Impact case study database

Research by Ulster in folate/folic acid in 2000-2020 has been instrumental in informing policy in the health and food sectors, tackling policy implementation issues and translating the evidence into practice for health professionals and policy makers, most notably concerning the prevention of spina bifida and related NTD. These birth defects occur when there is a failure of the neural tube to close properly in very early pregnancy, with devastating and lifelong implications for sufferers, their families and society. Preventing NTD is therefore an urgent priority globally, especially in Ireland where NTD rates are among the highest in the world. The impacts are thus greatest in the Island of Ireland, but have global reach and significance. Our research has underpinned impacts in 4 areas:

Impact 1: Our research findings, showing that folic acid (in supplements and fortified food) are beneficial in achieving optimal nutritional status of folate ( R4, R5), have had significant impacts in informing health policy for women of reproductive age aimed at preventing NTD occurring during the 3^rd to 4^th week of foetal life. Notably, Ulster author Professor H McNulty was invited as one of a panel of international experts in the field to participate in the BOND project convened by the US National Institutes for Health to review folate as a priority nutrient. The outcome of the panel’s research (in 2014-2015) was an extensive report ( R3), widely considered a state-of-the-art review of all aspects of folate biology and biomarkers, and which has proven to be highly applicable for international health policy and significant to policy makers. This, and our other research outputs, have directly impacted public health policy to prevent NTDs in countries worldwide: Ireland in 2016 ( C1: R3), the UK in 2017 ( C2: R2), New Zealand in 2018 ( C3: R2, R3).

Impact 2: Our underpinning research has also informed the evidence base to support other roles for folate throughout the lifecycle from pregnancy through to older age, and thus contributed to generating dietary recommendations for folate intake within populations worldwide. Our reports of beneficial effects of folate and related B vitamins (B12, B6 and riboflavin) in reducing homocysteine concentrations ( R4, R5, R6), highlighted the potential for these vitamins to protect against diseases of ageing, such as stroke, heart disease and cognitive decline. This research has provided valuable scientific evidence required to set new dietary folate recommendations across age and sex groups for population health, directly impacting policy in this area in European countries by providing the European Food Safety Authority (EFSA) with the necessary scientific opinion on dietary reference values for folate in 2014 ( C4: R4).

Impact 3: Research at Ulster has informed the risk-benefit assessment underpinning food policy for folic acid-fortification under discussion in the UK and Ireland. Mandatory folic acid-fortification of staple foods, aimed at reducing pregnancies affected by NTD, is now in place in over 85 countries worldwide (including North America and Australia), but this policy has not yet been implemented in the UK, Ireland or elsewhere in Europe. Our papers, reporting on benefits (R1, R4, R5, R6) and potential risks (R2, R4) of this population-based intervention , have provided greater understanding of the risks and the benefits, pivotal to bringing policy discussions to a successful conclusion. Our paper reporting on a dose-finding trial, showing that the dose of folic acid required for beneficial effects was much lower than previously believed ( R4), was selected for inclusion in the American Society of Nutrition’s Best of Nutrition compilation of papers, selected by experts for “ their impact in addressing evidence-based issues of our day in food, diet and health”. Our recent randomised trial evidence ( R2) addressed a major health concern for policy makers, by showing that exposure to supplemental folic acid at recommended levels during pregnancy had no adverse metabolic effects in mothers or their babies. In this way our research outputs have informed international health and food regulatory authorities in relation to folic acid fortification policy: Ireland in 2016 ( C1: R3), the UK in 2017 ( C2: R2) and New Zealand in 2018 ( C3: R2, R3).

Impact 4: Our research was pivotal in disseminating the scientific evidence by showing how optimal folate status can be achieved in practice in patients and consumers ( R2, R4, R5), so that the necessary public health policy could be effectively implemented ( C1, C2, C3) in order to ensure that women and their families (main beneficiaries) could benefit. Notably, Professor H McNulty chaired the Folic Acid Review Committee at the Food Safety Authority of Ireland (2014-2016), the outcome of which was an extensive policy document Folic Acid and the Prevention of Birth Defects in Ireland (C1). We have also contributed to translating evidence into practice guidelines for health professionals internationally in order to ensure that the patients they care for can benefit: Position Statement from the Canadian Paediatric Society in 2016 (C5); Professional Factsheet from the National institutes for Health USA in 2019 ( C6). Finally, as a pathway to impact to reach relevant users of the research and stakeholders beyond academia , Ulster contributed invited speaker (H McNulty) presentations to translate the science for health professionals and government bodies at numerous international conferences and workshops (2014-2020), in North America, Australia and Europe, as well as in Ireland and the UK; the latter included a presentation delivered in the House of Commons in 2017, at the All‐Party Parliamentary Group on Health.

Impact 1: Setting current vitamin D requirements for populations by policymakers and risk managers

• The EU: In 2016, our studies ( R1, R2, R4) were critical to the European Food Safety Authority’s (EFSA) approach (meta-regression) to assess intake-status for deriving dietary reference values (DRVs) for vitamin D for adults under conditions of minimal vitamin D synthesis from sunlight [ C1].

• The UK: The Scientific Advisory Committee on Nutrition (SACN, 2016) used our data ( R1-R3) as underpinning evidence [ C2] to revise the DRVs for vitamin D for the UK population aged 4 years and over. The UK government cascaded this information to all health professionals for dissemination to the public in the UK [ C2].

• The German-speaking countries: The German-speaking countries (D-A-C-H, 2015) used our data to set a DRV for vitamin D in adults aged <60 years ( **R1**) and for older adults aged >60 years ( R2) [ C3].

• The Nordic countries: The Nordic Council of Ministers (2014) considered a meta-regression analysis of supplementation studies (including R1, R4) in setting requirements for adults aged <60 years and supplementation studies (including **R2**) for adults aged >60 years [ C4].

Impact 2: Use of dietary recommendations by health professionals and food manufacturers

• Global reach: The current global reach of the impact is clear in that end users (e.g. health professionals and food manufacturers) of the recommendations based on Ulster’s underpinning research ( R1-R4) reside in more than 35 territories, including the UK, the 27 EU countries, the USA, Canada, Norway and Switzerland [ C1-C4]. This impact includes prevailing recommendations set by the The Institute of Medicine (for the USA and Canada) and The Health Council of the Netherlands using our research ( R1, R2). The significance and reach of the impact relating to our research is that dietary recommendations are crucial from a public health perspective for the prevention of vitamin D deficiency and low status, with benefits to populations worldwide. The recommendations are essential public health policy instruments developed with the evidence base and data available at that time (including R1-R4).

• COVID-19: The current COVID-19 pandemic caused the National Institute for Health and Care Excellence (NICE) in June 2020 to produce a rapid evidence summary, informed by the recent review ( R6), recommending all people to follow Government recommendations (based on data from R1-R3) on vitamin D [ C5]. NICE also published a medicines evidence commentary on vitamin D supplementation for preventing intensive care admission in people with COVID-19 [ C5]. The UK National Health Service (NHS), Public Health England (PHE), the British Dietetics Association (BDA) and the Need for Nutrition Education/Innovation Programme (NNEdPro) Global Taskforce for COVID-19 have recently (April-June 2020) emphasised the importance of vitamin D supplementation in advice for the general public [ C5]. A particular emphasis is given to the importance of following vitamin D dietary recommendations (based on data from R1-R3) for those with increased time spent indoors during lockdown, shielding/cocooning and in self-isolation during the COVID-19 pandemic [ C5].

• Food fortification: As a consequence of the revised dietary recommendations ( R1-R4), nationally implemented voluntary food fortification programmes have demonstrated vitamin D status improvements in populations, e.g. the Finnish policy has doubled the vitamin D status of the general population with deficiency rates <1% [ C6]. Similarly, in response to the revised dietary recommendations (based on data from R1-R4), vitamin D food fortification has been introduced or revised in countries such as India (vitamin D fortified milk and edible oils, 2014), the USA (doubling of vitamin D fortification in milk, 2016) and Sweden (dairy products and margarine spreads, 2018), [ C6].

• Food industry: Industry now uses these dietary guidelines on packaging and in promotional literature [ C7] in response to the revised recommendations as underpinned by Ulster’s research (based on data from R1-R4). These industry initiatives have economic benefits in line with addressing global nutritional needs. Revisions to the vitamin D dietary recommendations automatically impact the entire food industry in that every product with a claim relating to vitamin D will always comply with the applicable dietary recommendations (based on data from R1-R4) [ C1-C4] as set by the authorities in the relevant country or region.

• Elite athletes: Sport Ireland has revised its policy so that the vitamin D status of all athletes is now routinely monitored, with vitamin D supplementation implemented (if necessary) using protocols designed by Sport Ireland [ C8]. The Sport Ireland Institute, using resources based on our research, now educates athletes on their vitamin D requirements which has improved their status ( R5).

Impact 1: Setting dietary recommendations by policymakers for safe fish consumption during pregnancy and in childhood:

• Experts and global leaders in health have used the research undertaken in the SCDS to revise guidelines on fish intake during pregnancy. The SCDS remains the only series of longitudinal studies to address the risk of fish consumption in pregnancy with respect to MeHg and is the most informative for policymakers.

• The United States FDA in 2014 modelled the benefits to foetal neurodevelopment of PUFA and the possible harm to foetal neurodevelopment from MeHg for various fish (the “net effects” models [ C1]). These models showed that the benefits to foetal neurodevelopment from fish consumption during pregnancy exceed the possible adverse effects from MeHg until the mother consumes uncommonly large quantities of fish. Data from the SCDS were germane in reaching this conclusion and a total of 6 references to our work, including R1-R3, R5, are cited in the document [ C1] .

• The Panel on Dietetic Products, Nutrition and Allergies (NDA) of the European Food Safety Authority (EFSA) in 2014 published a Scientific Opinion on the health benefits of seafood consumption in relation to health risks associated with exposure to MeHg [ C2]. Data from studies undertaken in the SCDS ( R1, R2, R4) were central to these changes and conclusions. This Opinion was a landmark with respect to revising global recommendations for maternal advice on fish consumption during pregnancy and recognised the evidence from the SCDS that n-3 PUFA in fish may counteract potential negative effects from MeHg exposure. The Opinion considered that beneficial nutrients in fish may account for the positive outcomes in the SCDS study compared with the adverse outcomes in previous research undertaken in mother-child cohorts elsewhere.

• The Environmental Working Group (EWG) in America in 2014 utilised information from the SCDS ( R2) to inform the American members of the Codex Panel about the safe consumption of fish during pregnancy [ C3].

• Arising from our underpinning research, maternal advice has been revised by policymakers in several countries, including the Food Standards Australia and New Zealand (FANZS), to reflect better the direct benefits and risks of fish eaten during pregnancy [ C4, updated Dec 2020].

• In the updated 2015-2020 Dietary Guidelines for Americans [ C5], it was appreciated that a variety of seafood in recommended amounts outweighs the health risks associated with MeHg. In 2019, the most recent version of the advice given to pregnant women on fish consumption from the Environmental Protection Agency (EPA) and the US FDA [ C6], promotes the science-based recommendations of the 2015-2020 Dietary Guidelines for Americans.

• Most recently, the Scientific Report of the 2020 Dietary Guidelines Advisory Committee (DGAC) in the US used data from the SCDS ( R1) in its review which concluded that there was moderate evidence to indicate that seafood intake during pregnancy is positively associated with measures of cognitive development in young children. Using this information, the DGAC has been updating Dietary Guidelines for Americans 2020-2025 and the most recent update has used data ( R1) from the SCDS [ C7].

• In addition to setting dietary recommendations for fish consumption during pregnancy, our data (including R4, R6) were used in 2020 by the Food Safety Authority of Ireland (FSAI) in setting food-based dietary guidelines for n-3 PUFA for 1- to 5-year-olds in Ireland [ C8].

Impact 2: Use of dietary recommendations globally by health professionals to improve maternal and child health and by the food industry to promote its products.

• Globally, the dietary recommendations developed with input from the SCDS (including R1-R5) have been cited on various websites, including the American College of Obstetricians and Gynecologists [ C9]. This website is utilised not only by clinicians and health professionals when giving updated policy influenced advice to pregnant women, but is also directly accessed by the public for up-to-date evidence-based advice on a healthy pregnancy.

• In response to the revised dietary recommendations the food industry, and in particular the marine food industry, is now (from 2017) using these guidelines in promotional literature [ C10]. Our underpinning research, therefore, has economic benefits, in that industry is promoting fish consumption in line with addressing global nutritional needs.

• Furthermore, revisions to dietary guidelines automatically impact the entire food industry in that every product with a claim relating to fish consumption (on pack or elsewhere), will comply with the most recent guidelines set by the authorities in the relevant region; this in turn impacts public health globally. Such guidelines promoted by food manufacturers e.g., the State of Alaska and the Alaska Seafood Industry [ C10], reach a wide audience and give benefit to consumers who receive and act upon the evidence-based information.

Significance and Reach: Our research profiling myopia in white children has been instrumental in the establishment of myopia as a serious pan-ethnic public health concern and has directly influenced clinical practice, public health information and the global industry response to this significant public health concern.

I1: Clinicians’ Knowledge of Myopia is Enhanced

Our research has updated and deepened eyecare practitioners’ knowledge of myopia, enabling them to deliver more targeted and timely care. The UK’s leading optometric professional organisations, the College of Optometrists and the Association of Optometrists (AOP), have recognised the fundamental shift in clinical best-practice and patient expectation in relation to myopia. In response, they have produced a range of resources utilising NICER study outcomes ( R1, R2, R4) to increase eyecare practitioners’ understanding of childhood myopia and to improve their proactive detection and management of the condition ( C1, C2).

NICER-informed resources published by the College of Optometrists have reached over 12,000 optometrists (number of GOC-registered optometrists in UK=14,000) ( C1). The AOP, the UK’s premier membership association for optical providers, which provides legal representation for over 80% of UK optometrists, has disseminated NICER findings to over 7,000 optical practices through professional guidance and a family-focused children’s eyecare resource pack ( C2). Professional bodies and optical industries worldwide have responded to the clinical implications of NICER study outcomes by inviting our team to inform thousands of eyecare providers at national and international clinical training events (including in China and North America, and across Europe) and through articles in professional journals ( C3).

This activity has demonstrably improved professional knowledge: the proportion of UK and Irish optometrists surveyed who correctly recognised the growing prevalence of myopia substantially increased from 66% (2015) to 89.5% (2018) and, importantly, the proportion of respondents affirming the earlier age of onset of myopia in modern children also increased (from 40.9% to 64.4%) ( C4). Enhanced knowledge of the prevalence, expected age of onset and risk factors associated with modern myopia equips clinicians to target children at increased risk more accurately, resulting in earlier detection and treatment. Prompt detection and correction of myopia improves educational as well as visual outcomes and offers more opportunity to apply anti-myopia treatments.

I2: Management of Myopia in Clinical Practice is Modernised

Through the application of our research by professional organisations and industry, eyecare practitioners are better placed to proactively identify and manage myopia for the benefit of patients. Driven by growing evidence (including R4) supporting the need for myopia-retarding interventions such as anti-myopia eye drops, contact lenses and spectacles, the College of Optometrists introduced ‘Myopia Management Guidance for Optometrists’ in 2019 ( C5). NICER study outcomes ( R6) are continuing to inform the further refinement of this guidance. Outcomes from the NICER study ( R4) were also used to set new recommendations for the frequency with which children with, or at risk for, myopia should have an eye test during revision of the College of Optometrists’ Guidance for Professional Practice (2019-20) ( C5). This national Guidance is a key resource for optometrists in all clinical settings. It describes what constitutes good practice and supports practitioners in clinical decision-making.

CooperVision, one of the world’s largest contact lens companies, has used our research to drive the clinical imperative for practitioners to prescribe myopia-slowing interventions, using NICER outcomes (R4) in its promotional and instructional material for the anti-myopia MiSight® contact lens. Since launching in the UK, MiSight® uptake has been rapid: over 300 optometric practices have prescribed MiSight® to over 3,000 UK children since 2017. Worldwide, over 17,000 children have benefited ( C6).

I3: Public Health Resources are Updated to Reflect NICER Study Findings and NICER Study Data Support the Drive to Address the Global Myopia Challenge

NICER study data have been used to educate and empower patients and the public with guidance on modern myopia, its development profile and the risk factors with which it is associated. In 2018, the NHS website (previously NHS Choices), which is accessed by over 50,000,000 users a year, updated its advice on the age of onset of childhood myopia to reflect our research findings ( C7; R4). The College of Optometrists’ ‘Look After Your Eyes’ website uses our outcomes to inform parents about the increase in prevalence and earlier age-onset of modern childhood myopia ( C8; R1, R4, R5). The extensive coverage of our research ( R1-R4) in print and broadcast media including The Times, BBC1’s ‘Health: Truth or Scare’ and BBC Radio 5Live, has reached over nine million individuals ( C3).

The global reach of our research is evidenced in the optical industry’s response to the identification of myopia as a significant worldwide public health concern. Following a meeting of the World Health Organisation and the Brien Holden Vision Institute in 2015, the International Myopia Institute (IMI) was formed, bringing together an international consortium of experts to address the worldwide challenge posed by myopia. The IMI uses our data ( R4) to illustrate global myopia prevalence and to call for safe and effective solutions to the modern myopia epidemic ( C9). In 2019 the IMI included our research ( R2, R4, R5) in a landmark series of agenda-setting ‘White Papers’ ( C10) from which clinical summaries have been developed and translated into many languages. These resources include the most up-to-date information on myopia classification and patient management and are aimed at eyecare practitioners, governments, policy makers, educators and the general public.

Significance and Reach: Our research has shaped clinical best-practice guidance worldwide and improved the ability of clinicians to provide appropriately targeted care ( I1, I2). Our research has triggered commissioning of new NHS eyecare services for children with developmental disability in England ( I3). Furthermore, by providing clinicians with ‘plain English’ communication tools to enable effective reporting of children’s visual strengths and weaknesses to key supporters and educators, we have ensured that the findings from clinical assessments achieve maximum impact ( I4).

I1: Clinical knowledge and best practice have changed, enabling alleviation of visually-impairing focusing deficits in children with developmental disability.

Our research is recognised and utilised nationally and internationally by educators, therapists and health professionals. Our research outcomes highlighting the prevalence of sight-impairing visual deficits among children with CP and autism, and those validating an accessible method to diagnose poor focusing in children with developmental disability, have been used in key international eye and healthcare texts ( C1; R1, R3, R4). The outcomes are also incorporated into national and global clinical guidance, such as that issued by the College of Optometrists, whose members comprise over 12,000 of the 14,000 optometrists registered in the UK ( C2; R2, R6). North America’s leading professional organisation for optometrists, the American Optometric Association, which represents over 44,000 members, cites our work ( R3) in its clinical practice guidance ( C2) when identifying dynamic retinoscopy as a key assessment in paediatric eyecare.

Our research outcomes ( R1, R3, R4) are used in the Brien Holden Foundation’s Global Optometry Resources, an open-access curriculum curated to facilitate the implementation, delivery and advancement of optometric education in developing countries, and reflected in the curricula of the College of Optometrists’ Professional and Higher Professional Certificates in Paediatric Eye Care ( C3).

Since 2013, the number of children issued with bifocal spectacles (the primary means to correct focusing deficits) has increased by 24% in UK NHS practice ( C4). This change in eyecare practice in line with our research has enabled a greater number of children to experience better vision.

Our research is also used by Public Health England and third-sector organisations to inform and empower parents and other stakeholders. Public Health England’s ‘plain English’ guidance on reasonable adjustments for eye care for people with learning disability links to Ulster’s Vision Report ( R6), hosted by SeeAbility. In addition, the UK’s leading organisation promoting education, training, advancement and development of people with special/additional support needs, the National Association of Special Educational Needs (nasen), includes our research ( R5) in its stakeholder resources ( C5).

I2: Successful commercial development of a research-supported tool (UC-Cube) provides a means by which clinicians can identify focusing deficits.

In 2010 we translated our research outcomes ( R3, R4) into a novel commercial tool for assessing focusing accuracy. Commercialised to prioritise clinical uptake through a not-for-profit agenda, the UC-Cube provides clinicians with an accessible, objective method to quantify, diagnose and manage focusing difficulties in patients unable to communicate effectively and to contextualise outputs against our research-derived normative data. Manufactured and distributed in collaboration with Cardiff University and PAVision Ltd, the UC-Cube’s global sales (approximately GBP20,000) to practitioners and researchers, including in UK, Ireland, Sweden, South Africa, Antigua, India and the United States, have embedded the tool in clinical training programmes, hospital and primary eyecare services and specialist services for children with learning difficulties across the world. In a survey of NHS paediatric eyecare clinicians who introduced the UC-Cube into their practice, 92% agreed or strongly agreed that using the UC-Cube benefitted both their patients and their practice. Clinicians reported specifically that the UC-Cube improved detection of focusing deficits and treatment of near visual impairment ( C6).

I3: Eyecare services for children with developmental disability in England are transformed.

Our research outcomes ( R5) have been used by campaigners as evidence of the need for improved eyecare services for children with developmental disability. SeeAbility, the oldest disability charity in the world and one of the largest in the UK, successfully used our research outcomes to lobby for the funding and implementation of a national evidence-based eyecare service for children in special education settings ( C7). In 2018, as a direct result of our research activity, Professor Saunders was invited to join a Department of Health project board tasked with designing and implementing a new evidence-based eyecare service for children with learning disability. Our work demonstrating the measurable benefit of in-school eyecare to children in special education settings ( R6) provided key evidence needed to commission this targeted and accessible in-school eyecare service for all (over 110,000) children educated in special schools in England. Our evidence-derived validated tools, the UC-Cube and Vision Report proforma, are embedded in the service specification of this new nationwide service (2019) ( C8). The NHS England and NHS Improvement Programme Manager for Optical Services Commissioning acknowledges the pivotal role Ulster research outcomes played in the commissioning and design of the service:

“The starting point for every new NHS England programme is the need to evidence positive outcomes for patients. This was a significant obstacle for the special school eyecare programme because the evidence simply didn’t exist until the research was undertaken by Ulster University.  Ulster University’s research not only helped to secure internal traction for the programme, but has informed our work throughout, contributing validated tools with which to optimise the delivery and impact of the service.” ( C8).

I4: Research-derived resources enable clinicians to communicate the visual needs of children with developmental disability and help parents and teachers to ensure that those needs are met.

Our Vision Report proforma ( R6), co-designed with service users, industry, education and health stakeholders, is promoted by Public Health England ( C5) and embedded in NHS England’s service specification for in-school eyecare ( C8). The Vision Report equips parents, teachers and other key supporters of children in special education settings with clearer understanding of children’s visual needs and, when integrated into EHCPs, ensures that appropriate support is in place to allow children to participate fully in the educational curriculum and enjoy the benefits of improved vision and better care.

The Vision Report proforma is one of the most downloaded resources offered by SeeAbility ( C5) and is also available from the open-access Ulster Vision Resources (UVR) ( R1-R6; C9). The UVR curate research-based support tools for professionals, parents and lay people. These tools have been accessed by over 161,000 users across 75 countries since 2014. Google analytics provides evidence of consistent use/re-use by visitors from Africa, Asia, Europe, America and Australia ( C9). The Royal National Institute of Blind People and the College of Optometrists promote the UVR to parents and carers of children with visual impairment and to optometrists providing eyecare for patients with learning disability ( C10).

Impacts 1 and 2: Our research has direct application in the prevention and treatment of high blood pressure (hypertension), the number one cause of death globally, primarily from heart disease and stroke. Globally an estimated 26% of the world’s population (972 million people) have hypertension and this is expected to increase to 29% by 2025. Our research has resulted in the generation of a University Patent Portfolio entitled “Use of riboflavin in the treatment of hypertension” (C1 EP2139488A1) in collaboration with Western Health and Social Care Trust and Trinity College Dublin and in turn resulted in two Intellectual Property License Agreements (IPLAs) (C2, C3) during the current impact period. The technology is currently protected under patents in China, Mexico, Japan, Canada, Ireland, UK, Italy, Spain, France, Netherlands, Germany and Switzerland.

The health implications of these findings in preventing hypertension are considerable for the 1 in 10 adults worldwide (and much higher in some populations e.g. 32% in Mexico) who carry this genetic risk factor. In particular, patients with existing hypertension will benefit, as documented in a video investigating the patient experience showing that riboflavin intervention was not only highly effective at lowering BP, but was also very well received by patients (C4). Riboflavin supplementation thus offers a novel, non-drug treatment (and/or the potential to be combined with an antihypertensive drug) to effectively lower BP, most likely via an effect on nitric oxide ( R5) and improve BP control in genetically at-risk adults.

Two IP licensing agreements were signed during the current impact period (C2, C3).

• The first is a significant agreement for the development of a new product for eye health, Ocufolin, designed by US ophthalmologists to reduce the risk of age-related macular degeneration and diabetic retinopathy by decreasing homocysteine and consequently reducing microcirculation in eye diseases. The license with Aprofol AG, Switzerland (effective date 28-06-2016; date of variation 26-01-2018) provides exclusive use of ‘personalised nutrition’ claims related to degenerative eye disease in the European patent with the option to negotiate a patent license in China. Aprofol’s investment in Ocufolin to date is estimated at > EUR3M. Aprofol is using the license for sales of a ‘medical food’ (as defined by the US FDA) and Ocufolin products (for eye health) (C2).

The second license (C3) is with DSM Nutritional Products AG, Switzerland (effective date 06-02-2018). The license provides exclusive use of pharmaceutical claims under patent rights in China, Mexico, Japan, Canada and Europe and has realised an upfront payment to the University of EUR100,000 (02-2018) and significant company investment (additional to DSM’s research investment in grant income to the University of almost GBP1M, as detailed above). DSM has negotiated an agreement (confidential at this stage) with a global pharma company regarding the development of an antihypertensive-riboflavin combination for the prophylaxis and treatment of elevated BP, building upon the existing patent. In parallel, DSM has produced outputs focusing on hypertension treatment, including a white paper which presents an in-depth look at the science behind riboflavin as a treatment for hypertension and the latest research developments from Ulster (C5). The company has also run several promotions using both social graphics and a blog, and promoted a hypertension monograph to a global pharma audience (C6). DSM launched a campaign to promote the concept to a targeted list of pharma companies globally and has used this information successfully to attract the current pharma partner. DSM also engaged a human data science company (IQVIA) to conduct a global survey of doctors (n=736 from US, Germany, France, China) in order to understand the market potential of the concept of a riboflavin-antihypertensive combination (see Figure 1 below). As a result of our licensing agreement ( C3) with DSM, the company has filed a new international patent PCT/EP2019/077270 entitled “Medicaments containing riboflavin exhibiting improved flowability” WIPO Patent Application WO/2020/094319 (C7).

Figure 1: Global survey of physicians demonstrating their appreciation and knowledge of the proven effect of a riboflavin anti-hypertensive combination on resistant hypertension.

Impacts 3 and 4: In addition to the commercial impact, the underpinning research has impacted nutrition and health policy. Of note, the level of riboflavin (1.6 mg/day) found in our research trials to have beneficial effects on BP is within the range of what is achievable through normal dietary intakes, which is important given that our most recent research demonstrated that sub-optimal riboflavin status is associated with a three-fold increase in hypertension across adulthood (R6). Furthermore, riboflavin is entirely safe with no evidence of adverse effects, even at doses 100-fold higher than the 1.6 mg/day proven to be effective. In 2017, the European Food Safety Authority (EFSA) published its scientific opinion on “Dietary Reference Values for Riboflavin”. EFSA acknowledged for the first time among policymakers that riboflavin requirements were influenced by the MTHFR TT genotype based solely on the research from Ulster and R1-R4 were cited in the EFSA opinion (C8). Health professionals and food manufacturers in Europe use these dietary reference values daily in their work (C8). The underlying research (R1) was also cited in a health claim which was substantiated by EFSA and is authorised for use by the food / pharma industry on dietary supplements and any food product containing 15% or more of the reference dietary value for riboflavin, as well as being used by industry to promote their products.

In summary, the impacts are both commercial and health related. The patent portfolio has resulted in close engagement with global industry partners which has led to the development of a novel antihypertensive-riboflavin combination with a leading pharma company (C1-C7). The public awareness of the health benefits of riboflavin and their promotion by health professionals and industry are now on a global scale (C8-C9) through EFSA Dietary Reference Values for Riboflavin and the on-going promotion of products citing the EU generic health claim.

The impact of our research ( R1, R2, R3, R4) on care home culture as described in this case study refers to the impact of Ulster University’s My Home Life (MHL) Leadership Support and Quality Improvement Programme (hereafter referred to as the MHL programme). This 10-month programme commenced in 2013 and continues to be used as a conduit for changing care home culture through the translation of our research into practice.

In planning our impact strategy, Ulster University was one of the original partners in My Home Life, an international initiative and registered charity (No. 1187498) which promotes quality of life and delivers positive change in care homes. Each partner organisation works independently, and research findings and resources are shared with the care home sector and with other partners and stakeholders through the MHL website.

I1: Impact on policy

In 2018, the Permanent Secretary, DOH (NI) referenced our research when he outlined measures to address “unacceptable failings” in safeguarding and restore public confidence in care homes by supporting the “ implementation of initiatives aimed at improving the quality of life for people living in care homes such as the My Home Life initiative” ( C1). The significance of our policy impact is further evidenced by extra funding from DOH (NI) in 2020, to support care homes to participate in the MHL programme during the COVID-19 pandemic and to appoint a Project Manager to engage with 100 new care homes as part of the regional implementation of the MHL programme across NI (C1).

The reach and significance of our research impact ( R1, R2, R3) is evidenced by buy-in from the care home sector and partnership funding from its umbrella organisation Independent Health and Care Providers. This resulted in an increase in the uptake of the MHL programme from 15 managers in 2013 to 67 managers in 2020 from a diverse range of care homes (urban, rural, residential, nursing), representing approximately 1 in 7 care homes in NI (C1). The MHL programme was cited as an example of best practice in the Report of the Expert Advisory Panel on Adult Care and Support (DOH NI, 2017) and was recommended as a catalyst for remedial change in adult safeguarding in the report of the Independent Review Team commissioned by the DOH (NI) to investigate care home abuse and neglect in the region. “The HSCTs should explore … how change programmes demonstrate approaches to care and support which reflect human rights … and projects such as My Home Life at the University of Ulster would enhance this work” ( C2). Our research ( R1, R2, R3) has directly influenced DOH (NI)’s Reform of Adult Care and Support policy resulting in a request from DOH (NI) to submit a funding bid (GBP2.6m) for the regional implementation of Ulster’s MHL programme across all 484 care homes in Northern Ireland (C2). In 2017, our research on the concept of a nursing home as ‘home’ received extensive media coverage and was commended by the Irish Minister for Health and raised during parliamentary questions leading to an increased focus on the need to create a more ‘homely environment’ in care homes ( C3). Since 2013, the MHL programme ( R4) has received unwavering support from AgeNI who provided partnership funding for our programme and whose CEO described it as making “ a positive impact on the quality of care experienced by residents in care homes” ( C4). The impact of our research ( R2, R3, R4) has also been recognised by the Chair of Northern Ireland Regulation and Quality Improvement Authority (RQIA) who described the MHL programme as “ a great fit with RQIA’s aspirations for excellence in the care of older people” ( C4) and by Care Home Advice and Support (a voluntary organisation in NI) who stated, “ We want the DOH to use these findings to make the necessary improvements” ( C2) .

I2: Impact on culture in dementia care

Results of questionnaires completed by participating managers since 2013 showed a significant positive change in 89% of the responses measuring the impact of the MHL programme on care home residents, relatives and staff ( C5). Significantly, there were marked improvements in the quality of interaction between staff and relatives (54% of respondents agreed), quality of management and leadership (51%) and satisfaction with practice (49%) in care homes caring for 2,268 residents ( C1, C5). One participating manager commented: “I’ve been a care home manager for 20 years and this has been the most rewarding programme for me as a manager. I would do it all over again!” ( C4) . Another commented “I think the My Home Life programme should be the standard. I think all managers should take the opportunity to do it. In fact, I think it should be part of the process of becoming a registered manager” ( C6). Others spoke of how the MHL programme led them to change the focus of their work to more meaningful engagement, positive risk-taking and a recognition of the importance of relationships with older people and their families. “ It was… the best training I ever had for managing, leading and working in a care home, it was about relationships, and rights of older people, it was not just about health but about quality of lives, importance of family relationships and leading the team using these approaches has improved the staff and more importantly the care and support offered to older people” ( C2) .

The reach and significance of the impact of our research on culture is evidenced by the introduction of a range of research-based quality improvement initiatives ( R1, R2, R3) across the 67 care homes which implemented the MHL programme between 2013 and 2020 ( C7). These include the development of new pre-admission assessment protocols, the production of a short film on the transition to life in a care home, a new approach (‘This is Me Now’) to maintaining the dignity and identity of residents with advanced dementia, and the introduction of a ‘Decision Tree’ to facilitate the involvement of care home residents and relatives in decisions about life in their care home ( C7). Based on Ulster’s research, participating managers worked with residents and their families to co-create an information booklet on the transition to life in a care home which reached approximately 17,000 individuals and organisations in the wider care home sector across Northern Ireland and provided much needed guidance as part of the implementation of the Northern Ireland Dementia Strategy ( C7). In 2017 Sarah Penney (MHL Project Manager) was awarded the RCN Nurse of the Year, Learning in Practice award for the impact of the MHL programme on care home culture ( C7).

I3: Impact on understanding of dementia

Our reminiscence research provided significant evidence to the NHS of the viability of mobile device apps for people living with dementia, in terms of uptake and sustained engagement ( R5, R6). This led to additional funding to develop the InspireD reminiscence app which is now freely available on the Apple App and Google Play stores and in the HSC Apps4Dementia library, soft launch December 2020 ( C8). One person living with dementia said of the app, “It helped me find myself again, so it did” ( R6). The HSC Innovation & Digital Eco-system Lead highlighted the reach and significance of our work, and stated that the benefits described in Ulster’s research “ convinced us that the app should be widely deployed across Northern Ireland and beyond” as part of a wider digital transformation programme in health and social care, which is being led by Digital Health & Care NI with the support of the DOH (NI) ( C8).

Recognising the power of the arts to reflect the experiences of people living with dementia, we collaborated with a local theatre company to create a play ‘The Songbirds’ and share the findings of our reminiscence research ( R5, R6). Between 2019 and 2020, the play reached an audience of approximately 2,000 people in theatres and other venues across the island of Ireland ( C9). A questionnaire administered before and after the play showed a significant improvement in public understanding of dementia across 100% of the evaluation statements. Before seeing the play, 76% of audience members agreed that people living with dementia can learn new skills and 77% understood that long term memories are often intact for people with early to moderate dementia. Significantly, these figures increased to 91% and 97% respectively after seeing the play ( C10). Qualitative feedback on the play was collected via questionnaires, emails and social media tweets. A person living with dementia described the play as “ *just like watching myself… It gives a 100% perfect representation of a person with dementia, that is the truth. Families need to see this; they will know then what we feel, and experience and they will understand us better”. * Another posted a message on Dementia NI’s Facebook page saying, “It was fantastic. I would advise anyone to watch the play. What a brilliant way of getting the dementia message out to people”. The play has been described as “ superb” by the Alzheimer’s Society. It sold out within a matter of days at the ESRC Festival of Social Science, from where the Commissioner for Older People for Northern Ireland tweeted “ very powerful performance of #ThesongbirDs in AccidentalT tonight. Great portrayal of people’s journey with #Dementia. Well done to all who pulled it together” ( C10).

The purpose of this programme of work was to evaluate the impact of implementing the KPIs on the experience of care for patients, families and staff across different clinical contexts. Impacts I1 and I2 are interconnected within the implementation studies and are described simultaneously.

Enhancement of the health care experience for patients and families and for nurses

Through the Paediatric International Nursing Study (PINS), the eight KPIs were implemented across a range of sick children’s services (2013-2015) (R3). It involved 6 organisations in Australia (Princess Margaret Hospital for Children, Perth; Royal North Shore Hospital, NSW; Hornsby Hospital, NSW; Nepean Blue Mountains Local Health District, NSW; Women's and Children's Hospital, Adelaide; and the Sydney Children’s Hospitals Network) and 6 in Europe (Hans Christian Andersen Children's Hospital, Odense, Denmark; Temple Street Children's University Hospital, Dublin; Great Ormond Street Hospital, London, England; East Kent, England; Royal Belfast Hospital for Sick Children, Northern Ireland; and South Eastern Trust, Northern Ireland). Participating sites confirmed the value of the data captured by the KPIs as a means of highlighting “ the positive and excellent care that is provided and is recognised and appreciated by families”, whilst at the same time being able to act on “ immediate negative feedback that identifies people or interdisciplinary services and requires attention i.e. is unsafe or disrespectful” (I1, C1). It was this that drove practice change by providing meaningful information, permitting nurses to pinpoint directly what specific areas of practice needed improved (I1, C1, C2). Improvements focused on areas such as nursing documentation, bedside handovers (I1, C3) and supporting information for families (I1, C2). Similarly, there was evidence that using the KPIs embraced the value of nursing, impacting on staff morale and providing opportunities to celebrate good practice (I2, C1, C2).

As a result of PINS (R3), there was organisational roll out by the Women’s and Children’s Health Network in South Australia across 4 divisions, covering 8 nursing and midwifery teams (I1, C1). The KPI data collected from 2013-2020 had significant reach involving approximately 1,285 patients and families completing surveys or stories, resulting in approximately 80 action cycles (I1, C1). Examples include: allocation guidelines of patients to staff to improve consistency in care, and development of patient profiles for complex care so families don’t have to repeat their stories (I1, C1). Staff engagement in this process “ raise[d] awareness of the impact of care, what person-centred care looks like and what works and doesn’t work” (I2, C1).

Development of the iMPAKT App (Implementing and Measuring Person-centredness using an APP for Knowledge Transfer) offered a technological solution for collecting the KPI data and was evaluated as an effective method to measure the patient experience in real time (R4). Nurses (n=22) participated from a range of clinical contexts (5 sites in South Eastern Health & Social Care Trust, Northern Ireland and 6 sites in Illawarra Shoalhaven Local Health District, Australia). Illawarra Shoalhaven Local Health District has continued to use the iMPAKT app, engaging a total of 177 nursing and midwifery staff across a range of clinical settings. The number of beneficiaries totalled 677 patients and carers (C5). The impact on nursing practice included: an improved team focus approach to care delivery; changes to staffing allocations and rostering to enhance consistent care; development of person-centred nursing documentation; and improvement in visibility of nurses for patients (I1, C5). The positive impact on staff of using the KPI data to improve practice was also emphasised, with the introduction of regular staff celebrations. One unit also developed an employee of the month programme. Other staff benefits included: provision of clinical supervision and reflection; and increased opportunities to de-brief following challenging situations (I2, C5).

The KPIs have also been implemented by NHS Lothian, Scotland, as part of an organisational care assurance programme between 2017 and 2019. Across 3 hospital sites, 31 acute wards used the KPIs, with 7,940 patients completing the survey and 253 patients providing stories (C6). Clinical teams were considered the main beneficiaries, with the reporting of improved staff morale (I2, C6). Patient story feedback was also key in improving practice, such as changing ways of working and addressing long standing environment issues (I1, C6). Use of the KPIs within NHS Lothian led to further collaboration with South Eastern Health & Social Care Trust in Northern Ireland to test the implementation of the KPIs within a community nursing context (R5).

The significance of the original research (R1, R2) resulted in the implementation of the KPIs within chemotherapy units (n=5), across the entire region of Northern Ireland from 2018 to 2019 (R6). A key impact was nurses’ ability to truly involve patients in decisions about their care and the things that really mattered to them in their daily lives (I1, C7). This influenced a significant regional change in the electronic documentation system used in chemotherapy environments. There was no area in the documentation where nursing staff could capture what was currently important to the patient and their family, leading to significant inconsistency between what the nurse said was important to the patient and a review of the patient documentation. Consequently, the restrictive dropdown menu to record what was important to the patient was expanded with a free text option to ensure what is important to the patient was accurately captured and evidenced as an ongoing dialogue (I1, C8). The impact was also significant for chemotherapy nurses and influenced their ability to clearly articulate their role and enhance their contribution to the patient experience (I2, C7). Nursing teams felt disempowered to reduce waiting times for patients, but the KPI data encouraged them to think differently about this issue and as a result developed person-centred interventions. It was “ small simple changes that can play a big part of a patient’s experience and journey”, with examples including: offering complimentary therapies to reduce stress and anxiety and to facilitate relaxation; working with the catering department to install a fridge in the unit to provide patients with fresh cool bottled water; and developing a post-discharge pack to provide a range of information to enhance experience of patients after they have finished their chemotherapy treatment. These interventions led to an enhanced patient experience (I1, C7).

Influencing strategy and policy

Finally, there is evidence of the programme of work influencing strategy and policy. NHS Lothian, Scotland, illustrated this through the impact of the work on the Board’s Patient Experience Strategy (I3, C6). Similarly, within Illawarra Shoalhaven, Australia, the KPIs aligned with the Nursing and Midwifery Workforce Plan and “ provided a link between policy and practice” (I3, C5). Within Northern Ireland the KPIs are being used to inform policy for nursing through the Northern Ireland Cancer Strategy and the Nursing and Midwifery Task Group (I3, C9). Further implementation of the KPIs on an international stage is evidenced by the establishment of a Chief Nursing Officers’ Collaborative between Australia and Northern Ireland to further develop the iMPAKT app for large scale use (I3, C10).

Our research had the following impact:

I1: EU-wide regulatory decision requiring pharmaceutical companies to update patient information leaflets and add warnings of risks in pregnancy to packaging of the AED sodium valproate.

In 2016, the French medicines regulator cited our sodium valproate study [ R1] as evidence for increased risk of congenital anomalies associated with exposure during pregnancy [ C1]. The regulator presented this evidence at the European Medicine Agency (EMA) to highlight its concerns about the effectiveness of measures to increase awareness and reduce valproate exposure in females. Despite the warning to restrict valproate prescribing in women of childbearing age implemented in November 2014, studies reported that valproate was still being prescribed to these women.

In response to these concerns, the EMA published further official guidance in 2018 banning the use of valproate for migraine or bipolar disorder during pregnancy, or for the treatment of epilepsy during pregnancy unless no other effective treatment was available [ C2]. In addition, pharmaceutical companies were instructed to add visual warnings of the risks in pregnancy to the packaging of valproate medicines and to update the medicine information leaflet to ensure the risks during pregnancy are clearly stated [ C2, C3].

In 2018, Ulster was part of a consortium commissioned by the EMA to assess valproate prescribing trends in women and girls in relation to its 2014 warnings. We found that valproate

continued to be prescribed in women aged between 10-50 years in the UK, Italy and France [ R2].

This illustrates the reach and significance of the impact arising from our research as it led to EU-wide regulatory changes to highlight the warnings of risk of valproate exposure during pregnancy. Our research directly informed the EMA regulatory body that valproate continued to be prescribed to women of childbearing age in Europe.

I2 = National (NICE, UK) and international guidelines (WHO, US) include our research on safety of medications for pregnant women with depression, diabetes and epilepsy.

National: Our research assessing the safety of AEDs [ R1] has been included in NICE national guidelines on antenatal and postnatal mental health (2015) and has been used to build a body of evidence to guide and inform decision-making for the safe and effective use of AEDs during pregnancy [ C4]. In England, NICE reviewed the impact of the regulatory guidelines on valproate prescribing in women of childbearing age and reported that the number of females receiving a prescription for sodium valproate steadily decreased from 23,935 in early 2016 to 13,251 in the summer of 2020 [ C5]. This is evidence that clinical practice in relation to valproate prescribing in women of childbearing age is changing.

In 2017, the British Association for Psychopharmacology, which is the largest such national association in Europe, cited our research on the safety of valproate [ R1] and lamotrigine [ R3] in pregnancy in their consensus guidance on the use of psychotropic medication in pregnancy [ C6].

In 2018, our research on the safety of selective serotonin reuptake inhibitor antidepressants in pregnancy [ R5] was cited in The Maudsley Prescribing Guidelines in Psychiatry [ C7]. This textbook is an established reference source for ensuring the safe and effective use of medications for patients presenting with mental health issues.

The UK Teratology Information Service provides online monographs for health care professionals summarising key research studies that have investigated the effects of prenatal medication exposures on the fetus [ C8]. The “Selective Serotonin Re-uptake Inhibitors (SSRIs) in Pregnancy” monograph, issued in 2017, included our research on antidepressant use in pregnancy [ R4, R5].

International: In 2017, following a review of the literature on the safety of medications which included our research [ R3], lamotrigine was added to the list of essential medicines recommended by the World Health Organisation Expert Committee on the Selection and Use of Essential Medicines [ C9].

In 2018, our research [ R6] on the safety of metformin in pregnancy and risk of congenital anomalies was cited in the American College of Obstetricians and Gynecologists Practice Bulletin [ C10]. This Practice Bulletin provides current evidence-based information on the clinical management of pregnant women with pregestational diabetes.

In summary, there is national and international evidence of the reach and significance of our research as it is cited in current clinical guidance on the management of women with diabetes, depression and epilepsy in pregnancy [ C4, C6-C10]. The impact of our research benefits health care providers who wish to provide optimal treatment to pregnant women while decreasing potential risks that the medication may pose to the fetus. It also benefits pregnant women who have access to more evidence about medication safety in pregnancy.