Antibiotic resistance and new approaches to antibiotic evaluation and financing

Antimicrobial Resistance (AMR) is an escalating threat to global health. As pathogenic bacteria inevitably become more resistant to existing antimicrobial agents, the mortality rate and costs associated with AMR are expected to rise significantly over the coming decades unless adequate action is taken.

One of the main challenges in combating AMR is the lack of financial incentives for manufacturers to invest in the development of new antimicrobial drugs.

However, innovation in this field is constrained by a fundamental market failure: the traditional business model of pharmaceutical companies relies on revenue from sales, while antibiotics must be used sparingly and in minimal quantities to preserve their effectiveness. The use of a new antimicrobial drug is usually postponed in order to slow the development of resistance. Later, when the drug is finally needed due to resistance to existing treatments, generic versions may enter the market as the patent expires.

Uncertainty in resistance dynamics and patient numbers makes it difficult to predict long-term profitability, leading to a shortage of new drugs and prompting large pharmaceutical companies to exit the antibiotic market. Therefore, governments are seeking ways to make investment in the development of new antibiotics commercially attractive, ensuring that physicians have the necessary tools to combat infections.

In this context, Health Technology Assessment (HTA) plays a key role — it is a process that helps determine the value of new medicines and make informed funding decisions. However, the traditional “one-size-fits-all” HTA approach and standard modeling methods do not account for the specific features of antibiotic therapy and fail to capture the full value of antimicrobial agents.

Why Current HTA Requirements Don’t Work for Antibiotics

  1. Defining the Target Population and Comparators

The key problem is the heterogeneity and small size of patient groups who actually need a new antibiotic. For example, according to ECDC data, the prevalence of infections caused by resistant bacteria in the EU varies greatly — from 5% to over 50%, depending on the region and the pathogen type.

    Clearly defining the population is also complicated by temporal variability — the same bacterium can be resistant in one country but sensitive in another.

    In addition, in most cases, there is no direct active comparator — treatment for resistant infections often relies on the “best available” option, which may be insufficiently effective or unavailable. This makes randomized trials and comparisons difficult.

    2. Evaluating Clinical Outcomes – Going Beyond Traditional Metrics
    Traditional HTA focuses on QALYs and cost per patient. But antibiotics have a very different value profile.

    For instance, a drug that reduces the transmission of resistant bacteria by 10% could save hundreds of thousands of lives by preventing outbreaks, even if it doesn’t significantly improve an individual patient’s condition.

    These “collective” benefits are not captured by traditional models, leading to underestimation of the true value.

    Moreover, antibiotics “support” other medical technologies — chemotherapy, surgery, dialysis. Without effective antibiotics, the risk of complications rises sharply, worsening outcomes across many medical fields.

    3. Population Size and Resistance – A Dynamic Source of Uncertainty
    Currently, the market size for new antibiotics is small. It’s estimated that only 5–10% of all bacterial infection patients need new drugs due to resistance.

    At the same time, the number of such patients is projected to grow by 5–7% annually, meaning a significant increase in demand over the next 10 years.

    Another challenge is predicting the rate at which resistance to a new antibiotic will develop. This process can start as early as 1–3 years after market entry, and its pace depends on usage patterns and healthcare context.

    HTA should use dynamic models that reflect these changes and help forecast long-term value.

    Indirect comparisons, real-world data, and expert assessments are used instead, but these increase uncertainty and require flexible evaluation methods.

    4. Defining Relative Effectiveness
    Due to limited clinical trials and diverse populations, traditional RCTs are often impossible or irrelevant.

    Indirect comparisons, real-world data, and expert judgment are used, which, however, has a degree of uncertainty and requires flexible assessment methods.

    Expanded Value Assessment: STEDI and Multi-Criteria Decision Analysis (MCDA)

    The STEDI model has become an important tool in HTA for antibiotics, as it accounts for five key aspects previously ignored:

    • Spectrum value: A narrow spectrum helps preserve the microbiome and reduce the risk of developing resistance.
    • Transmission value: Treatments that reduce transmission have a “public health” effect.
    • Enablement value: Antibiotics enable the safe performance of complex medical procedures.
    • Diversity value: Maintaining diversity in the antibiotic arsenal prevents monopolies and loss of effectiveness.
    • Insurance value: A strategic reserve that ensures preparedness for future outbreaks.

    Using STEDI in combination with MCDA allows for more comprehensive decisions that account for medical, social, ethical, and economic factors.

    New Funding Models: Delinked Payment and Subscription Models

    A key innovation worldwide is financing models that decouple payment from sales volume.

    • NHS Subscription Model (UK): Fixed annual payments to manufacturers for ensuring access to their antibiotic on demand, regardless of usage. The payment size is based on the antibiotic’s assessed value for the NHS, determined through an adapted HTA process.
    • PASTEUR Act (USA): Provides investments for the development of new antibiotics and fixed-payment mechanisms to ensure availability. Establishes a national program of subscription-style contracts for innovative antibiotics chosen based on innovation, social value, and readiness for supply.
    • Sweden: Uses annual fixed payments that stabilize the market and support innovation. The government pays manufacturers a set annual fee for market availability of new antibiotics. This is a partially delinked model — payments are limited but independent of usage volume.

    These approaches help address the “market failure” in the antibiotic sector, balancing innovation incentives with responsible use.

    Conclusions and Outlook

    Health Technology Assessment for antibiotics requires a comprehensive, flexible, and multidisciplinary approach. Only then can it:

    • adequately reflect the full spectrum of antibiotic value;
    • forecast long-term consequences of resistance;
    • create effective financing mechanisms that stimulate innovation without harming society.

    It is crucial that HTA becomes not only an instrument of economic analysis but also a tool for supporting health strategies capable of tackling the global challenge of antimicrobial resistance (AMR).

    References:
    1. Gajic, I. et al. A Comprehensive Overview of Antibacterial Agents for Combating Multidrug-Resistant Bacteria: The Current Landscape, Development, Future Opportunities, and Challenges. Antibiotics 2025, 14, 221. doi.org/10.3390/antibiotics14030221
    2. Colson AR et al. Antimicrobial Resistance: Is Health Technology Assessment Part of the Solution or Part of the Problem? Value Health. 2021 Dec;24(12):1828–1834. doi: 10.1016/j.jval.2021.06.002
    Schurer M et al. (2023). Recent advances in addressing the market failure of new antimicrobials: Learnings from NICE’s subscription-style payment model. Med. Technol. 5:1010247. doi: 10.3389/fmedt.2023.1010247

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