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Complex Innovative Trials: rethinking clinical trials - a blog by HRA Engagement Manager Will Navaie

Last updated on 6 Jan 2020

In April 2018, Baroness Jowell spoke in the House of Lords about cancer care in the UK. What made Baroness Jowell’s speech so unique was that she gave it with an inoperable brain tumour and a terminal cancer diagnosis. She used this platform to ask for improvements in developing cancer treatments and getting them to patients quicker. More specifically she championed adaptive trials and asked that they were not just “put in the too hard box”. 

The effect of this personal plea was immediate. The government set up the Tessa Jowell Brain Cancer Mission where a £40million investment was made. Part of the mission was to accelerate the use of adaptive trials – to test different treatments at the same time and speed up the process. This made its way into the UK Industrial Strategy, Life Sciences Sector Deal. 

The HRA’s role in developing adaptive trials

Baroness Jowell’s speech helped bring the concept of adaptive trials into the wider public domain. Behind the scenes, the HRA was already beginning work with Cancer Research UK’s Experimental Cancer Medicine Centres (ECMC) network to look further at this way of doing research. The ECMC put together a working group of industry, clinical academics, Clinical Trials Units (CTU), regulators, Research Ethics Committee (REC) members, Research and Development (R&D) and pathology. I joined the group, along with Stephanie Ellis, chair of Hampstead REC, and together we drafted a number of consensus recommendations to add clarity to those wishing to set up Complex Innovative Design trials (CID) – often known as adaptive trials. CIDs use innovative and efficient designs that combine multiple clinical questions within a single study. These may test multiple medicines on a single population or a single medicine on multiple populations. Using very specific statistical analysis questions can be answered quicker using fewer patients, stopping and starting trial arms as data is analysed during the trial. These trials sometimes use genomic data to randomise to different arms in the study. They are really breaking ground in the quest for personalised medicine.

What we came up with

Today the consensus recommendation paper is published in the British Journal of Oncology.

It makes 10 recommendations for improving CIDs which you can read about in our news story

The HRA feels these are important recommendations which bring clarity for researchers. They are a statement of intent for the UK as a global leader in efficient and effective clinical research and we are proud to have helped develop them.

CID studies the HRA has worked on 

The HRA has already provided ethical review for some CID trials. These include:

which are both run by the Medical Research Council Clinical Trials Unit(MRC CTU). 

STAMPEDE

STAMPEDE is a large clinical trial that aims to assess new treatment approaches for people affected by high-risk prostate cancer. The trial, which has been open since 2005, was reviewed by the HRA as one study but over the years it has gone through lots of study amendments. Under the new CID study approach, the HRA hopes to work with researchers to minimise the bureaucratic impact of having to submit lots of amendments while continuing to protect and promote patients taking part in research.

FOCUS4

FOCUS4 aims to improve the efficiency with which new potential treatments for bowel cancer can be tested. The trial, which has been recruiting since 2014, involves a centralised molecular analysis of the patient’s tumour. The patient is then offered entry into the most appropriate trial based on the results of this test. Some trials adapt over time and use a multi-stage design that analyses the trial data at pre-specified timepoints to determine whether the new agent is having a strong treatment effect.

What happens next?

Although this innovative approach is only used at the moment in cancer research, this trial design is applicable to many other disease areas. 

The recommendations set out a framework that clearly articulates who, when and how different stakeholders should be engaged with in order to develop a good quality protocol and supporting documentation for CID trials. They cover the life of the trial from approval to dissemination of results and outline how to navigate the delivery of CIDs. 

We are now helping to raise awareness of CIDs. Last year CIDs were discussed at the Regional Research Ethics Committee (REC) training days with presentations from Medical Research Council Clinical Trials Unit who undertake a number of CIDs. We are now working with ECMC on developing podcasts for REC members in this area. 

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HRA Engagement Manager Will Navaie
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