CTTI

Meeting Presentations:

Session 1: Current status of drug development and ongoing challenges

Introduction to CTTI's Clinical Trials Transformation Initiative: Antibacterial Drug Development Project by Lisa M. LaVange
Summary of Regulatory Standards and Guidances by Joseph Toerner
Summary of unmet need guidance and statistical challenges by Daniel B. Rubin
Application of Pharmacokinetics/Pharmacodynamics in New Anti-Infective Drug Development: Current Challenges and Future Perspectivesby Seong Jang
Statistical Considerations for Antibiotic Drug Development by Aaron Dane

Session 2: Current research and additional opportunities for the future

Discordant MIC Analysis: Testing for Superiority within a Non-inferiority Trial by Dean Follmann, Erica BriDain, and John Powers
Hierarchical nested trial design (HNTD) for new antibacterial drugs in patients with emerging bacterial resistance by Thamban Valappil and Mohammad Huque
Response Adjusted for Duration of Antibiotic Risk (RADAR) by Scott Evans
Some Proposals in the Analysis of Antibacterial Drug Trials by Margaret Gamalo-Siebers and Ram C. Tiwari

The views and opinions expressed in this presentation are those of the individual presenter and should not be attributed to the Clinical Trials Transformation Initiative, or any organization with which the presenter is employed or affiliated.

Optimizing Operational Efficiencies for Data Collection in HABP/VABP Trials

NOVEMBER 12, 2013

CTTI Project: Streamlining HABP/VABP Trials

Meeting Background:

The goal of this meeting is to seek practical solutions to streamline the operational processes and build efficiencies for data collection in HABP/VABP trials.

Meeting Location:

Arlington, Virginia

Meeting Materials:

Meeting Presentations:

Introduction by Pamela Tenaerts

Session 1: Challenges in data collection for HABP/VABP trials

Session 1 Goal: Understanding the issues surrounding data collection in HABP/VABP trials

Session 1 Focus: Why reducing excessive non-critical data collection in HABP/VABP trials would improve data quality, and benefit investigators, sponsors, reviewers, and patients

Can we reduce complexity and safety data collection to improve the quality of the data and inferences we make? by Charles Knirsch
Challenges in data collection for HABP/VABP trials: Investigator’s perspective by Richard Wunderink
Data Collection in HABP/VABP Trials: Regulatory Perspective by Sumati Nambiar

Session 2: Regulatory requirements for AE data collection in registration trials

Session 2 Goal: Discuss different regulatory requirements and the challenges of meeting these requirements for data collection for HABP/VABP registration trials that are globally conducted, and evaluate whether future work is needed to harmonize approach to AE collection

Session 2 Focus: AE collection and adjudication of relatedness and seriousness; Reporting of SAE’s and SUSARS and evaluation

Safety data collection in late stage premarket and post-approval clinical investigations by Patrick Archdeacon
Managing safety data in multi-regional trials by Chris Wohlberg

Session 3: Strategies to simplify data collection using a QbD approach

Session 3 Goal: To simplify the recording, monitoring, and review to make HABP/VABP trials more feasible and economical

Session 3 Focus: Reduction in the amount of data collected by identifying data that are critical to quality and those that may be essential to determine the benefit/risk of the treatment for registration, and those may be less informative

Using QbD for data collection planning by Mark Behm
Guiding principles for efficient data collection- 20 years of cardiovascular outcomes trials by Lisa G. Berdan
Breakout discussion instructions by Sabrina Comic-Savic

The views and opinions expressed in this presentation are those of the individual presenter and should not be attributed to the Clinical Trials Transformation Initiative, or any organization with which the presenter is employed or affiliated.

Understanding Issues in Antibacterial Drug Development Webinar

APRIL 18, 2013

CTTI Project: Streamlining HABP/VABP Trials

Meeting Background:

This webinar provides a background and overview of the issues and many years-long discussions in antibacterial drug development for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP).

Meeting Objectives:

This webinar served to familiarize the diverse group of participating experts with detailed information on this research topic as a preamble to the HABP/VABP pilot study protocol workshop that occurred in Bethesda on April 22 - 23, 2013.

Meeting Location:

Online

All of the attendees of the April 22 - 23, 2013 Expert Meeting where invited to attend this webinar. CLICK HERE for a list of meeting invitees.

Meeting Presentation:

Improving Pediatric Trials in Antibacterial Drug Development | No Sick Child Left Behind

APRIL 05, 2016

CTTI Project: ABDD Peds Trials

Meeting Objectives

Present findings
Identify remaining gaps that may require further exploration
Present and obtain feedback on draft considerations to improve the successful conduct and execution of pediatric antibacterial drug trials
Develop initial consensus on the mechanisms for improving the conduct and execution of pediatric trials of antibacterial drugs

Meeting Location:

Sheraton Silver Spring Hotel, 8777 Georgia Avenue, Silver Spring, Maryland

Meeting Materials:

Meeting Presentations

CTTI History and Methodology: ABDD Program History by Jamie Roberts
Pediatric Product Development in the 21st Century by Lynne Yao, M.D.
Public-Private Partnerships to Support Pediatric Trials by Ed Connor, MD MBE
Opportunities: Pediatric Trials Network by P. Brian Smith MD MPH MHS
Pediatric Anti-bacterial and Anti-fungal Trials from 2007 to 2015: A Systematic Review of ClinicalTrials.gov by Joshua Thaden, MD, PhD
Quantifying BPCA and PREA Submissions – Pediatric Labeling for Antibacterial and Antifungal Drugs by John Farley, MD MPH
PENTA-ID by Mike Sharland
Parental Decision Making About Enrolling Children in Clinical Trials: An In-depth Interview Study by Diane Bloom, MPH, Ph.D.
Investigator Perspectives by Amy Corneli, PhD, MPH
Findings: Perspectives from Community Providers by Rachel G. Greenberg, MD
Industry Perspectives by Gary Noel
Communicating with Parents: Approaches to Informed Consent by Breck Gamel
Addressing the Challenges in Neonatal Infection Studies by P. Brian Smith MD MPH MHS
Improving Clinical Trial Design: Meeting the Needs of Investigators by John Bradley, MD
Breakout Report Outs

The views and opinions expressed in this presentation are those of the individual presenter and should not be attributed to the Clinical Trials Transformation Initiative, or any organization with which the presenter is employed or affiliated.

CTTI Antibacterial Drug Development: Statistical Issues Think Tank Meeting

AUGUST 20, 2012

CTTI Project: Unmet Need

Meeting Background:

A CTTI-hosted Statistical Issues Think Tank Meeting was convened to provide an opportunity for leading experts in clinical trial methodologies to discuss alternative approaches to design and analysis that may be useful for antibacterial drug development programs.

Meeting Location:

Bethesda Hyatt Regency, Bethesda, MD

Meeting Materials:

1) Hierarchical nested trial design (HNTD) for demonstrating treatment efficacy of new antibacterial drugs in patient populations with emerging bacterial resistance

Meeting Presentation:

CTTI Statistics Think Tank for Anti-Bacterial Drug Development by Lisa LaVange

Resulting Publications:

On June 23, 2014, Statistics in Medicine published an article by Huque et al. that describes a novel clinical trial model to address the increased prevalence of antibiotic-resistant bacterial infections. This paper resulted from the CTTI-hosted Statistical Issues Think Tank Meeting that author Mohammad Huque attended.

2) The Role of Statistics in Regulatory Decision Making

In February, 2014, this peer-reviewed article was published in Therapeutic Innovation & Regulatory Science. This paper resulted from the CTTI-hosted Statistical Issues Think Tank Meeting where author Lisa M. LaVange, PhD, attended and presented. In this publication, LaVange concludes:

This article presents the author’s view of the important role that statisticians play in regulatory decision making, beginning with a broad overview of current office initiatives, including the development of guidance documents and a recent push for open and transparent collaboration with industry on methods development. Several recent examples are provided to illustrate the impact that statisticians can have on regulatory decisions through the use of strategic quantitative thinking. Also discussed are areas where it is believed that innovative statistical solutions or greater clarity on existing approaches is still needed.

3) Bayesian approach to the design and analysis of non-inferiority trials for anti-infective products

On August 5, 2013, the Journal of Pharmaceutical Statistics published an article by Gamalo et al. that describes a Bayesian approach for the design and analysis of active comparator trials used in the development and market approval of antibacterial drugs. This work was presented in part at the CTTI-hosted Statistical Issues Think Tank Meeting.

“The CTTI Statistics Think Tank, a collaborative initiative with the FDA/CDER Anti-Bacterial Drug Development Task Force, was held in August, 2012 and provided an excellent opportunity for leading statisticians from academia, government, and industry to discuss innovative approaches for accelerating the development of new antibiotics. This article presents a comprehensive Bayesian approach to non-inferiority trials and represents but one of several approaches that were discussed at the Statistics Think Tank meeting. We look forward to additional research being published from the ideas generated at that meeting.” said Lisa LaVange Director of Biostatistics, Food and Drug Administration.

The Bayesian approach may allow for use of information from sources that include observational studies and early phase trials on the effect of the active comparator for study design. This approach may aid in reducing large sample size requirements and decrease study durations for antibacterial agents that enter late-stage clinical development.

The views and opinions expressed in this presentation are those of the individual presenter and should not be attributed to the Clinical Trials Transformation Initiative, or any organization with which the presenter is employed or affiliated.

Antibacterial Drug Development: Developing a Pilot Protocol for Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia

APRIL 22, 2013 TO APRIL 23, 2013

CTTI Project: Streamlining HABP/VABP Trials

Meeting Background:

The goal of this meeting is to seek solutions for challenges in study design and conduct of Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP) studies by applying the Quality by Design (QbD) principles.

Meeting Location:

Bethesda, MD

Meeting Materials:

Meeting Presentations:

Introduction and Meeting Goals by Pamela Tenaerts

Session 1: The Challenges of HABP/VABP Trials

Summary of Challenges Identified and Categorized by Brad Spellberg
Operational Challenges in HABP/VABP Trial Conduct by Charles Knirsch
Operational Challenges in HABP/VABP Trial Conduct by David Friedland

Session 2: How can QbD be used to address the challenges in HABP/VABP trials?

Introduction to a QbD Approach to Clinical Trials by Martin Landray
Enhancing Trial Efficiency While Promoting Quality-A Regulatory Perspective by Ann Meeker-O'Connell
Workgroup Instructions

The views and opinions expressed in this presentation are those of the individual presenter and should not be attributed to the Clinical Trials Transformation Initiative, or any organization with which the presenter is employed or affiliated.

Anti-Bacterial Drug Development: Issues in the Design of Trials in Patients with Unmet Need and in Patients with Hospital-Acquired and Ventilator Associated Bacterial Pneumonia

OCTOBER 11, 2012 TO OCTOBER 12, 2012

CTTI Project: ABDD Unmet Need

Meeting Background:

With rising antibiotic resistance becoming an issue of global concern, the Clinical Trials Transformation Initiative (CTTI) convened a 2-day Antibacterial Drug Development Workshop on October 11-12, 2012 in Crystal City, VA. The workshop is part of a series of expert meetings to explore approaches for accelerating the development of new antibacterial drugs. The two topics of focus for this meeting were exploring a new paradigm for antibacterial drug development in areas of unmet need, and for the treatment of patients with pneumonia that develops in the hospital or while on a ventilator. This workshop followed a think tank on statistical issues that was held on August 20, 2012, in Bethesda, MD, also hosted by CTTI.

There is an urgent need to develop new antibacterial drugs to treat patients with infections caused by bacteria that are resistant to available antibiotics. Antibiotic resistance has been increasing, creating an unmet public health need. This workshop was held in collaboration with FDA’s newly formed Antibacterial Drug Development Task Force within the Center for Drug Evaluation and Research (CDER).

The purpose of the workshop was to understand the challenges in the development of new antibacterial drugs for the treatment of patients with unmet medical need (e.g., patients with multi-drug resistant bacterial infections, who have limited or no options for treatment) and to identify potential solutions that would accelerate the drug development process. Novel endpoints and possible solutions to challenges in trial design for the development of new antibacterial drugs that treat patients with hospital-acquired or ventilator-associated bacterial pneumonia (HABP and VABP) were also explored. A broad range of stakeholders participated in the meeting, including experts from academic institutions, hospitals, pharmaceutical industry, government, and patient advocacy groups.

“The workshop provided an excellent opportunity to discuss new development pathways for antibiotic drugs targeting infections for which we urgently need new antibiotic therapies. Our collaboration with CTTI on this work is part of the CDER Antibacterial Drug Development Task Force’s efforts to accelerate the development of new antibiotics to address critical patient needs”, said Edward Cox, MD, Director of the CDER’s Office of Antimicrobial Products.

Meeting Objectives:

The goal of the first day of the workshop was to define potential pathways and explore new paradigms to accelerate the development of new antibacterial drugs that would address unmet medical need, including discussing acceptable levels of uncertainty related to the risks and benefits of such treatments. The second day focused on issues in clinical trial design including endpoints and operational efficiencies specific to the development of antibacterial drugs for treating patients with hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP).

Meeting Location:

Sheraton Crystal City Hotel, Arlington, VA

Meeting Materials:

Meeting Presentations:

1.1 Overview of Risk-Benefit within Antibacterial Drug Development by Ed Cox
1.2 Antibiotic Resistance by John Bartlett
1.3 2012 Update of Antibiotic Resistance in the Multidrug-resistant Organism Repository & Surveillance Network (MRSN) by Emil Lesho
1.4Drug Development Challenges: Facilitating Collaboration by Charlene Reed
1.5 Clinical Trials for Rare Diseases in CDER by Kathryn O’Connell
1.6 Novel Approaches to Further Antibacterial Drug Development: New Approaches to the Clinical Development Program by John Rex
1.7 Limitations of PK-PD in Clinical Trials: Focus on Vancomycin MIC and MRSA Infection by Vance Fowler
1.8 Possible Clinical Trial Approaches for Areas of Unmet Need by Ed Cox
1.9 CTTI Think Tank for Anti-Bacterial Drug Development: Unmet Medical Need and HABP/VABP by Lisa LaVange & Daniel Rubin
2.1 Hospital-Acquired Bacterial Pneumonia & Ventilator-Associated Bacterial Pneumonia by Joseph Toerner
2.2 Direct and Indirect Measures of Treatment Effects Including Surrogate Endpoints by John Powers
2.3 Endpoints in HAP/VAP trials: Mortality, Clinical Endpoints, Biomarkers by Richard Wunderink
2.4 Identifying Non-mortality Clinical Endpoints FNIH Approach to CABP and ABSSSI by George Talbot
2.5 Design Strategies to Improve the Feasibility of HABP-VABP Registration Studies by P. Prokocimer
2.6 Issues in Operational Efficiency of HAP/VAPClinical Trials: Current and Future State by Charles Knirsch

The views and opinions expressed in this presentation are those of the individual presenter and should not be attributed to the Clinical Trials Transformation Initiative, or any organization with which the presenter is employed or affiliated.

Antibacterial Drug Development Working Group Webinar

AUGUST 29, 2013

CTTI Project: Streamlining HABP/VABP Trials

Meeting Background:

The Clinical Trials Transformation Initiative hosted an Antibacterial Drug Development Program Working Group Webinar on Aug 29, 2013 to provide an update on the program, and to make further progress on developing streamlined elements for a Pilot Protocol for Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP). This webinar was a follow-up to a recently held workshop last April. The agenda for this collaborative effort included an update from the Foundation of the NIH (FNIH) HABP/VABP Working Group, followed by a lively discussion that focused on aspects of study design and endpoints. As with prior meetings, a variety of stakeholders attended the workshop, including academia, clinical experts, patient advocates, regulators, representatives from pharmaceutical companies, and others involved in the clinical research enterprise. The working group will incorporate the insight gained into the development of recommendations for elements for a Pilot Protocol for HABP/VABP studies.

"It is reassuring to see the progress made since the CTTI expert meeting held last October. A broader range of stakeholders has helped each person consider new possibilities in a much more open way, and should lead to a pilot protocol with better results that everyone can accept and act upon. I look forward to pushing the envelope further for all HABP/VABP patients, including a serious discussion of when superiority trials can be considered." Said Deborah Collyar, President, Patient Advocates In Research (PAIR) who attended the webinar.

Meeting Location:

Online

Meeting Materials: