Professor Mark Emberton FMedSci discusses the challenges facing cancer drug development at an increasingly challenging time for doctors, patients, regulators and a healthcare system that demands better medicines, faster and at lower cost. Using more innovative endpoints in clinical trials to prove how effective a medicine is could be a key step in enabling the system to respond to these demands.
An urgent need for new cancer treatments
The need for earlier patient access to life-saving cancer medications is increasingly a key topic of discussion among researchers, regulators, doctors and the public, in the context of compelling personal accounts such as the recent argument from Dame Tessa Jowell in the House of Lords. Before her death, Dame Tessa spoke powerfully about the challenges to getting medicines to patients sooner, the huge opportunities presented by greater involvement of patients in research and the role of adaptive trial design in speeding up drug development.
These issues were at the heart of discussions at the Academy and the Association of the British Pharmaceutical Industry’s FORUM workshop on oncology endpoints in clinical research which took place in July last year. The recently published meeting report for this event has come at a critical time, with growing discussion around the need to facilitate earlier patient access to new cancer medicines that fulfil areas of unmet need, whilst continuing to safeguard patient safety.
Currently, developing a medicine and carrying out clinical trials to prove that it is safe and efficacious can take decades and can be extremely costly. A key measure to determine the safety and efficacy – or in some cases effectiveness if used in clinical practice – of a medicine is known as an endpoint. Historically, most cancer medicines have been approved based on the endpoint of overall survival, which determines how much a medicine might extend lifespan. However, using overall survival as a primary measure means that studies can take many years and require large numbers of patients, slowing patient access to these medicines. In addition, other factors including quality of life (such as reduction of symptoms or ability to carry out normal daily activities) are often equally, if not more, important for patients and clinicians than simply longevity.
New ways of thinking to speed up the development of medicines
One way to enable faster development of cancer medicines is through adapting trial design and specifically, the endpoints used to determine efficacy. Therefore the research community is coming together to develop ‘new’ endpoints. These could be surrogate endpoints enabling earlier ‘read-out’ in trials by acting as proxy measures for traditional endpoints. For example, surrogate endpoints for overall survival that could predict lifespan rather than requiring a very lengthy trial following all participants until end of life. These measures can be supplemented with ‘real world evidence’ on the effectiveness of the medicine as it is used in the clinic. In addition, we are also developing new endpoints to better measure factors related to quality of life (for example pain, fatigue etc) which may be particularly important for decision-making on the best course of treatment for clinicians and patients.
Treatments that work for patients: generating the evidence
Novel endpoints in clinical trials are just one piece of the puzzle to improving cancer care, but innovating here has the potential to drive development of new therapies and support earlier patient access. However, as the Academy highlighted in its recent report on enhancing the use of scientific evidence in decisions about medicines, it is important to test new approaches to generating evidence using such novel endpoints to make sure they are fit-for-purpose. As highlighted in a recent article in the British Medical Journal, there is a strong urge for further research to better understand and validate new endpoints, and fully elucidate their association with outcomes of interest, so that they can be confidently used in the development of new medicines.
The Academy and ABPI’s report has sparked an important discussion about this important area, and the Academy plans to hold an event looking more broadly at adaptive approaches to clinical trials later in 2018. By thinking more innovatively about the way we assess cancer drugs, there is a hope that in future cancer patients will access treatments earlier.
Professor Mark Emberton FMedSci is Professor of Interventional Oncology at University College London. He was Chair of the recent Academy of Medical Sciences FORUM workshop on ‘Looking to the future: endpoints in clinical research’.
The Academy’s FORUM provides a neutral and independent platform for individuals from across academia, industry and the NHS to meet and take forward national discussions on scientific opportunities, technology trends and associated strategic choices in healthcare.