Aviva Investors and The University of Cambridge

Provide a brief overview of your project?
We know money talks, so what could it say to help antimicrobial resistance (AMR)?
The financial markets are arguably the most important global markets shaping the daily lives of billions of people through their money and influence. While investors are increasingly vocal on topics such as climate change, their awareness and action around AMR has received little to no attention. Aviva Investors kindly sponsored this masters dissertation at the University of Cambridge to explore if and how large investors could use their trillions of pounds of investments and their influence to tackle AMR, specifically in the pharmaceutical sector.
Inspired by the O’Neill Review, the research asks three questions:

• Why would investors care about AMR?
• Do investors have an interest in taking action?
• What, if anything, can investors do to help the AMR problem?

The results identify the most effective ways all stakeholders in the AMR field can tap into the power of investors to fast track progress on AMR and the barrier they face.

It offers recommendations covering a) what investors can do to stimulate the pipeline of new antibiotics, b) what action investors should be asking the companies they invest in to take around antibiotic stewardship and c) which lobbying activities are the most fruitful.
Please cite 3 examples of outcomes or impacts from the project on tackling AMR.

1) The research is the first academic research piece that applies the body of knowledge around responsible and sustainable investment to the topic of AMR.

2) The Investor year of Action on AMR, launched at the World Economic Forum in Davos in January 2020, will include:

• Events and webinars on AMR
• Inclusion of AMR as a discussion topic at institutional investor conferences
• Media articles and op-eds across global markets
• Research reports
• Public individual investor commitments on AMR

3) Awareness:
In 2020, the release of a report to plug the gap between the macroeconomic implications of AMR, per the O’Neill Report, and what this means in practice. For instance, Big Pharma invests up to 80 times more research and development budget on new oncology drug compared to research and development spend on new antibiotics, simply because oncology is much more profitable and therefore makes the investors in Big Pharma happy. However, oncology products rely upon effective antimicrobials and could be obsolete with runaway AMR.

How is the project to be developed in the future?
The primary vehicle for developing the research is under the 2020 Investor year of action. It is a collaboration between NGOs, Investors and the UK Government to galvanise investor effort to address AMR www.amrinvestoraction.org

The second area of development is around the funding gap specifically:

Define what the funding gap is for AMR innovation and a) if investors could help plug the funding gap on AMR and b) how this sits with the creation of a One Health AMR bond that is attractive to investors.

Great Ormond Street Hospital for Children

Provide a brief overview of your project?
In 2019 we launched the inaugural one day START conference at Great Ormond Street Hospital. This is the first UK conference dedicated to Paediatric Antimicrobial Stewardship and included a pre-meeting the day before with key opinion leaders to map out some important topics and issues for AMS. The conference was named START (Stewardship, Antimicrobial Resistance, Transmission) and aimed at addressing broad issues around AMS. This conference was particularly aimed at the basics of implementation of paediatric antimicrobial stewardship including how to write a business plan, impact of OPAT, and implementation of AMS from two different centers. This was supplemented by interesting research topics and drug resistance specific to paediatrics.
Please cite 3 examples of outcomes or impacts from the project on tackling AMR.

1. The UK-Paediatric Antimicrobial Stewardship network was created from the meeting prior to the conference which has led to many different collaborative projects (see separate award entry)
2. Bringing together key opinion leaders within antimicrobial stewardship in Paediatrics has led to important collaborations and interactions over the following year.
3. Following the meeting the AMS team distributed the slides to all delegates in order to take back learning to colleagues. In particular, specific individuals asked for templates of the business plan for building an AMS team and also some of the framework for the implementation of interventions such as ward rounds.

How is the project to be developed in the future?
START 2020 is being planned for July and builds upon the previous successful conference. The first conference concentrated on the building blocks and implementation of Paediatric AMS and this conference wants to widen the scope of talks to look at a variety of exciting and diverse topics that influence AMS (see poster enclosed). The key stake holder meeting prior to the conference will bring together key members to reflect upon the previous year and to build upon opportunities, including benchmarking outcomes, for the future.

University College Dublin

Provide a brief overview of your project?
Published in January 2020, my monograph “Pyrrhic Progress” analyses over half a century of antibiotic use, regulation, and resistance in US and British food production. Mass-introduced after 1945, antibiotics helped revolutionize post-war agriculture. Food producers used antibiotics to prevent and treat disease, protect plants, preserve food, and promote animals’ growth. Many soon became dependent on routine antibiotic use to sustain and increase production. The resulting growth of antibiotic infrastructures came at a price. Critics blamed antibiotics for leaving dangerous residues in food, enabling bad animal welfare, and selecting for antimicrobial resistance (AMR) in bacteria, which could no longer be treated with antibiotics. Pyrrhic Progress reconstructs the complicated negotiations that accompanied this process of risk prioritization between consumers, farmers, and regulators on both sides of the Atlantic. Unsurprisingly, solutions differed: while Europeans implemented precautionary antibiotic restrictions to curb AMR, consumer concerns and cost-benefit assessments made US regulators focus on curbing drug residues in food. The result was a growing divergence of antibiotic stewardship and a rise of AMR. The book’s comprehensive analysis of evolving non-human antibiotic use and the historical complexities of antibiotic stewardship provides important insights for current regulatory debates on the global burden of AMR and the challenges of risk communication.
Please cite 3 examples of outcomes or impacts from the project on tackling AMR.
Pyrrhic Progress is the first comprehensive historical account of antibiotics’ introduction and transformation of Western food production. Understanding the long-term structural trends of antibiotic use and different cultural perceptions of risk is crucial for improving antimicrobial stewardship. To stimulate meaningful change, the book aims to communicate the infrastructural dimension of antibiotic use in global food production to decisionmakers, producers, and the wider public in an accessible manner.

Research on Pyrrhic Progress was part of a wider interdisciplinary collaboration bringing together medical humanities and sciences researchers at the Oxford Martin School (Program on Collective Responsibility for Infectious Disease). Resulting insights regarding the historical evolution of regulation and usage have served as the basis for several policy recommendations (Van Katwyk et al., Lancet, 2019; Health Care Analysis, 2020, abc). It also informed an award-winning exhibition on the history of antibiotics and antimicrobial resistance at Oxford’s History of Science Museum in 2016/2017 (Back from the Dead, 50,000 visitors, winner Oxford Vice Chancellor Public Engagement with Research Award). Pyrrhic Progress has already been well-received by critics, long-listed for the Royal Irish Academy’s 2020 Michel Déon Prize in non-fiction, and was awarded the 2020 ICOHTEC Turriano Prize in the History of Technology. The Wellcome Trust has decided to finance open access via NCBI Book Shelf (https://www.ncbi.nlm.nih.gov/books/NBK554200/).
How is the project to be developed in the future?
Pyrrhic Progress is the first of a series of publications that explore how antibiotics became ingrained in global food production. As part of my new post at UCD (Wellcome Trust University Award 2020-2025), I will explore how antibiotics spread from high-income to low- and middle-income settings and how the global surveillance of antimicrobial resistance developed after 1945. Knowledge of the historical causes of potential surveillance blind spots and the long- and medium-term cultural and economic dimensions of usage outside of HICs will be key to reducing global antibiotic consumption over the next decades.

University of Leeds

Provide a brief overview of your project?
Background: Clinicians are encouraged to use antibiotics wisely to slow the development and spread of antibiotic resistant infections, yet unnecessary antibiotic use by dentists remains high. Dentists in England are responsible for around 1-in-20 of all NHS antibiotic prescriptions, around 3 million per year. Approaches to date, such as issuing guidance advising dental procedures rather than using antibiotics for toothache/infection, have been inadequate.

Aim of the research: To develop ways to support reduced antibiotic prescribing for adults with acute conditions during urgent NHS dental appointments in England.

How did I approach it? To understand the factors associated with dentists’ antibiotic prescribing behaviour, influences on treatment decisions were explored during urgent dental appointments in NHS high-street practices and out-of-hours dental clinics. Based on observations and follow-up interviews with patients, dentists and dental nurses, a list of factors influencing treatment decisions was produced. Next, people with experience of receiving urgent dental care, dental team members and service/policy managers prioritised the factors and identified those potentially amenable to modification. Finally, behavioural science was applied to underpin the development of an intervention to reduce dental antibiotic prescribing.

What was the outcome? A logic model was produced describing the theory of change and intervention components to reduce antibiotic prescribing by dentists for adults with acute conditions during urgent dental appointments in England. This has informed development of a complex intervention aimed at individual dentists/patients and the dentist-patient dyad. The arts-based element aimed at individuals can be viewed on-line: https://theatreofdebate.co.uk/New/Antimicrobial-resistance/

Dissemination: Co-production with patients and key stakeholders has provided a wide network for disseminating the findings of this research. Presentations at national and international dental, and antimicrobial stewardship conferences have generated extensive interest in the research. Most recently it has been incorporated into the FDI World Dental Federation white paper on tackling antibiotic resistance in dentistry.
Please cite 3 examples of outcomes or impacts from the project on tackling AMR.
This research was undertaken as part of Wendy Thompson’s doctorate degree at University of Leeds. It was supported through an NIHR Doctoral Research Fellowship and by her supervisors: Prof Gail Douglas, Prof Sue Pavitt, Dr Jonathan Sandoe and Dr Rosemary McEachan.

Outcomes from the project have had significant international impact and include:

1. Doctoral thesis published October 2019: Antibiotic Prescribing: Towards a reducTion during Urgent NHS Dental appointments in England (The APTiTUDE Study) (http://etheses.whiterose.ac.uk/25384/). The thesis includes one element of a complex intervention aimed at optimising dental antibiotic use: an arts-based intervention which uses story to address the beliefs of adults (patients and clinicians) about the risks of antibiotic use. This series of 5 micro-dramas can be accessed on-line as either videos or podcasts at: https://theatreofdebate.co.uk/New/Antimicrobial-resistance/
2. Published papers, posters and oral presentations, including:
   • Dental antimicrobial stewardship – Like pulling teeth. BSAC Spring Conference 2020
   • Antimicrobial stewardship in dentistry: an arts-based approach to intervention development. The Lancet, Volume 294, Special Issue S10, November 2019.
   • Factors associated with antibiotic prescribing for adults with acute conditions: an umbrella review across primary care and a systematic review focusing on primary dental care. Journal of Antimicrobial Chemotherapy, Volume 74, Issue 8, August 2019, Pages 2139–2152, https://doi.org/10.1093/jac/dkz152
   • Antibiotics Don’t Cure Toothache: UK Toolkit. International Association for Dental Research General Session, Vancouver 2019
   • Reducing dental antibiotic prescribing: developing a theory-informed complex intervention. ECCMID, Amsterdam 2019
   • Risks and Rewards: Why should business managers care about antibiotics? British Dental Conference & Dentistry Show, Birmingham 2019
3. On the basis of her research, Wendy Thompson was invited by FDI World Dental Federation to be lead author of its White Paper on Tackling AMR in Dentistry (https://www.fdiworlddental.org/news/20191122/meet-dr-wendy-thompson-lead-author-of-fdi-white-paper-on-tackling-antibiotic). This document is currently embargoed until September 2020.

How is the project to be developed in the future?
In partnership between BSAC and FDI World Dental Federation, a dental AMR MOOC is currently being developed which includes insights about dental antibiotic prescribing and behaviour change from this doctoral research. Further research to understand differences in rates of antibiotic prescribing around the world is underway with an international partnership of colleagues from Australia, Canada and USA; initial findings will be presented at ECCMID, Paris 2020. These differences emphasise the need for dental antimicrobial stewardship interventions to be context-specific and to start with an understanding of the problem driving over-prescribing before setting out to develop an intervention to address it.

In the UK, this doctoral research’s key found that a range of individual, team and organisational factors which mean that dental antibiotic prescribing is happening instead of providing dental procedures for people with acute dental conditions. Evaluation of the complex intervention elements developed to address these factors is planned.