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Showing impact case studies 1 to 9 of 9
Submitting institution
The University of Sheffield
Unit of assessment
3 - Allied Health Professions, Dentistry, Nursing and Pharmacy
Summary impact type
Technological
Is this case study continued from a case study submitted in 2014?
No

1. Summary of the impact

The Sheffield team has developed the HeadUp Collar, a revolutionary new cervical orthosis device that provides support for neck weakness caused by amyotrophic lateral sclerosis (ALS). Originally designed and realised with ALS patient involvement from its conception, the collar has shown to be superior to alternative options and has directly impacted on the quality of life and well-being of patients and their carers world-wide. It was licenced to TalarMade, a UK SME, in 2017 and is a world-wide commercial success with in-excess of 2,500 units sold globally since its launch in 2018. The impact of the HeadUp Collar has been recognised by the 2020 Queen Anniversary Awards.

2. Underpinning research

Note: The HeadUp Collar orthosis to which this impact case refers was named the Sheffield Support Snood during the development phase.

Amyotrophic lateral sclerosis (ALS), known in the UK as motor neuron disease (MND) is a progressive degenerative fatal neuromuscular disease that is caused by degeneration of motor neurones. Symptoms include muscle weakness and wasting, resulting in progressive paralysis. ALS/MND sufferers typically die within two to three years from diagnosis due to respiratory arrest. As the disease is incurable, the efforts to support patients are heavily focused on sustaining a maximum quality of life.

For patients with ALS/MND, when the muscle groups that co-ordinate to support and control head movements begin to weaken, the head drops or flops, usually forwards and/or sideways; it is estimated that up to 80% of people with ALS/MND experience head drop at some point in the illness. Head drop exacerbates problems with swallowing, breathing, eating/drinking and communication. This significant disability has a major negative impact on well-being. Current practice and guidelines recommend the use of neck orthoses for people with ALS/MND to counteract this.

Sheffield research highlighted that existing cervical orthoses provided for neck weakness in people living with ALS/MND are either too soft (and therefore do not provide sufficient head support) or too stiff (and cause excessive restriction of head movements) [R1]. In response, the Sheffield team instigated an interdisciplinary, participatory co-design process informing the development of a novel head and neck support for people living with progressive neck muscle weakness caused by ALS/MND. The HeadUp Collar was developed in collaboration with people living with ALS/MND, their families and ALS/MND healthcare professionals. User engagement in this process fundamentally changed the course of the project and some ideas were ruled out as a result of patient perspectives. The benefits of this participatory process, through workshops, illustrated in the strongest possible affirmation that researchers were listening.

This novel orthosis is specifically designed to make it easier for patients to carry out everyday tasks such as eating, driving and communication allowing freedom of movement whilst giving support to muscle weakness. It can be customised to provide support where it is needed most and to adapt to the changing needs of the patient [R2] (Figure 1).

Figure 1: The HeadUp Collar Embedded image

An initial evaluation in 20 ALS/MND patients identified key beneficial features of the HeadUp Collar compared to a range of existing supports used by the test subjects: notably, increased support while providing a greater range of movement, flexibility of use, and improved appearance and comfort [R3, R4]. The results of this evaluation highlight the value of the HeadUp Collar as an alternative option for people with ALS/MND, and potentially other patient groups who require a neck orthosis.

The Sheffield team went on to perform the first objective functional quantification of head movement impairment in 15 ALS/MND patients which quantitatively confirmed a general limitation in the ability of the ALS/MND patients to perform and control head movements [R4]. Using this validated quantitative assessment of head movement, the Sheffield team proceeded to show efficacy of the HeadUp Collar in facilitating functional head movements in 13 patients with ALS/MND [R5].

A subsequent larger assessment of the HeadUp Collar in 139 patients with neck weakness from 10 centres in the UK and Ireland confirmed these results. The HeadUp Collar scored significantly better (p<0.005) than previous collars used by patients in terms of satisfaction, level of support offered, residual head movement possible, appearance, and lack of interference with eating and drinking. There was a strong preference for the HeadUp Collar reported by individuals with ALS/MND and by healthcare practitioners. This study also reported that patients with a range of causes for head drop other than ALS/MND also benefited from the HeadUp Collar [R6].

3. References to the research

University of Sheffield researchers in bold.

Langley, J., Pancani, S., Kilner, K., Reed, H., Stanton, A., Heron, N., Judge, S., McCarthy, A., Baxter, S., Mazzà, C., & McDermott, C. J. (2018). A comfort assessment of existing cervical orthoses. Ergonomics, 61(2), 329–338. https://doi.org/10.1080/00140139.2017.1353137

Reed, H., Langley, J., Stanton, A., Heron, N., Clarke, Z., Judge, S., McCarthy, A., Squire, G., Quinn, A., Wells, O., Tindale, W., Baxter, S., Shaw, P. J., & McDermott, C. J. (2015). Head-Up; An interdisciplinary, participatory and co-design process informing the development of a novel head and neck support for people living with progressive neck muscle weakness. Journal of Medical Engineering & Technology, 39(7), 404–410. https://doi.org/10.3109/03091902.2015.1088092

Baxter, S., Reed, H., Clarke, Z., Judge, S., Heron, N., Mccarthy, A., Langley, J., Stanton, A., Wells, O., Squire, G., Quinn, A., Strong, M., Shaw, P. J., & Mcdermott, C. J. (2016). Evaluating a novel cervical orthosis, the Sheffield Support Snood, in patients with amyotrophic lateral sclerosis/motor neuron disease with neck weakness. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 17(5–6), 436–442. https://doi.org/10.3109/21678421.2016.1148170

Pancani, S., Rowson, J., Tindale, W., Heron, N., Langley, J., McCarthy, A. D., Quinn, A., Reed, H., Stanton, A., Shaw, P. J., McDermott, C. J., & Mazzà, C. (2016). Assessment of the Sheffield Support Snood, an innovative cervical orthosis designed for people affected by neck muscle weakness. Clinical Biomechanics, 32, 201–206. https://doi.org/10.1016/j.clinbiomech.2015.11.010

Pancani, S., Tindale, W., Shaw, P. J., Mazzà, C., & McDermott, C. J. (2018). Efficacy of the Head Up collar in facilitating functional head movements in patients with Amyotrophic Lateral Sclerosis. Clinical Biomechanics, 57, 114–120. https://doi.org/10.1016/j.clinbiomech.2018.06.016

Sproson, L., Lanfranchi, V., Collins, A., Chhetri, S. K., Daly, N., Ennis, M., Glennon, L., Gorrie, G., Jay, E., Marsden, R., McCarthy, A. D., Pryde, L., Roberts, R., Rutherford, A., Ryan, J., Stot, G., Tindale, W. B., Shaw, P. J., & McDermott, C. J. (2020). Fit for purpose? A cross-sectional study to evaluate the acceptability and usability of HeadUp, a novel neck support collar for neurological neck weakness. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. https://doi.org/10.1080/21678421.2020.1813308

Patents: Reed, A.H., Langley, J., Stanton, N.H., McDermott, C. J. Neck orthosis. Filing date 2014-11-13. Patent numbers: GB2516725B (granted 28-Oct-2015); PCT/GB2014/051432 leading to: EP14724145.9 and US141889828. https://patents.google.com/patent/WO2014181128A1

Key funding: National Institute for Health Research (NIHR) i4i funding programme (II-ES-0511-21003), £445,606; Motor Neurone Disease Association (MNDA) McDermott/Feb15/928-794, £19,995; NIHR Devices for Dignity Healthcare Technology Co-operative (HTC)

4. Details of the impact

Impacts include: health and welfare, public policy and services, practitioners and services, commercial. Main beneficiaries include: patients, industry, NHS.

Researchers and physiotherapists found that many patients with muscle weakness through ALS/MND would not wear their collars due to their discomfort and difficulty of use [R1]. The Sheffield team led a collaborative project to address the needs identified, bringing together patients, their families, researchers and designers to ensure a design of a collar truly fit for purpose [R1, R2]. The resulting HeadUp Collar is significantly improving patients’ lives and is a commercial success. The impact of the HeadUp Collar has been recognised by the 2020 Queen Anniversary Awards for research that has improved patient outcomes for people living with some of the most devastating neurodegenerative diseases [S1].

Improved quality of life of ALS/MND patients and their carers

The HeadUp Collar was launched in December 2017 at the International ALS/MND symposium in Boston, USA and has significantly improved the quality of life of ALS/MND patients. In the ‘100 Collars’ project the HeadUp Collar was trialled by 139 patients in 10 sites across the UK and Ireland; 70.9% of participants choose to keep using the device after the trial [R6, S2]. Some feedback [S2, R6] from trial participants and their carers included:

Patients:

  • “Other, more rigid collars were painful – I couldn’t wear them for too long, I can wear this collar for 8 hours straight – I wear it at work”

  • “I’ve tried the soft foam collars before but they don’t give enough support, they just crumbled”

  • “Comfortable – more confident when out in public. Brilliant. Feels warm – like having a hot water bottle on your neck – helps muscles. Looks good” … “everyone who sees me in it says it looked brilliant – like a polo neck. Less self-conscious now.”

Carers:

  • "I can see his face better now"

  • “Particularly useful when drinking as it enables him to flex his head to achieve an effective swallow"

Researchers and a user describe the benefits of the HeadUp Collar design and the difference it makes to simple everyday acts, often taken for granted, such as having a meal out or reading a book [S2, S3]. Testimonials of patients describing the benefit of the HeadUp Collar on their lives have featured in the media [S3a-c], including BBC [S3] and newspapers [S3]. A HeadUp Collar user saidIt looks like clothing, really, rather than a medical device. Without the collar, I wouldn’t be able to drive and that makes a huge difference. With a rigid collar, you can look ahead but you can’t turn your head to see the traffic, but with this collar you can do that. It’s life-changing really.” The new collar has "freed me up to have a much more normal life". "The quality of my life has been substantially different as a result of this collar, there's no doubt about that.” [S3].

Impact on clinician practitioners

The availability of the HeadUp Collar has changed clinical practice. All clinicians participating in the 100 Collar trial said they would like to have the collar in their range of products for patients, in a range of sizes [R6, S2]. They feel it could be useful for:

  • “any conditions with cervical weakness without shortness of breath”,

  • “any conditions with neck weakness – for example Parkinson’s disease, brain injury and Muscular Dystrophy”, and “neck weakness developed as a complication following radiotherapy for breast cancer”

The support of clinicians is backed up by the fact that the Collar has been directly purchased by 135 UK NHS Health Boards/Trusts [S4].

International commercial impact

The global 'patent and know-how' for the HeadUp Collar was licensed to UK SME, TalarMade, with the first commercial sale on 18 April 2018. As of 19 November 2020, in-excess of 2,500 collars have been sold globally with a commercial value of sales £320,000 [S4].

In the UK, the HeadUp Collar is available through all national and regional NHS Procurement Frameworks, and has been directly purchased by 135 UK NHS Health Boards/Trusts. Nineteen private UK Orthotic companies purchased over 300 units to service UK orthotic contracts. Full coverage of the UK in terms of areas purchased has been achieved [S4].

The collar has been purchased across Europe, including all of Scandinavia (up to 300 units so far), Germany, Ireland, France, Spain, and the Netherlands. An EU Representative is now employed to negotiate licence deals with European distributors Basko (Netherlands/Benelux), OrthoEurope (France), and ProWalk (Germany) [S4].

TalarMade recorded sales across North America (independent buyers via ALS Society and ALS Society Quebec, 200+ Units) and a Reimbursement ‘L’ Code (L0170) has been awarded in the US. This code allows healthcare providers to invoice for the specific orthotics. Distribution has been secured with Hanger Clinic, the largest Rehab Clinical provider in the US with over 1800 Clinicians practising out of over 800 clinical facilities via their procurement arm SPS, Cascade Supply (the largest independent Orthopaedic Supplier in the US) and Becker Orthopaedic [S4].

Further world-wide sales have been achieved in Australia/New Zealand (100+ Units) via partner OPC Health [S4].

As a result of the HeadUp venture, Talarmade have secured a similar arrangement with Strathclyde University to develop a unique wrist orthosis [S5]. The commercial success of HeadUp has played a major part in allowing Talarmade to continue to progress on numerous fronts and has sustained the employment of Talarmade staff through during the COVID-19 pandemic [S4].

5. Sources to corroborate the impact

2020 Queen Anniversary Award for research that has improved patient outcomes for people living with some of the most devastating neurodegenerative diseases ( https://bit.ly/31fDLMK).

Multi-centre evaluation - 100 collar project: MND Association ( http://bit.ly/30CE4kp)

Combined media coverage/MND patient testimonial on impact of the HeadUp collar: BBC News website, 29 May 2018 ( https://www.bbc.co.uk/news/av/uk-england-south-yorkshire-44293766) and BBC Look North Evening News, 30 May 2018 (https://www.youtube.com/watch?v=Z6tmADMDSgM&ab\_channel=TalarMadeLtd\), showcase the novel HeadUp Collar; The Yorkshire Post reports on the Head-Up collar on Tuesday 29 May 2018: “Sheffield MND patients inspire 'revolutionary' collar that will reach patients around the world” ( https://www.yorkshirepost.co.uk/health/sheffield-mnd-patients-inspire-revolutionary-collar-will-reach-patients-around-world-1761528); HeadUp Collar video ( https://vimeo.com/272414469); Head up Brochure (TalarMade, https://www.talarmade.com/wp-content/uploads/2017/12/V2-Online-Head-Up-Brochure.pdf) and Talarmade HeadUp Collar webpage ( https://www.talarmade.com/products/headup-collar/).

Letter from TalarMade CEO.

Submitting institution
The University of Sheffield
Unit of assessment
3 - Allied Health Professions, Dentistry, Nursing and Pharmacy
Summary impact type
Health
Is this case study continued from a case study submitted in 2014?
No

1. Summary of the impact

Weight management is critical for survival in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Gastrostomy feeding directly into the stomach is recommended to support patients with ALS/MND that develop severe dysphagia. Notwithstanding, there was a lack of evidence of optimal timing and method for gastrostomy insertion. Furthermore, the lack of authoritative lay information meant that patients tended to put off having the procedure until it was too late despite the opposite advice by health professionals. The ProGas study led by Sheffield researchers determined that gastrostomy should be done at 5% weight loss rather than 10% as was in the guidelines at the time, and that radiologically inserted gastrostomy (RIG) tubes should not be used. This has led to updated national and international clinical guidelines on nutritional support and the increased use of gastrostomy in ALS/MND disease patients. This research has also informed the creation of a unique online resource (MyTube, https://mytube.mymnd.org.uk/) for patients, carers, health professionals and the general public to inform and assist decision making for patients. As a direct result the lives of patients and carers were improved.

2. Underpinning research

Amyotrophic lateral sclerosis (ALS), known in the UK as motor neuron disease (MND) is a progressive degenerative fatal neuromuscular disease that is caused by degeneration of motor neurones. ALS/MND sufferers typically die within 2-3 years from diagnosis due to respiratory arrest. As the disease is incurable, the efforts to support patients are heavily focused on sustaining a maximum quality of life (QoL). Worldwide an estimated 450,000 patients are living with ALS/MND at any given time. Dysphagia (swallowing difficulties) is a common problem in patients with ALS/MND. Patients with severe swallowing difficulty experience malnutrition, dehydration, choking and an increased risk of chest infections. Traditional use of nasogastric tubes for feeding is problematic for ALS/MND patients and is not compatible with using non-invasive ventilation (NIV), the current standard therapy to manage respiratory insufficiency.

Long-term nutritional support of patients with severe swallowing difficulty can be achieved by placing a feeding tube, known as a gastrostomy, directly into the stomach; both the American Academy of Neurology and the European Federation of Neurological Societies recommend gastrostomy feeding in ALS/MND patients who develop severe dysphagia.

A meta-analysis and survey of the practice of gastronomy use in ALS/MND conducted by the Sheffield team, in which they reviewed the three main methods of gastrostomy insertion (percutaneous endoscopic gastrostomy (PEG); radiologically inserted gastrostomy (RIG); per-oral image-guided gastrostomy (PIG)) and conducted a meta-analysis of mortality data following gastrostomy, revealed a lack of high-quality evidence to indicate the optimal method and timing for gastrostomy insertion in patients with ALS/MND and indicated that RIG and PIG methods may be safer than PEG [R1].

A retrospective, qualitative exploration using semi-structured interviews was conducted with 27 paired patients and carers, out of which 23 underwent gastrostomy, in order to elicit their perceptions in relation to gastrostomy timing. It concluded that the advice for early insertion does not outweigh the personal perceptions and psychosocial factors for patients and their carers. It also found that understanding the factors that influence decision-making on an individual basis is important for information and care provision by healthcare professionals in aiding patients and their carers, to make informed decisions in relation to gastrostomy timing [R2, R3].

Following on from these studies, the Sheffield team initiated a world-first large, longitudinal, prospective cohort study (ProGas) that aimed to compare gastrostomy insertion approaches in terms of safety and clinical outcomes in ALS/MND. The ProGas study team worked with the Sheffield Motor Neurone Disorders Research Advisory Group to enable the public, patients and carers the opportunity to provide feedback on all aspects of ProGas and to contribute to shaping the final ProGas protocol. The membership of this group includes patients and carers who have experience of motor system disorders including ALS/MND. Between Nov 2, 2010, and Jan 31, 2014, 345 patients were recruited in 24 participating UK ALS/MND care centres and clinics of whom 330 had gastrostomy. 163 (49%) patients underwent PEG, 121 (37%) underwent RIG, 43 (13%) underwent PIG, and three (1%) underwent surgical gastrostomy. The study showed that while the three methods of gastrostomy seemed to be as safe as each other in relation to survival and procedural complications, the hazard of death after gastrostomy insertion was significantly affected by the percentage of weight loss from diagnosis to gastrostomy, and patients who received RIG had a significantly higher rate of tube-related complications, leakage and replacement. Accordingly, the ProGas Study recommended that gastrostomy should be done at 5% weight loss rather than 10% as was in the guidelines at the time, and that RIG tubes should not be used [R4].

3. References to the research

Stavroulakis, T., Walsh, T., Shaw, P. J., & McDermott, C. J. and the Progas Study (2013). Gastrostomy use in motor neurone disease (MND): A review, meta-analysis and survey of current practice. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 14(2), 96–104. https://doi.org/10.3109/17482968.2012.723722

Stavroulakis, T., Baird, W. O., Baxter, S. K., Walsh, T., Shaw, P. J., & McDermott, C. J. (2014). Factors influencing decision-making in relation to timing of gastrostomy insertion in patients with motor neurone disease. BMJ Supportive & Palliative Care, 4(1), 57–63. https://doi.org/10.1136/bmjspcare-2013-000497

Stavroulakis, T., Baird, W. O., Baxter, S. K., Walsh, T., Shaw, P. J., & McDermott, C. J. (2016). The impact of gastrostomy in motor neurone disease: challenges and benefits from a patient and carer perspective. BMJ Supportive & Palliative Care, 6(1), 52–59. https://doi.org/10.1136/bmjspcare-2013-000609

McDermott, C. J., Shaw, P. J., Stavroulakis, T., et al., on behalf of the ProGas Study Group (2015). Gastrostomy in patients with amyotrophic lateral sclerosis (ProGas): a prospective cohort study. The Lancet Neurology, 14, 702-709. https://doi.org/10.1016/S1474-4422(15)00104-0

4. Details of the impact

Impacts include: health and welfare, public policy and services, practitioners and services, commercial.

Main beneficiaries include: patients, carers, practitioners, NHS, NICE, general public, industry.

Gastrostomy feeding directly into the stomach is recommended to support patients with ALS/MND that develop severe dysphagia. These patients struggle to maintain weight, and without a tube they essentially cannot take in enough calories to survive. Prior to the ProGas study the practice of gastrostomy feeding was largely based on consensus and expert opinion rather than robust evidence. Furthermore, the lack of accessible information meant that patients tended to put off having the procedure until it was too late despite the opposite advice by health professionals. The ProGas study was stimulated by the research priorities identified by both the Dementias and Neurodegenerative Diseases Research Network (DeNDRoN) Clinical Studies Group for MND and the MND Association. ProGas has provided scientific underpinning for the practice of gastronomy in ALS/MND and provided an award-winning online information resource which have directly improved the lives of patients and carers.

Impact on UK and international guidelines

The ProGas Study has led to updated national and international guidelines on nutrition support and the use of gastrostomy in patients with ALS/MND.

In the UK, the British Medical Journal used the results from the ProGas study as evidence that gastrostomy before substantial weight loss might be beneficial as part of ongoing treatment options, in its BMJ Best Practice on ALS/MND publication [S1]. The Motor Neurone Disease Association, the only national ALS/MND charity in the UK and founding member of the international Alliance of ALS/MND associations, which has 40 members, included the recommendations of the ProGas study in its Guide for GPs and primary care teams [S2].

The results have been reflected in current National Institute for Health and Care Excellence (NICE) guidelines for MND, which state that the role of gastrostomy feeding should be discussed at an early stage but that it must be recognised that not all individuals will wish to proceed [S3]. Internationally, the European Society for Clinical Nutrition and Metabolism (ESPEN) has used the recommendations from the ProGas study in its guidelines on clinical nutrition in Neurology [S4].

Impact by public participation, involvement, and engagement: direct impact on the lives of MND/ALS patients

As a result of the ProGas study findings the MyTube website ( https://mytube.mymnd.org.uk/) was created in collaboration with the NHS and the Sheffield MND Care Centre and with support from the MND Association. Built for and by patients, the site offers insights into living with a tube or alternatives available through the use of short videos and information about tube feeding for people living with ALS/MND with the clearly stated objective to use patient stories to encourage change; myTube was launched in March 2017 [S5]. The myTube website has become the go to information resource for patients and carers: it has become the recommended information source by patient organisations such as the Motor Neurone Disease Association, the Parenteral and Enteral Nutrition Group (PENG) and the British Association of Parenteral and Enteral Nutrition (BAPEN) [S6]. Its influence and impact have further been recognised by several awards, including two British Medical Association (BMA) Patient Information Awards [S7a] describing it as “ a perfect medium for instructional information” and the Nutrition Resource of the Year Award from Complete Nutrition Magazine, the UK’s number one clinical, medical and health nutrition publication [S7b].

The myTube resource has helped patients and carers worldwide to make informed decisions; one patient commented “ I have just been diagnosed with MND and have been asked to start considering getting a PEG. This is fantastic information and very timely. I've already watched the first two 'videos' and they're great. Thanks to all participants...you're already helping someone in Australia.” While a carer said “ I'm sure this will help put people's minds at ease regarding PEGs and other things. Wish [husband’s name] could have seen this early on. He might not have resisted having his fitted till it was desperate” [S8].

Feedback was also received from clinics around the UK that the website is used regularly in their clinics to support patients [S8]. The use of myTube, in patient decision making, has been suggested as a reason for the increase in patients in Scotland undergoing gastrostomy ‘More people could be undergoing gastrostomy because of the increasing amounts of readily accessible information via social media and the internet for example https://mytube.mymnd. org.uk/.’ [S9].

Commercial impact

The myTube resource was designed by Ammba Digital architects ( http://ammba.co.uk/), a consultancy and digital product development company, in collaboration with Optical Jukebox (the film makers for myTube), the Sheffield team and ALS/MND patients and carers. Ammba’s involvement in the project team that delivered myTube has led to ongoing work for the company in the digital healthcare space. The myTube project allowed the company to take their specialism and skills from the education learning sector into the health sector. Ongoing collaboration with Optical Jukebox led to securing a £50K funding award from the Ufi VocTech programme to develop a digital learning resource to support carers working with those living with a neurological condition; a first for this sector [S10].

5. Sources to corroborate the impact

BMJ best practice amyotrophic lateral sclerosis ( https://bestpractice.bmj.com/topics/en-us/330) pp.22, 26.

Motor neurone disease: a guide for GPs and primary care teams ( https://www.mndassociation.org/app/uploads/px016-motor-neurone-disease-a-guide-for-gps-and-primary-care-teams.pdf) pp.32, 40, reference 44 on p.76

National Institute for Health and Care Excellence (NICE). Motor neurone disease: assessment and management 2016 ( https://www.nice.org.uk/guidance/ng42/chapter/recommendations#nutrition-and-gastrostomy) 1.10.6, 1.10.7, 1.10.8, p.243 of NG42

ESPN Guideline. Burgos, R., Bretón, I., Cereda, E., Desport, J. C., Dziewas, R., Genton, L., Gomes, F., Jésus, P., Leischker, A., Muscaritoli, M., Poulia, K.-A., Preiser, J. C., Van der Marck, M., Wirth, R., Singer, P., & Bischoff, S. C. (2018). ESPEN guideline clinical nutrition in neurology. Clinical Nutrition, 37(1), 354–396. https://doi.org/10.1016/j.clnu.2017.09.003. Clinical Question 12 and 13, Recommendation 17, 18,19.

Web link to the myTube website ( http://mytube.mymnd.org.uk/) combined with media coverage following the launch: patient with MND shares his story, with a view to helping others, on myTube on ITV News, 31-Mar-2017 ( https://www.youtube.com/watch?v=OJu6FSf0zQg&ab_channel=JasonLiversidge); Living with the cruelty of motor neurone disease: Brave Yorkshire families share their stories. The Yorkshire Post, 3 April, 2017 ( https://www.yorkshirepost.co.uk/news/living-cruelty-motor-neurone-disease-brave-yorkshire-families-share-their-stories-55332).

MyTube as a recommended information source by patient organisations: MNDA Resources: Living with MND: swallowing, eating and drinking ( https://www.mndassociation.org/support-and-information/living-with-mnd/eating-and-drinking/) and Dysphagia information sheet for health professionals (p.1, https://z9t2c4x9.stackpathcdn.com/app/uploads/information-sheet-p8-dysphagia-in-motor-neurone-disease.pdf); PENG Resources for Patients and HCPs ( https://www.peng.org.uk/publications-resources/resources-for-patients-hcps.php); BAPEN e-Learning Portal ( https://www.bapen.org.uk/71-resources-and-education/education-research-and-science/e-learning-portal).

Combined 2017 award information: BMA Patient Information Award and Nutrition Magazine Award. PDF available.

MyTube website metrics, feedback – report to MND 2017 by Optical Jukebox. Written by Registered Nurse filmmaker and videographer, Optical Jukebox.

Gorrie, G. H., Chandran, S., Colville, S., Newton, J., Leighton, D., Mcdonald, M., Pal, S., Forbes, R., Hair, M., & Swingler, R. (2019). Improved survival and 30-day mortality after gastrostomy in Scottish motor neurone disease patients: evidence from a national retrospective cohort study using STROBE criteria. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 20(3–4), 165–171. https://doi.org/10.1080/21678421.2019.1570271

AMMBA Collaboration information and correspondence ( http://ammba.co.uk/neurocare-knowhow-awarded-ufi-voctech-seed-2020-funding/).

Submitting institution
The University of Sheffield
Unit of assessment
3 - Allied Health Professions, Dentistry, Nursing and Pharmacy
Summary impact type
Health
Is this case study continued from a case study submitted in 2014?
No

1. Summary of the impact

Oral bacteria are implicated in 35-45% of cases of infective endocarditis (IE), a life-threatening heart infection. Antibiotic prophylaxis (AP) before invasive dental procedures is the only prevention measure recommended for individuals at increased risk of IE, but controversy surrounding its use led NICE to recommend against AP before invasive dental procedures in 2008. Our subsequent systematic review of prescription data and hospital discharge statistics identified a significant increase in IE incidence in England, and we have continued to research the link between oral bacteria and IE and the role of AP in IE prevention to inform guideline committee decisions. Our research has influenced the recommendations of AP guideline committees in the UK, the US, Sweden, and Japan and underpinned changes in advice to UK dentists and patients.

2. Underpinning research

Infective Endocarditis (IE) is a bacterial heart valve infection with a mortality rate of 30% in the first year. Approximately 35-40% of IE cases are caused by bacteria that originate from the mouth. Since the 1950s, international standards of care have dictated that antibiotic prophylaxis (AP) be given to dental patients at moderate or high risk of IE during invasive dental procedures. However, due to concerns about the risk of adverse reactions to AP, the overuse of antibiotics and the lack of randomised-controlled trial evidence for the efficacy of AP, from 2007 International guidelines began to recommend reducing AP use to only those at high risk of IE. In 2008, NICE recommended complete cessation of the use of AP, making the UK the only country in which AP was not recommended for those at high risk of IE.

From 2013, an international, multidisciplinary team led by Thornhill investigated the effect that the NICE guidelines had on AP prescribing and IE incidence in England [R1]. Using a retrospective secular trend study, analysed as an interrupted time series, the team compared the incidence of infective endocarditis before and after the introduction of the NICE guidelines using prescribing data from January 2004 to March 2013 and hospital discharge episode statistics for patients with a primary diagnosis of IE from January 2000 to March 2013. The Sheffield research found a large decrease in AP prescribing and a highly significant increase in IE incidence, with an increase of 35 cases per month compared to the number of cases before the NICE guideline changed. In 2016, this study was followed with a health economic analysis that established the cost-effectiveness of using AP to prevent IE in individuals at high-risk, with an estimated NHS savings of £5.5–8.2 million annually and an annual health gain of >2,600 quality of life adjusted years [R2].

In 2017, Sheffield collaborated with the Centre for Evidence-Based Medicine in Oxford, to conduct a comprehensive systematic review of AP efficacy. Having identified 178 eligible studies, 36 were included in the review (10 time-trend studies, 5 observational studies and 21 trials). The review concluded that despite the low-quality and limited evidence base, guidelines advising AP for patients at highest risk provide a pragmatic and justified approach [R3].

Although our research identified benefits for AP in relation to risk, definitions of what constitutes a high or moderate risk of IE have changed over the years, largely based on expert opinion. To clarify this basis for treatment, Sheffield used English hospital admission data to identify individuals admitted between January 2000 and March 2008 with diagnoses or cardiac procedures that might put them at risk of IE. This data was used to quantify and compare the risk of developing or dying from IE for patients who had predisposing cardiac conditions or various cardiac interventions. The results showed that some conditions that had been considered high risk are actually not, and that conversely, some conditions carry higher risk than had been thought [R4].

To investigate whether stopping AP for those at moderate risk of IE might increase IE incidence, we then performed the largest study ever on the impact of the 2007 AHA guideline change. High-risk, moderate-risk, and unknown/low-risk individuals with linked prescription and Medicare or commercial health care data were identified in the Truven Health MarketScan databases from May 2003 through August 2015 (198,522,665 enrollee-years of data). AP prescribing and IE incidence were evaluated by Poisson model analysis. The results confirmed the efficacy of AP for preventing IE in individuals at high risk of IE and demonstrated a much smaller, but still significant, effect in those at moderate risk [R5].

3. References to the research

Dayer, M. J., Jones, S., Prendergast, B., Baddour, L. M., Lockhart, P. B., & Thornhill, M. H. (2015). Incidence of infective endocarditis in England, 2000–13: a secular trend, interrupted time-series analysis. The Lancet, 385(9974), 1219–1228. https://doi.org/10.1016/s0140-6736(14)62007-9

Franklin, M., Wailoo, A., Dayer, M. J., Jones, S., Prendergast, B., Baddour, L. M., Lockhart, P. B., & Thornhill, M. H. (2016). The Cost-Effectiveness of Antibiotic Prophylaxis for Patients at Risk of Infective Endocarditis. Circulation, 134(20), 1568–1578. https://doi.org/10.1161/circulationaha.116.022047

Cahill, T. J., Harrison, J. L., Jewell, P., Onakpoya, I., Chambers, J. B., Dayer, M., Lockhart, P., Roberts, N., Shanson, D., Thornhill, M., Heneghan, C. J., & Prendergast, B. D. (2017). Antibiotic prophylaxis for infective endocarditis: a systematic review and meta-analysis. Heart, 103(12), 937–944. https://doi.org/10.1136/heartjnl-2015-309102

Thornhill, M. H., Jones, S., Prendergast, B., Baddour, L. M., Chambers, J. B., Lockhart, P. B., & Dayer, M. J. (2018). Quantifying infective endocarditis risk in patients with predisposing cardiac conditions. European Heart Journal, 39(7), 586–595. https://doi.org/10.1093/eurheartj/ehx655

Thornhill, M. H., Gibson, T. B., Cutler, E., Dayer, M. J., Chu, V. H., Lockhart, P. B., O’Gara, P. T., & Baddour, L. M. (2018). Antibiotic Prophylaxis and Incidence of Endocarditis Before and After the 2007 AHA Recommendations. Journal of the American College of Cardiology, 72(20), 2443–2454. https://doi.org/10.1016/j.jacc.2018.08.2178

4. Details of the impact

Impact on national and international policy and public debate

In 2015, NICE announced an immediate review of its guidelines stating that the publication [R1] “triggered an exceptional update” [S1]. While NICE concluded it would not re-introduce AP for those at high risk because the study was not a randomised controlled trial, the 2015 European Society for Cardiology (ESC) in depth review, citing [R1] concluded that “ the weight of evidence and opinion is now in favour of the efficacy and usefulness of AP in preventing IE in those at high-risk[S2, S3].

Other national guideline committees also reviewed their guidelines based on our research. The Swedish guideline committee, who had previously followed NICE guidance, switched to follow ESC guidance [S3]. The Japanese guideline committee changed their recommendations to include providing AP for invasive dental procedures to those at moderate or high risk of IE [S3]. The American Heart Association concluded their review in 2020 stating for dental procedures “ that antibiotic prophylaxis is reasonable for the subset of patients at highest risk of developing IE and at high risk of experiencing adverse outcomes from IE[S3].

NICE’s decision not to recommend AP for high-risk patients despite the findings [R1] attracted considerable scrutiny from the dental and medical press and national and international media [S4]. In addition, our research [R2] supported further scrutiny of and changes to the NICE guidelines. The MP for South Croydon helped a constituent whose husband died from IE following an invasive dental procedure to raise the issue directly with the CEO of NICE, using our research [R1] as evidence to support a change in the guidelines [S5]. Their efforts successfully influenced NICE to change the guideline wording in June 2016 [S6, S7]. The previous wording was changed to include the word “routinely”, as follows: “ *Antibiotic prophylaxis against infective endocarditis is not recommended routinely for people undergoing dental procedures.*” The NICE CEO said, “ This amendment should now make clear that in individual cases antibiotic prophylaxis may be appropriate[S2, S6, S7].

Impact on UK dental professionals and patients

Although the change in the wording of the NICE guidelines removed the barrier preventing dentists from providing AP, the NICE guidelines provided no advice about who should be considered for AP, which invasive dental procedures should be covered, or which AP regimen should be used, causing considerable confusion among dentists, cardiologists, GPs and patients. Our research informed our advice for dentists in the BDJ [S8] to help them navigate conflicting guidance. The Scottish Dental Clinical Effectiveness Program (SDCEP), which provides advice and guidance for dentists in Scotland, provided official advice Antibiotic Prophylaxis Against Infective Endocarditis [S9] in 2018 for the implementation of the NICE guideline 64 using our research findings [R1] and advice [S2, S8]. It adopted our advice [S8] that all patients at risk of IE should be advised of warning signs and symptoms after undergoing an invasive dental procedure, regardless of whether they receive AP, which is essential for early diagnosis, improved survival and better outcomes [S2]. The SDCEP advice was endorsed by NICE and the British Cardiac Society and the Chief Dental Officers for England, Wales, and Northern Ireland in 2018, making the advice applicable UK-wide [S9].

In 2019, we worked with the British Cardiac Society and British Heart Valve Society and helped them design a card that patients can carry to inform their dentists about any decision they have made with their cardiologist or cardiothoracic surgeon about their wish for AP when undergoing invasive dental procedures. It also provides information on AP and on the warning signs and symptoms of IE following any dental treatment or other invasive procedure based on the SDCEP advice [S10].

5. Sources to corroborate the impact

NICE Clinical Guideline 64.1 (Sept 2015) p9. The NICE 2015 review of its AP guidelines (CG64); the influence of R1 is detailed in paragraphs 1-3 on page 9.

Editorial in the British Dental Journal describes the important role played by our research in the changes that have occurred both in the NICE guidance and the development of the SDCEP Implementation Advice ( https://www.nature.com/articles/sj.bdj.2018.761).

Combined: confirmation of use of our Sheffield research in various international guidelines. An email from the Chair of the Japanese AP guideline committee confirming the important role played by our research in the decision of the guideline committee ( https://www.jstage.jst.go.jp/article/circj/83/8/83_CJ-19-0549/_pdf/-char/en). Evidence pertaining to the role our research played in determining the guidance of the ESC Guideline for the management of infective endocarditis ( https://doi.org/10.1093/eurheartj/ehv319). The AHA guideline 2020 ( https://www.ahajournals.org/doi/10.1161/CIR.0000000000000923).

Media articles (print and online).

Confirmation of Sheffield research use by the wife of a patient who died from dentally related IE to campaign for NICE to change its guidance and confirmation from the MP for South Croydon the importance of our research in the campaign for NICE to change its AP guidance.

Correspondence between MP for South Croydon and CEO of NICE confirming use of Sheffield research in direct lobbying from the MP and response from the NICE confirming that the word ‘routinely’ would be added to NICE CG64.

NICE CG64 with July 2016 update inserting the word ‘routinely’ on p 5.

Sheffield articles providing advice to practitioners on AP in IE in British Dental Journal ( https://doi.org/10.1038/sj.bdj.2016.49 and https://doi.org/10.1038/sj.bdj.2016.554).

Letter from the SDCEP Steering Group Chair confirming the important role played by our research in the development of the SDCEP advice and its adoption, not just in Scotland, but across all four devolved nations of the UK.

AP information card for patients. A BDJ article announcing the launch of the patient card that we developed with the British Cardiovascular Society and British Heart Valve Society to dentists along with a copy of the card (July 2019).

Submitting institution
The University of Sheffield
Unit of assessment
3 - Allied Health Professions, Dentistry, Nursing and Pharmacy
Summary impact type
Societal
Is this case study continued from a case study submitted in 2014?
No

1. Summary of the impact

In 2015 ambulance services in England responded to 6.5 million 999 calls compared to 3.5 million in 1995. With no equivalent increase in resources, they were unable to meet response times expected for the most critically ill. The Sheffield programme of work evaluated changes to processes of assessing, categorising and dispatching ambulances to 999 calls and helped set new performance standards. The evidence-based changes have been adopted in the NHS resulting in more consistent fast response to the most urgent calls and ensuring as far as possible people who call get the right response first time. Now all regional ambulance services meet the response time standard for the most serious calls compared to only 1/10 before.

2. Underpinning research

For over 20 years, research in the School of Health and Related Research (ScHARR) has provided the evidence base for major policy and operational reform, which has shaped how emergency ambulance services are delivered to patients in the UK. Our early work in 1995 assessing emergency call prioritisation systems underpinned the introduction of 999 call triage in UK ambulance services and response time targets for different levels of urgency.

In 2011, Sheffield researchers were awarded an NIHR Programme Grant for Applied Research - the Pre-hospital Outcomes for Evidence Based Evaluation Programme (PhOEBE). This research used statistical modelling of a data set linking ambulance, hospital, and mortality data to produce novel case-mix adjustment measures of ambulance service quality [R1]. Existing performance measures centred on response times so, whilst this was still considered important, it became part of a suite of potential quality measures that also reflected clinical care delivery and patient outcomes.

Using consensus methods, ScHARR researchers identified a shortlist of ambulance outcome and performance measures that were important to clinicians and service providers, service users, commissioners, and clinical academics, reflecting current pre‐hospital ambulance care and services [R2, R3]. Service user perspectives through patient and public involvement (PPI) was integral to the PhOEBE programme and continued to be used to investigate the aspects of emergency ambulance service care valued by users [R4]. Results showed service users valued similar aspects of their pre‐hospital care. Users were often extremely anxious about their health, and the outcome they valued was reassurance provided by ambulance service staff that they were receiving appropriate advice, treatment and care. This sense of being reassured was enhanced by the professional behaviour of staff, which instilled confidence in their care; communication; a short wait for help; and continuity during transfers. A timely response was valued in terms of allaying anxiety quickly [R4].

While this work was in progress it was becoming clear that ambulance services in the UK were under severe pressure. By 2015, ambulance services in England were responding to 6.5 million calls a year and a combination of increasing demand, changing population and no new financial resources meant almost all were failing to meet the expected response time targets. At that time half of 999 calls were assigned to the highest response category even though only about 10% were true emergencies and the targets themselves were creating poor dispatch practices. Almost all ambulance services in England were failing to meet expected response times and as a result, NHS England embarked on a large-scale review in autumn 2015 - The Ambulance Response Programme (ARP). Three significant changes were tested – i) more time to assess the urgency of 999 calls and identify an appropriate response, ii) a revision of call categories, and iii) new response time standards for each category. A similar exercise began at the same time in Wales. ScHARR’s expertise in related policy research led to the team being commissioned to undertake independent evaluations of the changes initiated by the ARP in England [R5] and the revised clinical response model in Wales [R6], providing the evidence needed for decisions about whether these should be permanently adopted.

The English evaluation of Phase 1 of the ARP (analysing over 14 million 999 calls) provided strong evidence that the introduction of longer call assessment times produced clear benefits for operational efficiency with an estimated 14,000 additional resources available for response per week across England. This translated into better response time performance for the most seriously ill patients with a 6% improvement in high priority calls receiving a response within 8 minutes and more stable and consistent fast response performance for calls in the revised highest call category. This became increasingly important as demand continued to rise [R5]. Evidence showed the new call category model had produced benefits without compromising patient safety (patients were more likely to get the right response first time), and did not result in longer waiting times for the 999 call population, thus having the potential to improve survival from out of hospital cardiac arrest by early identification of these critical calls. A staff survey found the changes were welcomed by ambulance staff [R5]. Findings from the PhOEBE programme supported changes to response time performance standards and how these should be reported.

The Wales evaluation showed that response time reliability for the most urgent category increased substantially, fewer resources were used per incident and direct costs decreased slightly and were redistributed to earlier steps in the Ambulance Patient Care Pathway [R6].

3. References to the research

Turner J, Siriwardena A, Coster J, Jacques R, Irving A, Crum A, et al. (2019). Developing new ways of measuring the quality and impact of ambulance service care: the PhOEBE mixed-methods research programme. Programme Grants Appl Res 19;7(3) https://www.ncbi.nlm.nih.gov/books/NBK540540/.

Coster, J. E., Irving, A. D., Turner, J. K., Phung, V.-H., & Siriwardena, A. N. (2017). Prioritizing novel and existing ambulance performance measures through expert and lay consensus: A three-stage multimethod consensus study. *Health Expectations, 21(*1), 249–260. https://doi.org/10.1111/hex.12610

Irving, A., Turner, J., Marsh, M., Broadway-Parkinson, A., Fall, D., Coster, J., & Siriwardena, A. N. (2017). A coproduced patient and public event: An approach to developing and prioritizing ambulance performance measures. Health Expectations, 21(1), 230–238. https://doi.org/10.1111/hex.12606

Togher, F. J., O’Cathain, A., Phung, V.-H., Turner, J., & Siriwardena, A. N. (2014). Reassurance as a key outcome valued by emergency ambulance service users: a qualitative interview study. Health Expectations, 18(6), 2951–2961. https://doi.org/10.1111/hex.12279

Turner, J., Jacques, R., Crum, A., Coster, J., Stone, A. & Nicholl, J. (2017). Ambulance Response Programme: Evaluation of Phase 1 and Phase 2. Final Report to NHS England. School of Health & Related Research, University of Sheffield. https://www.england.nhs.uk/wp-content/uploads/2017/07/ARPReport_Final.pdf

Public & Corporate Economic Consultants (PACEC), Turner J. (2017). NHS Wales Ambulance Service Emergency Ambulances Service Committee. Clinical model pilot evaluation. Final Report. PACEC LTD UK. http://www.wales.nhs.uk/sitesplus/documents/1134/Final%20evaluation%20report.pdf

4. Details of the impact

Sheffield research has resulted in the wholesale revision of the way 999 calls are managed, responded to and reported in England and Wales, and is underpinning the implementation of a new clinical response model for Emergency Medical Services (EMS) in Niagara, Canada.

Policy impact in England and Wales

In England, the National Medical Director for NHS England, Department of Health policy teams and other key stakeholders reviewed the comprehensive report [R5], produced by Sheffield researchers, on evaluating the safety and effectiveness of the three changes made by the ARP. Based on the evidence presented, the National Medical Director recommended all three changes be implemented across all eleven ambulance services in England [S1] and in July 2017 this was approved and announced in parliament by the then Secretary of State for Health the Rt. Hon. Jeremy Hunt [S2]. These changes were subsequently incorporated into the NHS Constitution [S3]. The scope and speed of this change is significant and a rare example of NHS policy being tested, evaluated, and a decision then made based on research evidence. This substantial national change has been developed and implemented in the space of two years. A wide range of stakeholders welcomed the changes and highlighted this work as a good example of evidence-based policy change [S4, S5]. In Wales, ScHARR’s report [R6] was shared with the Welsh Ambulance Service and key policymakers, and published in January 2017. Ministerial approval for implementation of the new clinical response model was given in February 2017, based on the findings of the independent evaluation [S8]. The new model was implemented across Wales from March 2017.

Impact on health service practice and patient experience

The impact of these changes on service delivery within the NHS for this sector is extensive and described in the NHS England programme review as the biggest substantial change in ambulance operating practice in England for 40 years [S2].

Ambulance services are now using resources more efficiently and have reduced the use of multiple responses to the same incident in order to “stop the clock” simply to meet a target. It also ensures they are more likely to send the right resource first time – for example a transporting, two crew vehicle to patients needing to go to hospital rather than a single paramedic in a fast response car and then a second vehicle for transport. Better resource use and a reduction from 50% to 10% of 999 calls for the most serious (category 1) cases has translated into improved response performance for this group. By July 2020, 9 out of 10 category 1 calls in England were receiving a response within 13 minutes (standard 15 minutes) [S6].

Patients: the service is more responsive for patients and their clinical needs. It has reduced long waiting times for second vehicles as 93% of patients who need to go to hospital get the right vehicle first time compared to about 80% before. In the longer term there is potential that this will also mean improved patient outcomes. The revised response standards and publicly available response performance for each service are now more transparent as they are reported as mean and 90 centile (i.e. 9/10 calls) times for each call category rather than the previous standard of percent responded to within 8 minutes [S7]. This change was implemented using evidence from the PhOEBE programme [R1].

Staff: the new response model has also resulted in improvements for staff, particularly those working in ambulance emergency operations centres managing 999 calls. Staff surveys included in the evaluation reports were overwhelmingly positive of the changes being tested, reporting that staff were able to do their job more effectively and could better manage the available resources. The most immediate effect on working practices was with Emergency Operations Centre/Hub staff with responses indicating substantial improvements in the ability to dispatch the right resource to the right patient [R5].

Impact on international emergency medical services

Internationally all EMS are coping with increasing demand and diminishing resources and there is a strong appetite for finding better ways of delivering services. As a direct result of the PhOEBE programme [R1] and the evaluation support provided to England and Wales [R5, R6], the research lead has been working with an EMS service in Niagara, Canada. Niagara EMS have embarked on an ambitious plan to implement a new clinical response model based on the Wales and England models. The evidence base generated by the two evaluations has supported rapid progress and the new plan was implemented in September 2019 [S9, S10]. The Ontario Ministry of Health and other Canadian provinces are closely watching progress in Niagara with a view to future more widespread adoption.

5. Sources to corroborate the impact

Factual statement from the National Medical Director, NHS England, 13 July 2017 ( https://www.england.nhs.uk/publication/ambulance-response-programme-letter-to-secretary-of-state/).

Implementation of recommendations of the Ambulance Response Programme Statement by Secretary of State for Health to Parliament, 13 July 2017 ( https://bit.ly/3qfHlR3) and NHS England Ambulance Response Programme Review (2018) NHS England Gateway Publication Reference: 08296 https://www.england.nhs.uk/wp-content/uploads/2018/10/ambulance-response-programme-review.pdf

Change in NHS Constitution ( https://www.gov.uk/government/publications/supplements-to-the-nhs-constitution-for-england/the-handbook-to-the-nhs-constitution-for-england).

Stakeholder example: NHS Providers on the day briefing Ambulance Response programme, July 2017 ( https://nhsproviders.org/media/3296/nhs-providers-on-the-day-briefing-ambulance-response-programme-13-july-2017.pdf).

Analysis article from the Guardian, 14 July 2017 ( https://www.theguardian.com/healthcare-network/2017/jul/14/ambulance-response-system-overhaul-deliver-improvements?CMP=share_btn_tw).

NHS England. Ambulance Quality and Systems Indicators. July 2020. ( https://www.england.nhs.uk/statistics/statistical-work-areas/ambulance-quality-indicators/ambulance-quality-indicators-data-2020-21/).

NHS England. Post ARP Ambulance Service System Indicators, Statistical Specification. 12 September 2019. (Labelled ‘20190912 AQI System Indicator Specification’). ( https://www.england.nhs.uk/statistics/wp-content/uploads/sites/2/2019/09/20190912-AmbSYS-specification.pdf).

Statement from the Cabinet Secretary for Health, Wellbeing and Sport, Welsh Assembly, 27 February 2017 ( https://gov.wales/written-statement-independent-evaluation-emergency-ambulance-services-clinical-response-model).

Public information film for Niagara EMS system transformation ( https://www.youtube.com/watch?v=HNX4hRCJnLI&feature=emb_title).

Factual statement from Niagara Emergency Medical Services, Director/Chief, 3rd May 2019.

Submitting institution
The University of Sheffield
Unit of assessment
3 - Allied Health Professions, Dentistry, Nursing and Pharmacy
Summary impact type
Technological
Is this case study continued from a case study submitted in 2014?
No

1. Summary of the impact

Sheffield University researchers developed a novel tailored therapy for some forms of cancer. This work was the first to show the selective killing of a tumour using an inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) to induce synthetic lethality, heralding a new era in personalised cancer therapy. The discovery was patent-protected, and the development rights were sold to AstraZeneca. Following successful clinical trials, the resultant drug was licenced worldwide. Disclosure of the findings stimulated intense investment in research and development and has revolutionised approaches to cancer therapy. Currently four PARP inhibitors developed by several leading pharmaceutical companies are clinically approved for the treatment of various cancers, extending the progression-free survival for patients in 73 countries. The PARP inhibitor, Lynparza®, developed by AstraZeneca has generated £1.2 bilion in sales since 2017.

2. Underpinning research

In 2005, Dr Bryant and Prof Helleday’s research group discovered that cells that had a loss of function in the BRCA2 gene were susceptible to inhibitors of poly(ADP-ribose) polymerase (PARP) leading to cell death [R1]. PARP and BRCA are DNA repair enzymes that are key to maintaining a cancer cell’s viability. The team proposed that cancer cells are dependent upon two DNA repair pathways in order to continue to replicate and grow leading to tumours. One pathway requires the PARP enzyme and the second depends upon BRCA2 with the pathways allowing redundancy in case one of the pathways fails. In cancer cells, if one of the pathways is lost, the other will still maintain the cancer’s survival but if both pathways are lost, the cell will die. By treating BRCA-deficient cells with PARP inhibitors, the cells will apoptose through a process known as synthetic lethality.

The team at University of Sheffield developed the idea of PARP inhibitors as a therapeutic agent in patients with BRCA2 mutations. In the research referenced, a mouse model was used to demonstrate that BRCA2-deficient tumour cell growth was suppressed by PARP inhibition whilst cells that contained a working copy of the BRCA2 gene were unaffected [R1]. This is the first evidence of synthetic lethality as a therapeutic agent.

Based on these findings, the University of Sheffield filed a patent application in July 2003 for the use of PARP inhibitors as a targeted therapy for tumours in individuals with BRCA2 mutations [R2]. The patent has been granted in numerous countries, alongside the publication of the research in Nature [R1] . The patents were licensed to KUDOS therapeutics who, with researchers at Newcastle University and King's College London, developed Olaparib and were acquired by AstraZeneca in 2006.

The paper published by Bryant and Helleday was highlighted in 2020 by Nature Milestones as a milestone in cancer research for personalised therapeutics. This work has instigated an entirely new field of research into the PARP pathway and how to utilise the mechanism for further drug discovery for treatment of other conditions. Tailored therapies, such as PARP inhibitors, have now been produced based upon genetic testing so cancers developed in these patients can be treated.

3. References to the research

University of Sheffield researchers are indicated in bold.

Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N. J., & Helleday, T. (2005). Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature, 434(7035), 913–917. https://doi.org/10.1038/nature03443

Patent: WO/2005/012524. Use of RNAi inhibiting PARP activity for the manufacture of a medicament for the treatment of cancer, The University of Sheffield and Thomas Helleday applicants. Publication date, 10.02.2005.

4. Details of the impact

Following successful phase II and III clinical trial completion using PARP inhibitor research from Sheffield, AstraZeneca was granted first in class drug status for Olaparib ( Lynparza®). Since then, the status has been applied to eighteen versions of the PARP inhibitor, four of which are directly attributed to the Sheffield Patent: Lynparza®, Niraparib, Rucaparib and Talazaparib [S1]. [Text removed for publication].

Building on those initial applications of PARP inhibitors, this work has led to a step-change in the development and accessibility of treatments for cancers with few options. In 2020 Nature Milestones cited R1 as a milestone in cancer research for personalised therapeutics [S3].

In 2014, Lynparza® became the world’s first PARP inhibitor approved for use in America and Europe [S4]. This success led to further AstraZeneca investment, launching a collaboration with MSD UK to develop treatments for additional cancers with a BRCA mutation. Lynparza® has now had positive phase III trial results in four different tumour types: pancreatic and prostate, as well as ovarian and breast [S5].

Initially indicated for the treatment of ovarian cancer, the successful trials led to Lynparza® expanding to further patient groups in 2017. It is now being prescribed by physicians in 73 countries for the treatment of multiple cancer types. This has increased progression-free survival time for an additional 15,000 patients [S6].

Increased survival of cancer patients worldwide

Germline BRCA1 and BRCA2 mutations account for 72% and 69% breast cancers in women by the age of 80. The BRCA1 mutation increases this risk of ovarian cancer from 1.3% to 44%, and for BRCA2 mutations, the risk increases to 17%. BRCA mutations also increase the risk of breast cancer in men as well as increasing the risk of prostate and pancreatic cancer. Clinical trials with PARP inhibitors have shown to delay progression by an average of 3 months compared to chemotherapy [S5].

Olaparib ( Lynparza®) was approved for use in Europe (EMA) and the USA (FDA) in December 2014 and Japan in July 2018. In 2015, NICE approved the use of Olaparib and Niraparib for NHS ovarian cancer patients, who had had three or more courses of chemotherapy, through the National Cancer Drug Fund [S4].

In 2018, Olaparib became available through NHS prescription as a first-line maintenance therapy in BRCA-mutated, advanced ovarian, fallopian tube and peritoneal cancer. Olaparib also became the first FDA-approved treatment for patients with gBRCAm HER2-negative metastatic breast cancer [S4].

The phase III POLO trial explored the efficacy of Lynparza® as 1st-line maintenance monotherapy in patients with gBRCAm metastatic pancreatic cancer whose disease has not progressed on platinum-based chemotherapy. The trial determined that the median progression-free survival was significantly longer in the treatment group. POLO is the first positive phase III trial of any PARP inhibitor in a disease where there is a critical unmet medical need [S8] and has resulted in FDA approval for Lynparza® in the US for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated pancreatic cancer [S5].

The AstraZeneca sublicensing of the Sheffield patent has led to the development of PARP inhibitors from other pharmaceutical companies for use as treatment of BRCA-mutated ovarian, fallopian tube, primary peritoneal and BRCA mutated breast cancers. Niraparib (GSK) and Talazoparib (Pfizer) have been approved for use in America since 2018 and Rucaparib (Clovis Oncology) was approved for use in America and Europe in 2019 [S1].

In Europe, the use of PARP inhibitors has been extended to ovarian, fallopian tube or peritoneal cancers to delay the next cycle of platinum chemotherapy, as well as increase survival.

Economic impact

Sales of Lynparza® in the census period have continued to increase each year and have exceeded $1.2 billion in 2020 [S6]. AstraZeneca developed a strategic oncology collaboration with Merck (MSD UK) to expand the uses of Lynparza® to other forms of cancer [S7]. This collaboration, which involved MERCK buying 50% of Lynparza® for $8.5 billion, has achieved phase III clinical trial success in BRCA-mutated pancreatic cancer, which has the worst survival rate of all common cancers [S7]. The collaboration went on to work with Myriad Genetics Inc on their BRACAnalysis CDx test to identify BRCA mutations in patients. This test is now used in the USA and Japan to better target PARP inhibitor treatment [S7].

The sublicensed patent enabled other companies to produce PARP inhibitors for additional cancer types. Tesaro’s agreement with AstraZeneca contributed to the development of Niraparib launched in 2016 for the treatment of ovarian, fallopian tube and primary peritoneal cancers [S8]. In January 2019, GSK bought Tesaro, for $5.1 billion, to strengthen their commercial oncology capability [S8].

The Sheffield group was recognised by Universities UK as one of the 2019 Nation’s Lifesavers – the top 100 individuals or groups based in universities whose work is saving lives and making a life-changing difference to health and wellbeing [S9].

5. Sources to corroborate the impact

Current drug approvals report: table documenting current drug approvals.

[Text removed for publication].

Nature Milestones 2005 cited R1 as a milestone in cancer research for personalised therapeutics ( https://www.nature.com/immersive/d42859-020-00083-8/index.html).

Regulatory approvals: UK NICE Guidance (TA598), Aug 2019 ( https://www.nice.org.uk/guidance/ta598); USA FDA approvals for Lynparza® from Dec 2014 to May 2020 ( https://bit.ly/38yxkIu) and Europe EMA list of approval from Dec 2014 to May 2020 ( http://bit.ly/30EoVPp).

List of Lynparza® trials and results showing increased progressions free survival ( http://bit.ly/38AYhLI); SOLO Trial Results (Moore, K., et. al. (2018). Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. New England Journal of Medicine, 379(26), 2495–2505. https://doi.org/10.1056/nejmoa1810858) and POLO Trial Results (Golan, T. et. al. (2019). Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. New England Journal of Medicine, 381(4), 317–327. https://doi.org/10.1056/nejmoa1903387).

Annual report of sales for AstraZeneca which contains Lynparza® sales to Q3 2020 ( https://www.astrazeneca.com/content/dam/az/PDF/2020/q3/Year-to-date_and_Q3_2020_results_announcement.pdf).

AstraZeneca and Merch (MSD UK) with Myiad sponsored the POLO trial and BRACAnalysis CDx testing to be used in selecting patients for treatment ( http://bit.ly/30EpwAD and http://bit.ly/2OsjwIL).

GSK acquisition of Tesaro statements: GSK Press release about buying Tesaro ( http://bit.ly/3rWd8rX). Statement around the licensing agreement and payment conditions with AstraZeneca, p.87 under technology licenses ( http://ir.tesarobio.com/node/10061/html).

Universities UK, ‘The ‘Nation’s Lifesavers’ – The exceptional 100 keeping us healthy’ ( https://www.universitiesuk.ac.uk/news/Pages/the-nations-lifesavers.aspx).

Submitting institution
The University of Sheffield
Unit of assessment
3 - Allied Health Professions, Dentistry, Nursing and Pharmacy
Summary impact type
Health
Is this case study continued from a case study submitted in 2014?
No

1. Summary of the impact

In the UK and internationally, demand for ambulance services, subsequent emergency department attendances, and hospital admissions is unsustainable for health economies. Between 2003 and 2013, Sheffield researchers evaluated the ability of new professional roles, Advanced Paramedic Practitioners (APPs) or Emergency Care Practitioners (ECPs), to reduce pressure on this system without compromising patient outcomes. The research is the only evidence underpinning National Institute for Health and Care Excellence (NICE) guidelines recommending the use of APPs and ECPs in urgent and emergency care settings and has been widely cited in key policy documents. The numbers of advanced paramedics employed by English ambulance services in 2014-2020 has increased from 600 to over 2,500. In that period, conveyance to the emergency department has reduced by over half a million patients, resulting in a conservative cost saving in NHS hospital care alone of over £50 million.

2. Underpinning research

The School of Health and Related Research (ScHARR) programme of research evaluated the impact on quality of care and costs of allied health professionals (primarily paramedics) working in extended or new roles as either Advanced Paramedic Practitioners (APPs) or Emergency Care Practitioners (ECPs) in urgent and emergency care settings between 2003 and 2013. ECP/APP are usually from a paramedic or nursing background and receive enhanced clinical training to operate as autonomous practitioners in a range of urgent and emergency care settings (such as ambulance, urgent care centres). The ECP/APP role is to improve the patient experience and journey by either discharging patients at scene or referring onward to the most appropriate service. The role aims to reduce unnecessary transfers to the emergency department (ED) or emergency admissions to hospital.

First, researchers evaluated the role of APPs developed and trained in Sheffield with extended skills in assessing and managing acute illness or injury in the elderly [R1, R2]. Between 2002 and 2005 a randomised trial (funded by the Health Foundation) was undertaken to determine the impact of ‘paramedic practitioners’ (PP) on the care of older people with minor illness or injuries who called 999 for help.

  • In the trial of 3,018 patients, PPs significantly reduced patient transfers to the Emergency Department (ED) by 24.9% and hospital admissions by 6.1% [R1] when compared with usual care. The service presented a cost saving of £150 per patient [R2] and operated safely, with very high levels of satisfaction for patients [R3].

A second study evaluated the impact of ECPs on patient care pathways. This was a controlled observational study undertaken in three NHS areas employing ECPs, funded by the Changing Workforce Programme of the Department of Health.

  • Comparative data on patients seen by both ECPs and usual providers in the three sites showed 54% of patients having contact with ECPs did not require onward referral to other services. The mean cost per ECP patient contact was £24 when compared with £55 for an ED contact. When compared with usual providers in these health settings, ECPs undertook significantly fewer investigations, provided more treatments, discharged more patients, and had higher levels of patient satisfaction [R4].

Following this, a multi-centre controlled trial funded by the National Institute for Health Research HS&DR Programme (2005-2008) was undertaken comparing patient care provided by ECPs working in a range of clinical settings with standard care in those services such as ambulance, GP out of hours services, walk-in centres, and urgent care centres.

  • The trial included 5,525 patient outcomes. ECPs significantly reduced onward referral to acute hospital services compared with their standard provider counterparts. This was especially the case when they provided a mobile service to the patient (e.g. ambulance services), were targeted at the elderly population and when ECPs operated at a higher level of skill than their counterparts (e.g. ECP vs paramedic) did [R5].

  • A related safety study found comparable quality or safety of care provided by ECPs when compared with their standard care provider counterparts [R6].

The research outlined above demonstrated that allied health professionals (primarily paramedics) working in extended or new roles as either APPs or ECPs were effective, cost effective, safe, and acceptable to patients.

3. References to the research

Mason, S., Knowles, E., Colwell, B., Dixon, S., Wardrope, J., Gorringe, R., Snooks, H., Perrin, J., & Nicholl, J. (2007). Effectiveness of paramedic practitioners in attending 999 calls from elderly people in the community: cluster randomised controlled trial. BMJ, 335(7626), 919. https://doi.org/10.1136/bmj.39343.649097.55

Dixon, S., Mason, S., Knowles, E., Colwell, B., Wardrope, J., Snooks, H., Gorringe, R., Perrin, J., & Nicholl, J. (2009). Is it cost effective to introduce paramedic practitioners for older people to the ambulance service? Results of a cluster randomised controlled trial. Emergency Medicine Journal, 26(6), 446–451. https://doi.org/10.1136/emj.2008.061424

Mason, S., Knowles, E., Freeman, J., & Snooks, H. (2008). Safety of Paramedics with Extended Skills. Academic Emergency Medicine, 15(7), 607–612. https://doi.org/10.1111/j.1553-2712.2008.00156.x

Mason, S., O’Keeffe, C., Coleman, P., Edlin, R., & Nicholl, J. (2007). Effectiveness of emergency care practitioners working within existing emergency service models of care. Emergency Medicine Journal, 24(4), 239–243. https://doi.org/10.1136/emj.2006.035782

Mason, S., O’Keeffe, C., Knowles, E., Bradburn, M., Campbell, M., Coleman, P., Stride, C., O’Hara, R., Rick, J., & Patterson, M. (2011). A pragmatic quasi-experimental multi-site community intervention trial evaluating the impact of Emergency Care Practitioners in different UK health settings on patient pathways (NEECaP Trial). Emergency Medicine Journal, 29(1), 47–53. https://doi.org/10.1136/emj.2010.103572

O’Hara, R., O’Keeffe, C., Mason, S., Coster, J. E., & Hutchinson, A. (2012). Quality and safety of care provided by emergency care practitioners. Emergency Medicine Journal, 29(4), 327–332. https://doi.org/10.1136/emj.2010.104190

4. Details of the impact

The landscape of the emergency care workforce has changed in the UK over the past 15-20 years due to the knowledge and evidence produced by ScHARR. Our research has resulted in substantial changes to national and international guidance, policy, and practice. This has produced cost savings to the NHS as a whole and benefits to patients themselves from the reduction in unnecessary journeys to hospital and care provided at home.

Changes to policy and guidance

In 2018 the NICE issued new guidance on service delivery and organisation for emergency and acute medical care in over 16s [S1], with the aim of reducing inappropriate visits to emergency departments (ED) and reducing hospital admissions. A recommendation within the guidance was to, “ Provide specialist and advanced paramedic practitioners who have extended training in assessing and treating people with medical emergencies.” This guidance was based exclusively on evidence referenced directly from the clinical and cost effectiveness research undertaken in ScHARR [R1-R4].

A number of key national policy documents have also referenced the ScHARR ECP/APP research [S2-S4]. The NHS England Urgent and Emergency Care (UEC) Review Team Report (S2) recommended the PP role for undertaking acute home visits, referencing [R1]. A Nuffield Report into UEC interventions [S3] found the PP role to be the intervention supported by the strongest evidence, referencing R2. Similarly, a Health Foundation Report [S4] recommended that developing new roles (including ECPs) represented a potential ‘best bet’ intervention to have a meaningful impact on ED attendances and hospital admissions, citing [R4]. Further to this, a House of Commons Health Committee report on winter Accident & Emergency (A&E) pressure [S5] recommended using extended paramedic roles to avoid unnecessary transport to the emergency department to reduce A&E attendances cited [R1 and R4].

Changes to practice

Growth in APP/ECP roles

The development of APP/ECP roles nationally started as a pilot in the South Yorkshire Ambulance Service, Sheffield. ScHARR was instrumental in assisting with the delivery of training and education to the first PPs in Sheffield. It then conducted the first study evaluating the impact of the role as an RCT [R1]. The role was then gradually rolled out across the country, and ScHARR provided more research that evaluated the role during this period [R4, R5]. Since then, there has been a considerable growth in numbers of paramedics employed by English ambulance services in advanced roles between 2014 and 2020, shown in figure 1. Since publication of the NICE guidance in 2018, underpinned by [R1-R4], there has been a particularly steep rise in the numbers of APPs.

Embedded image

Source: NHS Hospital & Community Health Service (HCHS) monthly workforce statistics, NHS Digital

Reduced conveyance to hospital

Alongside this growth in employment of APPs in England between 2014-2020, the numbers and proportions of ambulance patients not conveyed to ED (either seen and treated at scene or referred/transported to a non-hospital provider) has increased. In 2014, 2,279,815 (32.5%) of ambulance 999 calls were not conveyed to ED and by 2019-20 this had increased to 3,165,547 calls (39%). The impact of APPs on improved non-conveyance is supported by evidence from a recent National Institute for Health Research (NIHR) report [S6] examining variation in ambulance non-conveyance in England, which found overall non-conveyance rates varied between 23% and 51%, with the variation in part explained by the percentage of calls attended by advanced paramedics.

Potential cost savings by reduced conveyance to hospital

If conveyance rates to ED had remained at 2013-2014 levels (32.5%), an additional 551,558 ED attendances would have occurred in 2019-20. Based on 2018-2019 costs (latest available), an ED attendance for less acute cases (i.e. 'No Investigation with No Significant Treatment and Not Admitted') was £93 per attendance, equating to a conservative cost saving to the NHS of £51.3 million (for the ED attendance alone). Further cost savings would also include those saved by reduced ambulance transport to hospital and reduced hospital admissions for some cases. Based on updating our cost analysis [R2] to 2019 prices, we estimated a cost saving of £193 per patient, taking into account savings to the ambulance service and all hospital costs. Applying this cost to the reduced ED conveyances figure equates to a saving of over £100 million.

Changes to practice internationally

The work of the Sheffield clinical/academic team has influenced the establishment of similar schemes internationally. The cost effectiveness evidence from R2 has been cited by an Australian report on expanding the role of paramedics in minor injury and illness, funded by Health Workforce Australia (HWA) [S7].

5. Sources to corroborate the impact

NICE Guidance NG94. Emergency and Acute Medical Care in over 16s: Service Delivery and Organisation. Chapter 3: Paramedics with enhanced competencies. March 2018. https://www.nice.org.uk/guidance/ng94.

NHS England UEC Review Team and ECIST. Transforming urgent and emergency care services in England Safer, faster, better: good practice in delivering urgent and emergency care A guide for local health and social care communities. NHS England 2015 ( https://www.england.nhs.uk/wp-content/uploads/2015/06/trans-uec.pdf). Recommended the PP role for undertaking acute home visits (p.33), referencing the PPOPS study (R1) p.54.

Imison, C., Curry, N., Holder, H., Castle-Clarke, S., Nimmons, D., Appleby, J.,Thorlby, R., Lombardo, S. (2017). Shifting the balance of care: great expectations. Research report. Nuffield Trust ( https://bit.ly/38R8Zhi). PP role to be supported by the strongest evidence referencing R2 (Box 5, p48).

Molloy, A., Martin,S., Gardner, T., Leatherman (2016). A clear road ahead. Creating a coherent quality strategy for the English NHS. The Health Foundation ( https://www.health.org.uk/publications/a-clear-road-ahead). New roles (including ECPs) represented a potential ‘best bet’ intervention to have a meaningful impact on ED attendances and hospital admissions (see citing of R4 (p.38) and ECP recommendation under ‘Creating and developing new roles in the workforce to improve quality’ (p.67).

House of Commons Health Committee. Winter pressure in accident and emergency departments Third Report of Session 2016–17 Report ( https://publications.parliament.uk/pa/cm201617/cmselect/cmhealth/277/277.pdf). Cited evidence from two ScHARR publications (R1, R4), see ‘The Ambulance Service: Potential of paramedics’, p.31.

O’Cathain, A., Knowles, E, Bishop-Edwards, L. et al. (2018). Understanding variation in ambulance service non-conveyance rates: a mixed methods study. Health Services and Delivery Research, 6(19). 1-192. http://eprints.whiterose.ac.uk/132286/. Figures on non-conveyance variation (p.15 Fig 4). For significant effect of APP on non-conveyance (p.48) examining staff skill mix and non-conveyance.

Thompson, C., et. al. (2014). HWA Expanded Scopes of Practice Program Evaluation: Extending the Role of Paramedics Sub-Project Final Report. Centre for Health Service Development, Australian Health Services Research Institute, University of Wollongong. ( https://bit.ly/2QiJjnl). Supporting evidence of cost effectiveness from R2. P61, para 5.

Submitting institution
The University of Sheffield
Unit of assessment
3 - Allied Health Professions, Dentistry, Nursing and Pharmacy
Summary impact type
Health
Is this case study continued from a case study submitted in 2014?
No

1. Summary of the impact

Heart failure affects 26 million people worldwide, resulting in significant morbidity/mortality and health economic costs. Based on Sheffield research, Endotronix developed and brought to market the innovative CordellaTM Heart Failure System. This system permits daily, remote monitoring of pulmonary artery pressure and disease status to inform clinical decision-making and reduce hospitalisation, underpinning commercial and health impacts. Over 50 patients have been implanted with Cordella sensors in clinical trials, and over 200 patients use the CordellaTM Heart Failure System daily. Since 2016, the research has improved human health and underpinned commerce, involving more than $100 million in direct foreign investment and the creation of 70 FTE jobs.

2. Underpinning research

Background

Heart failure affects 26 million people worldwide and accounts for 1 million inpatient bed days per year (2% of the NHS total) and 5% of emergency medical admissions, costing ~£2 billion (2% of the total NHS budget). Optimisation of medical therapy requires careful alterations in medications based on patient symptoms and key physiological parameters that are typically measured in a hospital setting. With commercial collaborators, Rothman and Swift conducted research to design and develop a novel heart failure management system that enables remote continuous monitoring of key physiological parameters; a central part of the research was the design of a sensor implanted in the pulmonary artery that wirelessly transmits arterial pressure measurements to a reader device held on the patient's chest (Figure 1).

Procedure and Device Development: Proof-of-concept

Rothman developed acute [R1] and chronic [R2] models of increased pulmonary artery pressure and heart failure in large animals to demonstrate the safety and accuracy of the pressure monitor and to develop techniques to be used to implant the device in patients. [Text removed for publication] using these models, it was demonstrated, for the first time, the safe delivery of the pressure monitor to the desired implant location, device stability at the implant location, accurate measurement of pulmonary artery pressure over a range observed in patients, stability and accuracy of the readings over prolonged time periods, and safe interactions of the device with tissue at the implantation site (at a histological level) [R3]. [Text removed for publication] the development of a technique that facilitated percutaneous catheterisation lab-based implantation that critically contributed to securing funding and conducting the first-in-human study (the SIRONA study [R4]).

Embedded image Procedure and device development: Imaging the pulmonary arteries

The size and shape of the pulmonary artery in humans are not uniform. To ensure that a single pulmonary artery pressure sensor would be appropriately sized for the majority of patients, it was necessary to understand the relevant 3-D anatomy in a representative population. Based on research by Swift [R5], 3-D reconstructions of pulmonary arteries were made from a cohort of patients with heart failure from the UK (Sheffield) and the USA to evaluate the size distribution of the pulmonary arteries at the site of implant. Based on this work, the device anchors were sized in advance of the first-in-human study. For each patient enrolled the pulmonary arteries were reconstructed to identify the implant zone, optimise angiographic views and to measure vessel diameter and length and distance from the implant site to the location of the reader (Figure 2). This pre-procedure planning ensured device compatibility, readability and procedural safety.

Embedded image

Figure 2: A - 3-D reconstruction of the pulmonary arteries of a patient with heart failure. Labels 1 to 5 represent angulated planes for measurement of size and curvature of the pressure monitor implant site. Multiple scans were analysed for determination of population mean and variance to size the pressure monitor. B-D – CT scans from individual patients enrolled in SIRONA were reconstructed to determine implant site dimensions (B), distal wire/catheter capacity (C) and reader area (D).

Procedure and device development: design iteration

Rothman led the first-in-human study undertaken at independent centres with staff without experience of interventional pulmonary procedures. [Text removed for publication]. In proctoring cases, Dr Rothman was scrubbed in the catheterisation lab when all implantations were undertaken, advising and training operators for independent implantation.

Two specific changes were made based on the anatomical [R5] and cath lab-based research [R3, R4]: 1- A change of nitinol anchors was made during the study to accommodate a broader range of patient and vessel sizes and to improve stability of the device. The imaging and 3-D reconstruction of the pulmonary arteries [R5] enabled iteration of the device, lengthening and angulating the distal anchor to stabilize the device on the inferior‐posterior inflection of the pulmonary artery (Figure 3). 2- A device adjustment was initiated to make radio-opaque markers on the sensor asymmetric allowing the implanting physician to check orientation quickly (the Embedded image device must face forward) and accurately during the procedure (Figure 3).

3. References to the research

Rothman, A. M. K., Arnold, N. D., Chang, W., Watson, O., Swift, A. J., Condliffe, R., Elliot, C. A., Kiely, D. G., Suvarna, S. K., Gunn, J., & Lawrie, A. (2015). Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension. Circulation: Cardiovascular Interventions, 8(11), e002569. https://doi.org/10.1161/circinterventions.115.002569

Zhou, L., Zhang, J., Jiang, X.-M., Xie, D.-J., Wang, J.-S., Li, L., Li, B., Wang, Z.-M., Rothman, A. M. K., Lawrie, A., & Chen, S.-L. (2015). Pulmonary Artery Denervation Attenuates Pulmonary Arterial Remodeling in Dogs With Pulmonary Arterial Hypertension Induced by Dehydrogenized Monocrotaline. JACC: Cardiovascular Interventions, 8(15), 2013–2023. https://doi.org/10.1016/j.jcin.2015.09.015

Rothman, A. M. K., Arnold, N. D., Abou-Hanna, J., Forouzan, O., Swift, A. J., Dahaghin, P., Konganige, S., Middleton, J. T., Zafar, H., Suvarna, S. K., Kiely, D. G., & Gunn, J. (2020). Feasibility and safety of a telemetric pulmonary artery pressure monitoring system in acute and chronic porcine models of pulmonary hypertension. Preprint. https://doi.org/10.1101/2020.12.27.424411

Mullens, W., Sharif, F., Dupont, M., Rothman, A. M. K., & Wijns, W. (2020). Digital health care solution for proactive heart failure management with the Cordella Heart Failure System: results of the SIRONA first‐in‐human study. European Journal of Heart Failure, 22(10), 1912–1919. https://doi.org/10.1002/ejhf.1870

Swift, A. J., Dwivedi, K., Johns, C., Garg, P., Chin, M., Currie, B. J., Rothman, A. M. K., Capener, D., Shahin, Y., Elliot, C. A., Charalampopolous, T., Sabroe, I., Rajaram, S., Hill, C., Wild, J. M., Condliffe, R., & Kiely, D. G. (2020). Diagnostic accuracy of CT pulmonary angiography in suspected pulmonary hypertension. European Radiology, 30(9), 4918–4929. https://doi.org/10.1007/s00330-020-06846-1

4. Details of the impact

University of Sheffield research led by Rothman and Swift, in part under a consulting contract with Endotronix [S1], provided crucial data and played an integral role in the development of the CordellaTM Heart Failure System, the sole product made by Endotronix [S2]. Endotronix brought this digital health platform product to the clinic, and became commercially available in Europe and the U.S. in 2020. The system assists clinicians in remote medical management of patients, allowing continuous monitoring of key physiological parameters and the observation of increases in pulmonary artery pressure up to 30 days prior to disease worsening and/or hospitalisation, contributing to reduced hospitalisation rates and health costs.

The Sheffield research contributed critical evidence that led directly to financing of $32 million in July 2016 and $12 million in Jan 2017 and that was used in a further funding round raising $45 million in September 2018 [S2 and Figure 4].

Impact on commerce

The pre-clinical and clinical research carried out at Sheffield [R3, R4, R5] has been used to secure investment income of $102 million since 2016 (foreign direct investment) and $12 million in loans to develop the Endotronix Cordella Heart TM Failure System (the only product made by Endotronix) [S2]. Endotronix has made commercial sales in the USA, with Medicare and Medicaid reimbursement priced at [Text removed for publication]. As of July 2020, 50 patients had been implanted with the pulmonary artery pressure sensor with over 200 established on the online accessible care platform. The activities undertaken by Endotronix have led to the creation of 70 FTE positions within the company in the current REF period [S2].

Impact on health

As of July 2020, 50 patients had been implanted with the Cordella Sensor in clinical trials, including a European-based CE-marked study and a US-based FDA investigational device exemption study. Rothman led implantation training for all sites, personally training and supervising (scrubbed in) at all sites [S2, S3]. [Text removed for publication].

As well as daily physiological monitoring with the ability to set individual patient goals, the Cordella TM Heart Failure System offers easy patient communication with the care team and provides guideline-directed education tools to engage and empower patients in the management of their disease. Based on patient feedback on Cordella, 87% of patients believe their health has improved since using the system, and 100% feel more connected to the clinical care team [S4]. Daily readings take <5 min, and 93% of patients say the system is easy to set up and easy to use on a daily basis [S4].

Based on his expertise in remote monitoring developed through the research [R4], Rothman led the development of a clinical service within the National Pulmonary Hypertension Service at the Royal Hallamshire Hospital in Sheffield. The service allows remote care to be provided for 60 patients, with pulmonary artery pressure monitors, insertable cardiac monitors, and remote monitoring systems, including the Cordella TM Heart Failure System [S4]. The service facilitates remote care for patients, reducing the requirement for repeated hospital visits and increasing the number of therapeutic changes made. For example, in data collected from the clinical service, the number of therapeutic changes made in the 12 months preceding device implantation was 10 increasing to 68 in the 12 months following implantation. Along with this, the number of disease-related hospitalisation events decreased from 21 before device implantation to 4 events in the post-implantation period [S5]. Daily remote data have permitted the optimisation of therapy without the need for repeated hospital visits, which has been of immense importance during the altered working practices due to the COVID-19 pandemic. High-risk patients with complex disease have been implanted with devices, with initiation of treatment prior to early discharge coupled with remote data-driven therapeutic escalation from their own homes. This approach has reduced time in hospital and improved the patient experience, increasing patient-expert physician contact and providing evidence-driven therapy in a manner not previously possible [S5].

Embedded image Figure 4: Summary timeline of Endotronix product development [S6]

5. Sources to corroborate the impact

The University of Sheffield consulting contract number 5412.

Letter of support from the Endotronix CEO and founder confirming investment income, provision of crucial underpinning research (historic and ongoing scientific advisory board position) and number of jobs created.

Endotronix training and case review implant documents.

Endotronix usage, usability, and care data ( https://endotronix.com/heart-failure-management/).

Letter of support from the head of the Sheffield Pulmonary Vascular Disease Unit.

Scrollable timeline of Endotronix product development ( https://endotronix.com/about-endotronix/).

Submitting institution
The University of Sheffield
Unit of assessment
3 - Allied Health Professions, Dentistry, Nursing and Pharmacy
Summary impact type
Health
Is this case study continued from a case study submitted in 2014?
No

1. Summary of the impact

Fear of the dentist is common, affecting 30% of children in the UK and worldwide. Traditional approaches such as admission to hospital for general anaesthesia (GA) or sedation do not reduce child dental anxiety and are costly to the NHS. In response to this challenge, our research has transformed dental services provided for children with dental anxiety by developing a new low-intensity psychological intervention. This intervention has been adopted widely throughout the UK with benefits for dental services (improved attendance, reduced use of GA/sedation) plus improved outcomes for children and parents of reduced dental anxiety and better communication.

2. Underpinning research

Fear of the dentist is common, affecting 30% of children in the UK and worldwide. Children with dental anxiety experience unpleasant thoughts, feelings and symptoms and have more decayed and extracted teeth with worse quality of life than children without dental anxiety. The impacts of child dental anxiety are far reaching, causing upset for families, stress to dental professionals, and NHS costs. NHS costs include the cost of traditional approaches to managing child dental anxiety such as admission to hospital for general anaesthetics (GA) or sedation (approximately £700 per patient) plus the cost of missed appointments (approximately £157 per lost appointment) due to avoidance. In addition, these traditional approaches do nothing to reduce child dental anxiety in the short- or long-term resulting in dental anxiety being maintained into adulthood.

In 2012 Marshman and Baker from the University of Sheffield found a lack of psychological support available for dentally anxious patients and revealed that dental professionals struggle to manage them with limited resources and training available [R1]. Rodd and Marshman established that psychological interventions such as cognitive behavioural therapy (CBT) should be used to reduce dental anxiety in children [R2]. The review identified barriers to psychological interventions including the lack of psychologist-led services for children with dental anxiety and dental professionals reluctance to undergo lengthy training to deliver psychological interventions [R2]. CBT is a talking therapy which requires patients and professionals to work together to tackle the patient's problems. Differing intensities of CBT have been developed from low-intensity ‘self-help’ approaches to higher intensity psychologist-led therapies.

The research team in Sheffield developed the first ever low-intensity CBT intervention for dental professionals to use with children and their parents [R3]. In 2014, the initial stage involved child patients and their parents to explore their experiences of dental anxiety [R4] and provided unique insights not previously described. From these insights the intervention ‘Your teeth you are in control’ was developed in 2015 using a ‘person-based’ approach (involving children, parents, professionals, and Patient/Public Involvement (PPI) representatives) based on the Five Areas model of CBT. The intervention involved children and dental professionals working through a series of CBT-based activities together to change children's unhelpful thoughts (e.g. 'something will go wrong'), behaviours (e.g. cancelling appointments), physical symptoms (e.g. sweating), feelings (e.g. embarrassment, anger) and situational factors (e.g. poor patient-dentist communication) that maintain dental anxiety. One activity children suggested which was incorporated into the intervention was a ‘message to dentist’ children write to communicate with the dental professional.

In 2016 we evaluated the use of the intervention with 48 patients from two dental settings (one dental hospital and one community dental clinic) and found 86% engaged with the intervention which reduced child dental anxiety in 95% of patients, with a significant, large reduction in dental anxiety and improvement in quality of life. The intervention was acceptable to children, parents, and dental professionals (n=25) [R4]. Based on the findings, resources were developed by the research team for parents and dental professionals including an online training package.

The research was principally funded by the National Institute for Health Research.

3. References to the research

Sheffield researchers in bold.

Porritt, J, Baker, S, & Marshman, Z (2012). A service evaluation of patient pathways and care experiences of dentally anxious adult patients. Community Dental Health Journal, 29(3):198-202. https://doi.org/10.1922/CDH_2761Porritt05

Porritt, J, Marshman, Z & Rodd, H (2012). Understanding children's dental anxiety and psychological approaches to its reduction. International Journal of Paediatric Dentistry, 22(6), 397-405. https://doi.org/10.1111/j.1365-263X.2011.01208.x

Porritt, J., Rodd, H., Morgan, A., Williams, C., Gupta, E., Kirby, J., Creswell, C., Newton, T., Stevens, K., Baker, S., Prasad, S., & Marshman, Z. (2016). Development and Testing of a Cognitive Behavioral Therapy Resource for Children’s Dental Anxiety. JDR Clinical & Translational Research, 2(1), 23–37. https://doi.org/10.1177/2380084416673798

Morgan, A. G., Rodd, H. D., Porritt, J. M., Baker, S. R., Creswell, C., Newton, T., Williams, C., & Marshman, Z. (2016). Children’s experiences of dental anxiety. International Journal of Paediatric Dentistry, 27(2), 87–97. https://doi.org/10.1111/ipd.12238

Funding

National Institute for Health Research (NIHR). 'Development of a guided self-help Cognitive Behavioural Therapy resource for the reduction of dental anxiety in young people'. Research for Patient Benefit (RfPB) Programme. Grant Reference Number PB-PG-1111-26029. 2013-2015 £230,578 Principal Investigator: Marshman.

4. Details of the impact

The Sheffield research has resulted in changes to the way dental services across the UK treat child patients with dental anxiety. This research led to the creation of a low intensity CBT intervention, ‘Your teeth you are in control’, resulting in improvements in children’s health and wellbeing including reduced dental anxiety in the short- and long-term following use of the intervention. These impacts have been realised through the adoption of this intervention by community dental services, dental hospitals and dental practices and has transformed the way they provide dental care for children with dental anxiety.

Benefits for dental services and dental professionals

The benefits to dental services are patient-related and financial, including improved attendance rates, reduced demand for GA and sedation services, reduced need for referrals to secondary care and improved patient experiences and outcomes [S1]. A service evaluation found improved attendance when the full intervention was delivered. There was a reduction in the number of children not being taken to their follow-up appointments (the ‘was not brought’ (WNB) rate) of 10% with the intervention compared to 26% without the intervention. When a brief version of the intervention was delivered to all new patients the WNB rate for new patient appointments fell by 4% [S2]. Each patient assessment appointment missed costs the NHS £157. There was also a reduction in GA uptake (80% of the patients were referred for a GA, but only 15% required it). This is important as a GA brings with it risks of morbidity, mortality, distress for the child and their family plus they do not reduce dental anxiety long-term and are costly to the NHS [S2].

Benefits of the intervention for dental professionals include improved communication with patients, understanding of children’s dental anxiety and job satisfaction [S1] as illustrated by this quote, “much better communication with the anxious child. It develops a better sense of trust between patients and the dental team which is rewarding.”

Feedback from dental students using the intervention found it improved their patient management skills and reduced their anticipatory anxiety at treating children [S2].

Service delivery and intervention implementation

Since 2016, the team from the University of Sheffield have delivered 28 training events in the use of the intervention, mainly in the UK (by community dental services, branches of the British Society of Paediatric Dentistry (BSPD) and British Dental Association (BDA)) reaching over 1,000 dental professionals [S3]. Feedback found 90% of dental professionals who attended the training felt they would alter their clinical practice.

The contribution of this intervention to transforming the dental care for children with dental anxiety has been recognised by two endorsements. The BSPD endorsed and approved the intervention, the past President said “To have the tool available for use in clinical dental practice is empowering - for our patients and their families, and the clinical team…The name says it all – they ‘are in control” [S4] . The charity Anxiety UK has also recommended the intervention [S5].

Internationally, the team have responded to requests from paediatric dentists to collaborate to translate the intervention into nine languages [S1] for use in ten countries.

The intervention has been incorporated into the Dental Anxiety Management Pathway of NHS England Central Midlands and the number of services using it is increasing rapidly. It is being used in 18 of the 70 community dental services and 9 of the 19 dental hospitals across the UK so far. The intervention is also being incorporated into the national guidelines for health services for children and young people in Norway [S1, S6].

In addition, eight dental schools have revised their curricula to include teaching of the intervention to undergraduate and postgraduate dental students [S7]. Feedback from students using this intervention: improves their confidence in talking to children; improves their ability to assess their patient’s level of dental anxiety; provides practical tips for ways to support children and helps them anticipate problems that may occur during treatment [S7].

The intervention includes resources for children, parents, and dental professionals. These resources are available in two formats: paper-based and online. The paper-based resources are available to purchase at cost from the School of Clinical Dentistry online shop. There is no charge for online access.

Dental professionals, practices and services have purchased [S8]:

  • 2,465 guides for children

  • 5,140 message to dentist proformas

  • 1,835 resources for parents

  • 444 resources for dental professionals

The resources can be accessed via two websites. The first website is the dental section of the Living Life To The Full website hosted by our collaborators [S8] who are internationally recognized for their work publishing low-intensity CBT interventions. Between January 2017 and October 2020 there have been 373 registrations to this website. Subsequently, a second website, hosted by the University of Sheffield, was published providing information on research, links to the online training and direct access to the resources.

The intervention has been recognised by the following awards:

  • BDA Community Dental Service group - 1st prize for service improvement 2016.

  • British Medical Association Patient Information Award – highly commended and shortlisted for children award 2017.

  • Yorkshire & Humber Academic Health Science Network – Best Patient Driven Innovation Award 2018 [S9]

In October 2020, Professor Helen Rodd was awarded Member of the Order of the British Empire in the Queen’s belated birthday honours in recognition of her work to help children with dental anxiety in dental services throughout the UK.

Benefit to patients, parents, and the public

The main benefits for children include decreased levels of dental anxiety which were sustained following the use of the intervention. In 2017 a subsequent follow-up of 22 children after 12-18 months found 91% felt better about visiting the dentist showing the longer-term benefits [S10].

Service evaluations have been conducted in one general dental practice, two dental hospitals and three community dental services to date involving 240 child patients. The general dental practice, which is in a very deprived area of London, used the intervention with 84 children and found a statistically significant reduction in child dental anxiety [S10].

Feedback from parents as part of the service evaluations [S2] was positive with 58% reporting the brief intervention had a positive effect on their child prior to their appointment. One parent said “from start to finish the whole process of coming to the dental hospital and using the Your Teeth You Are In Control approach with my daughter has been amazing and has changed our lives”.

5. Sources to corroborate the impact

Results of an online survey of dental professionals in the UK and worldwide who are using the resources with details of use of translated versions.

Service evaluation report from Sheffield Teaching Hospital NHS Foundation Trust.

List of national and international training events with results of feedback.

Letter from the president of BSPD and press release issued when the intervention was endorsed.

Factsheet produced by Anxiety UK and the Centre for Dentistry recommending the resources.

Tannhelsetjemester tu barn o gunge – national guidelines for health services for children and young people in Norway recommending ‘Dine Tenner Du Har Kontroll’, the Norwegian version of ‘Your Teeth You Are in Control’.

Letter from the Teachers branch of British Society of Paediatric Dentistry (BSPD) recognising the contribution of the intervention to improving undergraduate and postgraduate teaching.

Purchase history and access to the intervention online - details of resources purchased and activity data on registrations and log-ins to the https://dental.llttf.com/ website and Second Website ( https://bit.ly/3suNZ7C).

Combined: Intervention Awards Certificates - BDA Community Dental Service group - 1st prize for service improvement 2016; British Medical Association Patient Information Award – highly commended and shortlisted for children award 2017 and Yorkshire & Humber Academic Health Science Network – Best Patient Driven innovation award 2018.

Published service evaluations:

Rodd, H. et. al. (2018). Children’s experiences following a CBT intervention to reduce dental anxiety: one year on. British Dental Journal, 225(3), 247–251. https://doi.org/10.1038/sj.bdj.2018.540

Bux, S., Porritt, J., & Marshman, Z. (2019). Evaluation of Self-Help Cognitive Behavioural Therapy for Children’s Dental Anxiety in General Dental Practice. Dentistry Journal, 7(2), 36. https://doi.org/10.3390/dj7020036

Rodd, H., Timms, L., Noble, F., Bux, S., Porritt, J., & Marshman, Z. (2019). ‘Message to Dentist’: Facilitating Communication with Dentally Anxious Children. Dentistry Journal, 7(3), 69. https://doi.org/10.3390/dj7030069

Submitting institution
The University of Sheffield
Unit of assessment
3 - Allied Health Professions, Dentistry, Nursing and Pharmacy
Summary impact type
Health
Is this case study continued from a case study submitted in 2014?
No

1. Summary of the impact

Cervical cancer has traditionally been detected by an invasive procedure called a colposcopy, with the test results taking weeks. Research at Sheffield on the use of non-invasive imaging led to the creation of a new hand-held device marketed as ZedScan™. This device non-invasively detects cervical cancer, allowing patients to immediate diagnoses and, if necessary, treatment. It is quick, sensitive, specific, acceptable to women and inexpensive. ZedScan™ has increased the accuracy and speed with which pre-cancerous conditions are detected and has been adopted by hospitals throughout the UK and nine other countries. Since 2018, it has been recommended by the National Institute for Health and Care Excellence (NICE) as an adjunct technique, especially in cases of low-grade abnormalities. ZedScan™ has improved patient experience, reduced overtreatment seven-fold, and reduced colposcopy costs by 24%.

2. Underpinning research

When abnormal cells are detected in the cervix, women are usually referred for a colposcopy. This is an invasive medical diagnostic procedure in which the clinician examines an illuminated, magnified view of the cervix and applies a solution (such as dilute acetic acid) to the cervix to identify where biopsies are needed. However, colposcopy has several disadvantages, including a wait time of up to 4 weeks for definitive histological results and limited diagnostic accuracy, with an estimated sensitivity of 68.5% and specificity of 75.9%.

International HP Schwan Award winner Professor Brian Brown pioneered electric impedance tomography (EIT) and worked with Professors Tidy and Sharp (Sheffield Teaching Hospitals) to develop this non-invasive imaging technology into a medical device [R1]. Research conducted by Brown’s team, funded by the NHS Emerging Technologies Scheme, showed that pre-cancerous or cancer tissues in which the tissue structure is altered, especially cervical epithelium, conduct more electricity than normal tissues [R1]. This provided the basis for the development of a non-invasive medical device [R1].

In 2003, Professor Brown and colleagues developed a next generation device that could measure the real-time electrical spectra of cervical tissue. The novel device was handheld (similar to an electric toothbrush), with electrodes at the tip of the unit (with a disposable sheath) to measure the flow of current into the cervical tissue. In 2005, Brown, Tidy and colleagues successfully tested the device in a prospective study of 87 women [R2] and patented their technology.

A prospective comparative, multicentre clinical study conducted by Brown, Tidy, and colleagues showed that since coming to market in 2013 as Zedscan™, the device has performed well against standard measures and minimises colposcopic subjectivity [R3]. The research showed that both sensitivity and specificity were significantly improved using ZedScan™ [R3]. The device was able to identify cases where immediate treatment could be carried out with a specificity of greater than 90% [R3]. A prospective cohort study by Tidy and colleagues also found that in populations with high-risk human papilloma virus (HPV) genotypes, the device, when compared to colposcopy, recognized an additional 42 cases of cervical cancer, irrespective of the risk genotype [R4].

3. References to the research

Brown, B. H., Tidy, J. A., Boston, K., Blackett, A. D., Smallwood, R. H., & Sharp, F. (2000). Relation between tissue structure and imposed electrical current flow in cervical neoplasia. The Lancet, 355(9207), 892–895. https://doi.org/10.1016/s0140-6736(99)09095-9

Brown, B. H., Milnes, P., Abdul, S., & Tidy, J. A. (2005). Detection of cervical intraepithelial neoplasia using impedance spectroscopy: a prospective study. BJOG: An International Journal of Obstetrics and Gynaecology, 112(6), 802–806. https://doi.org/10.1111/j.1471-0528.2004.00530.x

Tidy, J. A., Brown, B. H., Healey, T. J., Daayana, S., Martin, M., Prendiville, W., & Kitchener, H. C. (2013). Accuracy of detection of high‐grade cervical intraepithelial neoplasia using electrical impedance spectroscopy with colposcopy. BJOG: An International Journal of Obstetrics & Gynaecology, 120(4), 400–411. https://doi.org/10.1111/1471-0528.12096

Tidy, J. A., Lyon, R., Ellis, K., Macdonald, M., & Palmer, J. E. (2020). The impact of age and high‐risk human papillomavirus (hrHPV) status on the prevalence of high‐grade cervical intraepithelial neoplasia (CIN2+) in women with persistent hrHPV‐positive, cytology‐negative screening samples: a prospective cohort study. BJOG: An International Journal of Obstetrics & Gynaecology, 127(10), 1260–1267. https://doi.org/10.1111/1471-0528.16250

4. Details of the impact

In the UK, cervical cancer is the 14th most common cancer among women and the most common cancer in women under 35; it affects around 3,200 women every year, and incidence rates for cervical cancer are estimated to increase by 43% between 2014 and 2035. However, if diagnosed at its earliest stages, about 95% of women with cervical cancer will survive for five years or more.

Through their research, the Sheffield team developed a device that can be used as an adjunct to colposcopy to increase the chances of early detection of high-grade cervical intraepithelial neoplasia (CIN) or abnormal cell growth on the surface of the cervix. Brown founded a spin-out company, Zilico, that took the patented device to market under the name ZedScan™, which was released for worldwide distribution, ISO 13845, and CE marked in 2013. Since 2006, Zilico has grown to 12 employees and received £15m of investment, with ZedScan™ winning several innovation awards such as an HSJ Partnership Award for Medical Device or Hardware Innovation (2019) and an Excellence in Supply Award for Clinical Innovation (2018) [S1] and resulting in multiple impacts.

Increased accuracy and speed in the detection of pre-cancerous conditions

ZedScan™ offers quicker and more accurate real-time detection of pre-cancerous cells than standard colposcopy. A clinical study showed that the detection rate for women with known HPV status was higher for ZedScan™ (96.2%) than for colposcopy alone (83.4%) [S2]. Another clinical investigation found that using Zedscan™ with colposcopy increased the detection of high-grade lesions by 47.3% [S3]. The reported sensitivity of ZedScan™ with colposcopy was higher (93.3%) than that of colposcopy alone (61.3%) [S3]. ZedScan™ takes around 2 to 3 minutes to scan the cervix and display an immediate result, while colposcopy procedure takes around 15-20 minutes with a wait of up to 2 weeks for results.

Adoption of Zedscan™ across hospitals in the UK and other countries

During the impact period, forty-nine UK hospitals used ZedScanTM as an adjunct to standard colposcopy [S4] in 29,000 tests. In 2015, NICE included ZedScan™ in its guidelines and cited it as the first device of its kind to use EIT for the detection of cancerous cells. The guidelines recommended that the device be used in “assessing suspected cervical abnormalities”, especially when “standard colposcopy is subjective” [S5].

Regarding HPV screening, a clinical lead at Birmingham Women’s Hospital said ,   “I think adjuncts, particularly ZedScan™, will be very useful in helping to streamline the services […] we are going to be seeing a lot of women at the lower end of the spectrum and ZedScan™ will be able to help us be more confident in discharging women back to the community” [S4].

The lead colposcopist at NHS Grampian agreed, stating, “ Having this adjunctive technology with ZedScan™ means we can be more efficient […] For the women who have disease, we will increase the number we detect at the first visit [and] we’ll be able to offer them treatment” [S4].

The success of ZedScan™ has resulted in its adoption in nine other countries, including Australia, New Zealand, Finland, and Poland [S6]. In 2018, Zilico made a $12m royalties deal with China’s Max Health group to sell Zedscan™ to the Chinese market [S7].

Improved patient experience, increased treatment efficiency and reduced costs

As a result of the increased accuracy and speed with which pre-cancerous conditions are detected following the adoption of ZedScan™ in hospitals, women have reported a more physically comfortable procedure and reduced anxiety [S4]. One patient commented that being called back for a colposcopy left her not knowing what to expect, as she did not know what a colposcopy was and ‘googling’ colposcopy was very frightening; however, her clinician used ZedScan™: “ I was quite scared before the appointment, but I was pleasantly surprised….it was really quick actually, much better than I was expecting, I didn’t experience any pain at all” [S4]. She also reported feeling reassured that a device such as ZedScan™ could allow clinicians to obtain results with high accuracy and immediately determine where to take a biopsy if needed [S4]. The immediate results also allow patients with no evidence of disease to be quickly reassured.

In addition, ZedScan™ has had economic and clinical impacts by allowing clinicians to immediately offer the appropriate treatment to women identified as having severe abnormalities and while avoiding over-treatment. [Text removed for publication]. The use of ZedScan™ for women with CIN 2 or 3 (on a cervical cancer grading scale, where 1 is low and 4 is high) has reduced rates of over-treatment by seven-fold and reduced the number of follow-up appointments needed by 50% [S8].

Increased public awareness

The studies on the use of ZedScanTM to differentiate between normal, precancerous and cancerous cervical tissue have received considerable media coverage, e.g. in short informational videos [S9], as well as in The Guardian and The Scotsman newspapers, contributing to increased public awareness of cervical cancer. Information on the design and use of the ZedScan™ has also been reported in the Express & Star, Mail on Sunday, and The Daily Mail [S10].

5. Sources to corroborate the impact

Zilico wins the Medical Device/Hardware Innovation Award. HSJ Partnership Awards 2019 ( https://www.hsj.co.uk/partnership-awards/winners-of-the-2019-hsj-partnership-awards-announced/7024698.article).

Macdonald, M. C., Brown, B. H., Lyon, R. E., Healey, T. J., Palmer, J. E., & Tidy, J. A. (2017). Influence of high risk HPV genotype on colposcopic performance: A large prospective study demonstrates improved detection of disease with ZedScan I , particularly in non-HPV 16 patients. European Journal of Obstetrics & Gynecology and Reproductive Biology, 211, 194–198. https://doi.org/10.1016/j.ejogrb.2017.02.020

Muszynski, C., Dupont, E., Vaysse, B., Lanta, S., Tidy, J., Sergent, F., & Gondry, J. (2017). The impact of using electrical impedance spectroscopy (ZedScan) on the performance of colposcopy in diagnosing high grade squamous lesions of the cervix. Journal of Gynecology Obstetrics and Human Reproduction, 46(9), 669–673. https://doi.org/10.1016/j.jogoh.2017.08.007

Evidence of the benefits of ZedScan™ for hospitals and patients - Clinician and patient videos regarding ZedScan™ and its use hospital/Trust settings:

  1. Birmingham Women’s Hospital, Consultant Obstetrician & Gynaecologist and Colposcopy Lead, (June 25, 2018) ( https://vimeo.com/276834269/)

  2. NHS Grampian, Lead Colposcopist, (13 November 2018) ( https://vimeo.com/300517362)

  3. Patient testimonial (10 July 2017) ( https://www.youtube.com/watch?v=JIZrpNtIsS8 or https://vimeo.com/224927214)

NICE. “Adjunctive colposcopy technologies for assessing suspected cervical abnormalities: The DYSIS colposcope with DYSISmap and the ZedScan™ I”, (25 April 2018) https://www.nice.org.uk/guidance/dg32/chapter/3-The-diagnostic-tests

[Text removed for publication].

PDF Webpage. Evidence of Zilico's diagnostic device moving towards Chinese and global markets and gaining registration with the Chinese Food and Drug Administration (CFDA).

Peron, M., Llewellyn, A., Moe-Byrne, T., Walker, S., Walton, M., Harden, M., Palmer, S., & Simmonds, M. (2018). Adjunctive colposcopy technologies for assessing suspected cervical abnormalities: systematic reviews and economic evaluation. Health Technology Assessment, 22(54), 1–260. https://doi.org/10.3310/hta22540

A programme made by the Association of Health Tech Industries in 2019 on the ZedScan™ device ( https://vimeo.com/369843559).

“Breakthrough test could slash the cervical cancer death toll and DOUBLE the rate of early diagnosis”, The Daily Mail (13 January 2018), https ://www .da ilymail.co.uk/health/article-5266759/Test-slash-cervical-cancer-death-toll.html

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