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.
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
“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.”
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.
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)
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.
Convened experts and held a series of meetings and workshops to address the following:
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.
|Team Member||Barry Eisenstein||Merck & Co, Inc|
|Team Member||Ben Lorenz||Food and Drug Administration|
|Team Member||Charles Knirsch||Pfizer Inc|
|Team Member||Christina Reith||University of Oxford, CTSU|
|Team Member||Daniel Rubin||Food and Drug Administration|
|Team Member||David Friedland||Cerexa|
|Team Member||Demissie Alemayehu||Pfizer Inc|
|Team Member||Eric Pelfrene||European Medicines Agency|
|Team Leader||Gary Noel||Johnson & Johnson Pharmaceutical Research and Development|
|Project Manager||Gerrit Hamre*||Clinical Trials Transformation Initiative|
|Team Member||Helen Donnelly||Northwestern University|
|Project Manager||Jen Goldsack*||Clinical Trials Transformation Initiative|
|Team Member||Jonas Santiago||Food and Drug Administration|
|Team Member||Joseph Toerner||Food and Drug Administration|
|Team Member||Joshua Thaden||Duke University|
|Team Member||Kunal Merchant||RRD International LLC|
|Team Member||Radu Botgros||European Medicines Agency|
|Team Member||Richard Wunderink||Northwestern University|
|Team Leader||Rosemary Tiernan||Food and Drug Administration|
|Team Member||Sabrina Comic-Savic||The Medicines Company|
|Team Member||Thomas Holland||Duke University|
|Team Leader||Vance Fowler||Duke University|