TACKLING DRUG-RESISTANT INFECTIONS GLOBALLY

1 TACKLING DRUG-RESISTANT INFECTIONS GLOBALLY : FINAL report AND RECOMMENDATIONSTHE REVIEW ON ANTIMICROBIAL RESISTANCE CHAIRED BY JIM O NEILLMAY 2016 CONTENTS FOREWORD BY JIM O NEILL ..1 EXECUTIVE SUMMARY ..41. THE PROBLEM: WHY TACKLING AMR IS ESSENTIAL ..102. WE MUST REDUCE THE DEMAND FOR ANTIMICROBIALS SO THE CURRENT STOCK OF DRUGS LASTS LONGER ..17 INTERVENTION 1: A GLOBAL PUBLIC AWARENESS CAMPAIGN ..19 INTERVENTION 2: IMPROVE SANITATION AND PREVENT THE SPREAD OF INFECTION ..21 INTERVENTION 3: REDUCE UNNECESSARY USE OF ANTIMICROBIALS IN AGRICULTURE AND THEIR DISSEMINATION INTO THE ENVIRONMENT ..24 INTERVENTION 4: IMPROVE GLOBAL SURVEILLANCE OF drug RESISTANCE AND ANTIMICROBIAL CONSUMPTION IN HUMANS AND ANIMALS.

2 32 INTERVENTION 5: PROMOTE NEW, RAPID DIAGNOSTICS TO REDUCE UNNECESSARY USE OF ANTIMICROBIALS ..35 INTERVENTION 6: PROMOTE DEVELOPMENT AND USE OF VACCINES AND ALTERNATIVES ..40 INTERVENTION 7: IMPROVE THE NUMBER, PAY AND RECOGNITION OF PEOPLE WORKING IN INFECTIOUS DISEASE ..443. WE MUST INCREASE THE SUPPLY OF NEW ANTIMICROBIALS EFFECTIVE AGAINST drug resistant BUGS ..47 INTERVENTION 8: A GLOBAL INNOVATION FUND FOR EARLY STAGE AND NON COMMERCIAL R&D ..49 INTERVENTION 9: BETTER INCENTIVES TO PROMOTE INVESTMENT FOR NEW DRUGS AND IMPROVING EXISTING ONES ..524. HOW TO PAY FOR IT: TACKLING AMR IS AFFORDABLE ..645. IDEAS FOR IMPLEMENTATION AND NEXT STEPS ..69 SUMMARY OF RECOMMENDATIONS.

3 73 ACKNOWLEDGEMENTS ..76 ACRONYMS AND ABBREVIATIONSAMC Advance Market CommitmentAMR Antimicrobial resistance APIs Active pharmaceutical ingredientsBARDA Biomedical Advanced Research and Development AuthorityCDC US Centers for Disease Control and PreventionCFCs Chlorofluro carbonsDDD Defined Daily Dose DMS Diagnostic Market StimulusDNDi Drugs for Neglected Diseases InitiativeEMA European Medicines Agency EU European UnionFAO Food and Agriculture Organization of the United NationsFDA US Food and drug Administration FDC Fixed Dose Combination FIND Foundation for Innovative New DiagnosticsG20 The Group of 20 (Argentina, Australia, Brazil, Canada, China, France, Germany, India, Indonesia, Italy, Japan, South Korea, Mexico.)

4 Russia, Saudi Arabia, South Africa, Turkey, United Kingdom and United States, plus the European Union)G7 The Group of Seven (Canada, France, Germany, Italy, Japan, United Kingdom, and United States)GARD Global Antibiotic Research & Development Gavi Gavi, the Vaccine Alliance GBP British PoundGDP Gross domestic productGHRF Global Health Risk Framework for the FutureGHSA Global Health Security AgendaGLASS Global Antimicrobial Resistance Surveillance SystemHCAI Healthcare-associated infectionIDA International development assistanceIMI Innovative Medicines InitiativeIPC Infection prevention and controlJPIAMR Joint Programming Initiative on Antimicrobial ResistanceMDR Multi- drug resistantMPP Medicines Patent PoolMRSA Methicillin- resistant Staphylococcus aureusMSF M decins Sans Fronti res (Doctors without Borders)

5 ND4BB New Drugs For Bad BugsNGO Non-government organisationNIH US National Institutes of HealthOECD Organisation for Economic Cooperation and DevelopmentOIE World Organisation for Animal HealthOTC Over-the-counterPD PharmacodynamicsPK PharmacokineticsPMDA Pharmaceutical and Medical Devices Agency (Japan)R&D Research and developmentSARS Severe Acute Respiratory SyndromeSDGs UN Sustainable Development GoalsTB Tuberculosis UDR Usual drug resistanceUK United KingdomUN United NationsUS United StatesUSD US DollarWHA World Health AssemblyWHO World Health Organization 3Ps Push, Pull, Pool initiative for TB drug development 1 When I was asked to chair the Review on Antimicrobial Resistance (AMR), I was told that AMR was one of the biggest health threats that mankind faces now and in the coming decades.

6 My initial response was to ask, Why should an economist lead this? Why not a health economist? The answer was that many of the urgent problems are economic, so we need an economist, especially one versed in macro-economic issues and the world economy, to create the have very much kept this in mind ever since that first conversation and it has framed my team s is now clear to me, as it has been to scientific experts for a long time, that TACKLING AMR is absolutely essential. It needs to be seen as the economic and security threat that it is, and be at the forefront of the minds of heads of state, finance ministers, agriculture ministers, and of course health ministers, for years to has now become widely cited, our very first paper outlined a world in 2050 where AMR is the devastating problem it threatens to become unless we find solutions.

7 I deliberately chose 2050 as it is the same timeframe associated with the so-called BRIC (Brazil, Russia, India and China) inspired world that I became well-known for. We employed two consultancy teams, KPMG and Rand, to undertake detailed scenario analyses, which provided the basis for our conclusions. As is now quite well known, we suggested that without policies to stop the worrying spread of AMR, today's already large 700,000 deaths every year would become an extremely disturbing 10 million every year, more people than currently die from cancer. Indeed, even at the current rates, it is fair to assume that over one million people will have died from AMR since I started this Review in the summer of 2014. This is truly shocking.

8 As well as these tragic human costs, AMR also has a very real economic cost, which will continue to grow if resistance is not tackled. The cost in terms of lost global production between now and 2050 would be an enormous 100 trillion USD if we do not take action. As with all forecasts of this sort, it is of course possible that our estimates may turn out to be too large, but we believe it is even more likely that they could be too small. This is because we did not even consider the secondary effects of antibiotics losing their effectiveness, such as the risks in carrying out caesarean sections, hip replacements, or gut surgery. And in the short 19 months since we started, new forms of resistance have emerged that we did not contemplate occurring so soon, such as the highly disturbing discovery of transferable colistin resistance, reported in late setting out the scale of the problem if we do not act, we have been making recommendations on how we can avoid such a terrible scenario.

9 Whatever the exact number, which of course we hope will never become a reality, the 100 trillion USD cost of inaction means that our recommended interventions are extremely good value for money on a relative has already been some exciting progress since we began to set out our proposed solutions. In February 2015, we recommended that a dramatic boost in surveillance was needed to track resistance, especially in the emerging world. We are very pleased in this regard, that the UK government has initiated the Fleming Fund to improve disease surveillance focused on DRUG-RESISTANT INFECTIONS in low and middle-income countries, and has contributed 375 million USD to it. This work is incredibly important for TACKLING AMR and it must go hand in hand with the recent impetus to achieve truly effective global disease surveillance and to make sure that health systems are better prepared for also recommended that more research funding is needed for AMR to kick-start early research into new antimicrobials and diagnostics.

10 We are delighted that the UK and Chinese governments have each already agreed to contribute 50 million GBP (72 million USD) to a new Global Innovation Fund. This Fund will need to grow internationally and partner with other existing sources of funding for AMR, to fill the gaps left by traditional funding streams and make sure existing and new funding streams are well coordinated for the benefit of researchers everywhere in the world. It is greatly rewarding that many of our recommendations are already being taken forward, even before we published this, our final report . But so much more remains to be done over the rest of this year and the following years. We need to ensure that the appropriate global bodies are involved in reaching policy agreements, and I have spent considerable FOREWORD BY JIM O NEILL Indeed, even at the current rates, it is fair to assume that over one million people will have died from AMR since I started this Review in the summer of 2014.