CTTI News

CTTI Paper Highlights Clinical Criteria that Can Help Identify Patients at High Risk of HABP/VABP

Posted on by Hannah Faulkner

Although treatment of possible nosocomial pneumonia is common with patients in the intensive care unit (ICU) receiving respiratory support, more than half of those treated do not fit the standard clinical definitions of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). A new CTTI paper available online in CHEST® Journal, accompanied by an insightful editorial, “Heeding the Prophetic Call,” outlines how the use of simple clinical criteria may help to identify high-risk patients earlier and aid future research to improve prevention and treatment.

 

The paper highlights the Prospective Identification of Pneumonia in Hospitalized Patients in the ICU (PROPHETIC) study, a large, contemporary, prospective cohort clinical trial designed by CTTI that made several key observations.

 

“HABP/VABP is associated with high mortality and morbidity and may be caused by multidrug-resistant pathogens,” said John Farley, director of the Office of Infectious Diseases at the FDA.   “Conducting clinical trials in HABP/VABP is challenging, and data to understand the patient population is critical to improve trial feasibility.”

The study sought to define the incidence of HABP/VABP in an ICU population and identify characteristics associated with the development of HABP/VABP to inform the design and conduct of future clinical trials.

The study determined that 32 percent of 4,613 prospectively identified high-risk patients received antibiotics for possible HABP/VABP. It was also determined that only 12 percent of the aforementioned high-risk patients fit the FDA Guidance standard clinical definition of HABP/VABP.

“These findings indicate that the burden of HABP and VABP is significant and there is also some concern about antibiotic overprescription in this high-risk population,” said Vance Fowler, professor of medicine at Duke University. “Receiving antibiotics is itself a risk factor for developing pneumonia, carries risks of adverse events, and may preclude eligibility for HABP/VABP clinical trial enrollment.”

Additionally, the manuscript highlights the common characteristics and treatment exposures researchers identified that were associated with increased odds of developing HABP/VABP in high-risk patients.

“Application of the study results to prospectively identify patients at highest risk for HABP/VABP may help to facilitate the conduct of innovative and efficient clinical trials,” said Pamela Tenaerts, executive director of CTTI. “This will help to promote development of optimal preventive, diagnostic, and treatment strategies to improve management of this disease.”

Learn more about CTTI’s work on HABP/VABP Studies.

Recording Now Available: CTTI Releases New Resources for Adoption of a Quality by Design Approach

Posted on by Hannah Faulkner

A recording is now available of the public webinar held on Thurs., Nov. 12 to launch CTTI’s new resources for implementing a Quality by Design (QbD) approach to clinical trials. The webinar was led by Greg Pennock, EMD Serono; David Rodin, Amici Clinical Research; Karlin Schroeder, Parkinson’s Foundation; Ansalan Stewart, FDA; and Steve Young, CluePoints.

“We have worked with leaders and all stakeholders across the clinical trials ecosystem to develop new resources that can help research organizations appropriately plan and design clinical trial protocols by implementing, and thus demonstrating the value of Quality by Design,” said CTTI Executive Director Pamela Tenaerts, MD, MBA. “These new tools aim to help researchers implement QbD into their trial – an efficient approach that will help them focus on what matters most in their trial and proactively address important risks to patient safety and the credibility of trial results.”

The specific resources that CTTI released include:

  • QbD Maturity Model: This self-assessment tool can be used by organizations to assess their current implementation of QbD, and to identify a desired future state.
  • Metrics Framework: This QbD Metrics Framework provides nine example metrics that can help key stakeholders in clinical research organizations to self-evaluate QbD implementation and guide continuous improvement efforts.
  • Implementation Guide: This resource helps study teams plan and evaluate their implementation of QbD for an individual clinical trial, and is intended to serve as a guide to key elements of QbD that will often be important to incorporate in trial planning and execution.
  • Documentation Tool: This tool helps study teams capture and communicate decisions about what is critical to quality and how the most important risks will be addressed.

CTTI’s QbD toolkit serves as a one-stop-shop for any individual or organization looking to implement QbD, and may help meet the anticipated new guideline for ICH E8(r1), which is expected to be finalized in 2021 and emphasizes a QbD approach to trial design.

Both the webinar and the new resources can be found on the CTTI website.

New CTTI Project Aims to Improve Clinical Evidence with Practical Approaches for Embedding Trials Into Health Care

Posted on by Hannah Faulkner

Integrating trials that are intended for medical product review into clinical health care offers the promise of data that reflect real-world populations and settings, and improve efficiency by avoiding duplication of activities that already occur in clinical care. However, there are currently no guidelines or strategies to help clinical trial stakeholders operationalize this fit-for-purpose integration.

To remedy this issue, CTTI is starting work on a new project that will result in data, resources, and recommendations aimed at bridging the gap between trials and clinical care settings to improve evidence generation. This project aims to:

  • Identify when elements of interventional clinical trial integration into clinical settings would be feasible and the associated benefits and risks
  • Identify barriers and potential solutions to incorporating interventional trials into clinical care
  • Describe operational approaches to incorporating interventional trials into clinical care

CTTI will develop the new recommendations by conducting in-depth interviews that identify barriers and solutions with a wide variety of clinical trial and healthcare experts, compiling case studies on innovative operational approaches, and organizing a multi-stakeholder meeting to discuss strategies.

By taking a multifaceted approach, CTTI aims to create resources that will help clinical trial stakeholders overcome the barriers to integrating interventional research into real-world settings to create more relevant results.

New CTTI Steering Committee Positions Open for Patient/Caregiver Representative

Posted on by Hannah Faulkner

One of many ways that CTTI engages with and integrates patients into our work is by having patient/caregiver representatives on our Steering Committee. Now, through 11:59 p.m. ET, Sun., Nov. 22, we are accepting applications for this position. We are looking for patients or caregivers who are self-starters, have personal experience and familiarity with clinical trials, and can work with stakeholders across the research community.

During their three-year term, CTTI Steering Committee patient/caregiver representatives contribute ideas for projects, participate in their conduct and analysis, and are committed to disseminating CTTI recommendations and encouraging adoption of system changes that will improve the efficiency of clinical trials.

Learn more about the opportunity and apply today.

CTTI to Release New Resources for Adoption of a Quality by Design Approach During Nov. 12 Webinar

Posted on by Hannah Faulkner

CTTI will host a public webinar, Accelerating Evidence Generation: New CTTI Resources for Implementing a QbD Approach to Clinical Trials, on Thurs., Nov. 12.

“We have worked with leaders and all stakeholders across the clinical trials ecosystem to develop new resources that can help research organizations appropriately plan and design clinical trial protocols by implementing, and thus demonstrating the value of Quality by Design,” said CTTI Executive Director Pamela Tenaerts, MD, MBA. “These new tools aim to help researchers implement QbD into their trial – an efficient approach that will help them focus on what matters most in their trial and proactively address important risks to patient safety and the credibility of trial results.”

The specific resources that CTTI will release include:

  • QbD Maturity Model: This self-assessment tool can be used by organizations to assess their current implementation of QbD, and to identify a desired future state.
  • Metrics Framework: This QbD Metrics Framework provides nine example metrics that can help key stakeholders in clinical research organizations to self-evaluate QbD implementation and guide continuous improvement efforts.
  • Implementation Guide: This resource helps study teams plan and evaluate their implementation of QbD for an individual clinical trial, and is intended to serve as a guide to key elements of QbD that will often be important to incorporate in trial planning and execution.
  • Documentation Tool: This tool helps study teams capture and communicate decisions about what is critical to quality and how the most important risks will be addressed.

These new resources expand CTTI’s existing QbD toolkit, which serves as a one-stop-shop for any individual or organization looking to implement QbD, and may help meet the anticipated new guideline for ICH E8(r1), which is expected to be finalized in 2021 and emphasizes a QbD approach to trial design.

The free public webinar will begin at noon EST on Thurs., Nov. 12 and will feature the following presenters:

  • Greg Pennock, EMD Serono
  • David Rodin, Amici Clinical Research
  • Karlin Schroeder, Parkinson’s Foundation
  • Ansalan Stewart, FDA
  • Steve Young, CluePoints

Recording Now Available: CTTI’s New Robust Set of Resources to Assist with Designing and Running Master Protocols

Posted on by Hannah Faulkner

A recording is now available of the public webinar held on Tues., Oct. 13, to launch CTTI’s new set of resources that can be used to collaborate, communicate, and design master protocol studies. The webinar was led by Abby Bronson, Edgewise Therapeutics; Marianne Chase, Massachusetts General Hospital; Daniel Millar, Janssen R&D; and Nick Richardson, FDA, CDER.

While the interest in master protocol studies is growing, many organizations—particularly non-traditional drug developers such as patient advocacy groups and other nonprofits—lack the experience to design and implement this kind of study. In response to these challenges, through a high-level landscape review, a series of expert meetings, and a public open comment opportunity, CTTI developed a set of resources that include frameworks, case studies, and other interactive materials to assist in the planning and development of master protocols.

“With the success of master protocols in COVID-19 trials, there’s never been a better time to rethink the way you’re doing clinical trials in other disease areas,” said Pamela Tenaerts, executive director at CTTI. “In many cases, a well-designed and well-planned master protocol approach is an ideal way to get answers to scientific questions faster and serve patients better. Our new set of resources give sponsors, non-profit groups, and others a starting point and pathway for designing and conducting a successful master protocol study from start to finish in your disease area.”

The specific resources that CTTI released in conjunction with this webinar include:

  • Value Proposition Guide: outlines key considerations for presenting the value proposition of the master protocol to stakeholders such as collaborators and vendors
  • Study Simulation Tool: provides an overview of key modules that should be simulated in order to optimize master protocol design
  • Protocol Development Map: describes the unique aspects of developing a master protocol from the academic or nonprofit organization perspective
  • Operations Partner Assessment Tool: outlines considerations for engaging and selecting vendors as partners in master protocols
  • FDA Engagement Tool: describes the formal mechanisms that facilitate early interaction with the FDA and provides a general timeline for development of an FDA engagement strategy

Both the webinar and latest resources can be found on the CTTI website.

CTTI Paper Features Tool to Help Sponsors and Patient Groups Identify Mutually Beneficial Opportunities for Collaboration

Posted on by Hannah Faulkner

Effective engagement between patient groups and research sponsors can enhance the quality and efficiency of clinical trials, improve patient recruitment and retention, reduce costs, and speed the pathway toward new medical treatments. One opportunity for sponsors is to identify and prioritize new effective engagement activities. A new manuscript in Therapeutic Innovation & Regulatory Science details CTTI’s evidence-based prioritization tool to help sponsors and patient groups pinpoint mutually beneficial engagement activities.

The web-based tool provides 24 unique engagement activities that span the medical product development lifecycle. Using a three-step decision-making process, the tool helps sponsors and patient groups define the expectations, goals, and important roles that will have the biggest impact on the design, conduct, and dissemination of clinical research. The findings help teams apply CTTI’s recommendations for effective patient group engagement by supplying the results in an easy-to-use visual priority matrix grid.

Read the full manuscript.

Report Now Available: Stakeholder Engagement on ICH E6 Guideline for Good Clinical Practice

Posted on by Hannah Faulkner

The summary report of the web conference on “Stakeholder Engagement on ICH E6 Guidance for Good Clinical Practice,” organized by the U.S. Food and Drug Administration (FDA) in collaboration with the Clinical Trials Transformation Initiative (CTTI), is now available. The two-day Pan-American web conference was held June 4-5 with more than 1300 attendees worldwide.

The report provides an overview of the presentations from a diverse group of participants, including academic researchers, human subject protection and ethics experts, as well as patients. Members of the ICH Expert Working Group (EWG), which is tasked with updating the ICH E6 guideline, provided an overview of their approach to ensuring that the guideline is responsive to the needs of the community and that it facilitates advances in clinical trial design and conduct. The report also outlines key themes from the web conference’s line-up of stakeholders who shared their experiences with ICH E6(R2).  Further, the report also incorporates comments and input from web-conference attendees that were received via email or verbally during the web conference.

Check out the recording and the slide decks for each day of the web conference to learn more from the presenters.

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

CTTI to Release Resources for Designing and Running Master Protocols During Oct. 13 Webinar

Posted on by Hannah Faulkner

CTTI will host a public webinar on Tues., Oct. 13 to announce new resources that provide a roadmap for designing and running master protocols.

A master protocol approach allows researchers to answer multiple scientific questions within a single clinical trial infrastructure. With a flexible design and highly centralized operational features, the master protocol platform can eliminate several challenges, resources, and expenses associated with developing and running individual protocols.

“With the success of master protocols in COVID-19 trials, there’s never been a better time to rethink the way you’re doing clinical trials in other disease areas,” said Pamela Tenaerts, executive director at CTTI. “In many cases, a well-designed and well-planned master protocol approach is an ideal way to get answers to scientific questions faster and serve patients better. Our new set of resources give sponsors, non-profit groups, and others a starting point and pathway for designing and conducting a successful master protocol study from start to finish in your disease area.”

CTTI will release a complete master protocol design and implementation roadmap, case studies, and other resources including a:

  • Value Proposition Guide: outlines key considerations for presenting the value proposition of the master protocol to stakeholders such as collaborators and vendors
  • Study Simulation Tool: provides an overview of key modules that should be simulated in order to optimize master protocol design
  • Protocol Development Map: describes the unique aspects of developing a master protocol from the academic or nonprofit organization perspective
  • Operations Partner Assessment Tool: outlines considerations for engaging and selecting vendors as partners in master protocols
  • FDA Engagement Tool: describes the formal mechanisms that facilitate early interaction with the FDA and provides a general timeline for development of an FDA engagement strategy

“Due to the complexity of master protocol trials and the potential regulatory impact, a master protocol needs to be well-designed and well-conducted to ensure patient safety and quality data,” said Nicholas Richardson, clinical reviewer at the Center for Drug Evaluation and Research (CDER) at the U.S. Food and Drug Administration (FDA). “This requires significant upfront planning and resources, and CTTI’s new resources outline considerations and instructions for planning and executing a successful master protocol study.”

Through a high-level landscape review, a series of expert meetings, and a public open comment opportunity, CTTI created these resources to help organizations develop well-designed master protocols and create a network to facilitate their implementation.

“We need functioning resources that address obstacles in master protocol design and how to overcome them,” said Marianne Chase, director of research operations at the Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital. “With CTTI’s new offerings, we now we have a roadmap to follow—we can hit the ground running with development and, eventually, start to reap the many benefits that a master protocol approach has to offer.”

The free webinar will begin at 11 a.m. ET and will be led by Richardson; Chase; Abby Bronson, Edgewise Therapeutics; and Daniel Millar, Janssen R&D.

CTTI Collaborates with Multiple U.S. Organizations on First Successful Embedded Trial Using National Health Plans’ Data

Posted on by Hannah Faulkner

Today, at the ESC Congress 2020 – The Digital Experience, a group of U.S. investigators from several organizations including CTTI announced their collaborative findings from the Implementation of a randomized controlled trial to imProve treatment with oral AntiCoagulanTs in patients with Atrial Fibrillation (IMPACT-AFib) trial.

CTTI worked with Aetna, Duke Clinical Research Institute, the Harvard Pilgrim Health Care Institute’s Department of Population Medicine, Harvard Pilgrim Health Care, HealthCore Anthem, Humana, Optum, and the FDA, as well as a patient representative, to plan and conduct this ground-breaking, 80,000-patient, randomized clinical study. This trial was the first ever to leverage the FDA-Catalyst System network of electronic health data, which consolidates data from a diverse group of national health plan data partners.

The study involved identifying patients with atrial fibrillation (AF) who were at high risk of stroke and not currently taking any type of oral anticoagulant (OAC). The goal of the study was to learn if mailing educational information to patients and their providers could incentivize patients to initiate important OAC prescribing discussions with their doctors.

“It is imperative to identify all patients with AF who are at risk of stroke, especially because strokes can be prevented with OAC,” said Sean Pokorney, co-principal investigator at Duke Clinical Research Institute, who presented the findings at the event. “The underuse of OAC is a significant public health priority, and also a priority of health plans like those participating in this study, which is why we were so eager to collaborate on IMPACT-AFib.”

Although it had never been done before, the study relied upon administrative health plan data and pharmacy dispensing data from multiple national health plans to identify eligible patients and randomize them to an early or delayed intervention, and to assess clinical outcomes.

The study results showed that it would take more than one educational mailing to achieve the desired outcome. Moreover, the study sets a foundation for future clinical trials in AF and other diseases as an example of how the FDA-Catalyst System can help to conduct trials using new and resourceful methods. The goal is for solutions like this to help clinical trial stakeholders conduct future trials much faster than before.

“CTTI played a key role in the pre-work for this trial, proving the viability of running a large-scale trial using the FDA-Catalyst platform,” added Pamela Tenaerts, executive director at CTTI. “The study is a successful proof of concept of embedding a randomized clinical trial into a claims system, while confirming in a large scale experiment that the use of educational interventional approaches in medicine might be limited. We believe that all future clinical trials should maximally leverage available clinical and nonclinical data to minimize collection of necessary trial specific data, and the IMPACT-AFib trial is a fantastic example of that; it serves as a strong model for future research.”

Read the full press release.