Categories and Definitions
The definitions are intended to be applicable across the different One Health sectors. At launch the focus of the presented information in the Dynamic Dashboard is on human bacterial infections, therefore, the definitions are currently focused on this area. They will be updated appropriately when investments/projects addressing other One Health areas are included in the Dynamic Dashboard.
TABLE OF CONTENTS
- R&D in Scope
- Research Area
- Product-specific Definitions
R&D in Scope
Basic and applied research on AMR that covers all One Health sectors (human, animal, plant and environment).
The infectious agents in scope are provided here.
The activities could include but are not limited to:
- All types of product-oriented and product-based R&D, including research, discovery, development (including field trials), first registration and post registration studies for therapeutics, preventives, promotants and diagnostics
- Research of new or existing medical interventions
- Research into quality and fake or sub-standard products
- Basic research that improves understanding of the pathogen, virulence, transmission, impact of external factors and roles and interaction of different One Health sectors and is not necessarily geared towards a specific product, policies or operational processe
- Operational/implementation research such as exploring improvements to surveillance, access to and optimal use of products, epidemiology-related studies, digital products, infection prevention and control and disease management programs
- Research to inform policy or regulation development or revision
- Relevant research training (such as support for PhDs & post-docs) and network establishment
RESEARCH AREA DEFINITIONS
Research that addresses fundamental aspects of a concept or phenomenon and aims at increasing scientific knowledge, understanding about the disease, immune response, processes or pathogen but is not yet directed towards a specific product, policies, or operational processes.
This is sub-categorised into either ‘fundamental’ or ‘towards a product’ and could include but is not limited to:
Fundamental - no clear path to product development
- Research into the development and mechanisms of persistence, transmission, virulence, immunology, biology and pathology; genetics (including genetically resistant animals and plants); epidemiology and burden; and the interaction between One Health sectors
- Fundamental understanding of biological processes or chemistry involved in the synthesis of compounds, including adjuvants and antigens
Towards a Product - has the potential to become a product
- Search for a potential therapeutic, preventive or diagnostic target
- Early research for the development of imaging or detection technologies/assays
- "Platform technologies" e.g. for vaccines that broadly refer to a system that uses the same basic components as a backbone, but can be adapted for use against different pathogens by inserting new sequences (which then would become product-specific). Also includes the development of animal models to test products (such as mouse models for sepsis).
Any product-specific R&D designed for the treatment of infectionwith an antimicrobial across all product-specific R&D stages such as screening of compounds/antigens, early stages of optimising a hit or work to better understand a target to post registration studies. This could include but is not limited to:
- Improvement of current antimicrobials, treatment regiments and therapies
- Investigation of combination therapies
- Dose optimisation studies
- Investigation of old or off market antimicrobials for optimisation or new targets
- Development of new antimicrobials and therapeutic alternatives to ‘traditional’ antimicrobials, including but not limited to small molecules, natural products, antibodies, vaccines, probiotics and faecal transplant therapy, bacteriophages, antimicrobial peptides, lysins, antitoxins
- Drug quality (including fake or sub-standard drugs) and properties such as oral bioavailability, long half-life, etc that are secondary to activity but can be essential to market viability
- Characterise a target for which some evidence of its usefulness is already available
- Combining identification of target and other aspects such as screening/optimising of compounds
Any product-specific R&D designed to prevent systemic disease (no symptoms, could be both sick and healthy subjects). This could include but is not limited to:
- Identification of vaccine candidate(s): Screening of potential natural or synthetic antigens and other vaccine components (e.g. adjuvants) in a pathogen/disease-specific context and may include e.g. protein/peptide/epitope libraries, antigen-expressing vectors, substances derived from pathogens, weakened pathogens or their toxins, serological activity (neutralising and non-neutralising)
- Studies conducted to assess vaccine candidate for safety and efficacy (e.g. in tissue-culture or cell-culture and animal testing and clinical trials)
- Prophylactics – medication/treatment to prevent disease from occurring- e.g. administered of antimicrobial with appropriate therapeutic dose for limited and disease appropriate duration in healthy subjects at risk of specific infection or where infection/disease is likely to occur
Diagnostics - includes detection, screening and diagnostics
Any product-specific R&D aimed at the development or improvement of detection, screening or diagnosis. This could include but is not limited to:
- Identification of causative agent (including distinguishing between viral and bacterial) and identification of resistance (including resistance profiles), including susceptibility testing
- Development of diagnostic or prognostic tests for clinical use
- Tests and screening tools for population-based, epidemiological studies and surveillance routines aiming at the identification of determinants that are involved in the cause, risk or development of AMR
- Development of companion diagnostics – provide information for the safe and effective use of a corresponding drug or biological product
Any product-specific R&D designed to improve or maintain health and increase productivity and/or growth in the absence of disease/infection. This could include but is not limited to:
- Non-medically important antimicrobials at sub- or non-therapeutic doses used for an on-going duration
- Food/feed additives and/or enzymes, antibodies and microbiome intervention (such as pre-, pro- and syn-biotics)
Any product-specific R&D that does not fit under therapeutics, preventives, promotants or diagnostics. It does not include devices that are part of delivery systems for therapeutics, vaccines or diagnostics. This could include but is not limited to:
- Biocides: used as antiseptics and disinfectants – chemicals and biological agents used for the expressed purpose to control, deter, inhibit or kill harmful microorganisms
- Biofilm-related products (material, devices, particles, etc) that prevent, prohibit or interfere with biofilms
- Other products like medical devices, wound healing products/dressing, anti-adhesions, etc
Operational - includes operational and implementation
Operational and implementation research that aids in decision making and management strategies and could include but is not limited to:
- Infection prevention and control (IPC): Management and interventions aimed at optimizing clinical, veterinary or farming practice related to: disinfection, sterilisation and disease management programmes (e.g. biosecurity, husbandry methods, use of vaccination) and evidence-based guidelines/policies of IPC programmes
- Optimal use / Stewardship: Research and studies to optimise the uptake and use of products (antimicrobials, diagnostics and vaccines and other technologies) with the aim of reducing the emergence or rate of development of resistance and/or the need to consume antibiotics, and normally does not impact product-specific label (see registration and implementation). Includes trials which compare agents against each other to inform clinical practice and guideline development
- Access and Availability: Work that aims to improve the access and availability of AMR- and infection-reducing technologies
- Surveillance: population-level analysis of disease surveillance or monitoring, antimicrobial consumption/usage and resistance trends/development/susceptibility
- Epidemiology: Studies that analyse determinants of health and disease conditions in defined populations, specifically how, who, when, and where they occur. Major study areas include disease causation, transmission, outbreak investigation, disease surveillance, environmental epidemiology, occupational epidemiology, screening, biomonitoring, and comparisons of treatment effects such as in clinical trials
- Social Science: Research to inform behavioural change among humans (individuals, groups, organisations/companies) or in relation to animals, economic analysis to inform and quantify challenges or costs-solutions.Impacts of external factors (such as assessments of the contribution of pollution or contamination); the environmental impact of new antimicrobials; digital products
Capacity building - includes capacity building and infrastructure
Efforts aiming to improve the human or infrastructural resource capacity to address the challenges of AMR. May include but is not be limited to: laboratory capacity, staff training, network formation (for knowledge sharing only), infrastructural or process improvements for example clinical trial conduct – that goes beyond a single product.
Research or investments that will inform the development of, review or revision of policies and regulations (national and international). This could include but is not limited to:
- Relevant research, not listed above, with an objective of informing or proposing concrete changes to policy of influencing stakeholder-action in the field of AMR
- Impact of care services such as research into how social factors, financing systems, structures and processes, technologies and behaviours affect access to care, the effectiveness of care, and development and evaluation of interventions to improve services
- Economic impact, cost benefit analysis, economic models and incentives and market analysis
- Health technology assessments
- Supporting evidence of intervention into national health programmes (economic impact)
PRODUCT SPECIFIC DEFINITIONS
The discovery and preclinical testing of innovative methods, processes, active ingredients, antigens, adjuvants, delivery vehicles/methods, diagnostics. Several in vitro and in vivo methods are applied in order to assess biological activity, immunogenicity, efficacy and safety (toxicological studies) of potential candidates. The preclinical phase concludes with submission of an IND (Investigational New Drug) application with FDA-US or CTA (Clinical Trial Application) EMA-EU by submitting the IMPD (Investigational Medicinal Product Dossier).
- For therapeutics and drug preventives this includes target validation, the hit discovery process (hit identification, hit to lead, lead identification and optimisation)
- For preventative biologics such as vaccines this includes identification, selection and improvement/characterisation of vaccine components (antigen, adjuvant, carrier/delivery system, etc)
- For diagnostics, this includes concept, feasibility, prototype development, and development of technical specifications
The progression of selected candidates from discovery to commercialisation including reformulation and repurposing, validation of manufacturing processes, investigating the efficacy and safety of the product in the field (e.g. clinical trials).
- For therapeutics and preventives this includes clinical trial Phase 1 to Phase 3, also includes trials that will lead to an expansion of the product label (additional indications)
- For diagnostics this includes design lock, validation of manufacturing process, validation of accuracy and analytical performance in (clinical) trials, validation of performance and operational characteristics during uncontrolled routine use in programmatic settings
Approval and post-approval
Refers to the phase following first market authorisation (early-commercialisation) for a specific product. This could include but is not limited to:
- Filing in other, subsequent, legal jurisdictions (countries)
- All subsequent research and monitoring that is a requirement by regulators (post-approval requirements or post-authorisation obligations), such as: paediatric investigation plans (PIPs), pharmacovigilance (phase 4) etc
- Research into product optimisation (such as bioavailability, formulations)
- Clinical studies which help inform how a product should be used in a clinical setting to inform among others product formulary inclusion, guideline incorporation, value assessment and payor decisions
In general, public funding is sponsored by a government agency or other publicly-recognized organization, whereas private funds are donated mainly through private corporations or philanthropic efforts by a private organization or individual.
Public – government
Public funding provided at any level of government. This also includes agencies if located within a ministry/department portfolio.
Public – other
- Research councils: separate legal entities and politically independent from government (they may still be answerable)
- Public universities: state or government owned or receive significant public funds through government
Private – for profit
- Pharmaceutical and Biotechnology companies: entities that research, develop, manufacture, market, distribute, import, offers for sale or sell pharmaceutical products
- Small and medium-sized enterprises (SME): non-subsidiary, independent firms and are classified as micro-entities of up to 10 employees, small companies of fewer than 50, or midsized enterprises up to 250, or those organizations with annual turnover under EUR 50 million
Private – not for profit
Foundations: independent legal entities set up for charitable purpose and are funded by an endowment, an individual, a family or business (corporation). They are often controlled by an independent Board.
Refers to an alliance of multiple countries pursuing a common goal and deal with issues that are global priorities. Examples include the UN organisations such as WHO, FAO and UNEP and others such as OIE, World Bank, G20, EIB and GAVI.
In the AMR field funders support organisations that in turn fund external projects or invest in own activities. Both the upstream grants and the downstream investments will be captured. To avoid double-counting, the notion of funding distributor has been introduced in the data-base. Projects/investments made by a funding distributor are referenced to said funding distributor. This then also allows to trace back the funding flow to where the original investment came from.
Examples of such funding distributors are CARB-X and GARDP. The former is a funding organisation, the latter a product-development-partnership investing mostly in its own projects. Funding arrangements, where different funders work together through a “virtual pool of funding” are not considered a funding distributor, as the individual funded projects are each recorded only once from the respective funders.