Setting the foundations for precision medicine research


Insight magazine looks behind two platform trials to find out how the research infrastructure provided by the NIHR has helped to pave the way for recent advances in the delivery of precision medicine research.


Precision medicine, sometimes called stratified medicine or targeted medicine, is an emerging approach for disease prevention and treatment. It takes into account people’s individual variations in genes (genotype) and how their genetic make-up is affected by external factors such as environment and lifestyle (phenotype).

In precision medicine research data from patient samples is gathered and analysed then used to organise patients into different groups with common disease characteristics which are often called ‘biomarkers’. This helps us to target  treatments to specific groups of patients to determine which are most effective and develop evidence-based targeted treatment models for future patient benefit.

But conducting precision medicine research is challenging, not least because it increasingly needs to draw upon smaller and smaller sub populations of patients from a particular disease area. Often this can equate to just one or two percent of a disease population who display the specific biomarker(s).

Despite that, precision medicine in cancer research is gathering momentum in the UK. Two pioneering projects are underway which use a platform approach – a framework of trials in a specific disease area. FOCUS4 and The Lung Matrix are investigating targeted treatments for colon cancer and lung cancer respectively.

Within the framework a number of trials (or arms), involving novel drugs from different life-science companies, take place in parallel. When a new patient agrees to participate they are screened to see which biomarkers they express and therefore which arm of the study they best match to. This makes patient screening more efficient; having multiple treatment options via multiple arms  means that many more patients can be given the opportunity to participate in research.

Another key advantage is that the platform approach is designed in a way that allows new arms to be added when a new potential drug is developed by a new company. In comparison to setting up a new trial from scratch, this offers a faster more efficient route to getting a new drug into a clinical trial.

The platform approach departs significantly from the traditional approach of consecutive multi-phase trials, and is viewed as a significant step-forward in clinical trial design. Professor Tim Maughan, Chief Investigator of FOCUS4, explains how the confidence to make that leap can be traced back to the roots of the Clinical Research Network:

“It all stems from the National Cancer Research Institute (NCRI) Clinical Studies Groups which were set up in 2001 and were closely linked to the National Cancer Research Network, which later evolved to become the NIHR Clinical Research Network’s Cancer Specialty.”

The Clinical Studies Groups brought together expert cancer clinicians and researchers, the Clinical Research Network, the Clinical Trials Units and cancer charities. These groups have continued to work together very closely for over 10 years. Professor Maughan believes it has always been a very positive and supportive environment:

“As clinicians and researchers we had individual connections but now we suddenly had a national network of enthusiastic researchers and we realised very quickly that there was a lot of potential to grow the cancer research portfolio and conduct larger trials. The first major large-scale trial we attempted was the FOCUS trial and recruited over 2000 patients. Next came the COIN trial which recruited 2445 patients. Both these large trials and FOCUS4 have been designed and coordinated by the Medical Research Council (MRC) clinical trials unit and their expertise has also been critical to our success.

“That gave us the confidence and the track record to attempt something as big as FOCUS4. Having the whole research environment in that collaborative framework meant we had an experienced team with successes under our belt. Without the Network helping to enable those two prior large scale trials I doubt we would ever have had the confidence to attempt FOCUS4.

“Another key part is our engagement with Biomarker Pathology Genetics Group. On the back of those earlier large scale studies a lot of molecular work (or translational research) has taken place in the laboratory which has helped identify specific mutations and biomarkers and helped lay the foundations for further precision medicine research. Because the patient numbers in FOCUS and COIN were large, there was a lot of merit in doing this translational research work for those previous studies. Therefore we had geneticists, pathologist and biomarker people involved in the Clinical Trials Groups. That’s how we built the competencies that we currently have in the multi-disciplinary team, essentially it was on the back of high levels of Network recruitment.”

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FOCUS3, which preceded FOCUS4, was also supported by the Network and recruited 240 people within a 12 month period. That success demonstrated the feasibility of doing further research that selected treatment arms for patients based on the biomarkers identified during patient screening. Professor Maughan continues:

“Again that success was in part due to Network support and research nurse activity on the ground – that’s an important bit to put into the story because without that we wouldn’t have had the track record to get the funding for FOCUS4”.

Professor Maughan is quick to point out that the he wasn’t the sole architect for FOCUS4:

“It was definitely a collaborative effort which emerged from the NCRI Clinical Studies Group. It wouldn’t have been possible without support from Cancer Research UK, the NIHR Efficacy and Mechanism Evaluation funding programme, the Medical Research Council, the NIHR research infrastructure which includes the Experimental Cancer Medicine Centres and the Clinical Research Network, Leeds and Cardiff Universities, and the Clinical Trials Units. It is a real team effort.”

One of the researchers mentioned by Professor Maughan is Professor Gary Middleton who is also Chief Investigator of The Lung Matrix study based at the University of Birmingham. He agrees that collaboration is the golden thread running through both platform projects:

“Technically it has been a real challenge to get The Lung Matrix underway as it is a very new way of working. But everyone has pulled together to make it happen. Cancer Research UK have been fantastic, they have done all the engineering to bring people together to get pharma involved and committed. They have also been critically important in overseeing the patient screening programme aspect.

“The Clinical Trials Unit here in the University of Birmingham has been extremely good, as have the technical hubs here and in Cardiff. There are other people dotted around the country that have been key to establishing the platform. We have a Trial Management Group and a Trial Steering Committee which is another big collaborative aspect. Then of course we’ve got our pharma partners providing the drugs – Pfizer and AstraZeneca in particular – without drugs we don’t have any trials.”

So having taken a look at events to date that have helped pave the way for this latest advance in clinical trial design, how does the Clinical Research Network and other NIHR research infrastructure feature in the future?

“The platform programme was perceived as a novel forward-looking approach and was met with a lot of enthusiasm. The research community can see the potential. As science progresses, more molecular profiling will take place and we would hope that more platforms can be set up for different diseases.

“Then, one aspect of the Clinical Research Network support that will be important will be to offer infrastructure support to the concept of the hub and spoke model for referring and recruiting patients. So for example, referring patients from local district general and acute hospitals into specialist cancer centres where the research is taking place. The coordinating side of the hub and spoke model can be very complicated so to have someone that can coordinate the platform in each centre would be very useful.

“There is no way that you would attempt to set up a programme of studies like The Lung Matrix without solid research infrastructure. Having an organised, connected research infrastructure that fosters collaboration puts us in good stead for the future.”

An article describing the platform trial approach in more detail is also available.