The efficacy of an AntiMicrobial (ATM) is traditionally being measured using the Minimum Inhibitory Concentration (MIC); the derived Probability of Target Attainment (PTA) method is further used to evaluate the clinical efficacy at a specific dosing for a specific MIC value. But the MIC and PTA methods fail to capture the broad range of benefits an ATM could bring to the patient, leading to unoptimized value for patients, and a lack of differentiation between ATMs.
The BEAM Alliance has setup a dedicated scientific team, namely the BEAM Task Force-E (BTF-E), to work on this issue and propose solutions for a better match bewteen ATM’s efficacy and patients’ needs, by improving evaluation of ATM efficacy within a regulatory context.
Broken models in the field of ATM
Several knowledge gaps are contributing to the market failure phenomenon faced by the AMR field.
The relevance of the MIC/PTA method as a unique in vitro tool to characterize the efficacy of AMR products might lie at the heart of the problem. It is not appropriate for many of the numerous antimicrobial aproaches, and thus limits their evaluation by minimising the range of differentiation matrices, and possibly omitting specific features of the host, the pathogen or their mode of interactions.
This situation is feeding into a damaging cycle, from both clinical and business perspectives, as it drives drug development towards products with low differentiation margins. Consequences include inappropriate prescription, unoptimized use and low profitability.
Towards an extended vision of antimicrobial activities
Antimicrobial actions can arise from multiple pathways. Expanding the tractability of pharmacological effects will help to enable product differentiation thus improving clinical effectiveness and business attractiveness.
However, validated evaluation methods are still lacking.
The purpose of BEAM Task Force-E (BTF-E) is to develop a vision that will support the validation of a new outcome and ATM use which is appropriate to different pathologies and patient needs.
Based on the pathogenesis of infectious diseases, BTF-E have proposed a six-way approach to characterize ATM activity, with the aim of opening new doors in the field of pharmacological validation. This may also help to improve the definition and characterization of ATM and diagnostic tools.
This approach is summarized within a dedicated document that can be downloaded here.
We are now calling for a first batch of feedback on the concept!
Comments may cover the definition and scope of the different categories, the in vitro tools that could help measure the related activity, etc. Send your feedback to email@example.com
before September 5th, 2019, using the form that can be downloaded here.
BTF-E is interacting with regulators (EMA, EUCAST, FDA, etc.) to define and validate new outcomes supporting the various categories. An Innovation Task Force (ITF) procedure is being launched at EMA.
Lead actors and supports
The BTF-E team is led by:
· Nicolas Tesse
· Guennaelle Dieppois
· Thierry Bernardi
· Lionel Renaud
The work is supported by a grant from JPIAMR. Click here to know more.