title: Improving Conduct and Feasibility of Clinical Trials to Evaluate Antibacterial Drugs to Treat Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia: Recommendations of the Clinical Trials Transformation Initiative Antibacterial Drug Development Project Team.
abstract: BACKGROUND
  The etiology of hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP) is often multidrug-resistant infections. The evaluation of new antibacterial drugs for efficacy in this population is important, as many antibacterial drugs have demonstrated limitations when studied in this population. HABP/VABP trials are expensive and challenging to conduct due to protocol complexity and low patient enrollment, among other factors. The Clinical Trials Transformation Initiative (CTTI) seeks to advance antibacterial drug development by streamlining HABP/VABP clinical trials to improve efficiency and feasibility while maintaining ethical rigor, patient safety, information value, and scientific validity.
  
  
  METHODS
  In 2013, CTTI engaged a multidisciplinary group of experts to discuss challenges impeding the conduct of HABP/VABP trials. Separate workstreams identified challenges associated with HABP/VABP protocol complexity. The Project Team developed potential solutions to streamline HABP/VABP trials using a Quality by Design approach.
  
  
  RESULTS
  CTTI recommendations focus on 4 key areas to improve HABP/VABP trials: informed consent processes/practices, protocol design, choice of an institutional review board (IRB), and trial outcomes. Informed consent processes should include legally authorized representatives. Protocol design decisions should focus on eligibility criteria, prestudy antibacterial therapy considerations, use of new diagnostics, and sample size. CTTI recommends that sponsors use a central IRB and discuss trial endpoints with regulators, including defining a clinical failure and evaluating the impact of concomitant antibacterial drugs.
  
  
  CONCLUSIONS
  Streamlining HABP/VABP trials by addressing key protocol elements can improve trial startup and patient recruitment/retention, reduce trial complexity and costs, and ensure patient safety while advancing antibacterial drug development.
authors.affiliation: Pfizer, Inc, New York, New York.
authors.forename: Charles
authors.initials: C
authors.lastname: Knirsch
authors.affiliation: Pfizer, Inc, New York, New York.
authors.forename: Demissie
authors.initials: D
authors.lastname: Alemayehu
authors.affiliation: Office of Anti-infectives and Vaccines, European Medicines Agency, London, United Kingdom.
authors.forename: Radu
authors.initials: R
authors.lastname: Botgros
authors.affiliation: The Medicines Company.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Comic-Savic
authors.affiliation: Wockhardt USA, Parsippany, New Jersey.
authors.forename: David
authors.initials: D
authors.lastname: Friedland
authors.affiliation: Duke University, Durham, North Carolina.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Holland
authors.affiliation: RRD International, LLC, Rockville, Maryland.
authors.forename: Kunal
authors.initials: K
authors.lastname: Merchant
authors.affiliation: Johnson & Johnson, Raritan, New Jersey.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Noel
authors.affiliation: Office of Anti-infectives and Vaccines, European Medicines Agency, London, United Kingdom.
authors.forename: Eric
authors.initials: E
authors.lastname: Pelfrene
authors.affiliation: University of Oxford, United Kingdom.
authors.forename: Christina
authors.initials: C
authors.lastname: Reith
authors.affiliation: Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Jonas
authors.initials: J
authors.lastname: Santiago
authors.affiliation: Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Tiernan
authors.affiliation: Clinical Trials Transformation Initiative, Durham, North Carolina.
authors.forename: Pamela
authors.initials: P
authors.lastname: Tenearts
authors.affiliation: Clinical Trials Transformation Initiative, Durham, North Carolina.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Goldsack
authors.affiliation: Duke University, Durham, North Carolina.
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods*; D004341:Drug Evaluation; D004345:Drug Industry; D006801:Humans; D061214:Patient Safety; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy*; D055818:Public-Private Sector Partnerships; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration; D014495:Universities
chemical_list: D000900:Anti-Bacterial Agents
keywords: CTTI; clinical trials; hospital-acquired bacterial pneumonia; protocol development; ventilator-associated bacterial pneumonia