MENARINI Group

Piero Rijli

The rising resistance to antimicrobials observed among an increasing number of microorganisms represents a direct threat to human health. Antimicrobial Resistance (AMR) is far from even slowing down; on the contrary, it is steadily increasing. This has profound consequences for the treatment of infections because it limits the treatment options. This limitation in our ability to treat infections effectively has an impact on the sustainability of the health systems and more broadly on other economic sectors.

Patients infected with a resistant microorganism are less likely to recover with the first antimicrobial therapy and will require extra effort and treatment. This may impair the long-term effectiveness of antibiotics, delay access to effective treatments, increase the rates of treatment failure with concomitant complications, increase hospital stays and eventually lead to higher fatality rates. Resistance also affects empirical treatment – where the clinician selects an antibiotic for the treatment of an infection in the absence of microbiological results – which might result in an underestimation of the risk associated with specific infections and the use of inappropriate antibiotics. The use of accurate and easy-to-use rapid diagnostic testing at the point of care should be increased, to rapidly detect the pathogens responsible for the infection.

The impact of AMR is more dramatic in hospitalized patients and particularly for vulnerable patients such as the immunocompromised and the critically ill. These patients are also exposed to a higher risk of infection by resistant bacteria through contact with health care delivery services, the invasive procedures their conditions often require, and frequent antibiotic treatments.

The economic burden of AMR comes from the fact that its cost is not immediately visible because consumers and suppliers see only a small part of it. Furthermore, AMR compromises the success of many medical interventions that depend on the effective treatment and prevention of infection; for example, immunosuppressive therapies, chemotherapies, and surgeries. Thus, AMR can undermine the safety of hospitals and many interventions that require antimicrobial prophylaxis.

On top of that, AMR has potential detrimental impacts on several social and economic sectors (e.g., the labor market, livestock industries, the tourism industry, etc).

The effects of AMR on societal outcomes are determined mainly by the higher morbidity and mortality it leads to. These two factors affect the size of the labor force and labor productivity.

This has led to the current situation, where information on the economic burden of resistance is available, but the value of that information to those in charge of designing and implementing strategies to deal with resistance is limited.

There is a need to raise awareness and educate health economists, pharmaceutical companies, policy, and decision-makers that antibiotics are associated with multiple value elements and that economic evaluations need to be conducted at a population level to account for externalities related to antibiotic use.

This determines that as for other areas of unmet medical need, pricing and reimbursement of new antibiotics should reflect the real societal value and not just the price/volume dimension.

The regulatory authorities and reimbursement bodies need to work together. It is difficult to consider the health gain of an antibiotic in an economic evaluation looking only at non-inferiority trials. PK/PD data should also inform the decision together with microbiology surveillance data. Given that microbiology surveillance data can be seen as a kind of real-world evidence (RWE); agencies can also draw on guidelines on the use of RWE for reimbursement decision-making.

The reimbursement agencies need to adapt the methodological guidelines on the standard economic evaluation framework to accommodate the different value elements of antibiotics. More research is needed to assess the societal value of antibiotics in general and how the value elements of antibiotics can be aggregated.

The economic evaluations of new antibiotics submitted to HTA bodies attempt to incorporate value elements of antibiotics for society, not only for patients. Also, an economic evaluation needs to consider various modes of employing the new antibiotic, including its use as a last-resort treatment.

The existing economic models for new innovative antibiotics have limitations mainly due to the urgent need to reduce resistance through responsible use. Therefore, volumes are limited and the business case is often negative.

A cured patient is not only the manifestation of the success of individual treatment, but it is also the demonstration of a value to the society at large, in the fight against AMR. The standard economic evaluation today under-values antibiotics because their beneficial effect on society is not considered. On the contrary, the empiric use of existing antibiotics triggers disease transmission and resistance development.

Such an approach is required to maintain the value of antibiotics for current and future patients, and for enabling medical and surgical procedures that rely on antibiotic prophylaxis.

An assessment of the societal value of antibiotics will also act as a strong incentive for pharmaceutical companies to invest in the research and development of new antibiotics.