Program: Antibacterial Drug Development (ABDD)

About This Program

Project:

Streamlining HABP/VABP Trials

overview icon Overview

Streamlining Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP) Clinical Trials

In association with a hospital stay, some patients develop hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). Because HABP/VABP occurs in seriously ill patients, clinical trials testing antibacterials in this setting are especially challenging to conduct due. Specifically, HABP/VABP protocols are lengthy and overly complicated, patient recruitment is difficult, and safety data collection is burdensome.

CTTI has developed evidence-based recommendations for designing more feasible clinical trials for HABP/VABP. One set of recommendations outlines strategies for streamlining protocol elements to increase enrollment and reduce trial complexity. These include actionable proposals around early consent and endpoint selection as well as solutions employing Quality by Design principles and the use of central IRBs. A complementary set of recommendations describes methods to optimize operational efficiency in HABP/VABP trials by streamlining data collection. CTTI is testing the feasibility of these approaches in a proposed pragmatic clinical study to help drive adoption across the clinical trial enterprise.

“The CTTI project teams’ work is the type of science that can benefit the overall field of antibacterial drug development by advancing the science of clinical trials for hospital-acquired and ventilator acquired pneumonia. We look forward to continued progress of the CTTI effort and the results from additional studies that will evaluate proposed solutions to these challenges.”

Edward M. Cox, M.D., M.P.H. Director of the Office of Antimicrobial Products from the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research

A number of ideas fostered through CTTI’s Streamlining HABP/VABP Project were adopted by the FDA in its HABP/VABP guidance document & unmet need guidance.

in detail icon In Detail

HABP/VABP Antibacterial Drug Development (ABDD) trials are particularly challenging to conduct due to many reasons, including the length and complexity of the protocol and the challenges associate with the patient population, trial design, data recording, differences in international regulations, and operational concerns. These complications and obstacles have increased HABP/VABP trial costs and slowed ABDD.

CLICK HERE to read more about issues in ABDD.

ABDD Program: Streamlining Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP) Clinical Trials (2012-2016)

  • Identify barriers and seek solutions for the successful conduct of HABP/VABP studies
  • Simplify and reduce the amount of (safety) data collected in the HABP/VABP studies
  • Build a pilot network of sites to conduct HABP/VABP studies

The ABDD program will facilitate the development of new antibacterial drugs.

Specifically, the results from the Streamlining HABP/VABP Trials project will inform better processes and practices to employ in a HABP/VABP study protocol to be tested at participating clinical sites.

  • A study protocol using the recommendations developed from the workstreams will show that an innovative approach will work, leading to more ABDD clinical trials, which will eventually lead to more available antibiotics.
  • Additionally, streamlining data collection and recording will help accelerate study conduct and reduce the cost associated with excess data collection.

Convened experts and held a series of meetings and workshops to address the following:

  • Identify inefficiencies of current protocol elements and data collection processes in ABDD trial conduct.
  • Explore novel ideas and issue recommendations on designing scientifically valid, feasible, and clinically meaningful trials to establish the efficacy of antibacterial drugs for the treatment of HABP/VABP.
  • Build a pilot network of 45 sites globally (30 U.S. and 15 OUS) with a capability of conducting and implementing the HABP/VABP Studies.

Click on the meeting titles below to view associated materials, including agendas, participant lists, presentations and summaries:

Stakeholders from industry, academia, government, and patient groups met to identify areas in need of improvement in HABP/VABP protocols: the protocol design, the informed consent process (to address decisional impairment), use of a central IRB, and trial outcomes and endpoints. At expert meetings, stakeholders discussed best practices for defining the enrollment criteria, testing new diagnostics, obtaining informed consent from seriously ill patients, selecting an IRB, and pre-specifying trial endpoints in the protocol. Stakeholders also agreed that safety data collection in the HABP/VABP patient population is challenging and burdensome due to the large number of medical procedures, adverse events, and concomitant medications involved. Additional challenges include protocol complexity and the lack of harmonization in US and EU regulations regarding the conduct of HABP/VABP trials. Expert meeting attendees agreed that utilizing a QbD approach to protocol elements and trial planning is critical to facilitate streamlining of data collection and recording.

Based on this work, CTTI released recommendations for Streamlining Protocol Elements and for Optimizing Operational Efficiency for Safety Data Collection HABP VABP Trials. The recommendations appeared as part of a peer-reviewed supplement in Clinical Infectious Diseases that featured collaborative and innovative approaches by CTTI and others to address challenges associated with HABP/VABP trials.

The recommendations are also being applied to a proposed HABP/VABP Pragmatic Clinical Study.

A part of the Streamlining HABP/VABP project, a working group included key stakeholders, such as infectious diseases and pulmonary/critical care medicine experts, those experienced in designing clinical studies, and patient representatives, was convened to identify a network of sites for future studies. Master site contracts were negotiated in advance to minimize start up delays. There has also been outreach to the Innovative Medicines Initiative’s Combacte and New Drugs for Bad Bugs projects and their CLIN-net site were approached to expand the site list. The U.S. and European sites were used for the Risk Factors for HABP/VABP Study and will be approached to participate in the proposed pragmatic clinical trial.

Project Team Members

Role Name Affiliationsort descending
Team Member David Friedland Cerexa
Project Manager Jen Goldsack Clinical Trials Transformation Initiative
Project Manager Gerrit Hamre Clinical Trials Transformation Initiative
Team Member Thomas Holland Duke University
Team Member Joshua Thaden Duke University
Team Leader Vance Fowler Duke University
Team Member Eric Pelfrene European Medicines Agency
Team Member Radu Botgros European Medicines Agency
Team Member Ben Lorenz Food and Drug Administration
Team Member Daniel Rubin Food and Drug Administration
Team Member Jonas Santiago Food and Drug Administration
Team Member Joseph Toerner Food and Drug Administration
Team Leader Rosemary Tiernan Food and Drug Administration
Team Leader Gary Noel Johnson & Johnson Pharmaceutical Research and Development
Team Member Barry Eisenstein Merck & Co, Inc
Team Member Helen Donnelly Northwestern University
Team Member Richard Wunderink Northwestern University
Team Member Charles Knirsch Pfizer Inc
Team Member Demissie Alemayehu Pfizer Inc
Team Member Kunal Merchant RRD International LLC
Team Member Sabrina Comic-Savic The Medicines Company
Team Member Christina Reith University of Oxford, CTSU