengthen the UK offer for clinical research.
By building on the UK’s wealth of expertise in designing and executing CID trials, today’s recommendations will ensure that Government and industry can deliver on their commitment to further strengthen the UK clinical research environment.
The process of researching and developing new medicines is time-consuming, costly, and there is a high rate of failure. Anything we can do to improve this is a win for patients, the NHS and industry.
Dr Ali Hansford, Head of Regulatory Strategy Policy, ABPI