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What are new antibiotics really worth?

Bac­te­ria are bet­ter than any of us at adap­ta­tion. Repro­duc­ing in min­utes, evo­lu­tion can hap­pen rapid­ly. This is how antimi­cro­bial resis­tance occurs: the germ that devel­ops armour to med­ica­tion is able to pass this trait to its off­spring.

It’s sur­vival of the fittest. Humans are con­stant­ly play­ing catch-up and need new antibi­otics for when the old­er drugs no longer work. But we’re sim­ply not devel­op­ing them fast enough.

A lot of peo­ple think at the first signs of feel­ing slight­ly ill, go to the doc­tor and get an antibi­ot­ic. We need to stop treat­ing these things like sweets

Antimi­cro­bial resis­tance is a huge and ever-grow­ing prob­lem. Resis­tant bac­te­ria already cause more than 700,000 deaths glob­al­ly every year. For­mer UK chief med­ical offi­cer Pro­fes­sor Dame Sal­ly Davies recent­ly called for an Extinc­tion Rebel­lion-style cam­paign to help peo­ple and politi­cians see that antimi­cro­bial resis­tance is as much of a cri­sis as cli­mate change.

Econ­o­mist Lord Jim O’Neill agrees that pub­lic aware­ness of this issue is dan­ger­ous­ly low. From 2014 to 2016, he led an inter­na­tion­al assess­ment, the Review on Antimi­cro­bial Resis­tance (AMR), to analyse the glob­al prob­lem of ris­ing drug resis­tance and pro­pose con­crete actions for tack­ling it.

“Antimi­cro­bial resis­tance does­n’t have its Gre­ta Thun­berg. But the con­se­quences of not solv­ing the prob­lem are more known than cli­mate change,” he says. “It’s a major dilem­ma. A lot of peo­ple think at the first signs of feel­ing slight­ly ill, go to the doc­tor and get an antibi­ot­ic. We need to stop treat­ing these things like sweets.”

Greater aware­ness from the pub­lic could help as overuse of these med­i­cines has led to the prob­lem in the first place. But until phar­ma­ceu­ti­cal com­pa­nies invest in new antimi­cro­bials, the threat of a post-antibi­ot­ic era, when a sim­ple ear infec­tion could be fatal, will not go away.

Sig­nif­i­cant­ly, in July 2019, the Depart­ment of Health and Social Care announced that the NHS will test the world’s first sub­scrip­tion-style pay­ment mod­el to incen­tivise phar­ma­ceu­ti­cal organ­i­sa­tions to devel­op new drugs for resis­tant infec­tions.

Why aren’t new antibiotics being developed?

The tri­al will be led by the Nation­al Insti­tute for Health and Care Excel­lence (NICE), NHS Eng­land and NHS Improve­ment. Phar­ma com­pa­nies will be paid upfront for access to med­ica­tion based on its use­ful­ness, rather than the amount that will be pre­scribed.

We’re used to pay­ing for an antivirus sub­scrip­tion to pro­tect our tech­nol­o­gy, so could an antibac­te­r­i­al equiv­a­lent be what’s need­ed to safe­guard pub­lic health?

Dr Anna Maria Geretti, pro­fes­sor of virol­o­gy and infec­tious dis­eases at the Uni­ver­si­ty of Liverpool’s Insti­tute of Infec­tion and Glob­al Health, points out that some­thing needs to change. The emer­gence and spread of antimi­cro­bial resis­tance has out­paced inno­va­tion.

“Resis­tance to antibi­otics is a grow­ing threat glob­al­ly. There is increas­ing mor­tal­i­ty, espe­cial­ly with cer­tain types of infec­tions for which there are very lim­it­ed treat­ment options, such as gram-neg­a­tive bac­te­ria, that are recog­nised by the World Health Orga­ni­za­tion as ‘pri­or­i­ty pathogens’ and a glob­al threat,” she says.

Bloodstream infection

But for a phar­ma­ceu­ti­cal com­pa­ny, research and devel­op­ment costs for a new antibi­ot­ic are far and above the rev­enue gen­er­at­ed once the drug reach­es the mar­ket. As the med­i­cine will tar­get a high-risk infec­tion, its use would have to be restrict­ed so pathogens do not become resis­tant to it too.

“Appro­pri­ate usage, although an impor­tant health­care objec­tive, is in con­flict with phar­ma­ceu­ti­cal com­pa­nies’ rev­enue objec­tives,” says Beth Woods, senior research fel­low at the Cen­tre for Health Eco­nom­ics.

Launching a brand-new payment model

That’s where this new pay­ment mod­el comes in. It’s based on “delink­age”, where a drug’s prof­itabil­i­ty is iso­lat­ed from its vol­ume of sales. The scheme pro­pos­es that phar­ma­ceu­ti­cal com­pa­nies will be paid upfront for access to new antibi­otics based on how use­ful they are expect­ed to be for patients and the NHS, rather than how often they will be used.

Ms Woods is part of the team at the Pol­i­cy Research Unit in Eco­nom­ic Eval­u­a­tion of Health and Care Inter­ven­tions, which pro­vides cost-effec­tive­ness analy­sis to the Depart­ment of Health and Social Care. Her group will come up with a val­ue-based pay­ment for the new antibi­otics sub­mit­ted for the tri­al.

The first phase of the project will focus on devel­op­ing an out­line for the pay­ment mod­el and select­ing two antibi­otics to under­go the assess­ment, which is like­ly to con­clude at the end of 2020.

“We will learn through this tri­al how effec­tive it is in bring­ing inno­va­tion to patients in need. In the forth­com­ing months, we expect to see the first con­crete pro­pos­als from phar­ma­ceu­ti­cal com­pa­nies to NICE, NHS Eng­land and NHS Improve­ment,” says Pro­fes­sor Geretti.

Can pharma incentives tackle antibiotic resistance?

Under­stand­ably, some peo­ple might feel queasy about the tax­pay­er cre­at­ing incen­tives for big phar­ma. But is it so crazy that it just might work?

“It’s the only ini­tia­tive that any gov­ern­ment any­where in the world has come up with since the AMR review. So let’s give it a chance,” says Lord O’Neill.

But even if the UK scheme does turn out to be an impor­tant step in tack­ling antimi­cro­bial resis­tance, to address glob­al mar­ket fail­ure of new antibi­otics, oth­er health­care sys­tems all over the world will need to fol­low its lead.

Anoth­er dilem­ma is whether the val­ue NICE and the NHS place on a new antibi­ot­ic will be some­thing that is tru­ly attrac­tive to phar­ma­ceu­ti­cal com­pa­nies, while remain­ing eco­nom­i­cal for the health ser­vice.

Accord­ing to Rebec­ca Glover and col­leagues from the Antimi­cro­bial Resis­tance Cen­tre at the Lon­don School of Hygiene and Trop­i­cal Med­i­cine, the mod­el could cre­ate “per­verse incen­tives in the future, with com­pa­nies hold­ing back inno­va­tions in the hope that per­ceived val­ue will increase as antimi­cro­bial resis­tance rates get worse”.

Lord O’Neill believes we won’t see a sig­nif­i­cant shift on antimi­cro­bial resis­tance until phar­ma­ceu­ti­cal com­pa­nies show a firm com­mit­ment to putting pub­lic health before prof­it. “Less talk, more action,” is need­ed, he says.

“The amount of talk about the role of phar­ma­ceu­ti­cal com­pa­nies and new drugs that has gone on for the past four years is ridicu­lous rel­a­tive to the action. I would like the phar­ma­ceu­ti­cal indus­try’s lead­ers to show their Tes­la moments,” Lord O’Neill con­cludes.