Re: The new UK antimicrobial resistance strategy and action plan
This week’s slew of articles focusing on the issue of antimicrobial resistance raise important points about the future challenges of providing healthcare in a world where the previous assumptions about antibiotic treatment effectiveness will have changed 1–4. While further increments in antibiotic stewardship are critical, new and novel agents are required, particularly to address those increasingly prevalent organisms with inherent natural resistance to current antimicrobials (e.g. Acinetobacter baumannii) and those acquiring new resistance mechanisms (e.g. E. Coli and Klebsiella spp.), yet the pipeline of new classes of antimicrobial pharmaceuticals is running dry 5, 6.
Although touched on in these articles, the reasons for the dearth of new antimicrobial agents coming to market have perhaps not been given the attention they deserve.
In order to understand why few new antimicrobial agents are in the pipeline, it is necessary to examine basic economic theory. Porter’s 5 forces model of the dynamics of a competitive market place provide some useful insights 7. The antimicrobial marketplace (and the incentives to invest in new products) is influenced by the balances between the bargaining power of customers (patients / healthcare suppliers / governments) and suppliers (pharmaceutical companies / biotech startups) and the threat of substitutes (other companies’ products including generics) and new entrants (generics companies). Currently the balance is tipped in favour of antibiotic products being available at low cost relative to their social benefit. In addition, the high costs of bringing a new antibiotic to the market and the potential short life span (due to resistance) of any new product, all make the antimicrobial pharmaceutical business an unattractive one in which to invest / remain in 8.
Antimicrobial agents are cheap relative to their therapeutic and social benefit. For example, in the UK a seven day course of amoxicillin (250mg three times daily) costs 95p, and a lifesaving course of ceftriaxone for the treatment of meningococcal meningitis costs less than £142.52 (both treatments which can give many years of productive life for the individual and society after recovery) 9 10. Yet, society is prepared to pay substantially more for treatments where life expectancy may be more limited e.g. the use of trastuzumab (Herceptin ®) in metastatic breast cancer can cost many thousands of pounds (each vial costs £407.40) 11. Tackling this paradox has to be part of the solution to antimicrobial resistance.
Mossialos et al. examined the therapeutic benefit / social benefit pricing of antimicrobials and concluded that pricing based on their benefits to society and the individual could incentivise the development of new antimicrobial agents 8. This has some merit, however, would probably work best where the primary consumer is separated from the direct payment and also where the price paid for each agent is readily influenced. The UK is in such a position – a universal drug tariff, coupled with no direct consumer payment for inpatient antimicrobial therapy and fixed price costs (for consumers) for antimicrobials prescribed in the community would allow policy makers in the UK to take a lead in remodelling the antimicrobial therapy market.
Unless the fundamental mechanisms leading to the current market failure are addressed, it is probable that little progress will be made in improving the flow of new / novel classes of antimicrobials. Indeed it would appear that progress over the last 10 years has been limited. Livermore noted in 2003, that many statements had already been made about the urgency of the problem and that new antimicrobial agents were needed, yet a decade later we are still faced with few new drugs and classes of antimicrobials 5, 12 A paradigm shift in approach is needed, perhaps starting with a dialogue with pharmaceutical companies as to the prerequisites needed to incentivise new antimicrobial development.
1 Godlee F. Antimicrobial resistance--an unfolding catastrophe. BMJ 2013;346:f1663–f1663.
2 Kessel AS, Sharland M. The new UK antimicrobial resistance strategy and action plan. BMJ 2013;346:f1601–f1601.
3 Smith R, Coast J. The true cost of antimicrobial resistance. BMJ 2013;346:f1493–f1493.
4 Torjesen I. Antimicrobial resistance presents an “apocalyptic” threat similar to that of climate change, CMO warns. BMJ 2013;346:f1597–f1597.
5 Livermore DM. Bacterial resistance: origins, epidemiology, and impact. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2003;36:S11–23.
6 Antibiotic Action. http://antibiotic-action.com/whatwedo/ (accessed 19 Mar2013).
7 Porter ME. Towards a dynamic theory of strategy. Strategic Management Journal 1991;12:95–117.
8 Mossialos E, Morel C, Edwards S, et al. Policies and incentives for promoting innovation in antibiotic research. London:
9 Amoxicillin: British National Formulary. In: British National Formulary. London: : BMJ Group and Pharmaceutical Press 2013. 18.104.22.168.
10 Ceftriaxone: British National Formulary. In: British National Formulary. London: : BMJ Group and Pharmaceutical Press 2013. 22.214.171.124.
11 Trastuzumab:British National Formulary. In: British National Formulary . London: : BMJ Group and Pharmaceutical Press 2013. 8.1.5.
12 Kirby T. Europe to boost development of new antimicrobial drugs. The Lancet 2012;379:2229–30.
Competing interests: I have read and understood the BMJ Group policy on declaration of interests and declare the following interests: RP is Associate Professor of Health Protection at the University of Nottingham and Honorary Regional Epidemiologist for the Health Protection Agency East Midlands. RP commented on the draft DH strategy and action plan which led to some modifications. The views expressed here are his own and do not represent those of the University or HPA.