Optimising knee therapies through improved population stratification and precision of the intervention

Our vision is that patients with knee pain receive the right treatment at the right time.

In the UK, one third of people aged over 45 have sought treatment for osteoarthritis, and the disease costs the NHS over £5 billion per year. The knee is the most common site for osteoarthritis, with over four million sufferers in England alone. The aging population with expectations of more active lifestyles, coupled with the increasing demand for treatment of younger and more active patients, are challenging the current therapies for knee joint degeneration. There is a major need for effective earlier stage interventions that delay or prevent the requirement for total knee replacement surgery. There are large variations in patients' knees and the way that they function, and it is important that this variation is taken into account when treatments are developed, so that the right treatment can be matched to the right patient.

Through this ambitious programme of research we will develop novel testing methods that combine laboratory-based simulation and computer modelling to predict the mechanical performance of new therapies for the knee and enable their design and usage to be optimised. Importantly these tests will take into account the variation in patients' anatomy and knee biomechanics, as well as variations in device design and surgical technique. This will enable different therapies, or different variants of a device, to be matched to different patient groups.

The tools will be applied to existing treatments using clinical data to help validate that our model predictions are correct. The outcomes will better define which patients will benefit from a particular intervention and help optimise their usage. We will then apply the methods to new and emerging treatments, including regenerative devices, so that they can be tested and optimised before costly clinical trials take place. We will use these examples as case studies to demonstrate how the new testing methods can optimise the products before they reach the patient, and we will work with industry, standards agencies and regulators to promote the adoption of these methods across the sector.

This programme will benefit patients, the NHS and the growing UK industry and science base that are developing new therapies for the knee.

The testing methods developed through this programme will be used to examine and optimise current and emerging therapies for the knee, benefitting industry, patients and healthcare providers. The major beneficiaries of this research are as follows:

Society: the research will impact on patients and healthcare providers. It will enable treatments to be assessed under realistic conditions that represent the variance in the patient population and in the surgical procedure. It will allow existing treatments to be optimised by providing improved stratification criteria. It will enable the precision requirements for emerging interventions to be defined so that they can be optimally segmented and tuned to function across the spectrum of variation in the patient population. The timescales on the delivery of patient benefit are relatively short, with improved patient management guidance for existing therapies developed within the lifetime of the grant and the application to emerging therapies having potential to be translated cost-effectively as Class III medical devices in less than ten years.

Economy: The UK's Medical Technology sector is growing with orthopaedic devices being one of the top five sectors achieving over £1bn turnover per year. The UK is also potentially well placed to develop the emerging regenerative medicine industry due to its strong research base and unified healthcare system. Globally, annual product sales in the regenerative medicine market are estimated to exceed $20bn by 2021. This programme will support the continued development of the medical device sector and the growth of the regenerative medicine science base by enabling emerging products to be more effectively assessed and optimised at an early stage in the design cycle, prior to costly animal studies or clinical trials. It will help industry to develop segmented product ranges that are functionally matched to stratified populations, delivering greater efficiency and reliability. Our clinical and industrial project partners will enable rapid translation to product development and clinical usage, and we will define improved testing standards and regulation to benefit the wider sector. The research will also benefit experimental and computational simulation industry, providing improved methods for testing that can be commercialised by our Project Partners.

Knowledge: The proposed research will deliver major scientific advances in preclinical testing. It will develop novel techniques for laboratory testing and computational modelling that can be translated to other biomedical applications. The research methods and understanding developed through this programme of work will enable the regulatory requirements for new interventions to be improved, reducing the risk of early failure of new treatments after their introduction into clinical practice. Public and patient engagement activities undertaken through this programme, including major annual events and targeted activities with policy makers, will be used to raise awareness of this research field and help advocate the important role of engineering and physical sciences in healthcare.

People: Post-doctoral researchers employed through this programme and aligned PhD students, will develop multidisciplinary skills through their research, which will be complemented by individualised training including innovation management and career development, plus opportunities for secondments to build a wider industrial or regulatory expertise. These activities will produce highly-skilled staff with multidisciplinary expertise ready for careers in industry, healthcare and academia.