Impact case study database

Research by Prof Johnstone on dietary protein has shown it to be an effective means of managing hunger to achieve weight loss in obese individuals. She has also explored sustainable plant protein sources to promote healthy ageing. Together, these findings support the food industry to develop healthier food ranges, delivering economic impact in the food and drink sector, and enhancing public health and food industry understanding of the health benefits of improved protein consumption.

Supporting the food industry to develop healthier food ranges

While protein-rich diets have been shown to help achieve appetite control and to support an active lifestyle, the challenge for the food sector has been to develop health food ranges that incorporate a protein-carbohydrate formulation that is palatable, sustainably sourced and appetising, while also being compatible with a balanced (high fibre) diet. The Aberdeen research played a key role in developing high protein with balanced carbohydrate formations for the M&S range – ‘ Fuller Longer’, with Prof Johnstone as the academic consultant for M&S, described in the REF2014 impact case study, “Commercial health food for sustained appetite control”. ‘ Fuller Longer’ has since changed name to ‘ Balanced For You’ (BFY) and, 10 years on, testimony from the company confirms that the range continues to help customers to achieve their health goals and to contribute to the M&S Plan A sustainability goals [ S1]. The popularity of the brand is further illustrated by promotional media materials that highlight the ‘high protein and perfectly portioned carbs’ in the BFY range, attracting over 2.8 million views [ S2].

Since 2016, BFY has been provided as part of British Airways collaboration to offer M&S food on its short haul flights, recognising that passengers wanted ‘ choices that reflected what they would normally select when out and about’ [ S3]. BFY also features in M&S hospital franchise stores, contributing to their proportion of healthy choices that they must make available, according to the guidelines implemented by the Scottish Government in 2017. These guidelines require that food retailers on NHS grounds must comply with Heath Care Retail Standards as per NHS terms. The implementation was successful with 97% compliance from retailers of food and drinks on Scottish hospital sites [ S4].

The research from the Rowett Institute has led to Prof Johnstone being involved in two additional relationships. First, Prof Johnstone provided expert advice on the role of protein in satiety to the Jamie Oliver Group, to inform the preparation of the book ‘ Everyday Super Food’, published in 2015. Prof Johnstone is acknowledged in the book which was 11^th bestselling in the UK in 2015, with sales revenue of GBP7.3 million [ S5]. Second, a partnership began in 2018 with UK-based Tate &Lyle, who supply ingredients globally to the food and beverage industry. Prof Johnstone has presented elements of the research focusing on plant proteins to the Tate & Lyle Research Advisory Group (Aug 2018), a client group of their international producers (Jan 2019). Vice President of Global Nutrition and Open Innovation at Tate & Lyle has worked with Prof Johnstone as they seek to expand their portfolio of plant proteins to support health and wellness, and Johnstone is now leading a research and development project to assess ingredient formulations of plant proteins, specifically to examine the nutrition and health benefits of selected botanical proteins [ S6].

Delivering economic impact in the food and drink sector

The Aberdeen-M&S collaboration led to the creation of a GBP40 million health food range for M&S. ‘ Balanced for You’ accounts for 44% of total healthy meals sales for M&S, or 14% of overall meals space, and 18% of total sales (pre-COVID) [ S1]. The partnership was noted in the Scottish Parliament in 2014 as an example of excellent work in relation to the Food (Scotland) Bill [ S7, p75]; and as an exemplar for driving economic impact in the Food and Drink sector, contributing to GBP3.3 million gross value added to Scotland’s economy (estimated as GBP11.2 million in UK) in the 2017 BiGGAR economic report for Scottish Government [ S8, Case Study 9-1, pp38-39].

Enhancing public health and food industry understanding of the health benefits of improved protein consumption

Drawing upon the research undertaken in the Protein4Life project, Prof Johnstone led a collaborative team to produce a White Paper [ S9i], which has been used to inform public health and industry sectors on the opportunities for improving health expectancies in the population though improved protein consumption. Recognising the emerging threat of sarcopenia and associated health problems, this work identified that much of the UK adult population fails to consume adequate protein to maintain muscle strength and function in later life. Loss of muscle strength and function directly impacts the economy in both cost of healthcare and loss of workplace productivity. The white paper was presented to the UK Parliamentary and Scientific Committee in March 2019 to inform a discussion on challenges for a growing and ageing population [ S9ii] and is also promoted by British Dietetic Association Work Ready pages on Productive Healthy Ageing [ S9iii] The work was also presented at Food Matters Live 2019, with over 8,500 attendees from the ingredients, food production, food service and retail, and nutrition sectors [ S9iv]. SEFARI, the Scottish Environment, Food and Agriculture Research Institutes consortium hosts a blog by Prof Johnstone on the white paper, which since June 2020 received 65 views [ S9v].

The Rowett Institute’s approach to collaboration, led by Prof Johnstone and drawing on Aberdeen’s research in protein for satiety and nutrition, and in sustainable plant-based protein, provides a sound basis for the ongoing paradigm shift within the food sector.

The SIRAKOSS technology, underpinned by the Aberdeen research, addresses the unmet clinical needs for bone graft substitutes by creating an off-the-shelf synthetic bone graft that accelerates bone formation and repair so that the graft is fully remodelled and eventually replaced by new bone. The technology has enabled the growth and expansion of a spin out company, attracting equity investment, company led research funding, creating new employment and created 2 new products that fill unmet commercial needs.

Growth of a spin-out company, attracting investment, creating employment and winning awards

Since spinning out from the University of Aberdeen, SIRAKOSS has raised significant investment and grant funding for an early-stage medical device company, securing a total of approximately GBP6M in financing, which lead to an GBP8.4M acquisition within the REF period [ S1].

SIRAKOSS was acquired by OssDsign in November 2020, enabling the new partnership to market innovative products in the USA and Europe, the two major territories for this technology. The OssDsign deal of GBP8.4M to acquire SIRAKOSS yielded GBP3.8M to investors and other shareholders in November 2020, with final payments due in 2021 with additional future milestone and royalty payments agreed. [ S2]

The growth of SIRAKOSS led to an increase in headcount during the REF period, growing from 2 FTE to 7 FTE. Professor Gibson continues to work with SIRAKOSS/OssDsign on a 0.4FTE basis. The expansion also supported a range of subcontracted services by the company, including finance, IP, regulatory, IT and marketing/branding, all to UK-based companies [ S3].

OssDsign anticipate product launches based on the SIRAKOSS acquisition, starting in 2021. Completion of milestones to date, along with achieving major projected commercial milestones during the REF period, supported a significant increase in company valuation and a growth in company size, increasing the headcount significantly. These activities enable SIRAKOSS/OssDsign to market innovative products in the two major territories for this technology, in a bone graft market worth over USD3 billion. The next stage of growth anticipated in 2021, based on this acquisition, will be to build commercial sales in the USA and to capture clinical evidence.

Investment has been supported by industry recognition of the SIRAKOSS technology, through a number of awards. In 2014, the technology was awarded the Venture Prize from The Worshipful Company of Armourers and Brasiers [ S4]. The company has been shortlisted twice in the Scottish Enterprise Life Science Awards, first for the Investment of the Year (2016) and then for the Innovation Award (2020) [ S5].

Creating 2 new products that fill unmet commercial needs

The SIRAKOSS technology has led to the development of 2 new products, all of which address unmet clinical needs, namely the availability of a synthetic bone graft substitute material with a similar efficacy to biologics but with a lower cost and reduced risk. A CE Mark for the first product, Osteo³ Granules, was awarded in 2019 [ S6] and the second product, Osteo³ ZP Putty, a formulation with ready-to-use intra-operative handling characteristics, was cleared by the FDA in the USA for use in trauma and spine surgery in 2020 [ S7]. Current synthetic materials do not provide surgeons with a bone graft that performs at a level that reliably matches or exceeds that of autograft, or approach the efficacy of expensive biologics. A clear unmet commercial need exists for a synthetic material that achieves clinical outcomes that would meet or exceed autograft, and would approach the performance of biologics but at lower cost to healthcare providers. A US-based orthopaedic spine surgeon said “ the bone graft technology that has been developed by Sirakoss is very interesting and I found the existing data to be very compelling, demonstrating at a minimum an equivalent performance to autograft… I believe that these results will be of great interest to surgeons who rely on these types of bone graft substitutes. In summary, based upon my review, I believe that this novel material represents an exciting advance in synthetic bone graft technology” [ S8].

At the time of acquisition SIRAKOSS was a pre-revenue company but the acquirer, OssDsign, anticipate product launches in 2021. Innovation continues, including a new bone graft composition developed by SIRAKOSS in 2019-2020, with a patent application submitted in August 2020. This new composition will enable new clinical applications of the core science, extending into medical implants such as spinal cages.

The impact for this case study falls into three categories: health benefits, commercial impact, and intellectual property.

Health impact. Some 1,700 AD patients and 190 FTD patients have been enrolled in three global Phase 3 trials of hydromethylthionine. A further one hundred patients have been prescribed the medicine by their physician under compassionate use, with several noting that it has benefitted both their quality of life and predicted life expectancy. As yet, there is no licensed treatment for any form of FTD, however hydromethylthionine has shown to have potential health benefits for those in the trials. [ text removed for publication]

Commercial Impact. TauRx is the pharmaceutical spin-out that was formed by Professor Wischik with investors from SE Asia in 2002 and is incorporated in Singapore. The company has received the Frost & Sullivan 2019 Asia Pacific Neurodegenerative Disease Management Technology Innovation Award, in recognition of visionary innovation "developing novel treatments for neurodegenerative disease. [ text removed for publication] This demonstrates the successful creation of a commercial pharmaceutical company funded through the investment and based upon the research carried out at the University of Aberdeen.

A substantial amount of funding has been used to support basic scientific research both at the University of Aberdeen and in other academic research centres in Berlin, Warsaw, Frankfurt and at the University of Sussex. Wischik and Harrington serve as Executive Chairman and Chief Scientific Officer for TauRx, respectively. As well as continuing to support 38 full-time research positions at the University of Aberdeen, this investment has funded the continued employment of six researchers in Berlin, a further six in Warsaw (Aug 2013 onwards), and two scientists each in Frankfurt and at the Open University. Research funding is also provided to a collaborative group at the University of Sussex, with three scientists under the lead of Professor Louise Serpell, focused on determining the precise mechanism of action for lead inhibitory compounds at the molecular level [ S2]. [ text removed for publication]

As part of a collaborative research agreement with Prof Serpell at the University of Sussex, the research team have created Alzheimer-like filaments under physiological conditions and demonstrated the mechanism of action of methylthioninium, the first tau aggregation inhibitor originally reported by Wischik and Harrington in 1996.

Intellectual property. As a result of the research, more than 30 patent families have been filed, with 13 of these since 2013. [ text removed for publication] The granting of the many patents demonstrates that both the novelty and utility of the research have been acknowledged by patent offices throughout the world. As well as covering the treatment of AD and FTD, these patents include descriptions of novel uses of compounds for the treatment of mild cognitive impairment and Parkinson’s disease and for the use of compounds other than hydromethylthionine. [ text removed for publication] The group has published 32 research articles in peer-reviewed journals during the period 2014-2020, demonstrating the academic relevance of their research.

The demonstration of pharmacological activity of hydromethylthionine for bvFTD [ R5] is important since this is an orphan indication having no current treatment and provides a route for accelerated marketing approval.

University of Aberdeen research has created a new evidence base to help people with obesity in the UK and internationally. Specifically, it has (i) informed health guidelines for WMPs for adults with obesity in the UK, India, the United States and New Zealand; and (ii) underpinned the development of a successful weight management programme in the UK.

(i) Informing health guidelines for the management of obesity-related illnesses

In the UK

The first systematic review [ R1] provided four meta-analyses used by NICE since 2006 to inform guidance on weight management for adults with low-fat and 600kcal/d deficit diets [ S1 p541], adding behavioural interventions to diets [ S1, p562-4], adding physical activity to diets [ S1, p580-3], and the weight loss drug orlistat [ S1, p618-9]. NICE evidence was only partially updated in 2014, such that current 2014 NICE guidance on the above topics continues to utilise this evidence from 2006 given in Appendix M of its 2014 publication [ S1].

University of Aberdeen research on WMPs for men created an evidence base which has been used by the Men’s Health Forum and Public Health England, in their joint guidance document, ‘How to make weight-loss services work for men’ [ S2i-ii]. Aimed at people developing WMPs, this ‘How to Guide’ summarises the Aberdeen-led research, so that programme developers are made aware what works and what doesn’t. Martin Tod from the Men’s Health Forum has confirmed that the guide has been used in designing weight management services [ S3]. This was the first published guideline on weight management for men with obesity, nationally and internationally.

In India

Evidence from the first systematic review [ R1] was used in the 2015 Indian clinical practice recommendations on management of Type 2 diabetes, as evidence supporting behavioural support for lifestyle change for obesity [ S4i, pS17], stating ‘ Other important components of behavioural therapy embrace self-monitoring, goal setting and stimulus or cue control. Such strategies help in setting up realistic goals, guide patients in identifying stimulus that leads to excessive nutrient intake and eliminate them accordingly’. The same guidance citing R1 was repeated in subsequent Indian diabetes’ clinical practice recommendation updates, including in 2020 [ S4ii].

In the United States

The November 2013 American Heart Association/ American College of Cardiology/ Obesity Society Guideline for the Management of Overweight and Obesity in Adults utilises the first systematic review and all six associated publications from that systematic review for its guidance [ R1, references 36-40 and 54-55 in 2013 AHA report]. Guidance quotes benefits of weight loss, with or without orlistat, on fasting glucose, HbA1c, triglycerides, LDL cholesterol, blood pressure, prevention of Type 2 diabetes and reduction of premature mortality [ S5].

The 2019 update of the US clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures clinical practice guidelines references the University of Aberdeen team’s 2018 research [ R3] for decisions on types of surgery. The research provides the cost-effectiveness evidence in support of Roux-en-Y gastric bypass surgery compared to non-surgical weight management. [ S6, pO27-O28].

In New Zealand

The University of Aberdeen-led research has provided evidence to support national guidelines for adult WMPs in New Zealand in 2017. The evidence section on weight loss interventions for men with obesity relies on the team’s research:

‘A systematic review of evidence-based management strategies for obese men found that men preferred more factual information on how to lose weight and more emphasis on physical activity programmes than women did. They also preferred interventions delivered in social settings to those delivered in health-care settings (Robertson et al 2014 [ R2] *, Robertson et al 2016). Robertson et al concluded that weight reduction for men is best achieved and maintained with the combination of a reducing diet, physical activity advice or a physical activity programme, and behaviour change techniques.*’ [ S7, p11]

The document provides clinical guidance for health practitioners and others who provide advice on weight management for New Zealand adults, where 1-in-3 New Zealand adults is obese.

(ii) Underpinning the development of a successful weight management programme for men

In the UK, the University of Aberdeen-led systematic review [ R2] and resulting guidance from Public Health England and the Men’s Health Forum [ S2i] has informed the development of the MAN V FAT weight management programme (https://manvfat.com/about\-man\-v\-fat/\). MAN V FAT was founded by Andrew Shanahan, specifically for men in 2014, with a crowdfunding campaign aimed at launching a digital magazine about men’s weight and how to lose weight. The campaign attracted support from Jamie Oliver, the National Obesity Forum, Weight Concern and the British Dietetic Association, and was so successful that, along with the magazine, Shanahan also created a website and published a book to help men lose weight. In 2016, Shanahan launched MAN V FAT Football, which now has over 90 football leagues across the UK, all of which are Football Association affiliated, and a further 12 leagues – MAN V FAT Soccer – in Australia. Shanahan wrote in a 2015 media article that ‘ the really great thing about Avenell’s research is that it has galvanised weight management teams across the country…Man V Fat began to work with … Public Health England guidance to create a best practice weight management programme’ [ S8].

The value of the research is further confirmed in correspondence with Andrew Shanahan, where he stated that ‘ the principles of MAN v FAT Football are underpinned by the research, which found that provision of suitable programmes was previously lacking’ [ S9]. MAN v FAT Football is also accessible for free at a number of leagues in the UK due to localised public health funding. These include leagues in Westminster, Kensington, Strood, Lincoln, Boston, Hastings, Skegness, Eastbourne, Falmer, Basingstoke, Eastleigh, Andover and Aldershot. Collectively, the leagues have to date helped around 20,000 men lose weight and gain fitness. Over 90% of men lose weight on completion of their first season, with over 271,000lb lost to date.

The underpinning research has given voice to the argument that the contribution of Primodos to deformities in babies born decades ago cannot be ruled out. From 2017 to 2020, evidence provided by Professor Vargesson on the causal effects of Primodos informed parliamentary debate leading to a major UK independent public inquiry into Primodos. Throughout, Vargesson presented scientific expert opinion based on the underpinning research to UK parliament; the UK Commission on Human Medicines (CHM) - Medicines & Healthcare products Regulatory Agency (MHRA); and the European Medicines Agency (EMA). He also advised German Parliament and their MPs on current scientific understanding based on his research.

Impact in the UK

In March 2017, Sky Atlantic and Sky News aired a documentary - Primodos: The Secret Drug Scandal - in which the story of the affected families (1.5 million women given the tablets and hundreds of families affected according to the ACDHPT) was, for the first time since the 1970s, brought to public attention [ S1i] The documentary was subsequently nominated for a Royal Television Society Award - Best Documentary [ S1ii]. Broadcast to over 35 million viewers in the UK, Europe, the Middle East, Africa, South Asia, Asia Pacific, Australia and the Americas, the documentary featured an interview with Professor Vargesson, who discussed findings from his research (at the time, unpublished) on the teratogenic effect of Primodos components on vertebrate embryos [ S1i and S1iii]. The film sparked debate and Vargesson was invited to UK Parliament as an expert witness alongside a Sky news journalist, a historian of science, technology and medicine; and Chair of the ACDHPT, on 21^st March 2017 [ S1iii]. Following a parliamentary screening, Professor Vargesson discussed the findings of his research and provided answers to questions from MPs and Lords, which led to calls from MPs, Lords and the ACDHPT for a new independent public inquiry into the actions of Schering/Bayer (the German manufacturer of Primodos/Duogynon) and the UK government about the safety of the drug [ S1iv].

In November 2017, the CHM/MHRA Expert Working Group (EWG), published a controversial report [ S2i] concluding that Primodos had no causal association with birth defects despite Professor Vargesson’s evidence and expert opinion on drug action in embryos; this was primarily because the Aberdeen research had not yet been peer reviewed or published at that time. The report was criticised by journalists and MPs, including a Conservative MP, who condemned the report as failing to meet the terms of reference and remarking: “ The question of a causal link was not in its remit” [ S2ii]. The report had set out to determine: “ possible association between exposure in pregnancy to hormone pregnancy tests and adverse outcomes in pregnancy (in particular congenital anomalies, miscarriage and stillbirth)” [ S2i]. An EWG member also declared his disagreement with the committee’s conclusions, describing the Aberdeen research as “ very, very compelling” [ S2iii]. On December 14, Professor Vargesson addressed an All-Party Parliamentary Group (APPG) of MPs at Westminster, ahead of a parliamentary debate, where he voiced concerns about the report’s conclusions and presented suggestions for further work to be carried out [ S2iv].

Then, on 13 February 2018, the Aberdeen team’s research was published [ R2], generating significant media interest - reported by 74 international news outlets [ S2v]. A week later, Professor Vargesson advised the APPG about the research [ R2], its implications and the need for further research, resulting in the then Prime Minister and Health Secretary, to announce a new, independent inquiry. It was discussed in Parliament by the Health Secretary and several other MPs that Professor Vargesson’s newly published research was crucial to the new inquiry [ S2vi].

Therefore, in March 2018 the Independent Medicines and Medical Devices Safety Review (IMMDSR) was established to focus on safety of Primodos, Valproate and Vaginal. Professor Vargesson was invited and presented his published data [ R2] and also his group’s more recent data on Primodos components [Ci; pp39-67]. Professor Vargesson was also invited to discuss his work with a Panel of the European Medicines Agency (EMA) that was specially formed to evaluate the clinical relevance of his findings in zebrafish [ S3i and S3ii]. In October 2018, he also presented to the CHM/MHRA ad hoc group specially formed to discuss suitability of the zebrafish model for evaluating the effects of norethisterone and ethinylestradiol in human pregnancy. The ad hoc Group looked at the implications of the Aberdeen research for medicine safety, given that some of the components of Primodos are still used today in different medicines. The ad hoc Group concluding that “ further investigation could reveal additional effects” [ S3iii]. However, the ad hoc Group failed to consider the clinical dangers that Primodos components in use today may present. Professor Vargesson attended and spoke about his research and its implications at the IMMDSR oral hearing at King College London on 27 Nov 2018 [ S3iv], and the following day, he unveiled his latest research to the APPG at the Houses of Parliament [ S3v]. The House of Lords then discussed the Primodos scandal in February 2019 at a debate titled ‘Safety of Medicines and Medical Devices’, during which Professor Vargesson and Erskine’s research was referenced as revealing “ anomalies that mirrored the adverse effects on victims of Primodos” [ S3vi].

In April 2019, an APPG on Hormone Pregnancy Tests convened in Westminster Hall to discuss the “no causal association” conclusions of the CHM/MHRA EWG in 2017 and how affected families were wronged, despite their decades-long campaign. They agreed that the Aberdeen research should not be ignored [ S4i]. Gaining traction, the Primodos story took a new turn in August 2019 with the announcement of litigation between over 200 claimants and the UK Government and Primodos manufacturer Bayer (formerly Schering) [ S4ii].

The IMMDSR report titled “First Do No Harm”, was published in July 2020 [ S4iii]; concluding that systematic health care failures had let down those affected by Primodos (alongside those harmed by Valproate and pelvic mesh). The report also reflected on the EWG’s scrutiny of two pieces of scientific research on hormone pregnancy tests – one of which, was the key publication by Vargesson’s group [ R2] – and outlined procedural issues with EWGs, making recommendations for improved procedures of future EWGs [ S4iii]. The report outlined recommendations including a national apology and recompense for care and support for Primodos survivors [ S4iii]. The inquiry outcome was accompanied by a public apology from the Health Secretary [ S4iv]. The inquiry chair publicly said “ I and members of the Review team have conducted many reviews and we all agree – we have never encountered anything like this, the intensity of suffering, the fact that it has lasted for decades. And the sheer scale. This is not a story of a few isolated incidents. No one knows the exact numbers affected by mesh, Primodos and sodium valproate but it is in the thousands. Tens of thousands” [ S4v].

A new documentary entitled ‘Bitter Pill: Primodos’ – premiered on Sky Documentaries on 24 August 2020 and subsequently on Sky News (and repeated on both channels throughout the rest of 2020), and is also available on YouTube. It featured interviews with Professor Vargesson about his published work and his latest unpublished work about the dangers of Primodos components [ S4vi], reaching viewing figures comparable to the first documentary [ S1iii].

Impact in Germany

The German government contacted Professor Vargesson, who submitted an evidential document in March 2019 on the Primodos paper [ R2] and new research ahead of the German Parliament convening to debate Duogynon (the German trade name of Primodos) and its link to birth defects [ S5i]. His expert testimony helped contribute to the announcement in September 2020, that the German Government was establishing a far-reaching inquiry into Duogynon safety [ S5ii].

The Aberdeen work investigating the sources of human Campylobacter infection in Scotland was the first study in the world to do so on a national scale and this was reported in REF2014. Since then, the more recent Grampian-based studies have further refined and strengthened the evidence at a genome-wide resolution – detailing that retail poultry is the main reservoir of human campylobacteriosis. In the current REF period these data have driven the public health strategies of both Food Standards Scotland and Food Standards Agency in aiming to reduce Campylobacter from the 250 million ^a retail chickens produced in the UK each year. This has been achieved by industry interventions, listed by the British Poultry Council Chief Executive as including “ on farm biosecurity; catching practices; thinning practices; crates and modules; scalding practices; washing practices; heat treatments; cold treatments and novel packaging” [ S1] which have reduced the prevalence of birds with >1000 cfu/g (colony-forming units: a measure of viable bacteria per gram) from 18.4% to 5.8% between 2014 and 2019 ^b. Our work has had international impact across the EU, with its 445 million citizens, and annual consumption of over 15 million tonnes of poultry per year. Our work has had international impact by providing underpinning data on which to base current EU regulations on the permissible levels of Campylobacter in retail chicken.

Our work underpins EU regulations on Campylobacter in retail chickens

Our previous impact case study for REF2014 reported that in 2009, the Aberdeen team had provided the European Food Safety Authority (EFSA) BIOHAZ panel with evidence of the extent to which meat derived from retail chickens contributes to human campylobacteriosis, following which EFSA published scientific opinion and issued guidance in 2010 [ S2i]. EFSA, as a result of this and in combination with its risk assessment work issued advice on reduction of Campylobacter in retail meat production in 2011 [ S2ii]. This led to publication on 23^rd August 2017 of the EU commission regulation (EU) 2017/1495 [ S3] which stipulates the levels at which Campylobacter may be present in chicken carcases. Para 5 of this document quotes the EFSA opinion [ S2i] which as mentioned above is underpinned by the Aberdeen studies. The EU regulation came into force across the EU in January 2018. Hence, the Aberdeen studies have been central to the provision of underpinning evidence for food safety regulation across the 27 member states of the European Union, as evidenced in testimony from the EFSA Chief Scientist [ S2iii].

Our research drives food safety policy impacts in England, Wales and Northern Ireland

The Food Standards Agency (FSA), which is an independent Government department working across England, Wales and Northern Ireland to protect public health and consumers' wider interests in food, published its strategic plan 2015-20 FSA in 2015 [ S4i]. The plan’s “Food is Safe” theme states that “Campylobacter is the most common cause of human bacterial food poisoning in the UK…. … up to 80% of cases can be attributed to raw poultry meat”, a statistic arising directly from Aberdeen University’s research [ S4v]. The FSA plan used this evidence as a rationale for a campaign to significantly reduce levels of Campylobacter in retail chickens. Updates on the Campylobacter campaign were presented to the FSA board in July 2015 [ S4ii] and March 2016 [ S4iii] which detail results of surveys of Campylobacter in retail chickens as well as progress being made by the industry in reducing the prevalence of birds with >1000 cfu/g [ S4iv]. Hence the Aberdeen studies have been directly used as underpinning evidence to inform the policy making decisions of the FSA, as confirmed by FSA Senior Scientific Officer, who said “ The expertise of Professor Strachan has been of immense help to the work of the FSA in relation to Campylobacter reduction and his knowledge and expertise have aided the FSA in policy development in this space” [ S4v].

Our work provides the platform for chicken food safety policy in Scotland

In 2016, Food Standards Scotland (FSS) developed its 3-year Corporate Plan that lays out its programme of work [ S5i]. The plan states “ Reducing foodborne illness from Campylobacter is a priority for FSS. Current evidence suggests that between 55‑75 percent of all reported cases of Campylobacter infection in Scotland are associated with a chicken source, and that a significant proportion of fresh chicken on retail sale in the UK is contaminated with the pathogen.” The evidence quoted is from the Aberdeen studies and is used here to directly underpin FSS policy. The FSS corporate plan then goes on to state “ What we’ll (FSS) do….. ….generating programmes to reduce the risks of Campylobacter in Scottish-produced chicken…..” [ S5iv].

This evidence, together with updated evidence from our more recent source attribution studies in Grampian [ S5ii], was used in a recent (15^th May 2019) FSS board paper [ S5iii] on Campylobacter which states “chicken-related Campylobacter strains continue to be most commonly identified in human illness in Scotland (52-68%) followed by strains from ruminant (cattle and sheep) sources.” This then informs the policy which was agreed by the FSS Board at the meeting “to drive further reductions in Campylobacter in UK produced chicken by promoting sustained action by the major retailers, and supporting farmers and smaller producers/retailers in Scotland and the rest of the UK in controlling the risks.” Hence, the Aberdeen studies are being used as underpinning evidence to inform the policy-making decisions of FSS, the national food body of Scotland, as confirmed by the FSS Chief Executive, who said “ The policies of FSS and FSA, informed by the University of Aberdeen work, have been successful in reducing the levels of Campylobacter in retail chicken. This is evidenced by the implementation of industry interventions which have reduced the prevalence of birds with >1000 cfu/g from 18.4% to 5.8% between 2014 - 2019 and hence improving food safety” [ S5iv].

Therefore, the claimed impacts include: public health and disease prevention has been enhanced by research; decisions by a health service or regulatory authority have been informed by research; public awareness of a health risk has been raised. Impacts on commerce have been that industry (including overseas industry) have had to develop practices and/or change existing production and processing practices, to ensure that they produce retail chickens that satisfy EU and national regulations. Impacts on public policy and services have been that policy debate has been stimulated and moved forward by research evidence; policy decisions have been informed by research evidence. Impacts on production have been that decisions by regulatory authorities have been influenced by research. International policy development has been influenced by research.

^aDEFRA, Historical statistics notices on poultry and poultry meat production, 2018 https://www.gov.uk/government/statistics/historical-statistics-notices-on-poultry-and-poultry-meat-production-2018

^bFood Standards Agency (2019) Campylobacter Data Gathering Survey https://www.food.gov.uk/sites/default/files/media/document/campylobacter-data-gathering-survey.pdf

For decades, the legacy of the thalidomide tragedy has imposed upon the survivors and their families' lives filled with difficulty, pain and discrimination, in some cases without recognition or support. The Aberdeen research findings led to several impacts, including helping to identify and compensate thalidomide survivors, influencing international government responses by informing guidance for thalidomide embryopathy identification, and enhancing understanding of the effects of thalidomide.

Identifying and compensating thalidomide survivors

The group’s research findings revealed the drug’s actions on blood vessel development, and that a different range of damage can be induced depending on timing of exposure. This research has been used as expert opinion in a landmark case action for Lynette Rowe, an Australian thalidomide survivor in her 50s, born with neither arms nor legs. Distillers, the drug’s distribution company, continued to distribute thalidomide in the 1960s for 6 months after warnings were raised, but later, in the face of undeniable links between the drug and the deformed babies, devised a compensation scheme. However, Ms. Rowe was excluded from the compensation scheme due to her having no limbs, rather than partial limbs. Prof Vargesson was called upon by Australian lawyers in 2011 and 2012 to provide expert opinion on the mechanism of thalidomide embryopathy based on his and Prof Erskine’s research findings. Their research demonstrated that the claimant’s damage could be due to thalidomide, despite not being of the ‘classical’ recognised diagnostic criteria. The success of this case led to a further class action claim for another 107 disabled claimants in Australia and New Zealand, who received a collective settlement of over AUD100 million in February 2014. [ S1; S2] The large sums settled to the survivors will provide medical care, home adaptations and physical support for the rest of their lives.

Influencing governmental responses and informing guidance for thalidomide embryopathy identification in the wake of thalidomide

Aside from the consequences of the thalidomide disaster from the 1960s, babies are still being born with thalidomide-induced malformations. The drug, although now banned as a morning-sickness treatment, is given for indications including multiple myeloma in the western world and complications of leprosy in South America. At least 35 thalidomide births were identified between 1996 and 2014 in Brazil, where medicine regulation, distribution and safety were lacking, and which identified the need for better diagnostic criteria, medicine safety and regulation. In response, in 2014 the World Health Organization (WHO) brought together an expert team on Thalidomide Embryopathy. Prof Vargesson was invited to be a part of this team and used the research from Aberdeen regarding thalidomide effects on angiogenesis to contribute to the resulting report “Thalidomide Embryopathy: Report of a meeting of experts” [ S3]. The Medicines Safety Programme Manager at WHO (HQ) explained “ The report will not only assist in the diagnosis of thalidomide embryopathy, it will also provide a model for diagnosing other types of drug-related embryopathy” [ S4]. The WHO Meeting experts also inputted to the production of revised diagnostic criteria for thalidomide embryopathy, to help identify victims - published in 2018 [ S5]. The WHO report has also been cited in Canadian Parliament investigations into identification of thalidomide survivors [ S6i] and the establishment of compensation schemes.

This provision of expert advice based on the Aberdeen research has continued to influence and inform government responses to recognising and compensating thalidomide survivors in several countries around the world. In May 2017 Vargesson gave advice to the Canadian Parliament, on the drug’s actions and types of damage caused [ S6i]. The advice is cited in a letter of recommendation from the Chair of the House of Commons Standing Committee on Health to the Minister for Health, which explicitly calls for the government to “err on the side of compassion” and for claimants previously denied access to the Thalidomide Survivors Support Program to “be clinically evaluated to determine, on a balance of probabilities, the likelihood of thalidomide exposure” [ S6ii]. These recommendations were adopted in the new Canadian Thalidomide Survivors Support Program (CTSSP), launched in 2019 [ S6iii]. On the basis of his expertise in thalidomide embryopathy research, Prof Vargesson was invited to serve as an Advisor on the CTSSP multidisciplinary committee, assessing applications for recognition and compensation, since August 2019 [ S6iv]. Hundreds of applications are expected; this change finally opens up access for every Canadian thalidomide survivor, including those previously denied due to non-classical diagnostic criteria. The support available includes a tax-free lump-sum of CAD250,000; annual payments for life; and funding for extraordinary medical assistance for specialized health care and vehicle/home adaptation.

The group’s research on thalidomide mechanism of action and the wide range of damage it can cause to embryos was used to inform both the interim and final reports arising from the Senate of Australia Community Affairs Reference Committee Public Hearing in 2019 on support for Australia’s Thalidomide survivors. Prof Vargesson took part in the hearing by video conference and is cited throughout the reports (which refer to Committee Hansard, public hearing, Jan 31^st 2019 [ S7i; S7ii]) on his discussion of thalidomide embryopathy and the non-classical manifestations possible. The recommendations included a national apology; education programmes to inform clinicians about thalidomide embryopathy; schemes to identify additional survivors; and lump sum, annual payment and home/vehicle modification funding [ S7i; S7ii]. The Australian Government announced in October 2020 their support of the recommendations and commitment to provide compensation: lump sum and annual payments; health and living support costs; and to establish an eligibility scheme to identify as-yet unrecognized thalidomide survivors, akin to other nations [ S7iii].

Prof Vargesson provided advice to the Italian Government in 2019 and to the Italian Thalidomide Network group in 2019 [ S8i] and 2020 on thalidomide embryopathy, focusing specifically on supporting claimants who have non-classical damage. A book outlining the Italian Thalidomide Network Group’s work, including the proceedings of a Conference held in February 2020 at which Prof Vargesson presented, is being produced [ S8ii] and is aimed at further highlighting the needs of thalidomide survivors for support. Prof Vargesson is contributing to the book to explain that thalidomide causes far broader damage than currently recognized. This advice again builds upon the current understanding of the damage patterns which have been delineated by the Aberdeen research, the history of the diagnostic criteria and current viewpoints.

Developing learning material for clinicians

In Australia, one of the recommendations in the Senate report on support for thalidomide survivors [ S7i] was aimed at improving clinician awareness around thalidomide injuries. In response to this recommendation, Prof Vargesson was enrolled by the Australian government in 2019 as Advisor and Subject Matter Expert to the Royal Australasian College of Physicians (representing over 25,000 medical specialists and trainee specialists) for the development of an eLearning resource on thalidomide and thalidomide injuries to support the education of clinicians and medical professionals [ S9]. Vargesson created and developed learning objectives, historical overview of the drug, overview of the diagnostic criteria and devised self-assessment tools to test the reader’s understanding [ S9].

In the USA, journalists have called on Vargesson’s expertise in a series of articles for the New York Times highlighting the ‘forgotten’ alleged thalidomide survivors in the US and their ongoing quest for recognition and compensation [ S10] and led to communications between Prof Vargesson and the US Thalidomide Association. Vargesson in Sept 2020 presented an online seminar to the US survivors group, discussing his research and advising on how to engage politicians, with survivors from USA, UK and Canada joining the call [ S11].

Young people in families living with HD face unique challenges: the burden of being a young carer; social isolation; learning about their own high risk and deciding whether to seek genetic testing. The research by the team at the University of Aberdeen has been instrumental in identifying a need for age-appropriate information and resources about HD, professional and peer support, as well as parental guidance about disclosure to children. The research built an evidence base that has been used to inform support services for young people in Scotland and around the world, and to influence training for health and social care professionals.

Informing the development of new support services for young people in Scotland

Early in the research, the Aberdeen team was able to develop a collaboration with the Scottish Huntington’s Association (SHA). As well as a crucial avenue for recruiting research participants, the collaboration has informed the development of the SHA youth service (known as SHAYP), a dedicated service providing support to children and young people aged 8-25 in Scotland living in a family with HD. The CEO of SHA highlighted the Aberdeen research as key to SHAYP: “ A key element of the work is to support parents around the disclosure of HD in the family. The practice basis for this work is the research conducted by Keenan et al” [ S1]. Since August 2013, SHAYP has supported 163 young people and passed on the study findings to over 300 HD families, with four specialist youth advisors now employed to cover the whole of Scotland. Families attending a genetic clinic with children aged 8-25 in NHS Grampian and other Clinical Genetic Services in Scotland are told about the youth service, another route to reaching this vulnerable group. The SHA have also cited the research to access grant funding to support SHAYP to the value of GBP1,000,000 (Children in Need; Big Lottery) [ S1].

SHA staff have drawn directly on the research to inform their professional practice and to support parents to start early conversations with children about HD [ S2]. Aspects of the SHAYP approach that have been developed based upon the research include educational resources; one-to-one support; age-tailored group sessions; activity days; and residential breaks. Another key area of activity involves supporting young people through the predictive testing process. SHAYP has also reformulated its approach to working with partners of young people living with HD. Following publication of the research on disclosure to partners, SHA Specialist Youth Advisors included relationships and disclosure as part of their comprehensive assessment of needs, resulting in 70% of young people who have entered into serious relationships requesting at least one joint session with their partner and enabling them both to be able to plan better for the future. The SHAYP Children Services Manager said: “ The research… has positively influenced professionals’ knowledge and understanding of living in families impacted by HD, whilst also affording organisational change in how services are tailored and delivered to this vulnerable client group.” [ S2].

Informing the development of new support services for young people around the world

As well as informing support within Scotland, the research has also been pivotal in the services offered by the Huntington’s Disease Youth Organisation (HDYO). HDYO was founded in 2011 by Matt Ellison, who first heard about the Aberdeen research through Dr Keenan at the European Huntington’s Disease Network meeting in Prague, 2010 [ S3]. Matt grew up with an HD parent and wanted to change the landscape for other children and young people. He founded HDYO in 2012, as a non-profit organisation providing online support and education for young people around the world aged up to 35 (HDYO.org). The organisation provides age-appropriate educational content including a genetic testing section for teens and young adults, an information pack for schools highlighting the needs of young carers, and information for parents about disclosure to children, all of which draw directly upon the Aberdeen research [ S3]. For example, the genetic testing section specifically draws on findings about ‘the waiting period,’ the potential for isolation and the feelings young people may have when going through the testing process.

Since 2013, the website has had over 7,000,000 views, content has been translated into 13 languages and direct support has been provided to over 4,500 young people [ S4]. Founder Ellison had said that the Aberdeen research “ *provides an evidence base to underscore the important work of HDYO and to continue to obtain funding and support from partners.*” HYDO has secured approximately GBP500,000 in the REF impact period. Aberdeen researcher Keenan also served on the HYDO Board from 2012-2017 and is a member of the Feedback Team (hdyo.org/eve/about/105), supporting HYDO to use the research to understand the needs of young people and provide much needed support [ S3].

Influencing practice, training and support for health and social care professionals

As well as providing support for young people directly, SHA also works with genetic professionals to improve their practice. Aberdeen’s research on the variation in professional practice of genetic counsellors and clinical geneticists in Scotland, whose role is to facilitate communication within families about genetic risk, has directly influenced the development of a new strategic approach to supporting genetic professionals to hold such conversations. While this is a new development for the service, they have already received positive results, including one practitioner who said, “ My practice has been improved dramatically and I believe the benefit is to all family members now and not just the person receiving the genetic test. Had I not read the journal article, I would have continued with my old methods and would have been missing fully supporting families” [ S2].

Professional training has used the Aberdeen research to provide an evidence base. The Genetic & Genomic Counselling MSc at Cardiff University cites the Aberdeen research for subtopics in family matters and in predictive testing in their ethics module. This course has been delivered to 80 genetic counselling students since Aug 2013 all of whom have had the benefit of learning about the Aberdeen research [ S5]. Manchester University also provides clinical training in genetic counselling citing the Aberdeen research in their counselling and communication skills module [ S6].

The first-of-its-kind professional development course at Stirling University, ‘Huntington’s Disease: An Enabling Approach to Supporting Families’ developed in conjunction with the SHA, cites the Aberdeen research 12 times in the 200-hour, SCQF level 10 course. Since its launch in 2015, 82 professionals from across the four nations of the UK have completed the CPD module [ S7]. The CEO of SHA said of the Stirling course in relation to the Aberdeen research “ a key theme of the course is the impact of HD on the whole family, and recognition of the issues for young people and young adults is largely possible because of this body of work” [ S1].

The way in which this Aberdeen research demonstrated the burden of chronic pain in the general population led to a cascade of Government reports and policy initiatives on the issue. By enhancing the underpinning evidence base, both with primary research and systematic reviews, this research influenced health policy and improved how pain services are provided in Scotland.

Increased government investment in chronic pain, and reorganisation of pain services

In 2004, the ‘McEwan’ Report ‘Chronic Pain Services in Scotland’ was published [ S1]. This report, commissioned by the Scottish Executive, directly cites the Aberdeen epidemiological work [ R1] to conclude that chronic pain is a major medical and social problem and a massive drain on national resources. It went on to make 16 recommendations for the provision of chronic pain services in Scotland – including that each health board should establish an Integrated Pain Service, or separate Chronic Pain Service.

In 2007, the NHS Quality Improvement Scotland published the GRIPS report [ S2]. In the reprint (2008) Nicola Sturgeon, then Cabinet Secretary for Health and Wellbeing, highlighted the “lack of national commitment that recognises chronic pain as a key area of work” and acknowledged that the Scottish Government now recognised chronic pain as a condition in its own right.

In recognition of this issue, the Scottish government provided new funding of GBP60,000 a year to fund the Scottish Government Lead Clinician on Chronic Pain and GBP50,000 a year for two years to establish a managed clinical network for chronic pain in NHS Greater Glasgow and Clyde, which is now supported long-term by the Health Board [ S3]. In England also, this epidemiological work [ R1] was cited in the UK Chief Medical Officer's Report 2008 where it was argued that a model pain service or pathway of care with clear standards should be developed [ S4].

The Scottish Government Lead Clinician on Chronic Pain led the development of the Scottish Service Model for Chronic Pain, a model that involves reorganisation of resources to deliver pain management across four tiers:

1. Supported self-management;

2. Allied Health Professionals and primary care services;

3. Specialist multidisciplinary pain management; and

4. Specialist services and intensive residential services.

When a review by Healthcare Improvement Scotland found limited evidence of implementation of the model, Scottish Government decided to provide GBP1.3 million in new funding from 2014-2016 to embed it, a process which was supported by the establishment of Service Improvement Groups in all 15 Scottish Health Boards [ S5]. Aberdeen staff served on the National Chronic Pain Steering Group (Blair Smith) and the Service Improvement Groups (Paul McNamee) to provide expert guidance and advice on embedding this model.

This funding was spent differently in different Health Boards according to locally determined priorities – including recruitment of additional pain specialists (Orkney / Forth Valley); pain service reorganisation (Lothian); and GP-led chronic pain reviews (Greater Glasgow and Clyde) [ S6]. In one example of a funded project, the West Dunbartonshire Chronic Pain Management Pilot found that having pharmacist-led holistic pain reviews halved the number of secondary care pain clinic reviews that patients undertook, conserving GPs’ time and saving on medication costs as well [ S6]. This initial investment in chronic pain management on a national scale has been sustained by these Scottish Health Boards who continue to operate this multi-disciplinary model of care [ S6].

Informing international guidelines on non-pharmacological interventions for chronic pain management (Tiers 1-3 of the Scottish Service Model)

Following the implementation of the Scottish Service Model, work at Aberdeen directly contributed to the development of authoritative guidelines on chronic pain management:

• SIGN-136: Management of chronic pain in adults: This guideline produced by the Scottish Intercollegiate Guidelines Network (SIGN) provides evidence-based recommendations on the management of adults with chronic non-malignant pain, and cited three pieces of Aberdeen research to support their recommendations [ S7]. Psychological interventions [citing R3] are mentioned as a key clinical recommendation that should be prioritised for implementation, and [citing R5] the benefits of capsaicin for osteoarthritis pain are described. The guideline failed to make an explicit recommendation for the use of antidepressants in patients with temporomandibular joint pain, instead noting the insufficient evidence to determine their effectiveness [citing R6].

• NICE guidelines for chronic pain: Aberdeen work [ R3 and R4] have also been key in formulating the recommendations for cognitive behavioural therapy in the preliminary NICE guidelines for chronic pain [ S7].

• Guidance on the management of pain in older people: Aberdeen researchers collaborated with the British Geriatric Society and British Pain Society to produce the first UK guideline on the management of pain in older people [ S7]. The recommendations followed an extensive systematic review of the available literature and help health professionals consider the options available when managing pain in older patients

Development of educational materials with patients and patient partners

As part of the EoPIC study, Aberdeen researchers (McNamee and Schofield) developed new education materials that were co-designed with research participants, including a Facebook learning object for health professionals and a comic book to help children understand others’ chronic pain. The latter featured in the Times Higher Education “20 new ideas from UK universities that will change the world” [ S8]. Educational materials were also developed in collaboration with Pain Concern, the leading UK chronic pain patient organisation. This included episodes of the on-line programme “Airing Pain,” such as:

• Programme 1: Introduction to Pain (Sep 2010)

• Programme 2: Nerve Pain and how to manage it (Oct 2010)

• Programme 13: Culture, epidemiology, and back pain (Feb 2011).

Reported usage is 25,000 listens across all programmes during the first quarter of 2015 [ S8].

Putting chronic pain on the national agenda

Following the use of University of Aberdeen research in the UK Chief Medical Officer's Report 2008, chronic pain moved up the national agenda. Based on his recommendations, data on pain is now collected as part of the Health Survey for England to provide annual estimates of chronic pain in the community. The Health Quality Improvement Partnership, the British Pain Society and Dr Foster have delivered a comprehensive National Pain Audit to discover the quality and coverage of pain services.

In November 2011, the British Pain Society, Chronic Pain Policy Coalition, Faculty of Pain Medicine and Royal College of General Practitioners came together in the first English Pain Summit. One of the key recommendations emerging from the Summit was that a data strategy for chronic pain should be agreed through creation of an Epidemiology of Chronic Pain working group [ S9]. This working group was convened and chaired by Professor Macfarlane, with a sub-group chaired by Dr Jones; both researchers at University of Aberdeen.

Since 2014, studies show that there has been greater investment in nursing and clinical psychology posts dedicated to pain management, and 10 new multi-disciplinary pain clinics / programmes now operate in Scotland in 2018 [ S10]. Furthermore, NHS patient outcomes have improved; in a before-and-after implementation study conducted in the NHS, statistically significant and clinically meaningful improvements in health-related quality life were demonstrated using this approach of multidisciplinary pain management [ S10].