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.

Pregnancy Testing in Clinical Trials Expert Meeting

JULY 15, 2013 TO JULY 16, 2013

CTTI Project: Pregnancy Testing

Meeting Background:

Designing a pregnancy testing protocol for a clinical trial requires balancing the performance characteristics of a given test, the baseline risk of pregnancy in a given subject population, the potential risks to the fetus from study interventions, and the effect of the testing protocol on overall study implementation in terms of burden to subjects, burden on staff, and direct costs. There are no published data on the consistency of sponsors, investigators, or institutional review boards (IRBs) in applying these criteria to designing and evaluating pregnancy testing protocols. However, anecdotal reports indicate that there is widespread variability.

Development of evidence-based guidance that explicitly considers the level of acceptable risk to suggest appropriate pregnancy testing protocols will ultimately improve protection of research subjects, reduce the risk of unintended fetal exposure, and reduce the workload of sponsors, investigators, IRBs, and other stakeholders in the clinical trial enterprise.

Meeting Objectives:

Present survey findings and computer simulation model results from the CTTI project entitled, Developing Rational Guidance for Pregnancy Testing in Clinical Trials
Discuss practices and challenges in assessing the acceptable risk of pregnancy and implementing a pregnancy testing protocol for a clinical trial
Solicit additional feedback and develop consensus on factors to consider when assessing acceptable risk of pregnancy in clinical trials

Meeting Location:

DoubleTree by Hilton Hotel, Bethesda, MD

Meeting Materials:

Meeting Presentations:

Day 1

Welcome by Sara Calvert
Origin and Rationale of the Project, “Developing Rational Guidance for Pregnancy Testing in Clinical Trials” by Evan R. Myers
Why do we worry about pregnancy testing? – Teratogens and Teratogenic Risk by Melissa S. Tassinari
The Analytical & Clinical Complexities of Measuring hCG by Ann M. Gronowski
What does having a FDA cleared pregnancy test mean? by Denise Johnson-Lyles
Pharmaceutical Industry Process for Selecting a Pregnancy Testing Protocol by Sheila Ronkin
Summary of Results from CTTI Pregnancy Testing in Clinical Trials Survey by Evan Myers
Modeling Approach Background and Initial Simulation Results - Potential Resources/Tools to Guide Selection of Pregnancy Testing Protocols by Evan Myers

Day 2

Summary of Day 1 Recommendations for Designing and Evaluating Pregnancy Testing Protocols by Evan Myers
Next Steps by Evan Myers

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.

The Fastest Path to Effective COVID-19 Treatments: Using Master Protocol Studies

JANUARY 13, 2021

CTTI Project: Clinical Trial Issues Related to COVID-19

Meeting Overview:

CTTI hosted The Fastest Path to Effective COVID-19 Treatments: Using Master Protocol Studies Public Summit on Wed., Jan. 13. The summit, conducted as a webinar and moderated by Pamela Tenaerts, CTTI, included a welcome from Janet Woodcock, Operation Warp Speed; a call-to-action from Robert M. Califf, Verily and Google Health; and panel discussions moderated by Ester Krofah, FasterCures, and Mark McClellan, Duke-Margolis Center for Health Policy. The panel focused on solutions related to scaling master protocols, including:

Overcoming barriers to starting up sites
Increasing participants at existing sites
Using the COVID experience to inform our preparedness for future pandemics

The public summit also addressed the status of COVID-19 clinical trials, including results from a recent CTTI analysis of data from ClinicalTrials.gov and findings of a pre-summit survey that offered best practices and insights from those involved in COVID-19 treatment master protocols, specifically those setting up new sites and recruiting participants at existing sites.

This public summit is part of a collaborative effort with the Duke-Margolis Center for Health Policy at Duke University and FasterCures, a Center of the Milken Institute.

Meeting Location:

Virtual Meeting

Meeting Materials:

Watch Public Summit

Presentation Slides

Survey Results Slides

Articles of Interest

Master Protocol COVID Treatment Resources

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.

Stakeholder Engagement on ICH E6 Guideline for Good Clinical Practice

JUNE 04, 2020 TO JUNE 05, 2020

CTTI Project: Informing ICH E6 Renovation

Meeting Overview:

The U.S. Food and Drug Administration, in collaboration with the Clinical Trials Transformation Initiative, is organizing a free two-day Pan-American-focused public web conference on Thursday, June 4, and Friday, June 5, from 10:00 a.m. - 1:00 p.m. EDT, to learn more about stakeholder experiences with the International Council for Harmonisation (ICH) Good Clinical Practice guideline (ICH E6).

This stakeholder engagement web conference will inform the discussions of the ICH Expert Working Group (EWG), which is tasked with updating the guideline and making it more responsive to advances in clinical trial design and conduct. Members of the EWG will provide an overview of the ongoing work to update the guideline and will then hear from multiple stakeholders on their experiences with ICH E6(R2).

The registration process gives registrants an opportunity to submit questions. We will address themes from questions submitted before Tuesday, May 26, during a session on Friday, June 5. Please note the following regarding submissions:

Submissions must be in English.
Anyone can submit questions or comments.

Time slots for stakeholders to provide oral comments during the second day of the web conference are now filled. Please consider submitting questions when registering or sending written comments to cttievents@dm.duke.edu (External Link Disclaimer).

For additional information on the ICH E6 revision efforts, please refer to the following materials:

ICH E6 main page (www.ich.org)
ICH E6(R3) Concept Paper
Summary of the ICH E6 engagement proposal
CTTI's ICH E6 Renovation Work

Meeting details are available on FDA’s website.

Meeting Location:

Virtual Meeting

Full Presentation Set - Day 1

Meeting Materials:

Day 1

Session I: Introduction/ICH Process & Updating ICH E6 GCP Guidelines

Session II: CTTI ICH E6 Survey and Stakeholder Input

Session III: Perspectives from EWG Members

Session IV: Perspectives from Clinical Investigators

Session V: Perspectives from Patient Organizations

Day 2

Session I: Stakeholders Perspectives

Session II: Moderated Discussion of Themes from Stakeholders

Session III: Stakeholder Comments

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.

Master Protocol 2019 Expert Meeting

OCTOBER 22, 2019 TO OCTOBER 23, 2019

CTTI Project: Master Protocol Studies

Meeting Overview:
The purpose of the meeting was to explore and develop strategies to address common challenges related to the design and implementation of master protocols, including:

Mapping the pre-planning, planning, and execution processes of a master protocol trial.
Strategizing solutions to common roadblocks related to the pre-planning, planning, and execution of a master protocol study.
Identifying and prioritizing the creation of tools to support the adoption of emerging best practices outlined by CTTI’s roadmap.

Meeting Materials:

Full Presentation Set - Day 2

Welcoming Remarks & Meeting Overview

Introduction to the Clinical Trials Transformation Initiative (CTTI) - Annemarie Forrest, CTTI
VeloCTTI Master Protocol Project Overview - Kimberly Fisher, CTTI

Session I: Landscape Review

Landscape Review Findings - Nicholas Richardson, FDA, CDER
Multi-Stakeholder, Cross-Institutional Strategies for Change - Daniel Millar, Janssen Pharmaceuticals
Leveraging Master Protocols to Build Local Infrastructure & Technical Capacity for Low & Middle-Income Countries - Jay Park, MTEK Sciences

Session II: Building Capacity for Innovation

I-ACT for Children Overview - Ed Connor, I-ACT for Children
xCures Overview - Mika Newton, xCures

Session III: Small Group Breakout Sessions

Pre-Planning - Jane Perlmutter & Annemarie Forrest, CTTI
Planning - Marianne Chase, Massachusetts General Hospital & Kimberly Fisher, CTTI
Execution - Roger J. Lewis, Berry Consultants, LLC & Laura Shannon, CTTI
Large Group Discussion

Session IV: Tool Identification

Roadmap Strategy Session Instructions - Kimberly Fisher, CTTI
Breakout Session Facilitators
- Pre-Planning - Karen Dimick, Genentech & Annemarie Forrest
- CTTI Planning - Gene Vinson, Syneos Health & Kimberly Fisher
- CTTI Execution - Rajeshwari Sridhara, FDA, CDER, & Laura Shannon, CTTI
Large Group Strategy Session - Facilitator/Moderator: Nicholas Richardson, FDA, CDER

Session V: Next Steps & Closing Comments

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.

ICH E6 Guideline for Good Clinical Practice – Update on Progress

MAY 18, 2021 TO MAY 19, 2021

CTTI Project: Informing the Update of ICH E6

On behalf of the International Council for Harmonisation (ICH), the ICH E6 Good Clinical Practice (GCP) Expert Working Group (EWG) held a free public web conference to provide an update on the progress to revise this important and impactful guideline. This web conference was convened by the Clinical Trials Transformation Initiative (CTTI).

The EWG held two similar meetings on Tuesday, May 18, 2021 (8-11 a.m. EDT) and Wednesday, May 19, 2021 (6-9 pm JST) to reach a broad global audience across time zones. As you will note on the agenda, the same topics were presented each day with speakers from different regions to represent the global effort. All information and presentations was provided in English.

Recorded presentations of the public web conferences are available above.

Meeting Location:

Virtual Meeting

Meeting Agenda - May 18

Meeting Agenda - May 19

Watch May 18 Web Conference

Meeting Materials:

Video: ICH Guideline Development Process

Watch May 19 Web Conference

Presentations:

Session 1 – General Introduction

Session 2 – E6(R3) GCP Expert Working Group (EWG) Vision & Engagement

Session 3 – Principles & Stakeholder Reflections

Full Web Conference Slide Deck

Additional Meeting Details:

ICH E6 GCP is the international ethical, scientific, and quality standard for the conduct of clinical trials for the development of new drugs and biologics involving human participants that are intended to support regulatory applications. Due to the wide impact of this important guideline, the ICH Management Committee is taking this unique step to provide a status update on the revisions to the guideline.

In this web conference, members of the ICH E6 EWG discussed the work-in-progress to develop principles and annexes for ICH E6 GCP (third version or E6(R3)) that are intended to be responsive across clinical trial types and settings and to remain relevant as technology and methodologies advance. The draft, work-in-progress principles that were made public by the ICH on April 19, 2021, are designed to be flexible and applicable to a broad range of clinical trials. View the principles on the ICH website. The EWG is not taking public comments on the principles at this stage. However, once the ICH E6 guideline achieves step 3 of the ICH guideline development process, the EWG will invite and consider public input.

The EWG also discussed its plans and approaches to update the guideline in general and its engagement efforts with a variety of stakeholders that greatly enriched the discussions of the EWG. As part of these continued efforts to engage with stakeholders, the web conference included presentations from stakeholders on their vision and aspiration for clinical trial design and conduct that are responsive to the needs of the community.

View the full conference agenda here. For additional information on the ICH E6 revision efforts, please see the Reflection Paper on Renovation of Good Clinical Practice and the Concept Paper. For further information on the engagement approach, please see the published outline of the ICH E6 engagement proposal. Other materials, including the current guideline, "ICH E6(R2): Guideline for Good Clinical Practice," the business plan, work plan, an expert list, and reports of prior public engagements are available on the ICH website: https://www.ich.org/page/efficacy-guidelines.

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.

Expert Meeting on Large Simple Trials (LSTs)

MAY 13, 2013 TO MAY 14, 2013

CTTI Project: Large Simple Trials

Meeting Background:

The purpose of this meeting is to develop recommendations to facilitate and promote the adoption of LST designs for regulatory submissions or other purposes.

Meeting Objectives:

Discuss findings from a survey of practices
Discuss strategies that companies are using to implement LSTs
Discuss the challenges to LSTs

Meeting Location:

Hilton Washington DC/Rockville Hotel and Executive Center, Rockville, MD

Meeting Materials:

Meeting Presentations:

1.1 Welcome by Leanne Madre
1.2 Opening Remarks by Christopher Granger

Day 1 - Session 1: Landscape of LSTs

1.3 Perspectives on LST Trials by Michael Lauer
1.4 Patient Perspective on LST Trials by Carolyn Petersen
1.5 Opportunities for LSTs - Industry by Reshma Kewalramani
1.6 Opportunities for LSTs - Regulatory Sandra Kweder
1.7 Summary of Survey Results by Patrick Archdeacon

Day 1 - Session 2: Models of Approaches to LSTs

2.1 Models of Industry Trials for Regulatory Purpose (Efficacy/Effectiveness) by Christopher Granger
2.2 Models of Industry Trial for Regulatory Purposes (Safety) by Frank Cerasoli
2.3 Pragmatic Trials using EHR Platforms by Ryan Ferguson
2.4 Population-based trials with high cost-efficiency (VITAL) by JoAnn Manson
2.5 CHAMPION Program by Meredith Todd
2.6 CHAMPION Program – FDA Perspective by Stephen Grant
2.7 SHARP by Colin Baigent
2.8 JUPITER by Johannes Hulthe
2.9 SHARP and JUPITER - FDA Perspective by James Smith

Day 2

3.1 Summary of Day 1, including review of challenges to increased adoption of LST trial designs and potential solutions by Christopher Granger
3.2 Reflections on Challenges and Potential Solutions by Robert Temple

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.

Developing Effective Quality Systems in Clinical Trials: An Enlightened Approach

OCTOBER 13, 2010 TO OCTOBER 14, 2010

CTTI Project: Quality by Design

Meeting Background:

The Clinical Trials Transformation Initiative (CTTI) has been conducting a project to identify effective and efficient methods to monitor clinical trials. In seeking to identify how best to ensure the reliability of study results and the protection of trial participants, the project team has recognized that quality cannot be “inspected into” a trial but rather must be incorporated from the outset in the trial’s protocol design and operational conduct. To be effective, monitoring should be one component of an overall quality framework that allows potential issues to be identified and addressed as early as possible.

Meeting Objectives:

Describe, discuss, and evaluate novel approaches to clinical trial oversight
Propose an integrated model of quality management that will promote more efficient approaches to design, conduct and oversight of clinical trial
Identify the critical aspects of clinical trials that should be the focus of risk-based approaches to creating quality systems

Meeting Location:

Bethesda Marriott Suites, Bethesda, MD

Meeting Materials: