Regulatory Submissions + Approvals
CTTI Updates DCT Recommendations in Response to COVID-19
COVID-19 forced the clinical trials ecosystem to plan and conduct research in remote or virtual settings. In an effort to support this shift, CTTI is launching a project to update its Decentralized Clinical Trials (DCT) recommendations to ensure they reflect the latest learnings and emerging best practices from the pandemic.
CTTI’s current DCT recommendations, which launched in 2018 and focus on the use of telemedicine, mobile and local healthcare providers, and related topics, were the most frequently downloaded document on CTTI’s website in 2020, reflecting the increased demand for decentralized solutions in times of COVID-19.
This new project aims to support the accelerating adoption of DCT solutions in clinical trials going forward. The updated recommendations will focus on selecting and operationalizing DCT solutions, ensuring effective safety monitoring, and appreciating the needs and perspectives of investigators, sites, and participants.
This effort builds on CTTI’s initial recognition that running a DCT does not have to be all or nothing. DCTs can be completely virtual, but many will be partially decentralized using a hybrid approach. Regardless of where a trial falls on the decentralized continuum, it is always important to:
- Plan ahead as much as possible
- Involve all stakeholders early and often
- Focus on what matters
- Communicate and be transparent
Sponsors and CROs can use the revised recommendations to design a fit-for-purpose, efficient DCT—one that can reduce patient burden, improve enrollment, and more closely replicate real-world populations and scenarios.
Recording of Public Web Conference Now Available: Listen to ICH E6 Guideline for Good Clinical Practice (GCP) – Update on Progress
Recordings for the International Council for Harmonisation’s public web conference, held May 18 & 19, “ICH E6 Guideline for Good Clinical Practice (GCP) – Update on Progress,” are now available.
The web conference, which consisted of identical meetings at different times over two days to accommodate a global audience, opened with welcoming remarks followed by a video session wherein ICH E6 Expert Working Group (EWG) members shared the ICH guideline development process and the approach to updating ICH E6(R3). The second session of the web conference focused on the vision and goals for the work to update the E6 guideline and lessons learned from public input and stakeholder feedback. In the final session of the web conference, members of the EWG presented the published draft, work-in-progress principles. Then, experts and advocates provided their vision and aspirations on the clinical trial enterprise in general.
View the full slide deck for day of the web conference to learn more from each presenter.
For additional information on updating the ICH E6, 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
- ICH E6 Draft Principles – Published on the 19th of April, 2021
- CTTI’s Informing the Update of ICH E6 Work
- 2020 CTTI Research & Findings
Recording Now Available: The State of U.S. COVID-19 Treatment Clinical Trials Public Webinar
A recording for CTTI’s public webinar, The State of U.S. COVID-19 Treatment Clinical Trials, held Apr. 15, is now available. In the webinar, moderated by CTTI Acting Executive Director Leanne Madre, CTTI presented findings from an analysis of data downloaded from the database for the Aggregate Analysis of ClinicalTrials.gov (AACT) on the state of U.S. COVID-19 treatment studies. The presentation included an overview of the U.S. COVID-19 clinical trials landscape, the availability of results, and changes in the portfolio as time has progressed. The presenters – Robert Califf, Verily and Google Health; Harlan Krumholz, Yale School of Medicine; and Deborah Zarin, Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard University – discussed how the findings from the analysis can be applied to improvements needed across the clinical trials enterprise.
View the full slide deck for the public webinar to learn more from each presenter.
For additional information on CTTI’s COVID-19 work, please visit this web page.
CTTI to Host Free Public Webinar on the State of U.S. COVID-19 Treatment Clinical Trials Featuring Robert Califf, Harlan Krumholz, and Deborah Zarin
CTTI will host a free public webinar on the state of U.S. COVID-19 treatment clinical trials on Thurs., Apr. 15 at noon EST.
The U.S. has recently marked the one year anniversary of the official declaration of the COVID-19 pandemic by the World Health Organization. The pandemic thrust clinical research into the limelight like never before and – while daunting and challenging – the scientific community answered its collective call-to-duty with impressive vigor and determination. But our work continues and this anniversary provides an important opportunity for reflection, discussion and evaluation.
Many have pointed to a large number of initiated clinical trials as evidence of successful research in response to the global health crisis. However, the true measure of success should be in actionable and reliable research results that are available to inform clinical, policy and research decisions related to the diagnosis, treatment, and prevention of COVID-19 and its variants.
In this webinar, moderated by CTTI Acting Executive Director Leanne Madre, CTTI will present findings from an analysis of data downloaded from the database for the Aggregate Analysis of ClinicalTrials.gov (AACT) on the state of U.S. COVID-19 studies. The presentation will include an overview of the U.S. COVID-19 clinical trials landscape, the availability of results, and changes in the portfolio as time has progressed. The presenters, including Robert Califf, Verily and Google Health; Harlan Krumholz, Yale School of Medicine; and Deborah Zarin, Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard University, will discuss how the findings from the COVID-19 analysis can be applied to improvements needed across the clinical trials enterprise.
CTTI Announces New Playbook for Designing High-Quality, Diverse COVID-19 Trials
As the pandemic continues to endure worldwide, CTTI is leading the way in uncovering best practices for conducting COVID-19 trials. Following up on its first playbook focusing on conducting successful trials during the pandemic, CTTI is now releasing a second playbook with eight essential principles for high-quality, diverse COVID-19 trials.
These elements, fully outlined in the new COVID-19 playbook, recommend that stakeholders:
- Learn from the past and what’s being done now
- Make the time to design right, but move quickly
- Adequately power trials
- Randomize trials
- Maintain ethics
- Collaborate on study design
- Engage and enroll racial and ethnic minorities
- Use a core set of inclusion and exclusion criteria and endpoints
- Collaborate and coordinate
Beginning in April 2020, CTTI conducted an analysis of COVID-19 treatment trials in ClinicalTrials.gov, met with key stakeholders to discuss best practices for designing these types of trials, and launched a public survey on how to engage racial and ethnic minority patient populations in COVID-19 trials. CTTI communicated the resulting best practices during two CTTI-hosted webinars on designing high-quality COVID-19 treatment trials and engaging racial and ethnic minorities in COVID-19 trials.
These resources can help researchers adapt to the changing landscape and generate meaningful evidence despite the unprecedented challenges presented by the pandemic. Learn more about what CTTI is doing to address clinical trials issues related to COVID-19.
Recording Now Available: The Fastest Path to Effective COVID-19 Treatments: Using Master Protocol Studies Public Summit
A recording for CTTI’s public summit, The Fastest Path to Effective COVID-19 Treatments: Using Master Protocol Studies, held Jan. 13, is now available. The summit, conducted as a webinar, opened with a welcome from Janet Woodcock, Operation Warp Speed; a call-to-action from Robert M. Califf, Verily and Google Health; and included three panel discussions focused on solutions related to scaling master protocols.
The first panel, Practical Solutions to Setting Up Master Protocol Sites, moderated by Pamela Tenaerts, CTTI, with panelists Derek Angus, REMAP-COVID; Laura Esserman, I-SPY-COVID; and Manizhe Payton, ACTIV-2, examined key challenges and potential solutions to starting up new sites including contracting, competing trials, staffing, and IRB submission.
The second panel, Increasing Participant Enrollment in Master Protocols, moderated by Esther Krofah, Faster Cures, with panelists Kousick Biswas, Veterans Health Administration; Dan Cooper, UC Irvine; and Martin Landray, RECOVERY Trial, examined the key challenges limiting participant enrollment including competition with other trials, burden on staff, and discussed potential solutions to overcome hurdles such as co-enrollment.
The final panel, Lessons for the Future, moderated by Mark McClellan, Duke-Margolis Center for Health Policy, with panelists Sam Brown, Intermountain Health System; Adrian Hernandez, PCORnet; and Saye Khoo, AGILE, discussed policy changes needed to improve future pandemic preparedness.
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 from a pre-summit survey of those involved in COVID-19 treatment master protocols, specifically those involved in setting up new sites or recruiting participants at existing sites.
View the full slide deck for the public summit to learn more from each presenter.
For additional information on CTTI’s master protocols work, please refer to this web page.
This public summit is part of a collaborative effort with the Duke-Margolis Center for Health Policy at Duke University and FasterCures, of the Milken Institute.
CTTI to Host Jan. 13 Public Summit, The Fastest Path to Effective COVID-19 Treatments: Using Master Protocol Studies, Featuring Research & Healthcare Leaders
CTTI will host a public summit, The Fastest Path to Effective COVID-19 Treatments: Using Master Protocol Studies, on Wednesday, January 13. The summit, conducted as a webinar and moderated by CTTI Executive Director Pamela Tenaerts, will include a welcome from Janet Woodcock, Operation Warp Speed; a call-to-action from Robert M. Califf, Verily and Google Health; remarks from Mark McClellan, Duke-Margolis Center for Health Policy; and a panel discussion moderated by Esther Krofah, FasterCures. The panel discussion will focus 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
“As we’ve learned in the global pandemic, the faster we have reliable answers, the better,” said Tenaerts. “As we look to successfully accelerate progress for COVID-19 treatments, the need for collaborative trials that supply reliable insights has never been greater and in many cases, master protocol studies can provide the solution.”
This public summit will also address the status of COVID-19 clinical trials, including results from a recent CTTI analysis of data from ClinicalTrials.gov and other research, and examine the use of common platforms to optimize the design of master protocols for multiple therapies attempting to treat the same diseases or specific health problems.
The free public summit will be held from 10:30am until noon EST.
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.
CTTI Paper Highlights Clinical Criteria that Can Help Identify Patients at High Risk of HABP/VABP
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.