Weekend reading: HABP-VABP study design; Overview of AMR initiatives

Dear All:

Two papers (one with an editorial) that are worth your time.

First, we have publication of the long-awaited FNIH (Foundations for the NIH) paper on trial designs for studies of HABP-VABP (Hospital-Associated Bacterial Pneumonia and Ventilator-Associated Pneumonia). The paper also comes with an editorial:

  • Talbot, G. H., A. Das, S. Cush, A. Dane, M. Wible, R. Echols, A. Torres, S. Cammarata, J. H. Rex, J. H. Powers, T. Fleming, J. Loutit, S. Hoffmann and H. V. P. T. Foundation for the National Institutes of Health Biomarkers Consortium (2019). “Evidence-Based Study Design for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia.” The Journal of Infectious Diseases: jiy578-jiy578. (link)
  • Eby, J. C. (2018). “Exploring Standard Endpoints for Clinical Trials of Pneumonia Therapy.” The Journal of Infectious Diseases: jiy708-jiy708. (link)

This paper is one to read in detail. Two key messages to take away:

  1. Non-ventilated HABP is meaningfully different from ventilated HABP and from VABP. You can study the latter two together but non-ventilated HABP needs its own stratum or study.
  2. All-cause mortality (ACM) is a clear and useful endpoint but modern studies may find that ACM is low enough (< 15%) that the standard non-inferiority margin of 10% is not really acceptable. In this case, event rates can be usefully increased with an ACM+ (“mortality plus”) endpoint in which markers of toxic/septic shock are counted as endpoints.

The community owes a great debt to George Talbot for leading the charge on this as well as on the prior FNIH work on endpoints for skin and CABP. If you’ve not looked at them recently, now would be a good time to re-review the prior papers:

  • Talbot, G. H., J. H. Powers, T. R. Fleming, J. A. Siuciak, J. Bradley and H. Boucher (2012). “Progress on developing endpoints for registrational clinical trials of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections: Update from the Biomarkers Consortium of the Foundation for the National Institutes of Health.” Clin Infect Dis 55(8): 1114-1121. (link)
  • Talbot, G. H., J. H. Powers and S. C. Hoffmann (2016). “Developing Outcomes Assessments as Endpoints for Registrational Clinical Trials of Antibacterial Drugs: 2015 Update From the Biomarkers Consortium of the Foundation for the National Institutes of Health.” Clinical Infectious Diseases 62(5): 603-607. (link)

These have been enormous efforts — my notes on these project go back to at least 2010! THANK YOU, George!

Second, Arjon Van Hengel (Directorate-General for Research & Innovation, European Commission, Brussels) and Laura Marin (Swedish Research Council, Stockholm) have pulled together a survey paper that explains how initiatives spanning research, innovation, and policy are working together to combat AMR:

This brief paper summarizes the many projects of the recent years (JPIAMRND4BBCARB-XGARDPTATFARG7 Health Ministers, and more) and is a good reference to share if you need to introduce a new colleague to the type of work being done by the AMR community.

All best wishes, –jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog/

Upcoming meetings of interest to the AMR community:

  • 15 Jan 2018 (London): BSAC’s Antimicrobial Chemotherapy Conference 2019: “An ABC for everyone involved in developing new antimicrobials.” Details here.
  • 29 Jan 2018 (REVIVE webinar): “Clinical development for non-developers Part 3: Antibacterial Drug Enhancer Combinations and Non-traditional Products.” Register here.
  • 4-5 Feb 2019 (London): Hamied Foundation UK-India Antimicrobial Resistance Meeting 2019. This is a 2-day meeting focused on building research links between the UK and India with the specific aim of jointly addressing the challenge of AMR. Register here.
  • 14-15 Mar 2019 (Berlin): BEAM-, CARB-X-, Novo REPAIR-, DZIF-, ND4BB-ENABLE-sponsored (among a long list!) Berlin Conference on Novel Antimicrobials and AMR Diagnostics. Details here. Poster submissions are being accepted through 9 Jan (details here).
  • 21-22 Mar 2019 (Birmingham, UK): BSAC Spring Conference.
  • 26 Mar 2019 (London, UK): Sponsored by The Economist, a 1-day symposium entitled “Antimicrobial Resistance: Preventing an antibiotic apocalypse.” Register here.
  • 13-16 Apr 2019 (Amsterdam): Annual ECCMID meeting
  • 16-18 Apr 2019 (Utrecht): ICOHAR, International Conference on One Health Antimicrobial Resistance. Organized by the ESCMID Study Group for Veterinary Microbiology (ESGVM).
  • 24-26 Apr 2019 (Boston): Annual SHEA (Soc. for Hospital Epidemiology of America) Spring meeting
  • 6-11 May 2019 (Ljubljana, Slovenia): 37th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID). Details here.
  • 3-6 Jun 2019 (Philadelphia): Annual BIO meeting
  • [NEW] 10-11 June 2019 (Research Triangle Park, NC): AMR Action Summit on R&D and Commercialization. Sponsors include the British-American Business Council, the UK Gov’t, CARB-X, the NC Biotechnology Center, and others. Details here.
  • 20-24 June 2019 (San Francisco): Annual ASM Microbe meeting.
  • [Mark your calendar now!] 3-6 Sep 2019 (Boston). Annual ASM-ESCMID Conference on Antibiotic Development. The Bootcamp series will continue on 3 Sep with the main meeting on 4-6 Sep. Mark your calendar now and check back here for details.
  • 6-8 Sep 2019 (Bilbao, Spain): 5th ESCMID conference on Vaccines. Check back here for details.
  • 2-6 Oct 2018 (Washington, DC): IDSA’s annual IDWeek meeting.
  • 19-27 Oct 2019 (Annecy, France): International Course on Antibiotics and Resistance (ICARe) – A soup-to-nuts intensive residential training program on all things AMR, especially R&D for new antibiotics. See this link for details.

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