Section 1 - Basic information about you and your application:

Title of research project
Long-term wear safety of returning to high-impact activities after hip resurfacing arthroplasty in active patients.

Grant Type
The ORUK Early-career Research Fellowship

Research area
Treatment

Duration
18

Start date
February 1, 2024

Have you previously received funding from ORUK?
No.

Profession
Academic scientist

Your current job title/position
Lecturer

Are you an early-career researcher (ECR)? (definition of ECR)
yes

Section 2 - Lay summary

Lay summary:

Hip resurfacing (replacing the damaged hip-bearing surface with smooth artificial coverings) is an increasingly popular surgery option offered to younger and more active individuals with painful hips. A hip resurfacing conserves more bone than a traditional hip replacement which removes more leg bones surrounding the hip. Younger patients demand high-impact activities, like running, to be acceptable after hip resurfacing, not just gentle walking exercise. No studies have been conducted on the safety of high-impact activities after hip resurfacing surgery, only walking. We aim to solve the problem of knowing the optimal type and dose of activities that can be safely undertaken after hip resurfacing surgery.

The most common cause of painful hips is hip osteoarthritis (OA). In the United Kingdom (UK), 1 in 9 people over the age of 45 years old have hip OA. Globally, in 2019, the incidence of hip OA was 1.58 million. In the UK, close to 100,000 primary hip surgeries were carried out in 2019 before COVID. A total hip replacement was originally designed to treat older patients (greater than 65 years old). However, by 2030, 1 in 2 people who require a hip replacement is younger than 65 years old. The risk of having a second hip surgery in younger patients is 30% compared to a 5% risk in older patients. A second hip surgery after a first hip replacement is more challenging and costly than after a first hip resurfacing procedure. Hence, the demand for a hip resurfacing procedure will increase.

My research vision is to enable people living with musculoskeletal and orthopedic pain disorders to live more independent and active life. My ambition is to lead a multidisciplinary translational research group focusing on the development of biologically-inspired technologies to aid in the management of complex musculoskeletal and orthopedic diseases. This Fellowship will accelerate my development as a translational scientist, providing me with the funding to create and consolidate my research networks in the areas of mechanical engineering and biotribology. Findings from this project will enable clinicians to better counsel patients about a safe return to an active lifestyle. Implant companies can use our information for product safety testing and implant development.

We will host four Patient and Public Involvement and Engagement (PPIE) group meetings. These meetings will comprise people who have undergone or waiting for a primary hip surgery, and who have either returned to high-impact activities or contemplating to do so. Our PPIE group will help finetune our biomechanics testing protocol. We will engage with our PPIE members in the kind of results and the type of visualisations they think patients would find most beneficial. This will feed into our modelling and simulation work.

Section 3 - Purpose of research

Purpose of research:

Aims: A total hip replacement is a very common and cost-effective treatment used to treat end-stage hip arthritic conditions, most commonly osteoarthritis (OA). A hip replacement was once primarily provided to older (> 65 years old) and relatively sedentary individuals. However, hip replacements are increasingly being offered to younger and more active patients, who desire to return to high-impact sporting activities after surgery. For younger and active patients, a hip replacement offers very limited opportunities for a return to high-impact activities since such activities may increase the risk of complicated revision surgery. Hip resurfacing was developed as an alternative treatment to a hip replacement, to enable younger patients to return to high-impact activities. Surprisingly, there is no research to guide clinicians and patients about the safety of the type and volume of high-impact activities to return to. We aim to provide data on the long-term safety of various types of high-impact activities after a hip surfacing via a combined musculoskeletal-computer simulation approach.

Objectives:1) To understand the differences in hip joint contact forces during high-impact activities (e.g. running) and low-impact activities (e.g. walking) in individuals who have received a hip resurfacing, compared to an age-matched healthy control group. Also, we want to quantify the volume of high- and low-impact activities undertaken in daily living by people after hip resurfacing. 2) To determine the cumulated wear damage of the implant’s articular surfaces across different loading cycle scenarios of running, walking, and multidirectional activities.

Deliverables: We will publish the first open-access biomechanical and activity dataset of individuals after a hip resurfacing surgery. We will develop musculoskeletal and wear models of the hip, where the main function and some subroutines will be made open-source. A clinician-friendly ranked list of joint contact forces and implant wear for different activity combinations will be created.

Section 4 - Background to investigation

Background to investigation:

In the UK alone, close to 100,000 primary hip surgeries were carried out in 2019 before COVID-19 [1]; and this number will increase globally [2]. The most common primary hip surgery performed is a total hip replacement. A total hip replacement was originally designed to treat older (> 65 years old) and sedentary patients. By 2030, 1 in 2 people requiring a hip replacement will be younger than 65 years[3]. The risk of a revision hip surgery increases from 5% in people aged 70 years to 30% for those aged 50 years old [4].

High-impact activities (e.g. running) are discouraged after a hip replacement [5], since such activities may reduce the implant’s lifespan. Hip resurfacing arthroplasty (HRA) was developed to enable younger patients to return to high-impact activities [6]. There are many benefits of returning to high-impact activities after hip surgery. The World Health Organisation recommends all adults perform at least 75 min/week of vigorous activities. Vigorous activities, like running, are high-impact activities. High-impact activities have many superior health benefits than low-impact activities, such as being a better stimulus for bone adaptation [7], and better at improving mental health symptoms [8]. Multi-directional activities like football involve combinations of walking, running, jumping, hopping, landing, and rapid change of direction. Regular performance of such multi-directional activities also benefits many muscular, metabolic, and cardiovascular indices of health [9]. Members of our public and patient involvement and engagement (PPIE) group mentioned that running provided them with meaning and satisfaction in life after hip surgery, which walking could not.

The popularity of HRA surged when Andy Murray, a former Wimbledon tennis champion, successfully return to championship-level tennis after HRA. HRA preserves more bone to allow a less complicated revision surgery to be performed when required. Before 2007, 10% of primary hip surgeries in the UK were HRA. Since 2014, this reduced to <1% [1]. This decline in popularity is due to the health concern of metal-on-metal (MoM) HRA implants. One risk of MOMHRA is the release of metal debris which can cause severe soft tissue inflammatory reactions [10]. A return to high-impact activities after a HRA may accelerate this process. However, it is still anticipated that demand for a HRA will increase prospectively. This is due to the rapid advancements being made in the development of alternative materials (e.g. ceramic-on-ceramic) for a HRA implant, and an increasing demand by patients for a procedure that will enable a return to high-impact activities.

Surprisingly, there is no research to guide clinicians and patients about the safety of the type and volume of high-impact activities after surgery. Some patients with HRA have even returned to ultra-marathon distance running [11], though the safety of which is unclear. The long-term effects of high-impact activity participation on implant health can be assessed using physical joint simulators. However, current wear testing protocols do not use loading profiles and activity types/volumes that reflect the range of activities undertaken in active patients [12, 13]. For example, the ISO 14242-1 test standard uses a very simple “M-shaped” axial load for testing, which does not reflect hip loading even in walking. Also, high-impact activities may not always be more damaging as they may be done less often. No studies have quantified the type and volume of activities undertaken in active patients after a HRA.

A disadvantage of physical joint simulators is that they are very time-consuming and expensive to conduct. Computational models have emerged as accurate and efficient methods for wear testing. The Supervising investigator has developed and validated a new lubricated wear model of the hip. This lubricated wear regime was able to mimic the non-linear wear rate in physical joint simulators (Figure 1). We will apply this wear model to perform wear testing on HRA for the first time using joint loads and motions observed in high-impact activities.

Importance: As the demand for hip surgery shifts to the younger and active population, more will want to resume high-impact activities after surgery. Findings from this project will guide clinicians and patients on the optimal type and dose of high-impact activities that can be safely performed. Our findings will provide medical implant companies with new data and techniques for wear testing in high-impact loading situations.

Preliminary data

The PI has developed a full biomechanical and musculoskeletal modelling workflow, that was used for finite element analysis of the neck of femur during high-impact exercises (Figure 2). We will use this workflow in work package 1.

Track record

The PI is a physiotherapist and a Lecturer in Biomechanics. He has led funded research at the intersection of clinical biomechanics, musculoskeletal, and finite element modelling. He will supervise the project and train the research fellow in clinical biomechanics. The Supervising investigator is a Senior Lecturer in Biomedical Engineering. Her expertise lies in lubricated wear modelling of hip joint replacements. Her lubricated wear model will be used presently. The first Co-I is a Lecturer in Biomedical Engineering with expertise in physical joint simulators. He will ensure that our computational models closely approximate physical wear testing protocols for subsequent industry uptake. The second Co-I is a Chair in Orthopaedic Surgery with expertise in hip resurfacing. He will facilitate patient recruitment and public engagement, dissemination activities within the orthopaedic community, and ensure that our simulation results reflect clinical needs.

References

[1] National Joint Registry 19th Annual Report. 2022.

[2] Matharu G, et al. Ann R Coll Surg Engl 2022;104:443-8.

[3] Kurtz SM, et al. Clin Orthop Relat Res 2009;467:2606-12.

[4] Bayliss LE, et al. Lancet 2017;389:1424-30.

[5] Fouilleron N, et al. Am J Sports Med 2012;40:889-94.

[6] Van Der Straeten C. Hip Int 2022;32:353-62.

[7] Allison SJ, et al. J Bone Miner Res 2015;30:1709-16.

[8] Balchin R, et al. J Affect Disord 2016;200:218-21.

[9] Imperlini E, et al. Int J Environ Res Public Health 2020;17:2087.

[10] Pandit H, et al. J Bone Joint Surg Br 2008;90:847-51.

[11] Girard J, et al. Orthop Traumatol Surg Res 2017;103:675-8.

[12] Lunn D, et al. J Arthroplasty 2019;35.

[13] Morlock M, et al. J Biomech 2001;34:873-81.

Section 5 - Plan of investigation

Plan of investigation:

Figure 3 illustrates the general workflow of this project, with Figure 4 showing the Gantt Chart.

WP1 – Biomechanical modelling

We will recruit 5 participants who received a HRA who are at least 12 months post-surgery, participating in high-impact activities, and free from pain/injuries. We will also recruit 5 age-matched healthy and active participants. A previous study reported a mean difference in hip contact force between individuals with and without a hip replacement of 1.3 bodyweight (BW) [1]. The study (n= 15) also reported a 95%CI of 0.26BW, providing a standard deviation (SD) of 0.5. To estimate an effect size of 2.6 (1.3/0.5), a sample size of 10 in total will be recruited to achieve a statistical power of 0.90 at an alpha of 0.05.

Assessments (all participants)

Subjective: We will collect data on demographic characteristics, surgical information, patient-reported outcomes (e.g. Oxford Hip Score), and current self-reported physical activity levels. Objective. The maximal isometric strength of the hip extensors, flexors, abductors will be measured.

Motion capture: We will conduct a three-dimensional (3D) biomechanics analysis using our established protocol, involving the use of optical cameras, force plates, and electromyography (EMG) sensors. EMG sensors will be placed on the affected side’s gluteus maximus and medius, vastus lateralis, biceps femoris, soleus, and tibialis anterior. For running and walking, testing will occur at their self-selected speed. For unilateral hopping, participants will perform hopping at 2.2Hz and 2.6Hz. For countermovement jumps, participants will perform maximal height jumps from a self-selected squat depth. Unilateral drop landings will be performed from box heights ranging from 10cm to 30cm. For a change of direction running, participants will perform a side-step cut at 45°, 90°, and 180° at their self-paced running speed. These activities are routinely involved in many sports and were deemed feasible by our PPIE group.

Participants will wear an activity monitor for a week [2], after the biomechanics assessment. The daily duration spent walking or running will be calculated [2].

Musculoskeletal modelling (all participants)

A detailed musculoskeletal model of the trunk and lower-limb will be scaled to each participant. We will model the hip as a spherical joint. We will scale the maximal muscle strength of the model proportionally based on our strength assessments of each participant [3]. Static optimisation will be used to determine muscle and joint contact forces (JCFs). Validation of the model will be conducted by comparing the predicted hip JCFs with published in-vivo hip forces [4], and against our EMG data.

Statistical inference

The primary outcomes will be the hip JCFs. For each outcome variable and each task, we will compare the difference in waveforms between people with and without a HRA using a Generalised Additive Model (GAM). GAM enables us to quantify both the magnitude and timing of the differences across a movement cycle. Descriptive characteristics of the physical activities (volume, type) undertaken by patients with a HRA will be calculated.

Deliverables: Biomechanics and musculoskeletal modelling data of high-impact activities together with physical activity distribution produced. Novelty: This will be the first comprehensive biomechanics and physical activity dataset of high-impact activities after a HRA. Impact: The datasets and associated models will be available open-access for use in advancing implant wear testing.

WP2 – Wear simulation modelling

Wear modelling

We will use a validated hip lubricated-wear model for wear simulation modelling. The wear model is modified based on the Archard wear law. The wear depth is proportional to the wear coefficient, sliding distance, and contact pressure, and coupled with the lamda ratio between the film thickness and surface roughness. The lamda ratio represents an index of lubrication regimes, lamda ≤ 1 suggests boundary lubrication, lamda = 1 to 3 for mixed lubrication, and lamda ≥ 3 for full fluid film lubrication. The hip implant operates in mixed lubrication regimes. The mixed lubrication model solves the surface deformation, film thickness, fluid hydrodynamic pressure, and contact pressure simultaneously. The input of the lubrication model includes the non-Newtonian shear-thinning synovial fluid properties, patient-specific joint forces (from WP1), loading cycles (from WP1) and the specific geometry and materials of the ceramic-on-ceramic implant. The deformations of bearing surfaces will be calculated in the lubrication model. The Reynolds equation will be solved for the fluid flow.

Different loading scenarios will be simulated, some examples being: 5 million (ISO) cycles of walking, 60 million (based on ~ 25 years of 6,500 steps/day[5]) cycles of walking, the two scenarios with running, mixed walking, and running proportions (from WP1 activity monitoring), and multidirectional sports participation (e.g. football). Given that current activity monitors cannot quantify the physical demands of individual motor tasks (e.g. amount of running, jumping, change of direction) in organised sports such as football, we will use data from the published literature (e.g. [6]) for our simulation work. To provide clinically friendly outcomes, we will determine the wear volume and depth over periods of five to 25 years [7].

Statistical inference

The primary outcomes include the wear volume and depth for each loading scenario. The independent variable will be the different loading scenarios used in the wear modelling. Linear mixed models will be used for inference to account for repeated measurements per individual.

Deliverables: Wear models of the hip will be produced. A clinician-friendly ranked list of implant wear for different activities will be created. Novelty: This will be the first wear model of high-impact activities, incorporating real-world activity data. Impact: Clinicians can rapidly use our results for patient counselling. The main function of the wear simulation program will be made open-access for use within pre-clinical testing and advancement in computational models of joint implants.

References

[1] Li J, et al. Clin Biomech (Bristol, Avon) 2014;29:747-51.

[2] Skotte J, et al. J Phys Act Health 2014;11:76-84.

[3] Janik F, et al. Sports medicine – open 2021;7:47.

[4] Bergmann G, et al. PLoS ONE 2016;11:e0155612.

[5] Naal FD, et al. Clin Orthop Relat Res 2010;468:1891-904.

[6] Bloomfield J, et al. J Sports Sci Med 2007;6:63-70.

[7] Evans JT, et al. The Lancet 2019;393:647-54.

Section 6 - Research environment and resources

Research environment and resources:

The host University’s Department was ranked within the top 25 in the UK for research power in the 2021 Research Excellence Framework (REF). This project aligns with the research priorities of the University to develop “Globally Significant Transformational Research”. The School and University have spent approximately £2m since 2020, on biomechanics equipment purchase and laboratory space refurbishment. This includes two new three-dimensional (3D) motion capture (Vicon), a force-plate instrumented treadmill (Bertec), two in-ground force plates (Kistler), a 16-muscle electromyography (EMG) system (Noraxon), and ten activPAL activity monitors, all of which will be used in the present project. The University has a high-performance computing cluster comprising 2192 processors, 43.5Tb total RAM, 24 GPUs, and 1080Tb of dedicated storage. We will use this for our computational modelling. The Head of the Department of the principal investigator has committed to supporting this project, reducing the teaching/administrative load by 110 hours over 18 months to provide the headspace to lead the project and pursue more research funding to advance research in this critically important field.

The host University offers numerous opportunities to develop the principal investigator and research fellow, including programs delivered by our Impact Academy, such as Capturing and Evidence Research Impact. The principal investigator will also have access to the prestigious Future Leaders program, which focuses on developing professionalism, key decision-making skills, effective communication, and managing difficult situations. The principal investigator and research fellow will be able to engage with other cross-faculty academics via the university’s Cross University Research Event. There will be opportunities for the principal investigator and research fellow to apply for competitive university funding schemes (e.g. Priority Challenges Project Fund).

This research will be supported by Embody Orthopaedic, a local medical implant company. The company will provide the implant specifications for our modelling work and access to wide patient and clinical networks. The research team will have the opportunity to visit the second Co-I’s laboratory. One visit will coincide with the Programme Management Group meeting, and the cost associated with travel has been included in the budget. The laboratory houses a group of 34 clinicians, scientists, and engineers focused on musculoskeletal and orthopedic health and disorders. The laboratory consists of a fully instrumented gait facility, a three-dimensional laboratory for the detailed analysis of pathomorphology, and a robotic skills lab for training surgeons in complex and technically demanding procedures. This visit will enable the research team to co-develop future grant ideas relating to the advancement of primary hip surgeries.

Section 7: Research impact

Who will benefit from this research?

This project will have huge national and international benefits. In the UK alone, there are approximately 100,000 patients per annum receiving primary hip surgery. Although hip resurfacing is designed for active individuals, a critical question remains over “how much is too much” exercise. This research will benefit two groups of clinicians (e.g. surgeons): 1) those considering hip resurfacing, 2) those that manage people with hip resurfacing but remain unsure over the safety of high-impact activities. People who have undergone or waiting hip resurfacing surgery will also directly benefit. This group is generally younger (<65 years) and more active patients living with very painful and debilitating arthritic hip conditions. In the UK, 1 in 9 people over the age of 45 years have hip osteoarthritis – the most common hip arthritic condition. Our data can be used for post-surgery activity counselling, and allow more informed shared decision-making between clinicians and patients.

How can your research be translated in real-life?

We have the support of Embody Orthopaedic, which designed and produced a new ceramic-on-ceramic hip resurfacing implant design. The implant is currently being tested in a current non-randomised, observational cohort study. We will use the implant design specifications in our simulation work. Findings from this project will provide additional data on the long-term safety of returning to high-impact activities, which will be communicated to the company’s clinician and patient networks. Our data and simulation techniques can be adopted for official physical wear testing protocols by implant companies. There are still many unanswered questions if patients after hip surgery can return to high-impact activities. Clinicians will be able to use our findings for patient counselling on the risk associated with high-impact activities after surgery. We will reach (inter)national lay audiences via a contributing article in magazines, like Runner’s World, by Roger Robinson (an internationally acclaimed author).

How will your research be beneficial for ORUK and its purpose?

ORUK’s purpose is to fund research that will improve the musculoskeletal health of individuals and reduce the healthcare burden. Michael Rix- featured on ORUK’s community success stories, is one such person who has benefited from high-quality orthopaedic research. He successfully returned to competitive triathlon after a primary hip surgery. High-impact activities have many physical, psychological, and social benefits, over gentle walking exercises – the most notable of which is mitigating osteoporosis. Despite the health benefits of high-impact activities and the promotion of hip surfacing as a solution for active individuals, it is still unknown how much exercise is too much for these individuals. Findings from this project will help clinicians better advise patients on the relative risk-benefit associated with a return to high-impact activities. This will ultimately help individuals, like Michael, to fully realise their physical potential after hip surgery, and do so in a safe manner.

Section 8: Outreach and engagement

We will organise an online webinar with the British Orthopedic Association (BOA), to engage surgeons and clinicians with the latest data on the biomechanical outcomes associated with high-impact activities after a hip resurfacing arthroplasty. The impact of this webinar will be gauged by surveying the attendees before and after the webinar. This project has the support of Embody Orthopaedic, which has designed and produced a novel ceramic-on-ceramic hip resurfacing implant. Through the company, we will organise a second webinar with the patient and clinical networks. We intend to publish our findings through the company’s dissemination channels, such as brochures, link to scientific articles, and their social media platforms.

We will host four Patient and Public Involvement and Engagement (PPIE) group meetings. We will include an inclusive and representative sample of patients to which this project relates – such as people who have already returned to sports after hip surgery and does uncertain about doing so. An example of a strategy to be inclusive is to host our PPIE meetings both face-to-face and virtually, to enable people from any geographical location in the UK to be involved. Before ethics submission, we will engage with PPIE to finetune our biomechanics testing protocol, such as the duration of the assessment. They will be involved in the design of our information sheets and consent forms. Our PPIE members will be engaged throughout the project, to understand the kind of results and the type of visualisations they think prospective patients will find most beneficial. This will feed into our modelling and simulation work.

We have support from Roger Robinson, an internationally acclaimed author (three American awards for running journalism – the George Sheehan (2007), RRCA (2010), and Les Diven (2011) Awards) (https://www.roger-robinson.com/). Through him, we aim to disseminate our findings in significant press outlets, like Outside and Runner’s World, in America and UK. At the end of the project, we will submit an article on our findings to The Conversation, which attracts approximately 64.2m in the monthly audience.

Section 9: Research budget

Requested funding from ORUK

University fees (if any)
£0

Salary
£98164

Consumables
£1200

Publications
£0

Conference attendance
£2717

Other items
£6002

Total 'requested fund'
£108083



Other items
Note: In the Expression of Interest, JointMedica was put down as an industry partner. Since that time, they have withdrawn their interest in participating in this project. Another industry partner expressed interest in this project. The current industry partner is Embody Orthopaedic (https://www.embody-ortho.com/). Salary (£98,164.00): 1.0 FTE research fellow (PhD qualification) (only direct cost) - £77,730.00; Principal Investigator’s time at 0.05FTE (only direct cost) - £5,722.00; Supervising Investigator’s time at 0.05FTE (only direct cost) - £5,477.00; first co-investigator’s time at 0.03FTE (only direct cost) - £3,287.00; second co-investigator’s time at 0.02FTE (only direct cost) £5,948.00. Laboratory consumables (£1,200.00): Reflective markers, tapes & adhesives, electrodes, razors and alcohol wipes, return postage for activity monitor. Conferences (£2,717.00): British Orthopedic Association (BOA) Congress 3D2N (Registration: £200, Travel: £400, Accommodation: £360, Sustenance: £126) - £1,086.00 & Leeds-Lyon Symposium on Tribology 3D2N (Registration: £745, Travel: £400, Accommodation: £360, Sustenance: £126) - £1,631.00. Other items (£6,002.00): Travel to Supervising investigator lab for training 6D5N (Train: £180, Accommodation: £ 900, Sustenance: £252) - £1,332.00; Participant travel & accommodation at Wivenhoe house 2D1N (Travel: £110, Accommodation:£180, Sustenance:£80) - £1,850.00; Participant incentive voucher - £400.00; Programme Management Group meetings at the University: Travel for all three external investigators for two physical sessions - £840.00; all other PMG meetings held virtually; PMG meetings at the University: Refreshments - £200.00; Public and patient involvement and engagement meetings: Refreshments (4 meetings, 8 people) - £240.00; Public and patient involvement and engagement meetings: Vouchers (4 meetings, 8 people) - £640.00; Recruitment research fellow - £500.00



Other secured funds

Internal funding
£0

Partner (University)
£0

Partner (Commercial)
£0

Partner (Charity)
£0

Other sources
£0

Total 'other funds)
£0

Section 10: Intellectual property and testing on animal

Is there an IP linked to this research?
Yes

Who owns and maintains this patent?

The Supervising investigator will supply the existing hip wear modelling algorithm code to the project, which forms the background IP. All project partners will have free access to background IP for 18 months from the start of the project, and a non-exclusive option to negotiate a license for background IP for future research use on fair and reasonable terms. The new IP expected to be generated includes the computer wear model of the hip resurfacing implant to predict the accumulated wear for long-term performance under normal and high-impact activities. The main function of the simulation program (FORTRAN code) will be made open access. This allows other researchers to make use of the model and explore it to fit their needs. We will retain the rights of the IP of some subroutines addressing specific materials, geometries, or activities. The ownership of the new IP will be shared between the host University and the University of the Supervising investigator. The host University will negotiate with the collaborative partner the terms under which the company will have access to the foreground IP. Access to the IP will be negotiated with the University following the project completion. We will explore and pursue the potential commercialisation of the foreground IP, where appropriate, following project completion.

Does your research include procedures to be carried out on animals in the UK under the Animals (Scientific Procedures) Act?
No

If yes, have the following necessary approvals been given by:

The Home office(in relation to personal, project and establishment licences)?


Animal Welfare and Ethical Review Body?


Does your research involve the use of animals or animal tissue outside the UK?
No

Does the proposed research involve a protected species? (If yes, state which)



Does the proposed research involve genetically modified animals?


Include details of sample size calculations and statistical advice sought. Please use the ARRIVE guidelines when designing and describing your experiments.


There should be sufficient information to allow for a robust review of any applications involving animals. Further guidance is available from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), including an online experimental design assistant to guide researchers through the design of animal experiments.

Please provide details of any moderate or severe procedures


Why is animal use necessary, are there any other possible approaches?


Why is the species/model to be used the most appropriate?