Impact case study database

Funders of health-related research agree that although considerable research of high value exists, loss of any research because it asks the wrong questions, is poorly designed, is not published, or the reports are unusable is unacceptable. Chalmers and Glasziou estimated in 2009 that 85% of research finding was being avoidably wasted across the biomedical research area. UoP research contributed to addressing this issue through improving or evaluating the methods to prioritise or fund research across the research system and enhancing the approaches taken in health-related research funders.

Improving healthcare policy through research prioritisation

Nasser’s research enabled The Centre for Health Communication, La Trobe University, Australia, to design their priority setting exercise, using the methods developed at UoP. The exercise was a wide-ranging consultation process to identify research/topic priorities which informed the most relevant and useful Cochrane reviews to be conducted [5.1]. One identified priority entitled “Methods of consumer involvement in developing healthcare policy and research, clinical practice guidelines and patient information material” resulted in a Cochrane review that was incorporated in five clinical guidelines in Germany and one in the UK with the National Institute of Clinical Excellence (NICE) [5.2]. These guidelines ensure that research reviews are as useful as possible to the people who need to use, or might be affected by, the research, including health policy makers, health professionals, researchers, consumers and carers, and the wider community. Nasser’s research has also been used by the UK partnership of patients, professionals and public who set the research agenda for ENT, hearing and balance conditions that was supported by ENT-UK and British Academy of Audiology. This directly influenced decisions about which high-value research should be developed and conducted to inform them about what treatments work best and how they can most effectively deliver care [5.3]. In addition, Karimkhani and Nasser’s identification of acne as a disease with a high burden that is not adequately covered by systematic reviews in the Cochrane Library led to an identification of acne treatment uncertainties via a James Lind Alliance Priority Setting Partnership [5.4].

Nasser’s research identified the need for more involvement of patients and members of the public as part of research priority exercises. This directly informed a national patient and public colorectal consumer consultation. This led to a prioritization of research topics with patients and the public in 2015 [5.5].

UoP priority setting work also shaped the WHO Guidance on Research Methods for Health and Disaster Risk Management [5.6] that informs the work of WHO and local offices. This Guidance offers practical advice about how to plan, conduct and report on a wide variety of quantitative and qualitative studies that can inform questions about policies and programs for health-related disasters and emergencies across different settings and level of resources.

Informing research funders’ policies on how to add value to research

UoP research has influenced research funders’ policies and practice to reduce avoidable waste, improve research integrity, transparency and ultimately the impact of the research they support. The research informed the shaping of the Ensuring Value in Research (EViR) funders forum and contributed to the Adding Value in Research (AViR) framework.

The National Institute for Health Research (NIHR) is the major applied health research funder in the UK focusing on research that can improve patient care. Following a presentation at the NIHR Strategy Board, Nasser’s research informed the NIHR review to understand its performance and in turn led to the identification of a number of gaps which they are now addressing [5.7]. For example, the work informed internal continual improvement programmes and resulted in changes in NIHR policy that will have an impact on the entire research community they support: Any changes or improvement in their processes can shift what research gets funded and improves patient care. Nasser’s review was also influential in the EViR forum, developing its ten guiding principles which set out the areas all funders should focus on to ensure value, reduce waste and improve transparency and integrity of research [5.8]. These guiding principles were developed by funders to implement in each of their organisations. Eleven research funders publicly endorsed these guiding principles and committed to implementing them in full:

1. Forte (Sweden)

2. Graham Boeckh Foundation (Canada)

3. Health and Care Research Wales - Welsh Government (UK)

4. Health Research Board Ireland (Ireland)

5. Marie Curie (UK)

6. Ministry of Health Salute (Italy)

7. NIHR - National Institute for Health Research (UK)

8. PCORI – Patient Centered Outcomes Research Institute (USA)

9. The Scar Free Foundation (UK)

10. Association of Dutch Health Foundations (SGF)

11. ZonMW – The Netherlands Organisation for Health Research and Development (Netherlands)

Other funding agencies who are part of the forum implemented some aspects of these principles (e.g. Canadian Institute of Health Research and the National Health and Medical Research Council, Australia).

“These principles are now changing funder policies and practices around the world. [Nasser’s work] highlighted the importance of audit and monitoring of practices and how they contribute to reducing research waste and a number of policies, and actions of the EViR forum are aligned with that conclusion.” NIHR operations director and Chair of EVIR Forum [5.8].

This subsequently resulted in funding agencies undertaking internal audits and advancing their processes and practices. Heath Board Ireland (HBI) undertook a systematic audit of their practices against potential areas of research waste to focus on areas where they could make the biggest difference. “Analysing what you and your co-authors consider to be of likely great value to ensure value in research and factors less likely to relate to the framework was helpful in the re-phrasing of research call documentation… your ongoing academic contribution to support this is very valuable for this continuous improvement”. Head of Pre-Award, HBI [5.9].

The volume of cataract surgery has increased dramatically around the world over the past 20 years and there are approximately eight million cataract operations performed each year worldwide.  Many different types of artificial intraocular lens (IOLs) have been designed to correct various aspects of vision. These lenses need to be stable as a malposition will cause a reduction of vision which, if significant, requires a secondary procedure to either get the lens into the correct position or to explant the lens and put in a new one. Buckhurst’s research solved this problem through the development and clinical implementation of novel measures that demonstrated stability and visual function post cataract surgery, which has led to commercial and patient benefits.

Food and Drug administration (FDA) approval leading to commercial benefits

There have been rapid technological advances in IOLs; however, traditional measures of visual function do not demonstrate the efficacy of these lenses. Buckhurst developed innovative methods for establishing the rotational stability and centrational stability of novel IOLs and implemented these into multicentre clinical trials. Buckhurst’s method requires specialised training and, as such, prior to the start of each study Buckhurst trained (in person) at nine hospitals across North America and Canada [5.1]. Buckhurst’s research was used to demonstrate the safety and efficacy of the toric IOLs and led to the approval of the Trualign toric and enVista toric by the Food and Drug administration (FDA) in June 2018 [5.2]. The immediate beneficiary of this was the manufacturer, Bausch and Lomb (B&L). Their Director of Medical Affairs, Dr George Lau, said “[Buckhurst’s] work demonstrated the rotational stability of our toric IOL platforms which was pivotal to the FDA approval of the Trualign toric and enVista toric IOL.” [5.3] Following FDA approval, the Trualign toric has been implanted in 53,387 eyes resulting in an income of [text removed for publication] . In addition, the enVista toric has been implanted in 79,582 eyes leading to an income of [text removed for publication]  [5.3].

Demonstrating the safety of IOLs enabling regulation compliance

To sell medical devices in the European Union (EU), companies must obtain or apply CE Marking for their product.  However, from May 2020, a new set of regulations, the European Medical Device Regulation (MDR), that governed the production and distribution of medical devices in Europe were implemented. Compliance with the regulation is mandatory for medical device companies that want to sell their products in the European marketplace. Buckhurst’s research was instrumental in demonstrating the safety of the Incise IOL and it was the basis of evidence to support the claims and benefits for B&L’s Clinical Evaluation Report, needed to maintain CE-marking [5.4]. Their Director Surgical Global Medical Devices / Clinical Evaluation Group, Dr Anne Williart said, “Buckhurst’s research was instrumental in demonstrating the safety of B&L’s lens and it was the basis of the evidence to support the “claims and benefits” for our Clinical Evaluation Report, which we required to maintain our CE-marking under the new European Medical Device Regulation.” [5.5]

Buckhurst’s European study on the Incise IOL, Biflex M IOL, and Lentis MPlus X was used to promote these lenses in Europe. His data was included in B&L’s marketing brochures [5.6, 5.7 & 5.8] and used for their launch.  B&L’s Dr Anne Williart said “Y our independent work has supported both podium presentations during main congresses at the time of the launch, publications and Akreos brochures. The continued adherence to safety regulations and marketing of the lens has enabled us to sell 190,000 of the Incise IOLs since 2015.” [5.5]

National and international patient benefits

Domestically, Buckhurst’s collaboration with University Hospital Plymouth NHS trust led to them establishing a care pathway to undertake the toric IOL implantation in patients who were due to undergo routine cataract surgery. This collaborative approach to patient care was realised in November 2016 and Buckhurst’s research was pivotal for supporting the development of the pathway and for the ongoing assessment of performance through the analysis of visual outcomes.  This has led to a direct benefit to the patients whose vision is substantially better than if they had been implanted with a standard lens. Indeed, two thirds of these patients have vision better than or equal to the driving standard without the use of spectacles. Professor Nabil Habib, Consultant Ophthalmologist, University Hospitals Plymouth NHS trust said, “more than 80 patients having been implanted with a toric IOL at our hospital. The outcomes for these patients has been exceptional.’ [5.9] Before treatment, patients often struggle to see, both with and without glasses, and the implant of the toric IOL dramatically improves their quality of life. A patient who was implanted with toric IOLs to correct for both cataract and astigmatism in 2020 said. “I now have 20 20 vision in both eyes, simply lifechanging. I have clarity, colour and definition. Just fantastic. My quality of life has improved so much… I am a massive rugby fan and watching both live and on TV is now absolutely brilliant. I can see so much more.” John, patient [5.10].

Internationally, the implantation of 130,000 B&L toric IOLs within North America and a further 190,000 in Europe has led to wide reaching, life-changing benefits to patients.

Success in basic science rarely leads to effective treatments, as those that are shown to work in controlled laboratory conditions can be worthless when studied in human beings. Hobart demonstrated that many of the PROs used to test the efficacy of treatments in controlled conditions were not fit for purpose and consequently hindered advances in basic science. His research has increased the chances of reaching the correct conclusions about the effectiveness of treatments, which influence decisions on patient care and guide future research.

PROs supporting treatment developments, licensing approvals and clinical adoption

Hobart’s research influenced FDA (U.S Food and Drug Administration) policy (last REF period). which created an increased focus from regulatory bodies on the quality of clinical outcome measures within licensing decisions. Hobart’s PROs are referenced in the FDA compendium of clinical outcome assessments, which endorsed their global position as Gold Standard measures. Consequently, they have been deployed in clinical research of MS treatments in over 85 countries [5.1].

Between 1 August 2013 and 30 November 2020, five Hobart PROs have been licensed a total of 136 times including with global pharmaceuticals such as Roche, Merck, Sanofi, Novartis and Biogen [5.1]. The importance of the PROs informing clinical research and licensing decisions is reflected by the price companies are willing to pay, with charges up to £32,000 per clinical trial license and total fees in this period of over £1.26M [5.1]. Many of the trials have been of Disease Modifying Therapies which are now core treatments; particularly in MS, an incurable chronic disease currently affecting 2.3 million people worldwide. Since 1 August 2013, Hobart’s PROs have been directly involved in the clinical trials of 36 treatments, mostly in MS but also in other areas [5.1]. The global sales value of 11 of the most widely adopted MS treatments (using just the figures available between 2013 and 2020) equates to £80 Billion [5.2]. Moreover, we have evidence that they have reached over one million patients [5.2]. Novartis MS Global Brand Medical Directors Thomas Hach and Dee Stoneman stated that ‘The scales were used because of their scientific value and recognition in the clinical and regulatory community. The evidence generated from these studies help to inform clinical opinion and ultimately allow eligible patients to benefit from these treatments… [this demonstrates] the significant impact and value of the work Professor Hobart and his team at the University of Plymouth have in the area of MS research through the development and licensing of high quality Patient Reported Outcome Measures’ [5.3]

For example, the MS medicines Lemtrada (alemtuzumab) and Aubagio (teriflunomide) demonstrate the financial value of Hobart PROs in supporting licensing and clinical adoption. Hobart PROs played a key role in developing the evidence of the clinical benefits of these medications. Lemtrada secured market authorisation in Europe on 12/09/2013 and Aubagio on 26/08/2013. Data supplied by Sanofi highlights both the patient and commercial impact of these medicines:

• Lemtrada [text removed for publication].

• Aubagio [text removed for publication].

‘The data [above] is from the Sanofi annual investor report which outlines both the patient and commercial impact of these medicines… [this] demonstrates the… value of the work [of] Professor Hobart.’ Dr Eddie Guzdar, Head of Medical Affairs for the Neurology Franchise at Sanofi Genzyme UK and Ireland [5.4]

Similarly, Biogen have used Hobart’s PROs in the clinical trials of fampridine prolonged release (Fampyra) to evaluate the effect on improvement of walking in adult patients with multiple sclerosis with walking disability. Up to April 2020, this medicine has been used in over 50 countries and has treated 386,528 people treated worldwide [5.5]. In addition, Hobart’s PROs were used in clinical phase 4 trials of Ocrelizumab to treat relapsing and progressive multiple sclerosis. Paul Byrne, Life-cycle leader Ocrevus and James Overell, Principal Global Medical Director, Neuroscience at Roche said that ‘The data… is linked to increased clinical recognition of the benefit of Ocrelizumab, especially in early MS disease and in targeting progression which is the cause of long-term disability… The rigorous scientific development of the Hobart PROs gives us and the community confidence that we are measuring what is clinically important.’ [5.6]

Advising global companies on measurement strategies and data analysis for clinical trials

Hobart’s specialist knowledge and skills in health measurement have been used to support global companies with measurement strategies and data analysis. These have informed the companies’ decision making as they develop, trial and seek to license new treatments. For example, Since 2019, Hobarts guidance to Roche shaped measurement strategies in four clinical studies in MS. [text removed for publication]. ‘Professor Hobarts expertise has been important to us as a company in informing our measurement strategies in relation to Patient Reported Outcome Measures… These clinical studies are key components in assessing the safety and efficacy of our companies [sic] treatments in MS… It is anticipated this will improve the quality of clinical research and support the development, evidence and adoption of high-quality treatments that will ultimately improve outcomes for people with MS.’ Licinio Craveiro, Senior Global Medical Director, Roche.[5.7]

In addition to licensing the PROs within clinical trials, Professor Hobart collaborates with Novartis in the analysis of PRO data and strategic projects focussed on the improvement/development of PROs. He has been contracted in projects seeking to further analyse the PRO data from clinical studies, which have a combined total of over 3500 participants, to maximise the value of interpretations. He was engaged by Novartis to be co-chair of their global Patient Relevant Outcomes Steering Committee in Multiple Sclerosis (PROMPT-MS). This strategic forum seeks to empower people living with MS to communicate relevant outcomes to healthcare practitioners in order to enable shared decision-making and ultimately improve clinical outcomes of MS. These contracts, worth £141,000, demonstrate Hobart’s position as a global leader [5.3].

Advancing Care in Multiple Sclerosis (MS)

Time to a diagnosis of MS is often protracted, delaying access to specialist healthcare advice and treatment initiation which results in physical and cognitive decline, fatigue and reduced quality of life. Hobart worked alongside MS specialist neurologists to develop internationally applicable quality standards for timely, brain health focused MS care [5.9]. These became a key component of the Brain Health Matters in MS initiative, which has been endorsed by over 50 influential groups in MS care with champions in 55 countries.

The Brain Health Time Matters project team evaluated the success of this initiative through a survey which received 100 responses from 20 countries across four continents. Due to the MS Brain Health initiative recommendations and consensus standards, 84% of respondents said that they had made changes in their practice, services and/or management of MS. The recommendations and consensus standards had:

• In the case of health care organisation, changed their practices or services.

• In the case of people with MS or their carers, influenced how they managed their MS or the MS of the person they cared for, or

• In the case of respondents from commercial or patient support organisations, influenced how they, or their company, supported the MS community.

Of respondents from Health Care Organisations, 75% identified improvements in information given to people living with MS, whilst 65% felt the initiative had improved their knowledge of preserving brain heath. People with MS who responded to the survey noted multiple benefits. 80% identified that they had improved their knowledge of preserving brain health in MS and over 50% felt that as a result of the initiative they had taken a more proactive part in managing their own disease [5.9]. Case studies highlighting Global Impact on the MS Brain Health time matters website in seven countries include a doubling of treatments used for people with MS in Serbia and a parliamentary debate agreeing to increase funding for MS research in Australia [5.10].

Our research benefits diverse stakeholder groups, including individual sports people and women ante-and post-partum with pelvic girdle dysfunction. It enhances clinical service delivery by Healthcare professionals, performance capability of sporting associations and the productivity, competitiveness and resilience of the partner SME.

Traditionally, orthotics have been made of rigid materials that do not accommodate movement. In recent years, the research team’s work has been at the forefront of the development and use of elastomeric (lycra®) fabrics, which has revolutionised the approach to these orthotics for pelvic pain management. As underlined by Martin Mathews, Chairman of DMOrthotics Ltd: “The design of our dynamic orthoses have been directly informed by the laboratory based work undertaken at University of Plymouth, and our product line expansion has been enhanced by the demonstration of clinical effectiveness in this client group” [5.1].

Impact on health, well-being and performance

Pelvic girdle dysfunction accounts for an estimated 5% of all sporting injuries. With elite athletes, pelvic girdle pain can be particularly devastating, dramatically affecting performance.

Sporting performance:

Our research has been highly influential in providing a state-of-the art product to provide stable, pain-free movement and correct alignment, enabling improvements in motor performance and function. Evidence for improvements in athletes’ performance with this innovative orthotic is highlighted by “team DMO” (i.e. DMOrthotics). These athletes hail from a range of disciplines including Track and Field, Para-cycling, Para-archery, Para-canoe and Boccia. The line-up consists of World Champions and Paralympians including Kadeena Cox, Sophia Warner, Anne Dickins, Jeanette Chippington, David Smith, Jess Stretton, Patrick Wilson, Claire Taggart and Evie Edwards. These sports related orthoses have been adopted by Sport England for multiple gold medal winning Paralympians and Olympians where the smallest changes can sometimes mean the difference between being a medal winner or not. For some, the orthotics was so effective that they broke their personal best the first time they trialled this in training [5.2].

Paralympian and double gold world champion sprinter Sophia Warner commented in 2014: “I was blown away by how effective they were when I first put them on. The strength from the reinforcement panelling was so powerful. I was astounded – it felt like this was the first thing that would really work”. Sophia’s coach Jonas Taiwah was also impressed, highlighting that “Sophia’s main problem was that she was using muscles for stability instead of power down her left side which made her inefficient. The shorts (the lycra pelvic support shorts) changed this. This vastly increased the stability in her left leg, which in turn increased her stride length, improving her power output.” [5.3]). When Sophia first started using the orthotic, her times improved by 5.3%, which was enough to win the London Disability Athletics Challenge [5.4].

Pregnancy-related pelvic pain and dysfunction

Pelvic girdle dysfunction occurs in 70% of pregnant women (350,000 women in the UK at any point in time). Of these, 15% of women suffer severe antenatal pain, which results on average, in 7 weeks off work, an increased incidence of depression and a significant reduction in quality of life. Further, 10% of all women continue to suffer severe and chronic pain following delivery, which does not respond to a wide range of other treatments. Some endure this pain for over a decade. Such pain significantly affects everyday activities such as moving in bed, walking, carrying items, driving, and caring for their child. Women with severe pelvic girdle pain have increased health risks/costs as they have a higher request for induction of labour and elective caesarean section and safety issues related to care of the baby/toddler/child.

Our randomised controlled trial shows that in pregnant women, our innovative pelvic orthotic reduces pain (as assessed by a numerical pain rating scales) by an average of 17%. The reduction in pain is even greater post-partum with an average reduction in pain of 54% (range 18-90%) and average improvement in daily function (as measured by the Pelvic Girdle Questionnaire) of 46% (range 23-62%). This is reflected by the personal experience of women. One woman, for instance, commented that “ I was really struggling with my day-to-day function as my (1 year old) *son was wanting to be picked up and carried all of the time, and I was really struggling with the constant changes in position…(*The lycra support shorts) really made a massive difference… it gave me the support in the areas that I needed it to, to remind me of the posture I should be in…. it helped tremendously with my sleep … I wore it virtually every day, all day, for a good year or so” [5.5]. Her subjective experience is supported by objective clinical outcome measures, which demonstrated a reduction in pain of 56% and an improvement in daily function of 47%. This typifies the experience of women who have begun wearing these orthotics both during pregnancy and in the early (<6 months) and late (>6 years) post-partum period (6).

Impact on commerce and the local economy

Our research has been pivotal to DMO establishing a new division to their company, DMO Sports. The expanded DMO Sport range of bespoke products, such as the patented DMO REPS™, particularly targets high-performance athletes including Paralympians and Olympians. Chairman of the DMO Ltd (UK) Board Martin Matthews commented: “The results are phenomenal and we’re extremely proud to play a part in helping such an exceptional group of athletes reach their full potential.” [5.1]

Martin Matthews further stated that “Refinement of the basic methods of applying corrective and compressive forces, derived from our collaborative research, directly led to the company modifying pre-existing items such as our scoliosis suits, and expanding our product range, the audience we target and our mode of delivery” [5.1]. For example, at the end of 2019 the Company instigated production of stock items for both the sports and pregnancy products, enabling these to be sold at a reduced cost and in greater volume. This allowed the Company to continue to trade during the Covid-19 pandemic, when assessments for bespoke products were not possible. The design principles taken from our research also translated into stock items for other conditions such as hypermobility syndromes. Further, in May 2020 the pelvic orthoses were developed into customised pregnancy leggings with a fashion slant aiming at the high-end market. Overall, these research-driven developments have helped to make the company more resilient whilst other companies no longer have a market presence in this area of dynamic orthoses.

In addition, these developments have provided the company with a competitive advantage, affording the opportunity to gain increased market penetration and sales, including those overseas (Singapore, USA, Germany) necessitating the employment of a UK and Export Sales manager [5.1]. Since 2008 whilst UoP have been working with the company, DMOrthotics have increased its workforce from 15 to 55, its number of units produced per week from 40 to 250, with an accompanying threefold increase in factory footprint. Further, Martin Matthews Chairman of DMOrthotics Ltd stated: “ I can honestly say that the research directly impacted on this growth…. since working with you we have had 8 papers and multiple conference presentations … without this I would have been fried alive if we hadn’t had data to present … the work we have done with you has contributed to about 15% of all literature in the field”([5.1] Such data and evidence of effectiveness is now mandatory for all Class 1 medical devices (EU Regulation on Medical Devices 2017/745). Our research provided the required evidence and our research training has upskilled the Company’s workforce to systematically document and submit this evidence in August 2020 [5.7].

Impact on clinical practice and service delivery

Clinical Pathways are multidisciplinary evidence-based management tools for a specific group of patients with a predictable clinical course; they directly influence care provision. They are a key tool used to manage the quality and outcomes of healthcare through reducing variability in clinical practice. Our research has raised awareness of the significance of pelvic pain in pregnancy in collaborating clinical academics (e.g. Dr Lee Cameron, Clinical Lead Specialist Physiotherapist in Orthopaedics CYMRU NHS Wales). As a direct result, in 2019 Newport NHS Trust developed and implemented a Clinical Pathway to improve the management of pelvic girdle dysfunction in women during and after pregnancy. Dr Cameron stated: “ I developed the Clinical Pathway, which exists in the Trust, for managing women with pregnancy related PGP… As a direct result, women on this pathway could begin to access the orthotic (lycra support shorts) without barriers [5.8]”.

As well as contributing to the development of Clinical Pathways, our researchers and research outputs have influenced educational programmes within the clinical NHS setting, thereby enhancing the expertise and practice of clinicians delivering patient care. This is highlighted by the following quote referring to training of physiotherapists in Wales and South West England: “The Womens’ Health Team and I (Dr Cameron) were responsible for training related to ante and post-partum PGP, and education about the orthotics (lycra support shorts) was a key element of this. This has had considerable influence as we are one of the biggest Trusts in Wales. This knowledge, in turn has extended to other Trusts through the Advanced Practitioners training... There has been excellent feedback from the training sessions, with comments such as “I never used to treat women with this pain, but the training has provided the fantastic tools to be able to manage these women more effectively” [5.8].

In addition, to extend the implementation of our research findings outside the NHS, our research team has undertaken field-based educational sessions with sports physiotherapists and sports scientists at a variety of sporting clubs and organisations including Plymouth Argyle Football Club, Bristol Rugby Football Club, Football Association at St Georges Park Football Club, Wales Women’s Football Team and Sport England. This resulted in orders of these orthoses by these clubs [5.9].