Biomarkers Consortium - Hospital-Acquired Bacterial Pneumonia/Ventilator-Associated Bacterial Pneumonia Clinical Endpoint Development (HABP/VABP)

The Biomarkers Consortium’s Hospital-Acquired Bacterial Pneumonia (HABP) and Ventilator-Associated Bacterial Pneumonia (VABP) Project aims to develop clinically relevant endpoints in clinical trials to improve antibacterial trial feasibility. Currently, there are limitations in the information to quantitatively assess the effect of antibacterial drug treatments vs. no treatment or placebo and in comparisons between active agents. These undefined clinical endpoints impede the field of drug development for these indications and limit the ability to perform clinical trials in this area. The lack of outcome measures also impedes patient care since clinicians and patients cannot understand similarities and differences between therapeutic agents that are not measured in a well-defined, reproducible and clinically relevant manner. The goals of the HABP VABP project are to develop 1) reliable, well-defined and clinically relevant endpoints in clinical trials that measure tangible benefits for patients in terms of how they feel, function and survive, and 2) new design components that would improve trial feasibility. These goals will be achieved by a retrospective analyses of data from several existing industry-sponsored clinical trials and through the development of a HABP Patient-Reported Outcome (PRO) draft instrument.

Goals

  • Develop reliable and well-defined clinically relevant endpoints for use in clinical trials of antibacterial drugs for HABP and/or VABP that measure tangible benefits for patients in terms of how they feel, function and survive.
  • Identify potential changes to study design and analysis that could improve the feasibility of HABP/VABP registrational clinical trials based on a non-inferiority (NI) design.
  • Complete the content validity phase of a Patient-Reported Outcome (PRO) measure.

Results & Accomplishments

The FNIH HABP/VABP Project Team confirmed relevant outcome measures for both HABP and VABP through retrospective analyses and synthesis of data from modern day clinical trials. The data was used in the preparation of a briefing package that was submitted to the FDA docket on HABP and VABP to include symptomatic endpoints in the FDA Guidance. The HABP Patient Reported Outcome (PRO) draft instrument is complete, and the project has received $1.8M in support from FDA to evaluate the psychometric properties of the tool.

Guidance Documents

Submission to the FDA Docket: Considerations for Clinical Trial Design for the Study of Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia.

Guidance for Industry: Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia: Developing Drugs for Treatment. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (2014).

Scientific Publications

Patient-Reported Outcome Assessments as Endpoints in Studies in Infectious Diseases. Powers JH, Howard K, Saretsky T, Clifford S, Hoffmann S, Llorens L, Talbot G. Clin Infect Dis. 2016 Aug 15;63 Suppl 2:S52-6. doi: 10.1093/cid/ciw317. PMID: 27481954

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. Talbot GH, Powers JH, Hoffmann SC; Biomarkers Consortium of the Foundation for the National Institutes of Health CABP-ABSSSI and HABP-VABP Project Teams. Clin Infect Dis. 2016 Mar 1;62(5):603-7. doi: 10.1093/cid/civ927. PMID: 26668337

Selected Abstracts

Signs, Symptoms, and Existing Patient-Reported Outcome (PRO) Measures in Hospital-Acquired Bacterial Pneumonia (HABP): A Comprehensive Literature Review. Saretsky T, Clifford S, Hoffmann S, Powers JH, Talbot G, Howard K. FNIH Biomarkers Consortium HABP and VABP Project Team. Presented at OARSI 2015 World Congress March 31, 2015, Amsterdam, Netherlands.

Hospital-Acquired Bacterial Pneumonia: Development of a New Patient-Reported Outcome Instrument. Howard K, Saretsky TL, Clifford S, Cho M, Hoffmann SC, Talbot GH, Llorens L, Powers JH, FNIH Biomarkers Consortium HABP VABP Project Team. Presented at ISPOR 21st Annual International Meeting May 21-25th, 2016, Washington DC.

Alternatives to the All-cause Mortality Endpoint for Studies of Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia GH Talbot, A Das, A Torres, JH Powers, S Cush, A Dane, M Wible, R Echols, S Cammarata, JH Rex, T Fleming, S Hoffman, The Foundation for the National Institutes of Health Biomarkers Consortium HABP/VABP Project Team. 

Media

FNIH Web Announcement (October 3, 2018): Q&A with George H. Talbot, M.D.: Improving Antibacterial Drug Development Tools.

FNIH Web Announcement (July 20, 2017): FNIH Biomarkers Consortium Provides Recommendations to FDA to Facilitate Drug Development for Serious Bacterial Infections

Editorial Commentary: A Collaborative Model for Endpoint Development: Advancing the Science of Antibacterial Drug Clinical Trials. Toerner JG, Cox E. Clin Infect Dis. 2016 Mar 1;62(5):608-9. doi: 10.1093/cid/civ1007. No abstract available

ICON Press Release (Feb. 20, 2017): ICON Selected by the FDA to Validate Patient-Reported Outcome Endpoints for Antibacterial Drug Trials

Partners

Achaogen, Inc.
Actelion Pharmaceuticals Ltd.
American Thoracic Society
AstraZeneca Pharmaceuticals LP
Basilea Pharmaceutica International Ltd.
Bayer HealthCare Pharmaceuticals Inc.
Cubist Pharmaceuticals, Inc.
Food and Drug Administration
ICON plc.
InClin
Infectious Diseases Society of America
The Medicines Company
Melinta Therapeutics
Merck Sharp & Dohme Corp.
Nabriva Therapeutics AG
National Institute of Allergy and Infectious Diseases (NIAID)
Pfizer Inc.
Roche
Shionogi Inc.
Tetraphase Pharmaceuticals
Theravance Biopharma
Universitat de Barcelona

Contact

Stephanie Cush, Scientific Project Manager, Inflammation and Immunity, scush@fnih.org; Steve Hoffmann, Scientific Program Manager, Inflammation and Immunity, shoffmann@fnih.org