Concerned about the rising levels of drug resistance whereby microbes evolve to become resistant to antimicrobials, the UK Prime Minister asked economist Jim O’Neill to analyse this global problem of antimicrobial resistance (AMR) and propose concrete actions to tackle it internationally. In July 2014, the UK Government commissioned the Review on Antimicrobial Resistance in collaboration with the Wellcome Trust. The Review is independent and engages widely with international stakeholders to understand and propose solutions to the problem of antimicrobial resistance, from an economic and social perspective. In May 2015, Jim O’Neill, who is widely known for coining the term BRICs for the emerging economies of Brazil, Russia, India and China, was appointed to the House of Lords and became Commercial Secretary to Her Majesty’s Treasury in the UK. He continues to chair the Review on Antimicrobial Resistance in a personal capacity.
‘Push, Pu, Poo’ înîtîatîve or TB drug deveopment
GHSA
Goba Heath Securîty Agenda
R&D
Research and deveopment
PK
Usua drug resîstance
SARS
WHO
Advance Market Commîtment
AMC
uDR
OTC
Pharmacodynamîcs
PD
Methîcîîn-resîstantStaphylococcus aureus
MRSA
US Centers or Dîsease Contro and Preventîon
CDC
ACRONYMS AND AbbREVïATïONS
DND
FDA
US Food and Drug Admînîstratîon
ND4bb New Drugs For Bad Bugs
NGO
US Natîona ïnstîtutes o Heath
MSF
bARDAAdvanced Research and Deveopment Bîomedîca Authorîty
ïnectîon preventîon and contro
Drugs or Negected Dîseases ïnîtîatîve
uK
ïnternatîona deveopment assîstance
uN
Unîted Kîngdom
US Doar
uSD
uS
OrganîsatîonorEconomîcCooperatîonandDeveopment
OECD
Over-the-counter
Brîtîsh Pound
Actîve pharmaceutîca îngredîents
GbP
APïs
AMR
3Ps
NïH
OïE
Heathcare-assocîated înectîon
Gavî, the Vaccîne Aîance
Goba Heath Rîsk Framework or the Future
ïnnovatîve Medîcînes ïnîtîatîve
Goba Antîmîcrobîa Resîstance Surveîance System
G7
Ga
GHRF
GDP
Pharmacokînetîcs
SDGs
Pharmaceutîca and Medîca Devîces Agency (Japan)
PMDA
Tubercuosîs
Word Heath Organîzatîon
UN Sustaînabe Deveopment Goas
Gross domestîc product
Unîted States
Unîted Natîons
TheGroupoSeven(Canada,France,Germany,ïtay,Japan, Unîted Kîngdom, and Unîted States)
DeIned Daîy Dose
DMS
Dîagnostîc Market Stîmuus
CFCs
DDD
Fîxed Dose Combînatîon
ChoroLuro carbons
Antîmîcrobîa resîstance
TheGroupo20(Argentîna,Austraîa,Brazî,Canada,Chîna, France, Germany, ïndîa, ïndonesîa, ïtay, Japan, South Korea, Mexîco, Russîa, Saudî Arabîa, South Arîca, Turkey, Unîted Kîngdom and Unîted States, pus the European Unîon)
ïPC
ïMï
JPïAMRJoînt Programmîng ïnîtîatîve on Antîmîcrobîa Resîstance
ïDA
GlASS
HCAï
G20
FDC
Foundatîon or ïnnovatîve New Dîagnostîcs
FïND
Word Organîsatîon or Anîma Heath
Medîcînes Patent Poo
European Medîcînes Agency
Food and Agrîcuture Organîzatîon o the Unîted Natîons
MPP
MDR
Mutî-drug resîstant
EMA
FAO
European Unîon
Non-government organîsatîon
Médecîns Sans Frontîères (Doctors wîthout Borders)
Eu
FOREWORD bY JïM O’NEïll
When ï was asked to chaîr the Revîew on Antîmîcrobîa Resîstance (AMR), ï was tod that AMR was one o the bîggest heath threats that mankînd aces now and în the comîng decades. My înîtîa response was to ask, ‘Why shoud an economîst ead thîs? Why not a heath economîst?’ The answer was that many o the urgent probems are economîc, so we need an economîst, especîay one versed în macro-economîc îssues and the word economy, to create the soutîons.
ï have very much kept thîs în mînd ever sînce that Irst conversatîon and ît has ramed my team’s approach.
ït îs now cear to me, as ît has been to scîentîIc experts or a ong tîme, that tackîng AMR îs absoutey essentîa. ït needs to be seen as the economîc and securîty threat that ît îs, and be at the oreront o the mînds o heads o state, Inance mînîsters, agrîcuture mînîsters, and o course heath mînîsters, or years to come.
As has now become wîdey cîted, our very Irst paper outîned a word în 2050 where AMR îs the devastatîng probem ît threatens to become uness we Ind soutîons. ï deîberatey chose 2050 as ît îs the same tîmerame assocîated wîth the so-caed BRïC (Brazî, Russîa, ïndîa and Chîna) înspîred word that ï became we-known or. We empoyed two consutancy teams, KPMG and Rand, to undertake detaîed scenarîo anayses, whîch provîded the basîs or our concusîons. As îs now quîte we known, we suggested that wîthout poîcîes to stop the worryîng spread o AMR, today's aready arge 700,000 deaths every year woud become an extremey dîsturbîng 10 mîîon every year, more peope than currenty dîe rom cancer. ïndeed, even at the current rates, ît îs aîr to assume that over one mîîon peope wî have dîed rom AMR sînce ï started thîs Revîew în the summer o 2014. Thîs îs truy shockîng. As we as these tragîc human costs, AMR aso has a very rea economîc cost, whîch wî contînue to grow î resîstance îs not tacked. The cost în terms o ost goba productîon between now and 2050 woud be an enormous 100 trîîon USD î we do not take actîon.
Indeed, even at the current rates, ît îs aîr to “ assume that over one mîllîon people wîll have dîed rom AMR sînce I started thîs Revîew în the summer o 2014. ”
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As wîth a orecasts o thîs sort, ît îs o course possîbe that our estîmates may turn out to be too arge, but we beîeve ît îs even more îkey that they coud be too sma. Thîs îs because we dîd not even consîder the secondary efects o antîbîotîcs osîng theîr efectîveness, such as the rîsks în carryîng out caesarean sectîons, hîp repacements, or gut surgery. And în the short 19 months sînce we started, new orms o resîstance have emerged that we dîd not contempate occurrîng so soon, such as the hîghy dîsturbîng dîscovery o transerabe coîstîn resîstance, reported în ate 2015.
Sînce settîng out the scae o the probem î we do not act, we have been makîng recommendatîons on how we can avoîd such a terrîbe scenarîo. Whatever the exact number, whîch o course we hope wî never become a reaîty, the 100 trîîon USD cost o înactîon means that our recommended înterventîons are extremey good vaue or money on a reatîve basîs.
There has aready been some excîtîng progress sînce we began to set out our proposed soutîons. ïn February 2015, we recommended that a dramatîc boost în surveîance was needed to track resîstance, especîay în the emergîng word. We are very peased în thîs regard, that the UK government has înîtîated theFlemîng Fundto împrove dîsease surveîance ocused on drug-resîstant înectîons în ow and mîdde-încome countrîes, and has contrîbuted 375 mîîon USD to ît. Thîs work îs încredîby împortant or tackîng AMR and ît must go hand în hand wîth the recent împetus to achîeve truy efectîve goba dîsease surveîance and to make sure that heath systems are better prepared or epîdemîcs.
We aso recommended that more research undîng îs needed or AMR to kîck-start eary research înto new antîmîcrobîas and dîagnostîcs. We are deîghted that the UK and Chînese governments have each aready agreed to contrîbute 50 mîîon GBP (72 mîîon USD) to a newGlobal Innovatîon Fund. Thîs Fund wî need to grow înternatîonay and partner wîth other exîstîng sources o undîng or AMR, to I the gaps et by tradîtîona undîng streams and make sure exîstîng and new undîng streams are we coordînated or the beneIt o researchers everywhere în the word.
ït îs greaty rewardîng that many o our recommendatîons are aready beîng taken orward, even beore we pubîshed thîs, our Ina report. But so much more remaîns to be done over the rest o thîs year and the oowîng years. We need to ensure that the approprîate goba bodîes are învoved în reachîng poîcy agreements, and ï have spent consîderabe
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tîme ocusîng on thîs over the ast two years. Gîven my own background and the nature o the AMR chaenge, ît was obvîous that the G20 eaders as we as theîr Fînance Mînîsters woud need to pay a centra roe, and we are peased that the pîeces are în pace or successu progress. ït îs a hîstorîc opportunîty or goba governance that Chîna îs hostîng the G20 în 2016 or the Irst tîme; ît îs în Chîna’s power to ead the word în tackîng the AMR probem meanînguy and gobay rom theîr presîdency onwards.
Four înterventîons are goîng to be partîcuary împortant, out o the 10-poînt pan or tackîng AMR set out în our Ina report.
Fîrst, we need aglobal publîc awareness campaîgnto educate a o us about the probem o drug resîstance, and în partîcuar chîdren and teenagers. ï see thîs as an urgent prîorîty and urge înternatîona campaîgn deveopers, îndustry experts, and non-governmenta organîsatîons to consîder how they coud hep to support an urgent goba campaîgn on AMR. ï thînk thîs îs somethîng that coud, and shoud, begîn thîs summer î we are to reay make progress on AMR, and ît coud be supported at the UN Genera Assemby în September.
Secondy, we need to tacke the suppy probem: we need new drugs to repace the ones that are not workîng anymore because o resîstance. We have not seen a truy new cass o antîbîotîcs or decades. ït îs în poîcymakers' hands to change thîs. We have recommended that countrîes must revîew careuy how they buy and prîce antîbîotîcs, to reward înnovatîve new drugs wîthout encouragîng unnecessary use o new antîbîotîcs. ïn addîtîon to thîs work at the natîona eve, we need a group o countrîes such as the G20 to get together and provîde or a reward to deveopers o new antîbîotîcs ater they are approved or use by patîents. Thesemarket entry rewards, o around one bîîon USD each woud be gîven to the deveopers o successu new drugs, subject to certaîn condîtîons to ensure that the new drugs are not ‘over-marketed’ and yet are avaîabe to patîents who need them wherever they îve. ït îs great to see thîs îdea aready beîng dîscussed by senîor G20 oicîas. ï hope thîs dîscussîon wî transate înto tangîbe actîon durîng theîr Heads o States’ meetîng în September.
Thîrdy, we need to use antîbîotîcs more sparîngy în humans and anîmas, to reduce the unnecessary use that speeds up drug resîstance. To do thîs, we need a step change în the dîagnostîc technoogy avaîabe. ï Ind ît încredîbe that doctors must stî prescrîbe antîbîotîcs based ony on theîr îmmedîate assessment o a patîent’s symptoms, just îke they used to when antîbîotîcs
Irst entered common use în the 1950s. When a test îs used to conIrm the dîagnosîs ît îs oten based on a sow technoogy that hasn’t changed sîgnîIcanty sînce the 1860s. ï can understand why thîs îs the sîtuatîon: there aren’t enough good and rapîd tests to conIrm the proessîona judgment o the doctor, and the tests that are avaîabe are oten more expensîve than prescrîbîng the drugs ‘just în case’. Yet thîs îs not acceptabe: we need to encourage more înnovatîon and, împortanty, must ensure that useu products are used. ï ca on the governments o the rîchest countrîes to mandate now that by 2020, a antîbîotîc prescrîptîons wî need to be înormed by up-to-date surveîance înormatîon and a rapîd dîagnostîc test wherever one exîsts. Thîs wî open the door to învestment and înnovatîon, by showîng cever deveopers that î they buîd rapîd tests they wî Ind a market or them. Once the technoogy has împroved, markets în deveopîng countrîes can be supported wîth a system we have caed adîagnostîc market stîmulus, not dîssîmîar to the great work that Gavî, the Vaccîne Aîance, has done to împrove goba chîd vaccînatîon.
Iind ît încredîble that doctors must stîll “ prescrîbe antîbîotîcs based only on theîr îmmedîate assessment o a patîent’s symptoms, just lîke they used to when antîbîotîcs irst entered common use în the 1950s. ” Fourthy, we must reduce the extensîve and unnecessary use o antîbîotîcs în agrîculture. We Irst need to împrove surveîance în many parts o the word, so we know the extent o antîbîotîc use în the agrîcutura sector. We have then proposed that targets shoud be set by îndîvîdua countrîes or antîbîotîc use în agrîcuture, enabîng governments to have the Lexîbîîty to decîde how they wî reach ower eves o use. Aongsîde thîs we need to make much aster progress on bannîng or restrîctîng the use în anîmas o antîbîotîcs that are vîta or human heath. ï hope the Unîted Natîons meetîng în September wî take actîon on each o these poînts and make progress wîth the Word Heath Organîzatîon (WHO), Food and Agrîcutura Organîzatîon o the Unîted Natîons (FAO), and the Word Organîsatîon or Anîma Heath (OïE).
There are a number o ways to raîse the undîng requîred or actîon rom the pubîc or the prîvate sector: the amounts are
very sma în the context o both spendîng on heathcare and the costs o rîsîng AMR î we do not act. Gîven that antîbîotîcs are a shared resource that socîety and the pharmaceutîca îndustry depend on, there îs a strong case or pharmaceutîca companîes învestîng în AMR to sustaîn theîr own revenue rom other sectors such as oncoogy or surgîca operatîons. That îs why ï have proposed that governments shoud consîder a sma evy on the pharmaceutîca sector, as one o the optîons to raîse undîng or the market entry rewards or new antîbîotîcs. ï woud Ind such a undîng mechanîsm partîcuary attractîve î ît coud be appîed on a ‘pay or pay’ basîs, where those Irms who învest în R&D that îs useu or AMR can deduct theîr învestment rom the charge owed by a payers wîthîn the îndustry.
Athough AMR îs a massîve chaenge, ît îs one that ï beîeve îs we wîthîn our abîîty to tacke efectîvey. The human and economîc costs compe us to act: î we aî to do so, the brunt o these wî be borne by our chîdren and grandchîdren, and et most keeny în the poorest parts o the word.
Chaîrîng thîs Revîew has been one o the most stîmulatîng thîngs I have been lucky enough to do în my proessîonal career, and în addîtîon to many people to thank, I want to both thank and congratulate the UK Prîme Mînîster, Davîd Cameron, or havîng the oresîght to establîsh thîs Revîew, as well as the UK Chancellor, George Osborne. I would also lîke to thank the helpul guîdance o the Revîew’s steerîng group – Dame Sally Davîes, Dr Jeremy Farrar, John Kîngman, Karen Pîerce and Ed Whîtîng, as well as the enthusîasm o Dave Ramsden. And o course my Revîew team: Hala Audî, Jeremy Knox, Wîllîam Hall, Anthony McDonnell, Anjana Seshadrî, James Mudd, Nehanda Truscott-Reîd, Olîvîa Macdonald, Dr Flavîo Toxvaerd and Proessor Neîl Woodord.
May, 2016
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EXECuTïVE SuMMARY
Foowîng 19 months o consutatîon and eîght înterîm papers, each ocusîng on a specîIc aspect o antîmîcrobîa resîstance (AMR), thîs report sets out the Revîew on Antîmîcrobîa Resîstance’s Ina recommendatîons to tacke AMR în a goba way, as commîssîoned by our sponsors, the UK Government and the Wecome Trust.
The magnîtude o the probem îs now accepted. We estîmate that by 2050, 10 mîîon îves a year and a cumuatîve 100 trîîon USD o economîc output are at rîsk due to the rîse o drug-resîstant înectîons î we do not Ind proactîve soutîons now to sow down the rîse o drug resîstance. Even today, 700,000 peope dîe o resîstant înectîons every year. Antîbîotîcs are a specîa category o antîmîcrobîa drugs that underpîn modern medîcîne as we know ît: î they ose theîr efectîveness, key medîca procedures (such as gut surgery, caesarean sectîons, joînt repacements, and treatments that depress the îmmune system, such as chemotherapy or cancer) coud become too dangerous to perorm. Most o the dîrect and much o the îndîrect împact o AMR wî a on ow and mîdde-încome countrîes.
ït does not have to be thîs way. ït îs în poîcy makers and governments’ hands to take steps to change thîs sîtuatîon. Because mîcrobes trave reey, some o the steps that are requîred wî need to be taken în a coordînated way înternatîonay. What îs certaîn îs that no sînge country can sove the AMR probem on îts own and severa o our proposed soutîons wî requîre at east a crîtîca mass o countrîes behînd them î they are to make a dîference. Tackîng AMR îs core to the ong-term economîc deveopment o countrîes and our we-beîng. Soutîons to address ît must have goba access to heathcare at theîr heart and they must hep us to stop wastîng medîcînes that we rey on and yet are exhaustîbe.
To stop the goba rîse o drug-resîstant înectîons, there îs a suppy and demand probem that needs to be Ixed. The suppy o new medîcînes îs însuicîent to keep up wîth the încrease în drug resîstance as oder medîcînes are used more wîdey and mîcrobes evove to resîst them. At the same tîme, the demand or these medîcînes îs very bady managed: huge quantîtîes o antîmîcrobîas, în partîcuar antîbîotîcs, are wasted gobay on patîents and anîmas who do not need them, whîe others who need them do not have access.
Fundamenta change îs requîred în the way that antîbîotîcs are consumed and prescrîbed, to preserve the useuness o exîstîng products or onger and to reduce the urgency o dîscoverîng new ones. Governments shoud be hed accountabe on thîs
goa to reduce the demand or antîmîcrobîas and în partîcuar antîbîotîcs, as shoud the maîn sectors that drîve antîbîotîc consumptîon: heathcare systems, the pharmaceutîca îndustry and the armîng and ood productîon îndustry.
Frsty, thé spécîc stéps to rédûcé démand aré:
1. A massé goa pûc awarénéss campagn
We need to împrove goba awareness o AMR across the board, so that patîents and armers do not demand, and cînîcîans and veterînarîans do not prescrîbe, antîbîotîcs when they are not needed, and so that poîcy makers ensure that poîcîes to tacke AMR are taken orward now. The cost o runnîng a sustaîned pubîc awareness campaîgn across the word woud depend on îts nature and scope. Based on estîmates we have consîdered, ît coud cost between 40 and 100 mîîon USD a year. ït coud be met by a mîx o exîstîng pubîc heath programmes în hîgh-încome countrîes, support or programmes în ow and mîdde-încome countrîes and corporate sponsorshîp or major events.
2. ïmproé hygéné and préént thé spréad o nécton
ïmprovîng hygîene and sanîtatîon was essentîa în the 19th century to counter înectîous dîseases. Two centurîes ater, thîs îs stî true and îs aso crucîa to reducîng the rîse în drug resîstance: the ess peope get înected, the ess they need to use medîcînes such as antîbîotîcs, and the ess drug resîstance arîses. A countrîes need to act. Some în the deveopîng word wî need to ocus on împrovîng the basîcs Irst, by expandîng access to cean water and sanîtatîon. For other countrîes the ocus wî be to reduce înectîons în heath and care settîngs, such as îmîtîng superbugs în hospîtas. The sîmpest way that a o us can hep counter the spread o înectîons îs by proper hand washîng.
There are cîrcumstances where antîbîotîcs are requîred în agrîcuture and aquacuture – to maîntaîn anîma weare and ood securîty. However, much o theîr goba use îs not or treatîng sîck anîmas, but rather to prevent înectîons or sîmpy to promote growth. The quantîty o antîbîotîcs used în îvestock îs vast. ïn the US, or exampe, o the antîbîotîcs deIned as medîcay împortant or humans by the US Food and Drug Admînîstratîon (FDA), over 70 percent (by weîght) are sod or use în anîmas. Many countrîes are aso îkey to
use more antîbîotîcs în agrîcuture than în humans but they do not even hod or pubîsh the înormatîon. The majorîty o scîentîsts see thîs as a threat to human heath, gîven that wîde-scae use o antîbîotîcs encourages the deveopment o resîstance, whîch can spread to afect humans and anîmas aîke. We propose three steps to împrove thîs sîtuatîon. Frst, 10-year targets to reduce unnecessary antîbîotîc use în agrîcuture, întroduced în 2018 wîth mîestones to support progress consîstent wîth countrîes’ economîc deveopment. For thîs to succeed, governments must support and speed up current eforts, încudîng those o the Word Organîsatîon or Anîma Heath (OïE) and others, to measure antîbîotîc use and armîng practîces.Sécond, restrîctîons on certaîn types o hîghy crîtîca antîbîotîcs. Too many antîbîotîcs that are now ast-îne drugs or humans are beîng used în agrîcuture; actîon shoud be taken on thîs urgenty by an înternatîona pane. Thrd, we must împrove transparency rom ood producers on the antîbîotîcs used to raîse the meat that we eat, to enabe consumers to make more înormed purchase decîsîons.
Antîbîotîcs can reach the envîronment în many ways such as through sewage systems (încudîng rom hospîtas) and run-of rom ood-producîng unîts such as arms, and can then pose potentîa probems or AMR. One area that has not receîved enough ocus so ar îs the way that the actîve îngredîents or antîbîotîcs are manuactured, and partîcuary the împact o eluent rom actorîes on AMR în nearby water systems. To tacke thîs we need reguators to set mînîmum standards or the treatment and reease o manuacturîng waste; and manuacturers to drîve hîgher standards through theîr suppy chaîns. Both must take responsîbîîty and correct thîs unnecessary envîronmenta poutîon îmmedîatey.
4.ïmproé goa sûréancé o drûg résstancé and antmcroa consûmpton n hûmans and anmas
Surveîance îs one o the cornerstones o înectîous dîsease management, yet has untî recenty been oten îgnored and remaîns under-resourced în the Ight agaînst AMR. earnîng the essons rom Eboa, countrîes have started to încrease undîng în thîs area recenty, în partîcuar the US government vîa the Goba Heath Securîty Agenda (GHSA), the UK government wîth îts announcement ast year o the 375 mîîon USD Femîng Fund în response to eary recommendatîons made by thîs Revîew, and the Word Heath Organîzatîon (WHO) wîth îts deveopîng Goba AMR Surveîance System (GASS). Wîth oversîght rom the WHO, governments must buîd on these eforts to coect data about the consumptîon o antîmîcrobîas, the eves o resîstance, and the underyîng bîoogîca reasons
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or resîstance, supportîng countrîes that need ît most în doîng so. They must aso put systems în pace now that wî make the most out o the ‘bîg data’ on drug resîstance that wî be generated on an unprecedented scae as dîagnostîc toos are modernîsed and coud computîng îs embraced. These new toos are just round the corner, and ower încome countrîes may be abe to ‘eaprog’ înto usîng them to support surveîance în some cîrcumstances.
Rapîd dîagnostîcs coud transorm the way we use antîmîcrobîas în humans and anîmas: reducîng unnecessary use, sowîng AMR and so makîng exîstîng drugs ast onger. ït îs not acceptabe that much o the technoogy used to înorm the prescrîptîon o împortant medîcînes îke antîbîotîcs has not evoved substantîay în more than 140 years. Rîch countrîes must ead the way to change thîs: they shoud make ît mandatory that by 2020 the prescrîptîon o antîbîotîcs wî need to be înormed by data and testîng technoogy wherever avaîabe and efectîve în înormîng the doctor’s judgement to prescrîbe. Thîs wî spur învestment by gîvîng dîagnostîcs deveopers the assurance that efectîve tests wî be used. Our proposed Goba ïnnovatîon Fund or AMR woud support eary-stage research în thîs area. ïn ow and mîdde-încome countrîes where access and afordabîîty are the maîn barrîers, a dîagnostîc market stîmuus woud provîde top-up payments when dîagnostîcs are purchased, în a sîmîar way that settîng up Gavî, the Vaccîne Aîance, în the eary 2000’s revoutîonîsed goba vaccîne coverage în what was one o the best returns on învestment to support economîc deveopment and webeîng.
6.Promoté dééopmént and ûsé o accnés and atérnatés
Vaccînes can prevent înectîons and thereore ower the demand or therapeutîc treatments, reducîng use o antîmîcrobîas and so sowîng the rîse o drug resîstance. Other aternatîve approaches to both preventîng and treatîng bacterîa înectîons are aso beîng researched, and coud provîde aternatîves to antîbîotîcs în some cases în the uture. We beîeve these approaches shoud be eîgîbe or the same încentîves that we recommend or antîbîotîc deveopment. We thereore need to: 1) Use exîstîng vaccînes and aternatîves more wîdey în humans and anîmas; 2) Renew împetus or eary-stage research; and 3) Sustaîn a vîabe market or vaccînes and aternatîves.
ïnectîous dîsease doctors are the owest paîd o 25 medîca Ieds we anaysed în the Unîted States. ït îs no surprîse that there are not currenty enough candîdates to I hospîta traînîng vacancîes. A sîmîar story appîes to other proessîons reevant to tackîng AMR, rom nurses and pharmacîsts în hospîtas traîned to împrove stewardshîp, to mîcrobîoogîsts and other aboratory scîentîsts doîng surveîance, dîagnostîc testîng and R&D în academîa, governments, pubîc sector organîsatîons or companîes: ocusîng on AMR-reated specîatîes îs oten ess rewardîng Inancîay and în terms o prestîge than other areas o scîence and medîcîne. To change thîs we need an urgent rethînk and împroved undîng to împrove career paths and rewards în these Ieds.
Sécondy, wé mûst ncréasé thé nûmér o éfécté antmcroa drûgs to dééat néctons that haé écomé résstant to éxstng médcnés.
8. Estash a Goa ïnnoaton Fûnd or éary-stagé and non-commérca réséarch
There îs însuicîent prîvate and pubîc învestment în R&D ocused on tackîng AMR. To support eary-stage research, whether ‘bue sky’ or ocused on negected areas îke pharmacoogy or dîagnostîcs, we have proposed a Goba ïnnovatîon Fund endowed wîth up to 2 bîîon USD over Ive years. Excîtîng progress has aready happened durîng the îetîme o thîs Revîew, încudîng the UK and Chîna’s nascent ïnnovatîon Fund ocused on AMR, stepped up eforts în the US vîa the Bîomedîca Advanced Research and Deveopment Authorîty (BARDA), and în Europe vîa the ïnnovatîve Medîcînes ïnîtîatîve (ïMï) and Joînt Programmîng ïnîtîatîve or AMR (JPï-AMR) programmes. The spîrît o the Goba ïnnovatîon Fund we envîsage coud be achîeved by înkîng up and încreasîng the sîze o these înîtîatîves. ït îs crucîa however that ît becomes more than the sum o îts parts: undîng both eary-stage ‘bue sky’ scîence, and R&D that may not be regarded scîentîIcay as ‘cuttîng-edge’, and whîch acks a commercîa împeratîve, în a way that breaks down barrîers to entry and makes undîng avaîabe în countrîes and or organîsatîons that woud not have had access to undîng prevîousy.
9. béttér ncéntés to promoté néstmént or néw drûgs and mprong éxstng onés
For antîbîotîcs, the commercîa return on R&D învestment ooks unattractîve untî wîdespread resîstance has emerged agaînst prevîous generatîons o drugs, by whîch tîme the new antîbîotîc may no onger have patent protectîon or may soon ose ît. The tota market or antîbîotîcs îs reatîvey arge: about 40 bîîon USD o saes a year, but wîth ony about 4.7 bîîon USD o thîs tota rom saes o patented antîbîotîcs (that îs about the same as yeary saes oronetop-seîng cancer drug). So ît îs no wonder that Irms are not învestîng în antîbîotîcs despîte the very hîgh medîca needs. Thîs wî not change untî we aîgn better the pubîc heath needs wîth the commercîa încentîves. Governments must change thîs at the natîona eve by consîderîng possîbe changes to theîr purchase and dîstrîbutîon systems or antîbîotîcs, to Ind ways to support better rewards or înnovatîon whîe hepîng to avoîd over-use o a new product. Thîs can be party achîeved through adjustments to natîona purchasîng and dîstrîbutîon systems, to reLect the dîversîty o heath systems around the word. At the same tîme, or the drugs that are most needed gobay and or whîch goba stewardshîp and goba access are împortant, we need new ways to reward înnovatîon whîe reducîng the înk between proIt and voume o saes and ensurîng that deveopers gîve access and promote stewardshîp gobay. We have proposed a system o market entry rewards o around one bîîon USD per drug or efectîve treatments, whether they are based on new or od drugs that work agaînst resîstant pathogens în areas o most urgent need. As an exampe, tubercuosîs, gonorrhoea, so-caed ‘Gram-negatîve’ pathogens as we as some unga îndîcatîons are a recognîsed to represent a hîgh area o need that are currenty î-served by antîmîcrobîa deveopment. Fînay, harmonîsed reguatîons and cînîca trîa networks can pay an împortant roe în thîs area to ower drug deveopment costs.
Noné o ths w sûccééd wthoût ûdng a goa coaton or acton on AMR and wé consdér that to é oûr ténth récomméndéd ntérénton.
10.bûd a goa coaton or réa acton – a thé G20 and thé uN
AMR îs not a probem that can be soved by any one country, or even any one regîon. We îve în a connected word where peope, anîmas and ood trave, and mîcrobes trave wîth
them. Goba actîon îs thereore essentîa to make meanîngu progress over the ong-term. We ca on the G20 and the UN to ocus on thîs îssue în 2016 and to take actîon on both the suppy and demand o antîmîcrobîas, sparkîng a step-change în the Ight agaînst AMR.
What goa acton on AMR woûd cost
Our broad estîmate or the cost o takîng goba actîon on AMR îs up to 40 bîîon USD over a 10-year perîod.
Wîthîn thîs, we have estîmated that ît woud cost about 16 bîîon USD to overhau the antîbîotîcs and TB R&D pîpeîne usîng new market încentîves such as market entry rewards. Our costs are modeed on achîevîng 15 new antîbîotîcs a decade, o whîch at east our woud be breakthrough products targetîng the bacterîa specîes o greatest concern. We have aso recommended settîng up an AMR Goba ïnnovatîon Fund endowed wîth two bîîon USD over Ive years.
ït îs more dîicut to estîmate the cost o supportîng înnovatîve new dîagnostîcs and vaccînes and then roîng them out, as the cost woud depend very much on the type o products and the sîze o popuatîon who need them. At thîs stage o our work and based on ro out costs or other arge pubîc heath programmes, we estîmate that one to two bîîon USD a year to support take-up gobay woud make a very materîa dîference în these areas.
Further economîc anaysîs îs needed urgenty to understand the împact o reducîng the unnecessary use o antîbîotîcs în agrîcuture, whether that transîtîon woud împose a cost on the armîng sector, how bîg, how dîstrîbuted and or how ong. So ar most anaysîs has ocused on hîgh-încome countrîes and thereore more anaysîs îs needed o the împact în ow and mîdde-încome settîngs.
Fînay, we recommend înterventîons that are not specîIc to AMR but happen to hep address drug resîstance, such as good genera dîsease surveîance and better water and sanîtatîon. These costs are part o norma învestment to achîeve good heathcare and so are not part o the package o goba costs we descrîbe here.
So în tota, we estîmate that the word can avert the worst o AMR by învestîng three to our bîîon USD a year to take goba actîon. Thîs îs tîny în comparîson to the cost o înactîon. ït îs aso a very sma ractîon o what the G20 countrîes spend on heathcare today: about 0.05 percent.
Governments can aford to cover the cost o addressîng AMR by aocatîng resources rom exîstîng heath and economîc deveopment budgets: commîttîng unds to AMR now wî reduce the amount ît costs ater when ît deveops înto an even bîgger crîsîs, whîch wî înevîtaby a to governments. Most o the încentîves we recommend are structured as ‘payments or success’ so they do not requîre upront pubîc învestment înto projects that may not deîver împrovements.
Countrîes can aso decîde to create new streams o undîng to contrîbute to AMR and these woud not need to be the same everywhere, such as transerabe vouchers to reward new antîmîcrobîas, or taxes on antîbîotîcs. These optîons a have theîr pros and cons and în the end wî be reLected în the prîce socîety pays or heathcare.
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What matters most now îs that actîon starts quîcky to reduce unnecessary use o antîmîcrobîas and to revîve învestment în theîr deveopment. ïn thîs respect, one undîng optîon that coud be partîcuary efectîve to shît suppy-sîde resources towards AMR research îs an antîbîotîc învestment charge, whîch woud be împosed wîdey on the pharmaceutîca sector and appîed on a ‘pay or pay’ basîs, meanîng companîes coud eîther pay the charge or învest în R&D that îs deemed useu or AMR. The money rom companîes who pay the charge woud be used to împrove the commercîa market or the successu products such as news drugs, vaccînes or dîagnostîcs. Thîs woud push many more companîes to învest în AMR, matchîng theîr short-term Inancîa încentîves better wîth the act that the îndustry as a whoe depends on efectîve antîbîotîcs to sustaîn a range o areas rom oncoogy to joînt surgery.
Fînay, we hîghîght prîncîpes or how these înterventîons shoud be deîvered în practîce, to îmît new bureaucracy, and co-exîst wîth current înternatîona înstîtutîons and natîona heath systems. Untî the new încentîves are în pace at a goba eve, ît woud be very useu or governments, charîtîes and îndustry to try and test new îdeas and modes at a oca eve.
ït îs tîme to turn îdeas înto efectîve actîon and to sove the probem o drug resîstance. Thanks to the courage and determînatîon o a ew eaders în thîs area, the probem o AMR wî be dîscussed at the UN Genera Assemby ater thîs year and contînues to rîse up the agenda or the G7 and G20 groups o countrîes. eaders în these goba orums must now rîse to the occasîon and agree on practîca soutîons.
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Rééw on Antmcroa Résstancé
ïn 2014, the UK Prîme Mînîster Davîd Cameron commîssîoned the îndependent Revîew on Antîmîcrobîa Resîstance, Chaîred by macroeconomîst Jîm O’Neî, to examîne the growîng threat o AMR rom an economîc perspectîve and to recommend soutîons. The Revîew has been co-sponsored by the Wecome Trust and the Department o Heath. Over the ast 19 months the Revîew has pubîshed eîght thematîc papers that address dîferent aspects o the probem o AMR. These are as oows:
• Antîmîcrobîal Resîstance: Tacklîng a crîsîs or the health and wealth o natîons, December 2014
• Tacklîng a global health crîsîs: ïnîtîal steps, February 2015
• Securîng new drugs: The pîpelîne o antîbîotîcs,May 2015
• Rapîd Dîagnostîcs: Stoppîng unnecessary use o antîbîotîcs, October 2015
• Sae, secure and controlled: Managîng the supply chaîn o antîmîcrobîals, November 2015
• Antîmîcrobîals în agrîculture and the envîronment: Reducîng unnecessary use and waste, December 2015
• Vaccînes and alternatîve approaches: Reducîng our dependence on antîmîcrobîals, February 2016
• ïnectîon preventîon, control and surveîllance: Lîmîtîng the development and spread o drug resîstance, March 2016
Thîs îs the Ina report that pus together a our prevîous recommendatîons as a package o actîons that we beîeve wî be needed to tacke thîs rîsîng threat.