Asking the right questions in clinical research
Over the last year we have been looking at how we are set up to support the changing landscape of clinical research, with the ambition to maintain a broad portfolio and grow our overall investment in this area.
We have made changes to our clinical research funding structures, and introduced a new Statement of Intent to provide greater clarity around the types of clinical research applications we want to receive and fund in the future.
Clinical cancer research is becoming much more complicated both in terms of the questions being asked and the complexity of trial design. Clinical researchers need to be collaborating more widely to address the difficult underlying questions that are emerging, and a ‘one-size-fits-all’ trial design approach is no longer relevant for the vast majority of research questions.
At CRUK, this shift in the clinical cancer research landscape has been evident from the increasingly complex research programmes being proposed by the community. Researchers are designing ambitious programmes of work which include a clinical trial element alongside genomics and translational research. In response to this evolution, we have developed the way we support clinical research, to drive progress and ensure maximum patient benefit from all trials we fund.
In 2015, we set up a new Clinical Research Committee (CRC) to oversee funding decisions across our whole clinical research portfolio, including late phase clinical trials, feasibility studies, sample collections and biomarker projects. The committee is supported by two expert review panels: the Experimental Medicine Expert Review Panel and the Clinical Expert Review Panel. Alongside this new structure, we published a Statement of Intent to provide clarity on the kind of research that we want to support, to deliver the greatest impact to patients.
Professor Tim Maughan, Chair of CRUK’s new CRC, explains the recent changes and how these will help us deliver greater patient benefit.
Previously CRUK funding mechanisms did not have the flexibility, or the scope, to fund major adaptive trial programmes. Our funding opportunities needed to allow us to support major clinical research programmes incorporating both clinical and translational research. We are now in a better position to support research in non-drug modalities, such as radiotherapy and surgery, as well as to investigate new approaches like immunotherapy, which are becoming more centre stage.
New and updated funding schemes
“The changes mean that CRUK, and the CRC in particular, has greater strategic oversight of all clinical research funded by CRUK, helping us to support scientifically rich and complex studies,” explains Tim.
The new two-tiered review process uses the Expert Review Panels (ERPs) to assess the scientific rigour of the clinical research proposed. The committee then applies a more strategic filter which helps bring to life the clinical ambitions of our Research Strategy.
To support more biologically rich clinical research, we have introduced a new scheme, the Experimental Medicine Programme Award. Tim describes how this fills a gap in the CRUK portfolio. “The scheme provides a new avenue for in depth scientific evaluation of translational questions in a clinical setting. These types of studies are vital for us to understand what’s happening when we treat people and what is happening as cancer develops.”
Alongside this new award, we have updated the scope and guide costs of our other clinical research funding schemes to enable more translational work to be embedded into trials.
Delivering the greatest benefit from every trial
"The changes are designed to make sure we maintain the best of what was being funded previously," says Tim, "whilst ensuring there are the right opportunities for research that will change technical practice and improve outcomes for patients. As researchers, we know that to drive game-changing research we need to learn much more from all patients on our clinical trials."
A key aim of the Statement of Intent is to drive innovation in trial design so that research we fund can push boundaries across all modalities and disease sites.
Tim goes on to explain what the committee hopes to see from future applications. “Clinical researchers need to be engaging with the best basic researchers in their field to better understand the big questions of today, such as the diversity within patient responses to treatment. By collaborating with scientists who have complementary expertise, they can create an integrated application with clinical leadership and strong science. This approach will enable researchers to identify ways of tailoring the right treatment, for the right patient, for their greater benefit.”
Our ambition is to maintain a broad portfolio of clinical research and learn as much from every patient as we possibly can. We believe the new structures will support researchers to attempt ground-breaking research that will produce highly valuable biological and clinical information.
plasmaMATCH is a multiple parallel cohort, multicentre Phase IIa trial jointly led by Dr Nicholas Turner and Professor Judith Bliss at The Institute of Cancer Research, London.
This study exemplifies the genomically complex trials that we hope to see more of within our portfolio.
The trial combines a screening component, based on assessment of circulating tumour DNA (ctDNA) from a simple blood test, and a therapeutic component, evaluating the activity of different novel agents directly targeted towards the mutation identified through ctDNA screening. It aims to generate proof of principle efficacy data for these targeted therapies in metastatic breast cancer (MBC). Current treatment for MBC is non-curative, often involving cytotoxic chemotherapy, and advanced stages of the disease are associated with considerable morbidity.
The novel trial design attempts to match patients with a rare mutation identified by circulating tumour DNA (ctDNA) screening, regardless of tumour histology, to a drug expected to work through the mutated pathway. plasmaMATCH aims to establish an alternative, non-invasive method of characterising tumour molecular profiles with ctDNA. This would simplify screening, reduce costs, and reduce risk to patients by avoiding an invasive procedure to biopsy the patient’s tumour. The study will underpin and inform the feasibility of ctDNA as a screening tool; if it is successful, there is the potential for future integration into routine NHS practice.
Featured in this article
Professor Tim Maughan
CRUK/MRC Oxford Institute for Radiation Oncology
Chair of CRUK Clinical Research Committee (CRC)
Find out how we can support your research
If this story has inspired you to think about how our new flexible funding could support your research, find out more about eligibility and how to apply to our new Experimental Medicine Programme Awards, or explore the recent updats to other funding schemes overseen by the Clinical Research Committee.
The next deadline for Experimental Medicine Programme Awards is 26 September.
This story is part of Pioneering Research: our annual research publication for 2015/16.