Impact case study database

HCM is an inherited heart disease affecting 1 in 500 people globally (approximately 36 million people). SCD remains the most devastating and feared clinical event for both HCM patients and their cardiologists. Effective prevention of SCD using ICD therapy significantly reduces SCD events and has provided HCM patients with the chance of normal life expectancy. However, ICD implantation carries a substantial risk of major complications for patients. The risk model developed by Professors Omar and Elliott accurately predicts the risk of SCD in HCM patients and is now used in the clinical management of HCM patients to make treatment decisions regarding optimal implantation of ICDs.

Improved clinical guidelines with more accurate and individualised SCD risk prediction for HCM patients

The risk prediction tool has been incorporated in to the 2014 ESC guidelines for the management of HCM patients endorsed in 57 countries ( S1, S2). The ESC unites all national cardiac societies from around the world and disseminates evidence-based scientific knowledge to cardiovascular professionals so they can better care for their patients. Professor Omar and collaborators subsequently conducted a meta-analysis summarising all available published data relevant to the 2014 ESC guideline performance for SCD prevention. The meta-analysis showed that HCM-risk-SCD model provides accurate SCD risk estimates that can be used to guide ICD therapy in accordance with the 2014 ESC guidelines ( S3). In addition, the HCM Risk-SCD tool was validated independently in a wider patient group including HCM patients who had treatment with alcohol septal ablation - a non-surgical procedure to treat obstruction. This international multicentre cohort study also showed good predictive ability of the risk tool ( S4).

The risk model’s use is recommended to clinicians during the “first evaluation and re-evaluation at 1-2 years of HCM patients, as well as whenever there is a change in clinical status” ( S1). The ESC has classified the risk algorithm as a class I tool, which means that its recommendation by ESC is based on “evidence and/or general agreement that a given treatment or procedure is beneficial, useful and effective” ( S1). This tool was also recommended in “Essential Messages” memo (2014) by the ESC, called for informing practitioners about the newest recommendations in an easily interpretable manner. The essential messages released by the ESC on hypertrophic cardiomyopathy in the “take home messages” section stated: “The use of a new risk calculator (HCMRisk-SCD) (http://doc2do.com/hcm/webHCM.html\) is recommended to guide the use of implantable cardioverter defibrillators (ICD)” ( S1).

The risk calculator has been made globally accessible through two different routes:

• Free online access of the risk stratification tool (http://doc2do.com/hcm/webHCM.html\)

• Free downloadable application on apple and google store, available since 2015. (https://play.google.com/store/apps/details?id=com.icreadomain.hcmcaluculator&hl=fr&rrdi=com.icreadomain.hcmcaluculator\)

Improved clinical decision making for the management of HCM patients

ICD implantation carries a significant risk (estimated to be 9%) of major complications requiring intervention or further hospitalisation of the patient. Furthermore, ICDs can lead to poor quality of life, especially when patients receive inappropriate shocks which can be painful and estimated to occur in 11% of patients. ICD implantation should therefore only be considered for patients for whom the potential benefits of ICD implant outweighs the potential harms. The pre-2014 clinical guidelines used for assessing the risk of SCD in HCM patients had a low predictive accuracy (positive predictive value of 10.5 to 23.3%), resulting in unnecessary and potentially harmful prophylactic ICD implantation in a substantial number of patients who are at intrinsically low risk of SCD. It has been estimated that 85% of HCM patients who get an ICD never receive an appropriate, life-saving shock ( S5). Using the HCM-SCD risk tool to classify patients into SCD risk groups (low, moderate or severe) based on their predicted probabilities enables clinicians to provide targeted management of patients in whom ICD has the greatest potential to prevent SCD and allows reassurance for the large majority of patients who are at very low risk. The risk prediction tool complements clinical reasoning by providing objective individualised prognostic information.

The Medical Director of the Sarver Heart Center at the University of Arizona affirmed that the guideline algorithm identifies a group with substantially elevated risk for sudden cardiac death, which is important for patients that are young, as the complications associated with an ICD at a young age are significant. She states “Accurately identifying that patient at risk is terribly important clinically” ( S6). Physicians can download an app to their phone or computer “to help you [physician] with a patient at high risk and whether you [physician] should counsel that patient about the risks and benefits of defibrillator implantation” ( S6).

The HCM Risk-SCD tool, therefore, offers improved decision-making for clinicians and is a major landmark in the management of cardiomyopathy. The tool is currently used in cardiac centres worldwide and is mentioned in patient referral letters. 695 cardiologists from across 25 countries participated in a survey conducted by the ESC on the use of the risk tool in clinical practice between February 27^th and April 1^st 2019 ( S7). The survey revealed that there is a widespread use of the tool with 76.3% of the respondents reporting using the tool between 1-5 times in a 6 month period, 12.5% reported using it of 6-10 times and 11.2% reported using it more than 10 times in 6 months. Approximatively 82% of the respondents reported that the tool has improved clinical decision making ( S7). The Clinical Lead for cardiomyopathy at the Guy’s and St Thomas NHS Foundation Trust attested that they “(...) use the sudden death risk prediction model (HCM Risk-SCD) in routine clinical practice” and found that the tool “(…) helps in clinical management of patients with hypertrophic cardiomyopathy” ( S6). Additional supporting letters are available from 2 other cardiac centres including from the clinical lead for heart failure and inherited cardiac conditions at Oxford University Hospitals, which has also confirmed the utility of the tool in their practice “(…) the HCM risk-SCD calculator are fundamental to our daily practice as we strive towards improving patient outcomes in this area. (…) we have adopted (…) HCM Risk-SCD and use it routinely in our clinical practice to guide the risk assessment in our large population of HCM patients and to help rationalise the management of patients with this condition” ( S6).

Improved care and communication for patients facilitating a shared decision making process with their clinicians

It is estimated that for every 13 high-risk patients who receive an ICD as recommended by the 2014 ESC guidelines based on this risk prediction tool, 1 patient could potentially be saved from SCD. The tool also saves unnecessary and potentially harmful ICD implantations in patients who are at intrinsically low risk of SCD.

The tool provides information to patients that empowers them by helping to understand the relative merits of the primary preventative treatment with ICD and their risk of SCD, for example, the implications of no ICD; and the benefits and the risks of treatment with an ICD. It facilitates patient involvement and enables a shared decision making process on treatment between patients and their clinicians, offering patients more personalised care based on their individual risk assessment. The aforementioned ESC survey showed that approximately 77% of the 695 cardiologists who responded from 25 countries worldwide, routinely discuss the risk estimates from the risk algorithm with their patients and that the tool helped in their communication with patients ( S7). This meets the NHS Long Term plan recommendations in improving patient satisfaction through the delivery of a better integrated care involving patients, which has been set has a new challenge for the government in a recent report released by the Health and Social Care Committee (committee appointed by the House of Commons) ( S8). The Chief Executive of Cardiomyopathy UK (the heart muscle charity for patients) said: “This new research shows that this tool, which is already making a real difference to the lives of people with cardiomyopathy, should now be rolled out worldwide so more people can make informed decisions about the treatment options that are best for them” ( S9).

Reducing NHS costs

The underpinning research ( R4) showed that the HCM Risk-SCD tool can be used to avoid unnecessary ICD implants. A very low number of SCDs was observed in HCM patients who had a 5-year predicted risk of SCD of <4% supporting the 2014 ESC recommendation not to implant an ICD in these patents. Consequently, an optimal management of ICD implantations in HCM patients balancing with their SCD risks can be achieved using this tool. The ICD implantation rate in the UK rose sharply until about 2014 and then has been reducing gradually. England showed a 10% drop in the number of ICDs implanted for the year 2017/18 compared to previous years which corresponds to approximatively 1,000 fewer ICD implantations, potentially resulting in cost saving of at least GBP10,000,000 (one ICD device costs the NHS approximatively GBP10,000, then there is additional cost of hospital equipment and stay) ( S10).

Contribution to the understanding of the relationship between patients’ characteristics and SCD

The risk prediction tool has allowed a better understanding of the relationship between the left ventricular maximal wall thickness (MWT), one of the risk factors of SCD, and the risk of SCD. Until recently, the clinical perception was that the more severe the thickening of the heart muscle is the higher the risk of SCD and MWT was one of several clinical features used to guide prophylactic ICD therapy. The development of the risk tool has revealed a non-linear relationship between MWT and the risk of SCD, suggesting that the risk of SCD increases with increase in the thickness of the heart muscle to reach a plateau and declines thereafter ( S11). Thus, the tool has contributed to a better understanding of pathophysiological mechanisms and an improvement on the guidance of ICD implantations, recommending that ICD implantation should not be guided solely on the severity of the left ventricular hypertrophy but a more global SCD risk assessment integrating other risk factors should be used ( S11).

NHS England commissions surgical centres and other services for children with CHD centrally. The following are crucial to this commissioning framework: the service standards set in contracts; the quality dashboards used to assess performance on a quarterly basis; and financial incentives for the provision of specific services. CORU’s research transformed how local clinicians and national regulators monitor CHD surgical outcomes, and how these outcomes are reported in national audit. It resulted in funding for new services, increased the quality and accessibility of outcome data, and improved public understanding of this complex and highly emotive topic. The OR [Operational Research] Society recognised the “significant impact on the lives of children with congenital heart disease” when awarding CORU the 2019 Lyn Thomas Impact Medal for “the academic OR research which best demonstrates both novelty and real-world impact” ( S1).

Research informed national standards for improving the quality of care:

In July 2015, NHS England published recommendations for an improved model of CHD care in the “New Congenital Heart Disease Review” ( S2). CORU’s research on the development of online resources for interpreting survival data ( RP2) and measuring surgical complications ( RP1) was discussed in detail and formed the basis for recommendations. In addition, the review acknowledged the improvements in data quality resulting directly from implementation of PRIAS model: “The PRAiS model (…) enabled meaningful analysis to be performed on 30-days mortality. The development of PRAiS and improvement in data quality has led to a high level of confidence in the 30-day mortality information produced” ( S2).

Subsequently, NHS England published new “Congenital Heart Disease Standards & Specifications” in May 2016. These stipulate the use of PRAiS software by hospitals in monthly reviews of their outcomes: “The Network will (…) review dashboard metrics including PRAiS mediated variable life adjusted display plots (VLAD) outcomes and unplanned re-interventions, discussion of mortality, morbidity, adverse events and resultant action plans” ( S3) . In addition, they specified quality metrics for a national dashboard to help prevent premature deaths that included the use of PRAiS and the measurement of post-surgery complications ( S3). Since 2016, these metrics have been submitted quarterly to the NHS Congenital Heart Paediatrics Specialised Services Quality Dashboard (SSQD) used to monitor service quality and support improvements. In the two years to September 2019, the inclusion of complication data based on RP1 led to seven instances of hospitals being identified as outliers by the NHS England Quality Surveillance Team ( S5). Subsequently, these hospitals had to account for high complication rates and detail the measures put in place for improvement.

CORU’s research on targeting improvements ( RP3) directly informed commissioning of CHD services. Specifically, recommendations from this research were implemented by NHS England setting standards on: 1) the information that should accompany children if their care is transferred between services; 2) the employment of more cardiac liaison nurses; 3) each child having a named cardiac liaison nurse; and 4) on the need for regular review of deaths outside hospital by staff working in primary, secondary, tertiary and community care ( S5).

Another recommendation of the research prompted NHS England to introduce, within the Commissioning for Quality and Innovation (CQUIN) framework, financial incentives for the development of home monitoring services for children with just one functioning ventricle. This resulted in the provision of this beneficial service across centres in England that perform cardiac surgery in UK children ( S5).

Improved quality assurance of CHD programmes:

The PRAiS software ( R2) was adopted by the NCHDA and by all 13 hospitals in the UK and Ireland performing children’s heart surgery within one year of its release in March 2013 (purchased through UCL Business at GBP3,000 per licence). CORU’s updated model and software, PRAiS2 ( R3), were adopted by NCHDA and the 13 hospitals within two weeks of its release in June 2016.

Death rates have fallen from 2.5% in 2010-2013 to 1.5% in 2016-2019 ( S4) equating to 40-50 fewer children dying within 30 days of surgery each year. While attributing this improvement to any one factor is not possible, transparency of outcome data is widely recognised as a precondition for, and a key driver of, sustained quality improvement in healthcare. The former Chair of NHS England’s congenital heart services clinical reference group acknowledged “The risk-adjustment for case-mix, user-friendly front-end to the software and the intuitive presentation format have engendered a renewed focus of attention on performance and outcomes throughout provider units. Monthly review of outcomes using these metrics has been a major contributor to enhanced clinical governance, engendered a culture of service review and improvement and in turn improved surgical outcomes.” ( S5)

In April 2015, following CORU’s extensive programme of patient and user engagement, NCHDA adopted seven of the nine complications CORU had recommended for measurement in R4 for national routine collection ( S4), including two particularly driven by parental needs . Prior to CORU’s research, the incidence and impact of these complications was unknown. Data from all UK centres on these complications were reported for the first time in NCHDA’s 2017-18 report (published in 2019), which acknowledged that monitoring them “offer[s] important data (…) of value to parents, the clinicians at the centres undertaking the operations and specialist commissioners” ( S6) .

Five hospitals have monitored complications with a further tool developed by CORU. Its application has increased understanding and enabled better data granularity as evidenced by a Clinical Nurse Specialist: “More frequently we need to use data visualisation tools like this to explain the complexity of the data. The automated slides are easy to use and understand and the fact that in essence we can drill down to see more specific data makes this a powerful and efficient tool for reviewing morbidity outcomes. This tool helps us a lot and is especially useful when trying to explain this sort of data to parents and young patients” ( S7). The Clinical Lead of NCHDA acknowledged the impact of CORU’s research: “CORU’s research in the field of CHD has established state-of-the-art quality assurance metrics (…). The research work with CORU has been and will continue to be a major factor in why the NCHDA is regarded as an exemplar, both nationally and internationally, for outcomes analyses, quality assurance and targeted quality improvement initiatives in the field of paediatric and congenital cardiology” ( S4).

Improved public understanding on children’s heart surgery outcomes:

NCHDA’s survival data on children’s heart surgery is used by journalists, politicians, and the public to make difficult judgements about whether heart surgery is “safe”. The Understanding Children’s Heart Surgery Outcomes website developed by Prof Pagel ( R5) launched in June 2016. The site has approximately 3500 users per year, consistent with it being widely used among parents of the 4000 children per year who have heart surgery in the British Isles. The website provides in-depth, state-of-the-art explanations for this sophisticated and complex form of outcomes analysis and is “highly regarded nationally by parent groups, NHSE, the CQC, individual centres and clinicians, as well as internationally, as an exemplar for public reporting of outcomes following CHD surgery” ( S4). One parent acknowledged, “it [is] reassuring to know there is a site we can go to for impartial and trustworthy information. (…) I also now understand what the existing data on children's heart surgery can and can't tell us” ( S8). The website was complimented in the national press and endorsed by major stakeholders including charities, clinical specialists and Royal Colleges ( S9) . An editorial in leading medical journal The Lancet commented that the website “does an excellent job of explaining what these statistics can and cannot tell parents and how they should be used” and that “many more areas of medicine requiring risk communication should take this initiative as a long overdue and most welcome example” ( S9).

Prof Pagel’s research for the website “had a strong influence on the development, functionality and success of our Hospital Navigator”, an online portal developed by the Conquering CHD charity and the Society of Thoracic Surgeons to help parents access and interpret USA survival outcomes after heart surgery ( S10). The design, language, and content of Hospital Navigator were inspired by Professor Pagel’s work, which is “highly regarded and became recognised as best practice” ( S10).

Professor Smith investigated and modelled various aspects of aircraft icing impacts. Accurate information on the accumulation of ice on aircraft flying through cloud (at or below freezing temperature) is crucial for planes’ performances and has been a significant factor in a number of accidents. AeroTex UK (AeroTex) used UCL’s research findings to underpin its specialist icing work, ranging from ice accretion physics to the design and certification of ice protection systems for customers in Europe, Asia and North America, including Meggitt Aerospace, GKN Aerospace, Zodiac-Intertechnique (now part of SAFRAN) and Villinger R&D (trading as Laminar De-Ice). The realistic modelling has informed the design of aircrafts and ice protection systems, resulting in improved aircraft safety. The collaboration between UCL’s team and AeroTex influenced the development of new methods to fulfil regulatory requirements. It also improved productivity and financial performance of the company.

Development of new methods and their influence on capabilities and industry standards

Investigations into several plane crashes in the 1990s and early 2000s found that accidents were caused by ice build-ups on the wings during conditions such as freezing rain. In 2010, FAA proposed new regulations that require airplanes most affected by SLD and ice crystals to meet certain safety standards during icing conditions. These proposals formed the basis for the final rule approved in 2014 . The European Aviation Safety Agency (EASA) proposed similar updates to their certification specifications for large aeroplanes in 2011. It is now mandatory to certify new aircraft against the new requirements, for Large Aircraft (CS-25), and is strongly encouraged for smaller business jet and regional aircraft (CS-23).

AeroTex provides industrial solutions for clients (such as Boeing and Airbus) to comply with the FAA and EASA regulations. Professor Smith’s research has enhanced the modelling capabilities of AeroTex since 2014 through the development and adaptation of computational codes for ice growth, ice crystal impact, splashing, disintegration and particle trajectories within the company’s modelling framework for complex icing problems. Stated by the founder of AeroTex: “Over the course of our collaboration with Prof Smith’s team at UCL, the developments related to our icing work have significantly increased our modelling capabilities. Early work with Prof Smith integrated the icing physics that is included in our 2D Lagrangian code into a 3D Eulerian code allowing the analysis of complex 3D geometries that were previously outside of our capabilities” ( S1). These codes formed the basis of the Aircraft Icing Design (AID) analysis tool that AeroTex uses for analysing the on-plane ice protection systems for major industry clients.

AeroTex supports aircraft manufacturers, airframers and systems suppliers in gaining icing certification for their products by providing accurate simulation tools. In one of several recent projects, AeroTex implemented methods developed by Professor Smith and his team to efficiently and accurately calculate the heat transfer coefficient over a range of aircraft geometries and airflows. This enabled AeroTex to model a wider range of scenarios and physical dynamics as well as to increase the scope for the application to a diverse range of aircrafts (from helicopter rotors and inlets, through to business jets and large commercial aircrafts). As stated by AeroTex's owner: “With the valuable input provided by UCL to our code development, we have managed to maintain our position as one of the leading suppliers of aircraft icing design support services worldwide” ( S1).

Furthermore, testing in a wind tunnel can take many days and cost approximately GBP50,000 per day ( S1). [TEXT REDACTED FOR PUBLICATION].

Increased commercial performance of AeroTex

The application of methods developed by UCL helped AeroTex to become competitive in aerospace consultancy and to secure commercial and development bids. [TEXT REDACTED FOR PUBLICATION].

Capacity building for aircraft safety assessment

AeroTex benefited from the computational codes developed by Professor Smith’s team as part of their industry placements. These codes allowed the company to apply expertise in modelling for the analysis of large droplets, and hence improve Aerotex’s abilty to “assess more physical aspects of the large droplet phenomena. This allows [us] to predict the details of the impingement more accurately on various aircraft surfaces and therefore tailor heater positions, power and scheduling, to fully address these issues” ( S1). AeroTex continued contributing to the sector’s understanding on aircraft icing, modelling and prevention part of several large international programmes (FP7 STORM; Cleansky 2 – InSPIRE & GAINS; SENS4ICE) between 2014 and 2020 ( S1).

Professor Baio’s BESTII research on the decisions to fund the nine-valent HPV vaccine have been cited directly by several international jurisdictions in Italy, Canada and the UK, with authorities later modifying policy guidance for HPV vaccination based on Professor Baio’s recommendation. The policy change has led to the extension of HPV vaccination programme to 2,000,000 males in Italy (with approximately 35% already vaccinated), generating savings of approximately EUR71,000,000 per year for the Italian national healthcare service. In addition, Professor Baio’s research on the cost-effectiveness of Meningococcal group B bacteria vaccination informed policy changes and promoted the protection of 800,000 babies per year in the UK.

Extending the vaccination programme against HPV in Italy

Italian teams of economists collaborating with the UCL research team presented the BESTII study results to the Italian Medicines Agency and Servizio Sanitario Nazionale (SSN; the Italian equivalent of NHS). The latter used these results as part of the evidence base to motivate changes in the national guidelines on the vaccination programmes (‘Piano Nazionale Prevenzione Vaccinale’, PNPV 2017-2019), which were revised in January 2017 to expand HPV vaccination to 12-18 year old males. The PNPV 2017-2019 guideline directly cites the UCL team’s work as evidence to EUR71,000,000 reduction of direct costs estimated for diseases caused by HPV virus: “a recent economical evaluation model (…) estimates a 64% reduction of HPV-related events in males following a universal vaccination” ( S1). Following this change in regulation, the SSN covered the costs of HPV vaccinations for approximately 2,000,000 males aged 12 to 18 years old ( S2). The long-term savings for SSN are estimated at EUR71,000,000 per year (approximately GBP63,000,000) ( S1), due to a reduction in male HPV-related diseases and their subsequent diagnosis and treatment.

Economic impact on the HPV vaccine manufacturers

The development of more advanced quadrivalent vaccination exhibited a potential benefit through targeting 4 strains of HPV. However, it involved higher acquisition costs compared to the bivalent vaccine, which at the time was provided in Italy for female vaccination at the age of 12-15 years old, in accordance with national guidelines. In addition, there was inconsistent evidence regarding the potential effects on population health of including young males in the vaccination programme. As a result of the impact of the BESTII study [ R2] and the subsequent change in the Italian guidelines, the overall annual expenditure for HPV vaccines in Italy increased by 17.4% in 2017. The Italian National Vaccination Plan provides universal anti-HPV vaccination with Gardasil-9 produced by Merck, with an estimated income for the vaccine manufacturer of EUR23,100,000 ( S3).

Informing policy changes to the HPV vaccination programme in the UK

Results from underpinning research informed the letter that Professor Giampiero Favato wrote to the then UK Health Secretary Jeremy Hunt on 13th June 2016, urging the UK Government to extend the national HPV vaccination programme to include all adolescent boys, potentially protecting over 400,000 boys per year ( S4). In addition, these results were part of the evidence presented to the Joint Committee on Vaccination and Immunisation (JCVI), the UK’s independent expert advisory committee to ministers and health departments on immunisation. In July 2018, the JCVI concluded that “(…) a gender neutral programme would provide resilience against short-term fluctuations in uptake as well as offer the prospect of better control of the main cancer causing types of HPV” ( S5), thus resulting in the Government’s implementation of the gender-neutral HPV vaccination in the UK since September 2019. Currently, 12 and 13 year olds are routinely offered the first HPV vaccination, while a second dose is offered 6 to 24 months later ( S5).

Officials stated that the universal vaccination programme is “[…] firmly grounded in evidence to ensure that we can get the best outcomes for patients”, while the Head of Immunisations at Public Health England stated: “I’m pleased that adolescent boys will be offered the HPV vaccine. Almost all women under 25 have had the HPV vaccine and we’re confident that we will see a similarly high uptake in boys. This extended programme offers us the opportunity to make HPV-related diseases a thing of the past and build on the success of the girls’ programme, which has already reduced the prevalence of HPV 16 and 18, the main cancer-causing types, by over 80%. We can now be even more confident that we will reduce cervical and other cancers in both men and women in the future” ( S6).

Towards establishing a universal vaccination programme against HPV in Europe and Canada

The BESTII study, together with other evidence, informed the European Parliament’s European Immunisation Week campaign in 2017, which saw the launch of a new report: “Improving health equity and cancer prevention outcomes: HPV vaccination for boys and girls” ( S7). Moreover, the BESTII study has also provided evidence on the cost-effectiveness of adding males to current HPV vaccination protocols to “Public consultation on draft guidance for introduction of HPV vaccines in EU countries: focus on 9-valent HPV vaccine and vaccination of boys and people living with HIV” from the European Centre for Disease Prevention and Control in April 2019 ( S7). Indeed, many more countries have already implemented or are preparing to implement universal HPV vaccination, including Croatia, Norway, Germany, Serbia, and New Zealand ( S7). The results from the BESTII study were also part of the evidence on the economic advantages of extending HPV vaccination age in both females and males that informed the Canadian guidelines on HPV immunization programme. Based on BESTII and other reviewed studies, The Canadian Agency for Drugs and Technologies in Health extended the vaccination programme to males up to 26 years old ( S7).

Informing policy changes to the Meningococcal group B bacteria vaccination programme in the UK

In 2013, the JCVI decided against recommending the use of Bexsero, the first vaccine developed against Meningitis B bacteria (MenB; one of the leading infectious killers in young children, with 5% mortality rate, and responsible for more than 90% of meningococcal infections in children under one). Bexsero had been approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) and was one of only two vaccines available against MenB. The decision was based on the analysis, developed by researchers at Warwick and the London School of Hygiene & Tropical Medicine (LSHTM), of the impact and cost-effectiveness of different vaccination strategies using a model based on ODE’s, which concluded that the vaccine did not represent value-for-money, at the price requested by the manufacturer (originally Novartis).

[TEXT REDACTED FOR PUBLICATION]

Bexsero (then marketed by GSK) was added to the UK infant immunization schedule starting from September 2015, enabling the annual protection of 800,000 babies (at a cost of GBP16,000,000). In the first three years of the vaccination programme against MenB, cases of the disease decreased by almost 62% in children who received at least two doses. Specifically, between 2015 and 2018, an estimated 277 out of 446 expected cases were prevented because of the vaccine ( S10).

UCL’s research has led to impacts in three key areas: algorithms, modelling disease outbreaks, and non-Newtonian fluids. Through research, its application and public engagement, Dr Hannah Fry and Professor Helen Wilson have cultivated a greater awareness of the use of mathematics applied to real-world scenarios. Engagement via broadcast and press media as well as social media have increased the appreciation of mathematics in a global audience of millions. Outreach engagements with schools have had a strong and positive impact on encouraging further studies in mathematics among GCSE and A-level students. By presenting female mathematicians as role models, they demonstrated that mathematics is not a purely male pursuit.

Improving public understanding of the applications of mathematics: algorithms

The use of spatial decision‐making in crime prevention ( R2) is one of the chapters in the book Hello World ( R1) that has engaged over 140,000 readers ( S1). It was also discussed by Fry in two YouTube videos “Being Human in the Age of Algorithms” and “The Mathematics of Crime and Terrorism” which were watched approximately 30,000 and 700,000 times, respectively ( S1). The videos have stimulated public interest in mathematics with viewers commented “I'm studying safety and security right now and this is really interesting”, “This makes me want to understand maths better than I do” ( S1).

By discussing the benefits of algorithm applications and the consequences of their misuse in Hello World ( R1), Fry has encouraged changes in the understanding of maths among readers on various career paths, as evidenced by feedback: “I’ve just finished reading your book Hello World and it’s an amazing read. I absolutely back everything you say, spot on! (...) I’m slowly changing the mind-set of the global organisation I work for and will personally purchase a number of your books to give as gifts to global CEO and CTOs” ( S2);

“(…) your book has provided a valuable contribution to my thought process, both personally and for teaching students” ( S2);

“I posted a short blog referencing you as I saw a powerful link between the challenge you present and the concepts, I have been encouraging execs to think about the distinction between decisions and choices” ( S2);

“(…) I am a computer scientist and I am very sceptical about AI, and I really thank you for pointing out the flaws of AI and how to use AI in a way that is truly advantageous” ( S1).

Improving public understanding of the applications of mathematics: how disease is spread

In the project Contagion! The BBC Four Pandemic, engagement with the public was a key part of the research itself. Fry’s contribution to the BBC Four’s Contagion! citizen science project encouraged sign-ups from almost 30,000 participants and over 10,000 App downloads from the Google Play store ( S3). The Contagion! documentary was aired in March 2018 with a viewership of 547,000, making it the most watched show during its debut week ( S3). Fry has been acknowledged for using mathematical modelling to improve public understanding of how a pandemic is spread ( R4). She played “a strong role in preparing for future potential pandemics, by providing movement and interaction data for over 30,000 people” ( S4). The Commissioning Editor for Natural History and Specialist Factual commented on the wide public interest and involvement in the project thanks to which “(…) each download is a step closer to being more prepared for when the next pandemic does strike” ( S3). Indeed, in 2020, the Contagion! documentary continued to encourage discussion on how lockdown could help reduce the reproduction rate (R rate), and mathematical models developed for the Contagion! project continued to be used by media outlets such as BBC Science Focus and Business Insider to communicate the importance of hand washing in the current Coronavirus pandemic. As such, there has been a cascade of information from Contagion! being used to change public attitudes.

Most recently, the Contagion! documentary has been selected for re-broadcast in 6 other countries (Sweden, Norway, Switzerland, Turkey, Taiwan, Hong Kong) to better inform the public and quell misinformation regarding the pandemic caused by SARS-CoV-2 virus ( S5). The CEO of Magnify Media commented “(...) an intelligent and informative documentary, but it’s also a timely one in the light of the misinformation and uncertainty surrounding the coronavirus. Contagion! is a sensitively made programme that explains how pandemics evolve and move around communities, based on reliable modelling techniques and technology” ( S5).

Fry continued using mathematical models ( R5) to explore the future effect of COVID-19 in BBC’s Coronavirus: A Horizon Special. The programme was watched live by 1,800,000 people and was referred to as “[containing] more clear and concise scientific fact in the first five minutes than we’ve had in the last month or so” and “the most fascinating and informative thing I have seen about COVID-19” by viewers on Twitter ( S6). The programme served as an exemplar of contact tracing with key learning reported by the Scientific Advisory Group for Emergencies (SAGE) ( S7).

Inspiring uptake of mathematics among school students, especially on girls

Fry’s principal contribution to inspiring the next generation of mathematicians comes from the research she carried out that led to her book Hello World ( R1), which has sold 143,000 copies worldwide, and its subsequent engagement events. Recognised for her “qualities which are meaningful to young people considering careers in STEM subjects ”, Fry was awarded the 2018 Royal Society Insight Investment Science Book Prize. In 2019, Fry presented the Royal Institution’s Christmas Lecture series, largely based on the book, and including discussions on spatial algorithms from her earlier research ( R2). The Christmas Lecture series was broadcasted on national television as well as online, receiving over 1,800,000 views in total across the episodes ( S8). Due to demand (the live event was oversubscribed 20-fold), the lectures were also live-streamed at 18 school venues across the UK. In addition, Fry’s original ideas detailed in the book Hello World inspired the Christmas Lecture’s Self-Driving Cars Debate Kit which was distributed to over 2,000 teachers and partners (including over 1,000 schools) ( S8). After using the kit, teachers said it had benefited the students for its “use of technology and gets students to think about areas of employment for the future” and that it put “STEM learning in a real-life context” ( S8). An associated event online called “I’m a Mathematician Christmas Lectures Zone” saw 1,156 participants from 55 schools take part. It was highly successful in stimulating students’ interest, with UCL academics providing more than 40 answers and over 200 lines of live chats addressing questions mainly about education and careers in mathematics/STEM. This direct engagement with UCL academics motivated many students. One stated, “I have loved finding out about your inspirations and it has motivated me to do better” ( S8).

Since Wilson and Townsend’s research on the fluid dynamics of the chocolate fountain in 2012 ( R6), the modelling described in the paper has been used as a way to engage interest in mathematics, particularly among secondary school students. The paper has been downloaded directly over 28,000 times and been shared in at least 20 news outlets globally, including the Washington Post, Daily Mail, The Independent, the Smithsonian Magazine, Corriere della Serra and Wired Italy ( S9). In particular, its coverage in First News, a national newspaper for children, has reached a readership of 2,235,888 ( S10). Delivered as part of an interactive activity, the chocolate fountain demonstration has been taken to 14 school events and 8 large multi-school events since 1^st August 2013, inspiring over 5,250 students in the process ( S11).

When Wilson and Fry presented their research on chocolate and crime (respectively) at the Institute of Mathematics and its Applications (IMA) 16+ lectures, a survey revealed that 95% of the 126 attendees gained a greater awareness of how maths is applied to real life and 36% are more likely to consider studying maths at university ( S12). Further impact on the attending students can be demonstrated from this quote from one Head of Maths who stated “(...) some of the talks engaged our students and more than usual of our top set chose to take Further Maths as well as Maths for A-level” ( S13).

To inspire girls into mathematics, both women have presented the underpinning research at a series of events, including the Royal Institution’s “Celebrating Women in Mathematics” (2014 and 2015) and the UCL “Inspiring Women in Mathematics” events. As one teacher commented “our journey home on the tubes was full of Maths Chat. It was wonderful to hear the conversations that were occurring between 13/14-year-old girls”. Many attendees were also inspired to pursue mathematics for A-levels and at university; one noted “(how…) useful the event was in allowing us to think about pursuing maths at A level or University. I have definitely been persuaded and have already looked at careers in operational research. I also believe that education facilities everywhere should hold events such as this to help teens to realise that a career like maths has hundreds of opportunities” ( S13).

Fry’s achievements in public engagement were recognised by the IMA and the London Mathematical Society (LMS) with the Christopher Zeeman medal, the highest award for the Communication of Mathematics in the UK. Nominations cited early dissemination of the research, which eventually formed the book Hello World. Excerpts from the citation for the award state “Hannah Fry is a truly outstanding ambassador for mathematics and it is fitting that she is awarded this prize in acknowledgment of her remarkable impact” for “(…) her most significant achievement (which) is to have inspired a generation of girls in a way that has not been done before” ( S14) .

The number of people living with dementia is rising rapidly owing to increased longevity. Two-thirds of people with dementia (approximately 567,000 in the UK) live at home, with their family providing most of their care ( S1). According to the Alzheimer Society’s estimation, more than 600,000 family members provide GBP13,900,000,000 per year of unpaid dementia care in the UK, however, 40% of the family carers have a clinical depression or anxiety, while others have substantial psychological symptoms ( S1). Family care is pivotal as it exerts a 20-fold protective effect against the risk of care home admission ( S1). Therefore, the wellbeing of family caregivers and providing them with effective support is crucial.

The usefulness of the START psychological intervention for family carers was evaluated in a well-conducted randomised trial, which relied on use of optimal statistical methodologies to ensure accurate and unbiased estimates of the intervention effect. This trial provided robust evidence of clinical and cost-effectiveness of the intervention and has subsequently influenced decisions about guidelines, policy and practice for supporting family caregivers.

Approximately 66% of trial participants continued to use the techniques they had been taught after the programme ended ( S2). The manual and associated resources to deliver the intervention are freely available and can be downloaded (in English, Urdu, Spanish and Japanese) from the UCL website ( S3). The page has been viewed approximately 30,000 times until the end of 2020 ( S4).

Changes to UK guidelines and policy on improving dementia care

The evidence of START’s effectiveness has led policy makers to cite it in national guidance and policy documents. The UK Government included START in The Prime Minister’s Challenge on Dementia 2020 (published in 2015), which set actions to improve dementia care, support and research in England ( S5). They noted that “Carers of people with dementia undoubtedly provide a vital role and we know that the availability of appropriate care and support and the quality of services has a significant bearing on whether carers feel able to take a break from their caring responsibilities” ( S5). The government recommended carers of people with dementia should be aware of and be offered the opportunity for respite, education, training, emotional and psychological support, to better enable them to cope with their caring responsibilities. To allow carers to have a life alongside caring, the guidelines recommend that more employers should have carer friendly policies and practice enabling more carers to continue working and caring. The Government also mandated that NHS England (2016-2017) should provide measurable improvements in all areas of the policy, including quality of post-diagnosis treatment and support for people with dementia and their carers ( S5).

The Chief Executive of Alzheimer’s Research UK (the country’s leading dementia research charity) acknowledged the programme’s importance: “Around 23,000,000 people in the UK – roughly a third of the population – have a close friend or family member with dementia, and it’s these unsung heroes who take on much of the strain of the condition. It’s important to find ways to support carers and protect their health, and these results suggest that the START programme can help reduce anxiety and depression for carers” ( S6).

START was evaluated in the National Institute of Clinical Excellence (NICE) guidelines on Dementia (NG97 Assessment, management and support for people living with dementia and their carers; June 2018). The NG97 evidence committee noted, “The evidence from the 2014 Livingston HTA report which demonstrated that successful non-pharmacological interventions for managing non-cognitive symptoms could be cost saving, due to the reductions in subsequent treatment costs for those receiving early interventions. The committee agreed that this recent HTA report represented the best quality economic evidence available and supported the recommendation for the first line use of non-pharmacological management” ( S7). Whilst the document recommended a variety of approaches for carer support, such as START or a similar intervention, the committee agreed that “the topics covered by START are a good representation of the topics that should be covered in this type of intervention” for carers ( S7).

Improving mental health of dementia patients’ carers and support workers

The publication of the START intervention has generated a lot of interest and enthusiasm from NHS trusts for its adoption and it is now being delivered in one third of London memory clinics.

The Alzheimer’s Society (the UK’s leading dementia support charity) provided funding for dissemination of START, allowing training of 134 clinical psychologists and 39 admiral nurses in 9 UK locations from October 2014 to September 2015. Since then, the UCL team has provided training for 30 staff members in another London trust (NELFT) and others are being trained by the members of the dissemination groups. These trained professionals then cascaded training to others in their area, and this resulted in START being delivered locally to 136 carers across 11 service areas in 2016. A survey carried out in July 2018 by the UCL team indicated that START is being used by at least 24 services over 12 NHS trusts, with approximately 192 carers having received the intervention in 2017 ( S8) . Individuals who completed the training reported better understanding of the condition and how it can cause challenging behaviour. This understanding made it easier for them to cope with psychological distress and improved their wellbeing, with a related improvement in their ability to provide care: “Yesterday I had the feeling of happiness I haven’t had in a long time. I suddenly felt positive and ‘able” ( S8). This is echoed by voices from the dementia support workers, START facilitators and managers at the Alzheimer’s Society:“The work I got to do with START was really meaningful. Personally, I feel that START gave me the opportunity to work closely with carers, building a relationship that I normally wouldn’t get to, helping them to deal with the everyday practical sides of caring”;

“I really enjoyed making an actual difference to people’s lives, literally (…) the feedback from the carers is that it does work (…) it’s nice to know that there is a tool that can help carers that are really struggling”;

“That day is hard, seeing the consultant, trying to get ready and it’s a heavy day. Whereas with this, it’s in someone’s comfortable space and it’s at their own time and it’s looking at strategies (…) The things that maybe aren’t discussed with GPs or even a support worker on a home visit. This really opens up quite a lot more, it helps with exploring a lot more detail into what’s happening in the home and I think that’s really good”;

“I felt like it really highlighted and made my job more meaningful, because often I would come away thinking I’ve not done anything other than sat with a family for an hour and a half and talked about what dementia is (…) START actually gave them that one to one, especially for the carer [to] actually help the person with dementia in the long run” ( S8).

Worldwide implementation of the START intervention

The START intervention has also been adopted by the international community. An online video conferencing version of START was developed in Australia to enable delivery of the intervention from Melbourne and Perth to people in remote communities . By November 2018 , 4 therapists had completed extensive training provided by UCL researchers and 28 carers had already completed the 8-week programme ( S9). Work in 2018-20 enabled delivery to the South Asian community (Urdu translation) . Translation of the START manual into Japanese (2019) enabled 14 people to receive the intervention in an ongoing study in Japan, with 27 receiving training by February 2020 ( S9). A START pilot project was conducted in Hong Kong, where 13 family carers have received training since the manual was translated into Chinese in 2017. Translations into Tamil and Hindi have been trialled successfully and START is now being delivered remotely in India (Chennai, Mysore and New Dehli) ( S10) . In Spain it was trialled in 4 people after consultation about the translation. Unfortunately, plans for the regional authorities to begin implementation in Northern Spain have been delayed by the COVID pandemic ( S10).

START has been adapted (in collaboration with UCL) for delivery in several different contexts and populations. The UCL Institute of Neurology adapted and trialled START for patients with Parkinson’s Disease dementia, and it has been adapted to Lewy Body Dementia (with training already delivered to carers through third sector partners). Furthermore, the success of the START intervention built a team and a method that led to funding further research programmes focused on dementia. These include the DREAMS-START intervention involving a similar style of intervention to improve sleep in people with dementia living at home and a project to improve quality of life in people with dementia.

The 13th Sustainable Development Goal of the United Nations is “take urgent action to combat climate change and its impacts”. To assess the effects of potential future climate changes, and to evaluate the effectiveness of proposed strategies for alleviating them, it is becoming increasingly common to build computer simulators of the systems of interest, and to generate synthetic weather sequences to drive these simulators and determine the system response. The underpinning research provided a tool for generating such sequences, in cases where detailed representations of the underlying weather structure are required. This is fundamental in hydrological applications where the response of a system can be sensitive to both the quantity and timing of precipitation as well as other variables that control evapotranspiration rates. The RGLIMCLIM software package addresses these needs, encourages a structured approach to weather generator construction and proves to be efficient and flexible. In Australia, this research has been used to inform climate change adaptation strategies and analyse rainfall trends. The analysis result supported the decision of the Western Australia Department of Water to double the capacity of the Binningup seawater desalination plant to 100,000,000,000 litres per year, at a cost of around AUD450,000,000 ( S1). The desalination plant continues to operate through this REF period at the increased capacity fulfilling approximately 30% of Perth's water supply requirements ( S2).

Impact on productivity and performance at Mott Macdonald and population of Jamaica

Mott Macdonald is a global engineering, management and development consultancy focused on guiding its clients through many of the planet’s most intricate challenges. During the submission period, the company has won USD500,000 worth of contracts for three international projects in which the RGLIMCLIM software played a fundamental role in climate vulnerability assessment and in capturing climate change impacts; and has carried out a GBP44,000 pilot project for Anglian Water, successfully demonstrating that RGLIMCLIM can improve on standard industry practice in simulating changes in the frequency, duration and magnitude of droughts ( S3).

The international contracts are for projects in Jamaica, Barbados and Sierra Leone. These contracts benefit the consultants in terms of earned fees, and also the communities and civil agencies in regions where projects are being executed. The Jamaica project completed in 2019; the others are ongoing, due to delays that are partly due to COVID-19 which has prevented travel for fieldwork and site visits. In Jamaica, the Essex Valley Climate Change Vulnerability Assessment was commissioned in 2019 by the Ministry of Industry, Commerce, Agriculture and Fisheries as part of the Essex Valley Agricultural Development Project (EVADP). The EVDAP aims to enhance the production and productivity of farmers in an area of around 1,000 hectares, in a socially inclusive, gender equitable and climate sensitive manner: it benefits approximately 150,000 people ( S3, S4). The Government of Jamaica received an amount equivalent to GBP35,515,000 from the United Kingdom Caribbean Infrastructure Partnership Fund (UKCIF) towards the cost of this project. Mott Macdonald was commissioned to perform a detailed hydrogeological characterisation of the water supply aquifer, as well a complete climate vulnerability assessment (CVA) of the different assets of the irrigation scheme (renewable power plant, boreholes, mains and secondary pipes, hydrants and roads). For its work on the CVA Mott Macdonald received USD150,000. The challenges for this project recognised by Mott Macdonald included:

1. “Standard” climate models were unable to provide direct information at a sufficiently fine scale to assess changes in the region’s aquifer recharge or flood risk, both of which are subject to local controls due to shallow soils and limestone geology.

2. The rainfall record in the study area itself (of only three years’ duration) was very limited, so a defensible tool was needed for extracting relevant information from longer records in neighbouring catchments.

Based on their knowledge of industry practice in this kind of project, Mott Macdonald identified that most “standard” approaches would not be suitable but that RGLIMCLIM provided the necessary capability. RGLIMCLIM was therefore used as part of the climate change impact assessment on rainfall, to feed the groundwater recharge model. It allowed a weather generator to be developed quickly, with diagnostic checks to give confidence that the outputs provided a defensible characterisation of future precipitation patterns. The use of RGLIMCLIM enabled reliable estimation of aquifer recharge, which would not have been possible otherwise. The results of the CVA, which was completed in 2019, highlighted the need for additional sources of water and informed the selection of crops in the subsequent EVADP ( S3).

Knowledge exchange and capacity building for commerce

RGLIMCLIM is an open-source software, provided as a library to be run in the R programming environment taking advantage of R’s intuitive interface and graphical capabilities. However, the effective use of its sophisticated methodology can be challenging for those without advanced statistical training. This inevitably limits its uptake in industries where there are established industry-wide practices and resistance to investing time in high-level technical training. The partnership with Mott Macdonald has demonstrate the potential added value from such an investment. The strategy for further building impact from this research has been to develop capacity within Mott Macdonald, which they consider gives them a competitive advantage when tendering for contracts ( S3). The capacity development is being done through short consultancy contributions. Specifically, in the Jamaica project, the weather generator was developed by Professor Chandler, who provided a documented step-by-step approach to the entire process that could be followed in subsequent projects. This has been used as a template by Mott Macdonald staff, with occasional input from Professor Chandler where necessary, when developing weather generators using RGLIMCLIM in other applications.