Regulatory Submissions + Approvals
CTTI Charts New Pathways for Pediatric Antibacterial Drug Development
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:
- Improving planning for pediatric drug development
- Streamlining processes for protocol development and trial design
- Refining approaches to seeking and obtaining informed consent
- Engaging with healthcare providers
- 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.
CTTI to Lead Breakout Session and Offer Insights into Using Mobile Tech and Novel Endpoints in Clinical Trials at 2018 SCOPE Meeting
This year’s Summit for Clinical Ops Executives (SCOPE) conference will feature a notable presence from CTTI as part of the annual meeting’s first-ever Sensors, Wearables and Digital Biomarkers in Clinical Trials track. The meeting will take place in Orlando from Feb. 12-15.
CTTI, which recently published a set of recommendations and resources for developing and incorporating novel technology-derived endpoints into clinical research as part of its larger Mobile Clinical Trials (MCT) Program, will lead a breakout session focusing on findings from this project and what they mean for site investigators and patients. Discussion will center on use cases developed from four therapeutic areas—Parkinson’s disease, heart failure, diabetes, and Duchennes muscular dystrophy—and will describe strategies for identifying, developing, and implementing novel endpoints derived from new and emerging technologies, including mobile devices.
The breakout session will be accompanied by a pair of related CTTI presentations taking place over the next two days. The first will provide insights from CTTI’s MCT Stakeholder Perceptions Project exploring patient and investigator views of research involving mobile technologies, and will examine ways to develop a successful patient-centered approach to leveraging mobile technology in clinical trials. The second presentation will offer expert perspectives from CTTI’s MCT Novel Endpoints Project, which addresses uncertainties about how best to incorporate mobile technologies into clinical research and offers pathways for leveraging data derived from such technologies to accelerate research and therapeutic development.
We hope you will join us in Orlando on Feb. 13-15 as we explore evidence-based approaches to integrating novel technologies and endpoints into clinical research.
Interactive Breakout Discussion: Selecting, Developing and Incorporating Novel Endpoints, Generated from Data Captured by Mobile Technologies, for Use in Clinical Trials
Date and time: Tues., Feb. 13, 4:00 p.m. EST
Presenters: Jennifer Goldsack (CTTI), Rob DiCicco (GSK), Amy Calvin (Eli Lilly), and Christian Gossens (Roche)
Presentation: New Findings on Patient and Site Perspectives from the Clinical Trials Transformation Initiative
Date and time: Thurs., Feb. 15, 12:25 p.m. EST
Presenter: Hassan Kadhim (Boehringer Ingelheim Pharmaceuticals)
Presentation: Identifying, Developing and Incorporating Technology-Derived Endpoints into Clinical Trials: A ‘How-To’ Guide
Date and time: Wed., Feb. 14, 11:15 a.m. EST
Presenter: Rob DiCicco (GSK)
Two CTTI Papers Explore Perceptions on Enrolling Children in Clinical Trials
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.
- “Perceived barriers to pediatrician and family practitioner participation in pediatric clinical trials: Findings from the Clinical Trials Transformation Initiative” shares findings from an online survey conducted by CTTI of pediatric providers across the U. S. The survey found that lack of awareness of existing pediatric trials was a major barrier to patient referral by providers, in addition to consideration of trial risks, distance to the site, and time needed to discuss trial participation with parents. The paper notes “understanding the barriers that limit pediatric providers from collaboration or inhibit their participation is key to designing effective interventions to optimize pediatric trial participation.”
- “Parents’ perceived obstacles to pediatric clinical trial participation: Findings from the Clinical Trials Transformation Initiative” discusses the results of in-depth interviews with parents who were approached to enroll their children in a clinical trial. The interviews found that establishing trust, appropriate timing, a transparent discussion of risks and benefits oriented to the layperson, and providing motivation for children to participate were key factors that impacted parents’ decisions. The paper recommends solutions related to budget allocations, staffing, and the consent process as ways to make parents’ priorities and considerations a central focus in clinical trials.
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.
New Results on Cost Drivers in Phase 3 Drug Trials for HABP/VABP
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.
Finding Solutions to Legal and Regulatory Challenges of Conducting Mobile Clinical Trials
Mobile clinical trials (MCTs) offer several potential advantages, such as greater patient convenience, efficiencies in data collection, potential for novel endpoints, and enhanced participant retention.
However, despite the successful conduct of several MCTs for regulatory submission, the MCT model has yet to be widely adopted. This is due in part to presumed legal and regulatory issues in the U.S., such as the complexity of navigating different state medical licensing laws, patient and investigator oversight, and issues with the drug supply chain of custody.
In July 2017, CTTI convened a multi-stakeholder expert meeting to explore the legal and regulatory challenges inhibiting more widespread practice of MCTs, and to identify potential solutions. A meeting summary is now available highlighting main points from the discussion, including the following:
- Highly varied state laws and regulations need to be thoroughly understood and recorded in an accessible location, e.g., a public database.
- Guidance from regulatory bodies is needed to define principal investigators’ responsibilities regarding patient care oversight and potential delegation of activities,
- Trials with a mobile clinical component should not be held to higher standards than traditional trials.
- Patients and regulatory agencies should be engaged in trial design early in the development phase.
CTTI’s MCT Legal and Regulatory Project team will leverage themes and specific solutions from the multi-stakeholder discussions to develop recommendations and tools that will help address legal and regulatory challenges currently associated with MCTs.
This work is part of CTTI’s MCT Program, which is also exploring other topics and barriers related to planning for and conducting MCTs.
CTTI Update: Advancing the Use of Mobile Health Technology to Transform Clinical Trials
Mobile technology has the potential to revolutionize clinical trials, but putting mobile clinical trials (MCTs) into action requires consideration of issues such as data integrity, legal and regulatory barriers, scientific and technological challenges, and perspectives of potential trial participants, investigators, and site staff. For the past two years, CTTI’s MCT Program has systematically explored barriers to MCTs, gathered evidence, and convened multiple stakeholders to tackle these issues.
By developing best practices on how to effectively integrate mobile technologies into clinical trials for regulatory submissions, CTTI intends to promote quality, efficient, and more cost-effective research. Recent developments include the following:
- CTTI’s Recommendations for Developing Novel Endpoints Generated by Mobile Technology for Use in Clinical Trials were released in June and are prominently featured in a recent mHealth Action Plan from the Duke-Margolis Center for Health Policy.
- CTTI’s recommendations are accompanied by several practical tools and case examples that describe the process of novel endpoint development for MCTs.
- A survey of potential research participants, as well as in-depth interviews with site investigators on issues related to MCTs, are underway. Analysis of these results will begin this fall and will inform recommendations to overcome barriers to the use of mobile technology in clinical trials as perceived by key stakeholders.
- CTTI presented “Turning Opportunity Into Reality: Real Data and Practical Guidance for Incorporating Mobile Technology in Clinical Trials” at the DPharm Disruptive Innovations Conference in September 2017. The presentation included—as it relates to mobile technology—the patient perspective, tips for dealing with large volumes of data, and engaging with the FDA during trial design, execution, and monitoring.
- Two expert meetings were held in 2017, one on legal and regulatory issues and one on scientific and technological challenges affecting MCTs. Official CTTI recommendations and resources on these topics will be issued in early 2018
CTTI Shares Challenges and Solutions to Enrolling Participants in Pediatric Trials at AAP 2017
At the upcoming American Academy of Pediatrics National Conference, CTTI will offer insights into some of the biggest challenges currently affecting pediatric clinical trial enrollment and conduct. Through a podium presentation and poster sessions, CTTI will share survey-based findings that shed new light on obstacles affecting pediatric trials and discuss possible solutions that can help streamline these studies and reduce burdens on patients, families, and providers.
Although clinical trials are essential for ensuring access to safe and effective therapies for children, many studies struggle to enroll pediatric participants and families and providers often lack information to help them make the best possible treatment choices. This problem is especially acute for children and infants at risk of harm from bacterial infections, many of which are increasingly resistant to antibiotic treatment. For this reason, maintaining a strong pipeline of safe and effective therapies is an urgent priority.
CTTI’s Peds Trials project, part of the larger Antibacterial Drug Development Program, is actively addressing these gaps and has created evidence-based recommendations designed to improve and streamline pediatric trial development and conduct. We hope you will join us in Chicago this Sept. 16-19 as we share new insights into challenges affecting pediatric trial enrollment, including reasons that parents refuse trials and provider perceptions of obstacles.
Poster & Podium Presentation: Obstacles to Pediatric Clinical Trial Enrollment: Why Parents Refuse; Findings from the Clinical Trials Transformation Initiative
Date & Time: Monday, Sept. 18, 12:35 p.m.–12:50 p.m. (oral presentation)
Monday, Sept. 18, 1:00 p.m.–5:00 p.m. (poster session)
Presenter: P. Brian Smith (Duke University)
Poster: Barriers to Pediatric Clinical Trial Enrollment: Findings and Recommendations from the Clinical Trials Transformation Initiative
Date & Time: Monday, Sept. 18, 1:00 p.m.–5:00 p.m. (poster session)
Presenter: P. Brian Smith (Duke University)
CTTI Advances Mobile Clinical Trials at DPharm 2017
Mobile technology has been used in a variety of ways, but it has yet to be widely incorporated into clinical trials—despite its great potential to increase trial quality and efficiency. As part of its Mobile Clinical Trials (MCT) Program, CTTI has implemented four projects to identify and address the challenges related to planning for and conducting clinical trials that use mobile technology. This week, CTTI will present strategies and insights from the program at DPharm 2017 Conference, held in Boston on September 6-8.
At the 2-day conference themed “Disruptive Innovations US,” CTTI will bring together key industry leaders who are collaborating on recommendations for the use of mobile technologies in regulated clinical trials after the point of informed consent. This will include—as it relates to mobile technology—the patient perspective, tips for dealing with large volumes of data, and engaging with the FDA during trial design, execution, and monitoring.
Presentation: Turning Opportunity Into Reality: Real Data and Practical Guidance for Incorporating Mobile Technology in Clinical Trials
Date & Time: Friday, Sept. 8, 2:30–3:10 p.m.
Moderator: Komathi Stem (monARC Biotech)
Panelists: Ray Dorsey (University of Rochester), Cindy Geoghegan (Patient and Partners), and Gary Grabow (Genentech)
Also, at DPharm’s pre-conference program, “Mobile in Clinical Trials,” CTTI will share recommendations that clarify the pathway for developing novel endpoints from data generated using mobile technology in clinical trials.
Presentation: CTTI Findings Are in From Their Mobile Clinical Trials Program: Recommendations on Novel Endpoints
Date & Time: Wednesday, Sept. 6, 9:20–9:40 a.m.
Presenter: Jennifer Goldsack (CTTI)
In addition to Novel Endpoints, CTTI is also working on recommendations to address challenges and opportunities related to Mobile Devices, Legal and Regulatory, and Stakeholder Perceptions, as part of the MCT Program.
Addressing Challenges of Using Mobile Devices in Clinical Trials
Mobile devices hold great potential to transform clinical trials by their ability to capture objective, real-world health data directly from study participants. While this technology shows promise to improve the quality and efficiency of medical product development, questions remain on how to successfully integrate mobile devices for data capture into clinical trials.
On June 16, 2017, CTTI convened a multi-stakeholder expert meeting to further refine solutions to the scientific and technological challenges preventing widespread adoption of mobile devices in clinical trials. A meeting summary is now available, including the following:
- The recommended best practices for studies using mobile devices for data capture do not differ significantly from many of the best practices that we already apply to clinical trials.
- Studies using mobile devices for data capture should not be held to higher standards than traditional trials.
- Efforts to leverage mobile devices for data capture should strive to engage patients in study design and endpoint selection.
The MCT Mobile Technologies Project focuses on using mobile devices in FDA-regulated clinical trials after initial participant consent—in other words, the use of devices for data capture rather than for recruitment, retention, or as the study intervention. The project team will use findings from the expert meeting to develop recommendations and tools that guide the adoption of mobile devices for data capture in clinical trials.