New Guidelines Urged for Complex Cancer Trials

Peter Russell

January 06, 2020

Cancer experts called for new guidelines to be adopted to transform and improve Complex Innovative Design (CID) trials.

The authors of the study, published today in the British Journal of Cancer , said 10 recommendations they developed for CID trials could lead to new drugs being offered to patients through a faster and more efficient process.

Prof Pam Kearns, director of the Cancer Research UK clinical trials unit at the University of Birmingham, who co-authored the paper said: "The concept of the complex innovative design is increasingly applied now in clinical trials. The reason for it is that it's really a more efficient way to try and answer the questions, for example, about new drugs."

However, she acknowledged that the technique required a rewriting of the rule book.

"The current traditional way of drug development is to do a first-in-man trial [phase 1 study], check out the safety, creep up to the right dose, then work out if the drug's effective, and then do a randomised trial," she told Medscape News UK. "Each of those is a separate trial, and each of those takes quite a long time."

CID Trials 'Could Halve the Timescale for New Drugs'

Prof Kearns said: "The average time frame of trying to get a drug from first into the clinic to being standard practice is 12 years."

Although it was too early to say how CID trials might accelerate the process of getting new treatments to patients she said: "I would suspect it's going to halve the time of drug development."

Clinicians, funders, regulators, and the pharmaceutical industry should support the recommendations and help in their rapid implementation, the authors stressed. They said there were currently no practical guidelines for teams that fund, design, and conduct CID trials in Europe.

The Experimental Cancer Medicine Centres (ECMC) network, funded by Cancer Research UK, the National Institute for Health Research (NIHR), and the health departments in Scotland, Wales, and Northern Ireland, convened a working group of academics, funders, pharmaceutical industry representatives, patients and regulators, including the Medicines and Healthcare products Regulatory Agency (MHRA) to address this challenge.

Dr Aoife Regan, head of the ECMC Secretariat, said: "Our community of researchers and clinicians said that one of the challenges they were facing was the increasing number of complex trials of all different shapes and forms. They identified this both as a challenge and an opportunity from a workforce point of view, from a scientific methodology point of view, and from a regulatory point of view."

She added: "We used our convening power to bring together the group of authors you see who created the paper."

The CID approach enables researchers to carry out more complex trials that address multiple clinical questions at once.

'Complex but More Efficient'

"The reason for us moving towards this type of trial is it's just more efficient," according to Prof Kearns. "You can ask more questions in one trial."

She said: "We're running a trial in Birmingham called the National Lung Matrix Trial, where the indication is lung cancer that's not responding to conventional treatment. But each of the treatment arms is stratified according to the molecular profile of that individual patient's cancer. Then you can tailor the drug treatment according to that molecular profile.

"So, we have multiple arms open at the same time, with drugs from different drug companies, all asking questions about 'does this work in lung cancer?'

"If we did that as multiple trials – 30 trials – it would take a really long time to set it all up, and it wouldn't be very efficient."

Dr Regan told Medscape News UK that the authors "spent a long time drilling down to what are the new challenges around these new trial methodologies".

That led to the 10-point recommendation, each covering a specific stage of the clinical trial pathway, which included trial planning and design, protocol development, patients and public involvement, staff training, and evaluating the impact on public health.

The authors argued that change was needed to take into account improvements in our understanding of disease. "We know, particularly in the cancer arena – but I suspect this is true of a lot of other diseases – so much more about the biology of diseases, particularly with all the initiatives looking at genomics, in the 100,000 Genomes Project for example," said Prof Kearns.

"As a consequence, there are a vast number of new drugs coming out of the research and development programmes, both in universities, but particularly from the pharmaceutical industry.

"And it's been recognised that if we sequentially evaluate all of them, we will never get through and work out which are the best ones."

Role of the Regulators

Dr Regan said: "One of the other game-changers is that the regulators are now welcoming these types of new methodologies.

"I think there was some nervousness because people were comfortable with the types of methodologies that they had used previously and were a bit nervous about change. But now I think we've got MHRA who are saying they are interested in these studies."

Dr Kirsty Wydenbach from the MHRA, confirmed that support. "Understanding of the regulatory aspect is important for researchers, but this paper has also been important for MHRA to be able to appreciate the complete process and wider recommendations that can now be considered in our work moving forward," she said.

Juliet Tizzard, director of policy at the Health Research Authority, said: "These important recommendations now bring clarity for researchers in terms of how they should be running high quality CID trials."

Dr Ali Hansford, head of regulatory strategy policy at the Association of the British Pharmaceutical Industry and co-author of the recommendations, said: "By building on the UK's wealth of expertise in designing and executing CID trials, these recommendations will ensure that Government and industry can deliver on their commitment to further strengthen the UK research environment.

"Doing more of this type of research in the UK would be a win for patients, industry, and the NHS."

Blagden, S.P., Billingham, L., Brown, L.C. et al. Effective delivery of Complex Innovative Design (CID) cancer trials—A consensus statement. Br J Cancer (2020) doi:10.1038/s41416-019-0653-9


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