Research Agenda Herman Goossens Chair Scientific Advisory Board - - PowerPoint PPT Presentation

Presentation of the Strategic Research Agenda

Herman Goossens Chair Scientific Advisory Board

Members of the SAB

Antoine Andremont Fernando Baquero Marc Bonten Yehuda Carmeli Niels Frimodt-Møller Petra Gastmeier (10/2013) Bruno Gonzalez-Zorn Hajo Grundmann Stephan Harbarth Birgitta Henriques Normark Patrice Nordmann (till 09/2013) Arnfinn Sundsfjord Timothy Walsh Paul Williams Herman Goossens (Chair)

Mission Statement

The SRA of the JPI on AMR will develop integrated approaches to pursue unique world-class research on AMR that will be translated into new prevention and intervention strategies that improve the public health and wellbeing of populations, and delivers economic and societal benefit throughout Europe and beyond.

Overall Goals

To reduce the burden of AMR by:

• Identifying gaps, obstacles and opportunities for

understanding and controlling AMR.

• Stimulating research into the causes, prevention,

diagnosis and treatment of infections caused by resistant organisms.

• Generating novel approaches for improved

healthcare.

• Translating this knowledge into step changes in

policy and practice to safeguard future generations.

Criteria for Selecting Research Priorities

• Be ambitious and broad
• Be groundbreaking at European level
• Have high expected returns
• Be of urgency for Europe and other regions
• Reinforce Europe’s contribution to global public health
• Provide guidance for developing the research agenda

in Europe and globally

• Be complementary, with clear links and synergies

within and across themes

Development Process of the Strategic Research Agenda

• Five meetings of the Scientific Advisory Board
• A consultation process with stakeholders
• A series of expert workshops
• An online public consultation process (1st

September – 15 October 2013)

– 44 questionnaires – 11 national advices of participating countries

Six Research Priorities to Reduce AMR

Therapeutics Diagnostics Transmission Surveillance Environment Interventions

Minimizing antimicrobial resistance Enabling activities

Research Priorities (A-C)

• Development of novel antibiotics and alternatives

for antibiotics – from basic research to the market.

• Design strategies to improve treatment and

prevention of infections by developing new diagnostics.

• Standardisation and extension of surveillance

systems to establish a global surveillance program

• n antibiotic resistance and antibiotic use.

Research Priorities (D-F)

• Transmission dynamics.
• The role of the environment as a source for the

selection for and spread of AMR.

• Designing and testing interventions to prevent

acquisition, transmission and infection caused by AMR.

Agenda: Discuss each priority (background and objectives)

Research Priority A: Development of novel antibiotics and alternatives for antibiotics – from basic research to the market

New systemic antibacterial agents approved by the US FDA per 5-year period Boucher et al, Clin Infect Dis 2013; 56:1685--94

Research Priority A: Development of novel antibiotics and alternatives for antibiotics – from basic research to the market Objectives

• New antibiotics and alternatives to antibiotics

(e.g. Immunotherapy, anti-virulence and anti- colonisation approaches)

• Improve existing antibiotics, including
• ptimisation of drug use, dosage and delivery
• Regulatory and economic aspects, in close

collaboration with private (e.g. EFPIA) and public (e.g. EMA, FDA) bodies

Research Priority B: Design strategies to improve treatment and prevention of infections by developing new diagnostics

Fenn et al 2008; Harvard Business Press, Cambridge Becker, 2009; Lab Chip 9, 2119 – 2122

Diagnostic Targets Product Prototype Lab & field evaluations Test adoption Test introduction: implementation research Epidemiology Genetics & Genomics Proteomics Pathogenesis Immunology Animal models Proof of Principle Technology platform

Innovation Pathway for Appropriate Diagnostics

Microscopy Serology Microfluidics Nanotechnology

Regulatory Approval: 2 – 5 Years Policy and Uptake: 5 – 7 years

Target Product Profile

Adapted from Okeke et al, Drug Res Updates, 2011

Research Priority B: Design strategies to improve treatment and prevention of infections by developing new diagnostics Objectives

• Roadmap for the development of rapid

diagnostics

• Sustainable business models
• Clinical validity, clinical utility and cost-

effectiveness

• Identifying barriers for acceptance of rapid

diagnostic tests

Research Priority C: Standardisation and extension of surveillance systems to establish a global surveillance program on antibiotic resistance and antibiotic use

% ESBL-Producing

• E. coli - 2012

(EARS-Net) % ESBL-Producing Enterobacteriaceae (AAC 2009; 53:3280-4)

Research Priority C: Standardisation and extension of surveillance systems to establish a global surveillance program on antibiotic resistance and antibiotic use

Versporten et al, LID , 20 March 2014

Antibiotic prescriptions, per age- groups, 1987-2013, Sweden.

Lack of Standardisation of Surveillance of Antibiotic Use in Hospitals

• Numerator:

– Weight (g or kg or units of treatment) – Vials – Agent days – Courses – Treatment periods – Percentage of patients exposed to antimicrobials – Antibiotic days or Days of Treatment (DOT) – DDD (Defined Daily Dose) – PDD (Prescribed Daily Dose)

• Denominator:

– Per month or year – Per 1000 inhabitants-days – Per 100 or 1,000 patient-days – Per 100 or 1,000 administrative bed-days – Per 100 or 1,000 occupied bed-days – Per 100 or 1,000 admissions – Per 100 or 1,000 discharges – Per month/occupied bed – Per Thousand Finished Consultant Episodes

Research Priority C: Standardisation and extension of surveillance systems to establish a global surveillance program on antibiotic resistance and antibiotic use Objectives

• Operational research on the standardisation

and extension of surveillance systems, in collaboration with WHO

• Pilot study regarding a global surveillance

programme, based on new technologies (e.g. genomic sequencing)

• Surveillance on antibiotic use in humans,

agriculture and aquaculture

household members & pets animals food travel

Research Priority D: Transmission dynamics

Emergence of Carbapenemase: Story of Pandemics of Clones, Plasmids and Genes, but Why…???

• Example of clonal spread:

– Klebsiella pneumoniae ST258 with KPC gene

• Example of plasmid spread:

– IncL/M plasmid with OXA-48 gene

• Example of gene spread:

– NDM-1 carbapenemase gene

Research Priority 4: Transmission dynamics Objectives

• Unravel the complex dynamics of selection

and transmission of antibiotic resistance

• Identifying factors for the persistence and

spread of resistant organisms and resistance genes

• Understanding the different systems of health

care, animal production and global trade and their impact on AMR

Research Priority E: The role of the environment as a source for the selection for and spread of antimicrobial resistance

Research Priority E: The role of the environment as a source for the selection for and spread of antimicrobial resistance Objectives

• Identification of interventions that reduce the

burden of AMR in the environment

• Risk assessment to estimate key

environmental transmission pathways

• Understanding the basic biological processes
• Development of industrial systems to reduce

AMR in the environment

% Invasive MRSA 2002 - 2012

• Hand hygiene campaigns?
• Improvements of contact

isolation and environmental control, with reduced cross transmissions?

• Screening for MRSA carriage?
• Antibiotic policies with reduced

antibiotic selective pressure?

• Natural fluctuation of certain

clones with regression to the mean?

Reasons for success?

Research Priority F: Designing and testing interventions to prevent acquisition, transmission and infection caused by AMR

“One Health”

0.1 0.2 0.3 0.4 0.5 2005/06 2006/07 2007/08 2008/09 2009/10 2010/11 2011/12 2012/13 Prescriptions per 1000 population per day SAPG guidance on antibiacterials with a higher risk of C difficile infection

National reduction in “4C” antibacterials in primary care in Scotland (Scottish Antimicrobial Prescribing Group Primary Care Prescribing Indicators reports, 2010 and 2012-13)

Research Priority F: Designing and testing interventions to prevent acquisition, transmission and infection caused by AMR Objectives

• Research into effectiveness of AMR prevention

and control strategies (e.g. cluster-randomized trials)

• Comparing and combining AMR prevention

and control practices (including cost-efficacy trails)

• Real-world implementation (e.g. testing

clinical algorithms)

Enabling activities to strengthen the impact

• Developing a publicly accessible database of

research activities in the EU:

– ensure that research is complementary and that there are no major overlaps, – aid in identifying gaps and research opportunities – assist in decision making for the different funding bodies, – enable the monitoring of the impact of research.

Enabling activities to strengthen the impact

• Developing a biobank of clinical specimens and

strains, linked to a database:

– Inventory of and link between existing cohorts, patient registers, and collections of samples and data through previously funded research projects – Open-access – Samples and strains that carry known and newly identified antibiotic-resistance genes – Standardised methods for data collection and storage – SOPs for ethical and intellectual property issues.

Acknowledgement

• Mats Ulfendahl, Chair MB
• The Management Board
• The JPIAMR secretariat of the Swedish

Research Council (Pontus, Laura, Cecilia …)

• ZonNW (Jolien, Kris, Willem, Jeanet,

Martijntje, Dunja, …)

• MRC (Rebecca, Ruth, …)
• …