Novel Endpoints

CTTI Article Explores Facilitators and Barriers Perceived by Investigators to Successful Pediatric Antibacterial Drug Trials

Posted on by Lorri Bingham

Growing rates of antibiotic resistance have made the development of new antibacterial therapies an urgent public health need. This is especially true for the pediatric population, where it may take up to 10 years for clinical trials to determine safety and dosing information.

A CTTI article recently published in Contemporary Clinical Trials Communications shares findings from a survey of 73 investigators to determine facilitators and barriers to the successful conduct of much-needed pediatric antibacterial drug trials. The survey was conducted as part of CTTI’s Peds Trials work.

As outlined in the article, almost all investigators identified two factors as very important facilitators: having strong site staff and adequate funding. Other facilitating factors were related to staff expertise. Investigators rated parent concerns and obtaining consent as the most critical barriers. Other barriers included concerns about the number of blood draws and other invasive procedures, as well as having overly narrow eligibility criteria.

The survey findings suggest three areas in which to focus efforts to help facilitate ongoing pediatric antibacterial drug development:

  1. Improving engagement with parents of children who may be eligible to enroll in a pediatric antibacterial drug trial.
  2. Broadening inclusion criteria to allow more participants to enroll.
  3. Ensuring adequate staffing and establishing sustainable financial strategies, such as funding pediatric trial networks.

These results were used to develop CTTI’s actionable recommendations for facilitating and improving antibacterial drug trials in the pediatric population.

CTTI Charts New Pathways for Pediatric Antibacterial Drug Development

Posted on by Lorri Bingham

In an article recently published in the Journal of the Pediatric Infectious Disease Society (JPIDS), CTTI researchers lay out a roadmap for addressing an urgent public health issue: pediatric antibacterial drug development.

Antibacterial drugs are critically important for treating infectious diseases, but growing rates of antimicrobial resistance have made the development of new antibacterial therapies a priority for researchers and physicians. The problem is especially acute in pediatrics, because even when new drugs are developed for adults, it may be up to 10 years before the pediatric clinical trials needed to provide vital information about safety, effectiveness, and dosing in children are completed. The result of these delays is a chronic shortage of information to guide the use of new therapies in pediatric populations.

The JPIDS article, which was distilled from the results of CTTI research and expert stakeholder meetings, identifies five key areas for action aimed at overcoming barriers to conducting timely and efficient trials of new antibacterial drugs in children, including:

  1. Improving planning for pediatric drug development
  2. Streamlining processes for protocol development and trial design
  3. Refining approaches to seeking and obtaining informed consent
  4. Engaging with healthcare providers
  5. Emphasizing the rapid incorporation of new information into product labeling

The article reflects recommendations from CTTI’s Pediatric Antibacterial Drug Development Project, which focuses on creating efficient, evidence-based processes for developing, testing, and using antibacterial therapies in children. The “Peds Trials” Project itself is part of the larger CTTI Antibacterial Drug Development Program.

By fostering collaborative approaches that involve all stakeholders, CTTI hopes to accelerate the development of safe and effective pediatric antibacterial drugs—and to equip physicians and other healthcare professionals with the information they need to make the best possible decisions for the health of the children under their care.

Four Key Areas Where CTTI Has Transformed Clinical Trials

Posted on by Lorri Bingham

This year, CTTI marks its 10th year of working with a variety of stakeholders to positively change clinical trials, making them more streamlined, efficient, and patient-focused. To commemorate this milestone, we will #CelebrateCTTI throughout the month of January. Join us for the celebration—visit this blog, follow us on Twitter, and register to attend our 10 Year Anniversary Symposium on Tues., Feb. 6.

Since its inception in 2007, CTTI has made transformational shifts in the design and conduct of clinical research. Let’s take a look at the evolution of clinical trials in four key areas, among many, in which CTTI has played a critical role in moving the industry toward more efficient, high-quality, and patient-centric trials:

Trial Quality

Regulators have long acknowledged a need to change how the industry approaches clinical trial quality in order to focus on reducing errors that undermine data integrity and patient safety. Drawing on the expertise of key stakeholders, CTTI issued recommendations on effective and efficient trial monitoring in 2012. The following year, FDA issued final guidance on a risk-based approach to monitoring, reflecting principles from CTTI’s work. CTTI also developed the concept of Quality by Design, taking the focus from a reactive approach using audits to a proactive approach that builds quality into clinical trials at the outset. CTTI released its Quality by Design recommendations and toolkit in 2015, and its work in this area has been cited in FDA guidance and incorporated into GCP guidelines.

Patient Engagement

CTTI has been a pioneer in patient engagement, involving patient representatives in its organizational leadership and throughout its project teams. Spurred by the FDA’s Safety and Innovation Act of 2012, CTTI initiated the Patient Groups & Clinical Trials Project to establish best practices for engaging patients in clinical research. In 2014, CTTI released landmark recommendations that are currently used by multiple stakeholders to facilitate productive relationships with patient groups around clinical trials. In 2017, CTTI and FDA announced a partnership on a new initiative, the Patient Engagement Collaborative, to improve patient engagement across the FDA.

Central IRB

Although U.S. regulators are enthusiastic about the use of a central IRB to promote more efficient multi-site clinical trials, enterprise-wide implementation has lagged. CTTI initiated the Central IRB Project in 2010, creating recommendations and resources to help organizations identify and address barriers to the adoption of a central IRB. The NIH issued a draft policy in 2014 referencing CTTI’s recommendations and a final policy in 2016 requiring all NIH-funded multi-site clinical trials to use a central IRB effective in 2018.

Real-World Evidence

Since its inception, CTTI has recognized that “real-world evidence” from electronic health records, mobile devices, and other sources can provide unique insights into important clinical questions and could improve the efficiency of clinical trials. The FDA Amendments Act of 2007, which mandated FDA to develop a system to link safety data from multiple sources, paved the way for the use of connected datasets in clinical trials. After partnering with the FDA and Harvard Pilgrim Health Care Institute to assess the feasibility of using the Sentinel database for clinical research, CTTI supported the first trial using Sentinel. CTTI also launched a program in 2016 to support the use of mobile technology in clinical trials, issued recommendations in 2017 on how to use registries as reusable platforms for trials, and announced a Real-World Evidence Project in 2017.

Two CTTI Papers Explore Perceptions on Enrolling Children in Clinical Trials

Posted on by Lorri Bingham

Two papers from CTTI’s Peds Trials work on barriers to enrolling children in clinical trials were recently published in Contemporary Clinical Trials Communications. Despite the fact that pediatric trials are required for new drugs, these trials can be especially difficult to design, enroll, and complete. CTTI’s papers explore the challenges from both the provider and parent perspective and suggest ways to overcome them.

Based on feedback from parents, providers, and other stakeholders, CTTI developed actionable recommendations to address the challenges of enrolling children in clinical trials. These recommendations offer practical, evidence-based strategies that can be applied by research sponsors, investigators, and site staff to improve the quality and efficiency of pediatric trials.

Perceived Barriers to Pediatrician and Family Practitioner Participation in Pediatric Clinical Trials: Findings from the Clinical Trials Transformation Initiative

Posted on by Hannah Faulkner

Perceived Barriers to Pediatrician and Family Practitioner Participation in Pediatric Clinical Trials: Findings from the Clinical Trials Transformation Initiative

CTTI Launches New Project to Accelerate Use of Real-World Data in Clinical Trials

Posted on by Lorri Bingham

New approaches to clinical research that harness diverse sources of “real-world data” (RWD) could accelerate the pace of clinical trials, reduce costs, and provide new insights into patient experiences. Keeping at the forefront of this movement, CTTI today announced a new Real-World Evidence Project that is designed to foster greater awareness of these data sources and explore effective ways to leverage them for clinical trials.

Unlike conventional clinical trial data gathered using specialized, costly, and complex systems, RWD is captured from existing sources such as electronic health records (EHRs), billing and insurance claims databases, disease registries, patient generated data, and even mobile devices. When combined and analyzed, these data can yield “real-world evidence” (RWE) that may provide a more accurate and complete picture of patient outcomes and experiences.

However, despite this potential, there have been relatively few attempts to incorporate RWE into trials intended to support regulatory decision making for new medical products and labeling indications—in part because stakeholders have not yet agreed on valid and effective approaches.

CTTI’s RWE work is helping to meet these challenges by:

  • Describing how these sources of data can be leveraged to plan and conduct trials;
  • Identifying and addressing barriers to such use
  • Identifying when RWD/RWE usage may be impractical or unwise; and
  • Developing practical approaches to embedding RWE in clinical research.

Ultimately, broad adoption of RWE for regulatory trials may benefit patients and other stakeholders by efficiently creating high-quality, reliable evidence about the safety and effectiveness of medical products.

CTTI Shares New Insights on Early Enrollment, Barriers to Remote Clinical Trials, and Improving Investigator Trainings at PRIM&R Advancing Ethical Research Conference

Posted on by Lorri Bingham

CTTI will present findings during three sessions at the upcoming PRIM&R Advancing Ethical Research (AER) Conference.

On Mon., Nov. 6, CTTI will share data on stakeholder perceptions of early informed consent and enrollment in clinical trials. While early enrollment could improve the ability to conduct trials that evaluate the efficacy and safety of treatments for hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP), questions remain about implementing it ethically and effectively. CTTI will share findings from its HABP/VABP Studies Project on the acceptability of an early informed consent approach for high-risk patients and essential information that should be shared with key stakeholders.

On Wed., Nov. 8, CTTI will discuss findings from its MCT Legal & Regulatory Project on actual and perceived barriers that may be preventing the widespread use of mobile technology in clinical trials. Presenters will explore potential challenges and opportunities of conducting clinical research remotely, and solicit input from clinical enterprise stakeholders on potential ethics implications. The project is part of CTTI’s Mobile Clinical Trials (MCT) Program.

In a separate session, CTTI will also present findings to date for its Investigator Qualification project and Investigator Community recommendations. The presenter will examine whether current GCP training methods actually provide the knowledge and skills necessary to conduct quality clinical trials. Further, he will detail recently released recommendations that aim to strengthen the clinical trials investigator and study team community through better training and other approaches.

We hope you will join us in San Antonio, Texas, Nov. 5-8 as we share new insights into these noteworthy clinical trials topics.

Presentation: Stakeholder Perceptions on Early Informed Consent for Clinical Trials
Date & Time: Mon., Nov. 6, 3:30 – 4:45 p.m.
Presenters: Amy Corneli (CTTI) and Thomas Holland (Duke University)

Presentation: Clinical Trials Transformation Initiative (CTTI) Mobile Clinical Trials, Legal, and Regulatory Project
Date & Time: Wed., Nov. 8, 11:15 a.m. – 12:30 p.m.
Presenters: David Babaian (Kinetiq), Linda Coleman (Yale University), and Jan Hewett (FDA

Presentation: Beyond Good Clinical Practice (GCP) Training: Expanding the Tool Set for Preparing Investigators
Date & Time: Wed., Nov. 8, 11:15 a.m. – 12:30 p.m.
Presenters: Gerrit Hamre (CTTI)

New Results on Cost Drivers in Phase 3 Drug Trials for HABP/VABP

Posted on by Lorri Bingham

Drug-resistant infections are on the rise, and one type of serious infection that can be caused by drug-resistant bacteria is hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Despite the desperate need for effective new therapies for HABP/VABP, clinical trials for this condition are lagging due to difficulties in conducting these trials and low expected return on investment. A new study from CTTI and the Tufts Center for the Study of Drug Development, published in Clinical Infectious Diseases, calculates the cost of phase 3 trials for HABP/VABP and identifies areas of opportunity to lower costs and boost investment in these critically important studies.

“To meet the urgent public health need for new antibacterial drugs, clinical trials must be more efficient, cost-effective and feasibly executed. Our study identified several factors driving clinical trial costs that can be targeted to optimize the development of new treatments,” said Ken Getz, an associate professor and researcher at Tufts University involved in the study.

“Leveraging evidence to direct meaningful changes in clinical trials is what CTTI is all about,” said Pamela Tenaerts, CTTI executive director. “We hope this information will help target efforts to streamline HABP/VABP trials, which will ultimately benefit patients.”

Key findings include:

  • The cost of a phase 3 HABP/VABP clinical trial averages $89.6 million, which is over double the average cost of a phase 3 oncology trial
  • Per patient, phase 3 HABP/VABP clinical trials were $2,300 more expensive than oncology clinical trials and $31,900 more expensive than endocrine trials
  • Screening failure rates and the cost of screening failures were the biggest drivers of cost, suggesting sponsors and research sites should consider ways to increase the number of potentially eligible patients

CTTI released recommendations for streamlining HABP/VABP trials and is testing novel approaches to make these trials more feasible, such as using predictive models to find and consent patients earlier in the disease process.