Rethinking clinical trials – how Tessa Jowell’s intervention could benefit people with cancer

Image: Pill bottles for clinical trials

Former cabinet minister, Baroness Tessa Jowell, sparked a debate on access to innovative and experimental treatments on the NHS this week after her appearance on BBC Radio 4’s Today programme. The Labour peer called for more patients to be given the opportunity to take part in ‘adaptive trials’, and gain better access to new treatments.

Baroness Jowell, who was diagnosed with the brain cancer glioblastoma in May 2017, received a standing ovation in the House of Lords after she made an emotional speech to the House of Lords on Thursday. She hopes people with cancer can access new treatments more quickly, in part by changing the extensive process of clinical trials.

As well as highlighting the need for greater flexibility around access to new treatments, Baroness Jowell’s call also raises the urgent need for more basic research into brain cancer, something The Institute of Cancer Research has long recognised and is working to address. 

Brain cancers are highly complex – more than 130 different types of brain tumours are currently known. Effective treatment options are limited, and because they arise in relatively small patient populations, it has been challenging to run robust clinical studies.

Across the research community, we need to invest more time and money to help us understand the basic biology of brain cancer. This is crucial so we can identify new drug targets, as the vital first step to enable us to discover innovative drugs that can be evaluated through smart trials. 

Advances in the way we run clinical trials won’t on their own be enough to benefit patients, if they’re not accompanied by the vital laboratory research that is needed to first stock the drug pipeline.  

The challenges of conventional clinical trials

But Baroness Jowell is right that a more innovative and flexible approach to running clinical trials is part of the answer to ensuring patients with brain cancer benefit from better treatments. 

All clinical studies of new medicines go through a series of phases to test whether they are safe and effective. The new treatment type is often tested against a control, and patients are randomised to either the treatment or a control group.

Bringing innovative drugs and treatments to patients with cancer is a lengthy and expensive process. On average it takes 10-12 years to bring a new cancer drug to market – from the point of patenting through to licensing. We know that the cost and time investment needed also has implications for the development of novel compounds.

The ICR long recognised this and encouraged better ways to do clinical trials. Professor Paul Workman, Chief Executive of the ICR, argues:

“By conducting trials in a smarter, more efficient way, we can make sure patients get the drugs that are best suited to them, and can be switched to an alternative treatment more quickly when there are signs that a drug isn’t working.

“We believe intelligent trial design can also play a vital role in reducing the time it takes for new treatments to reach patients by helping to generate the required standard of evidence for drug approvals more quickly, such as from phase II clinical trials.”

Adaptive trials: innovating around trial designs

In adaptive trials, researchers can build in greater flexibility to the study design, to include different treatment types as different arms of the study.

Any individual patient can then be switched between different treatment types, depending on how well (or badly) they are responding to a particular treatment. Trials are more flexible, efficient and fast – and by cutting down on the cost and time factor, this could also be a boost for novel clinical research.

Other innovative trial design examples include basket or umbrella trials, where patients are given treatments according to their specific tumour profile rather than simply by their broad cancer type and stage of disease.

The complexity of these alternative trial designs does however pose difficulties for data and statistical analysis. Because amendments are often introduced over the course of a study, the target patient population may shift as a result – in what has been described as a ‘moving target patient population’.

The trial may also find it moves in a direction away from the original clinical research question, and adaptations can introduce biases to data collection.

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Allowing patients to ‘take the risk’

Speaking on the Today programme, Baroness Jowell recounted her experiences of being told that she couldn’t be given any further treatments on the NHS, before being offered an additional option of trying immunotherapy following a consultation with a doctor in Germany.

She told listeners: "Brain cancers happen very quickly, you have to show that there's been change quickly and if you don't do that then basically nothing changes."

"That (adaptive trials) is exactly the kind of risk that patients should be free to take, it should be a risk that they have the chance to take, and it's certainly what somebody like me wants.”

Early access to medicines

In 2016, the Department of Health published the Accelerated Access Review, outlining areas for improvement to make it easier for NHS patients to gain access to innovative medicines, medical technologies, diagnostics and digital products.

As a result of this review, a new Accelerated Access Pathway will be rolled out in April 2018 - a specialised system designed to streamline regulatory and market access decisions for ‘breakthrough’ products.

While this is good news, the scheme is predicted to apply to only five products per year. And this covers everything from new medicines and diagnostics to other forms of medical technology including innovative digital products, across a wide range of disease areas.

At the ICR, we carry out fundamental research into the molecular causes of cancer, and translational research, working with our hospital partner The Royal Marsden NHS Foundation Trust, to advance early-stage innovations to the point where they can be assessed in patients.

Dr Udai Banerji leads the Clinical Pharmacology and Trials team at the Cancer Research UK Cancer Therapeutics Unit at the ICR, and is the Deputy Director of the Drug Development Unit. He is involved in multidisciplinary aspects of early drug discovery and works with preclinical biology and pharmacology teams at the ICR and The Royal Marsden to get drugs into the clinic. He said:

“Finding new treatments for rare or orphan diseases like glioblastoma is challenging in many ways. There is often less funding to do research in this area, difficulty in conducting clinical trials as patients are spread across a wide geographical area and finally a lack of incentive to commercialise treatments.

“We should not shy away from these challenges as the lives of every patient is important to us and research into rare cancers often lead to insights in biology related to more common cancers.’’

More flexibility needed

We believe that there is still much more to be done across the whole system of drug discovery, development and approval to improve access to new treatments – particularly in cancer.

Cancers are increasingly being classified into smaller, multiple subgroups through advances in our understanding of the genetics and biology of the disease. Regulatory systems therefore need to show more flexibility in the types of evidence required to approve drugs for use in small populations, and to address barriers to the use of novel trial designs.

Professor Workman recognises the urgent need for brain tumour research that Tessa Jowell has highlighted:

“Baroness Jowell is such a brave and inspiring individual. We need more research into the biological basis of brain cancers which will allow us to discover the innovative new treatments we desperately need for patients.”

The patient perspective

For patients and their loved ones, getting access to treatments that work is of course the most important thing.

Baroness Jowell said: “Like thousands of others diagnosed with cancer every year, I have had to learn a huge amount very quickly about the disease I am living with.

“I hope this debate will help to raise awareness of the need for more research into effective treatments for brain tumours, as well as for the continuing development and improvement of cancer services generally in the UK."