Recommendations for using Real-World Data to Plan Eligibility Criteria and Enhance Recruitment
Real World Data
Webinar Now Available: CTTI’s New Recommendations for Using Real-World Data Sources to Enhance Trial Quality and Efficiency
A recording is now available of the public webinar held on Thurs., Oct. 17, to launch CTTI’s new recommendations for using real-world data (RWD) to plan trial eligibility criteria and recruit participants. The webinar was led by Sudha Raman of Duke University, and Jack Sheehan of Janssen Scientific Affairs.
CTTI conducted research and collaborated with stakeholders across the clinical trials ecosystem to develop these recommendations and resources, including three in-depth case studies that elucidate the process of integrating RWD into trial design. The case studies offer a look into the specific challenges faced by each sponsor, how they used RWD to address those challenges, and what they learned along the way.
This project is one in a growing portfolio of CTTI work focused on improving quality in trials and embracing novel trial designs. Other related CTTI efforts include:
- Co-leading a proof-of-concept study to assess the feasibility of using the FDA Sentinel System infrastructure to conduct randomized clinical trials.
- Recommendations on how to assess and design registries so that the data can meet expectations for the FDA review of new products.
- Recommendations and a robust toolkit to help drive a Quality by Design (QbD) approach, which engages a broad range of stakeholders and focuses resources on the errors that matter to decision making.
Both the webinar and CTTI’s latest recommendations and resources can be found on CTTI’s website.
CTTI Unveils New Recommendations for Using Real-World Data Sources to Boost Trial Quality and Efficiency
CTTI today released new recommendations, resources, and case studies for using electronic medical records (EHRs) and claims data to plan trial eligibility criteria and recruit participants. The work fills an important gap across the clinical trials ecosystem, where the potential benefits of real-world data (RWD) have been widely acknowledged, but few resources have emerged to lead sponsors and others through the process of formally integrating RWD into their trial designs.
“We are excited to unveil this comprehensive set of work, which enables the use of RWE to plan for appropriate eligibility criteria and optimal recruitment in clinical trials,” said CTTI Executive Director Pamela Tenaerts. “These recommendations add to CTTI’s growing portfolio of work focused on improving clinical quality and, when appropriate, embracing novel approaches for better trial design and execution.”
CTTI conducted research and collaborated with stakeholders across the clinical trials ecosystem to develop these recommendations and resources, including three case studies that elucidate the process of integrating RWD into trial design. The case studies offer a look into the specific challenges faced by each sponsor, how they used RWD to address those challenges, and what they learned along the way.
Other CTTI efforts related to the new work include:
- Co-leading a proof-of-concept study to assess the feasibility of using the FDA Sentinel System infrastructure to conduct randomized clinical trials.
- Recommendations on how to assess and design registries so that the data can meet expectations for the FDA review of new products.
- Recommendations and a robust toolkit to help drive a Quality by Design (QbD) approach, which engages a broad range of stakeholders and focuses resources on the errors that matter to decision making.
The RWD recommendations, resources, and case studies can be found on CTTI’s website.
CTTI to Launch New Work Highlighting the Opportunities for Using Real-World Data to Enhance Trial Quality and Efficiency
CTTI will host a public webinar on Thurs., Oct. 17, to announce new recommendations, resources, and case studies on how to use real-world data (RWD) to evaluate trial eligibility criteria and recruit potential participants.
“Until now, there have been few resources available to help sponsors and others optimally integrate the use of RWD into their trial design,” said CTTI Executive Director Pamela Tenaerts. “The work we are launching today fills that gap—our new recommendations and resources provide a clear path for using EHR and claims data to help plan eligibility criteria and recruit for clinical trials in a way that enhances quality and efficiency.”
CTTI conducted research and collaborated with stakeholders across the clinical trials ecosystem to develop these recommendations and resources, including three in-depth case studies that detail the specific challenges faced by sponsors, how they used RWD to address those challenges, and what they learned along the way.
This project is one in a growing portfolio of CTTI work focused on improving quality in trials and embracing novel trial designs. Other related CTTI efforts include:
- Recommendations and a robust toolkit to help drive a Quality by Design (QbD) approach, which engages a broad range of stakeholders and focuses resources on the errors that matter to decision making.
- Co-leading a proof-of-concept study to assess the feasibility of using the FDA Sentinel System infrastructure to conduct randomized clinical trials.
- Recommendations on how to assess and design registries so that the data can meet expectations for the FDA review of new products.
The webinar is open to the public and will begin at noon ET, featuring speakers Sudha Raman, Duke University, and Jack Sheehan, Johnson & Johnson/Janssen.
Article Outlines Lessons Learned from First Large Pragmatic Trial Using Sentinel
A new article in Clinical Trials, co-authored by CTTI, outlines lessons learned from the planning phase of the implementation of a randomized controlled trial to improve treatment with oral anticoagulants in patients with Atrial Fibrillation (IMPACT-AFib) trial, the first large pragmatic clinical trial that used the Sentinel infrastructure. This work is part of CTTI’s larger effort to advance trials that use real-world data sources.
The FDA’s Sentinel System uses electronic health records (EHR) and insurance claims from 18 health plans and delivery systems covering about 45 million individuals enrolled in commercial health plans, in addition to 22 million Medicare recipients.
The IMPACT-AFib trial, launched in 2017 by collaborators including CTTI, identified patients with atrial fibrillation who were at high risk of stroke, and randomized them to either an early or delayed intervention. The Sentinel System helped the trial team assess the size of the potential trial population, examine baseline measurements, and determine there were significant gaps in care, which showed there was a need for the trial.
In selecting participants for the trial and conducting other planning analyses, the trial team used Sentinel’s common data model and reusable analytic programs, which accelerated the planning and budgeting for the trial while keeping member-level data safe.
The IMPACT-AFib team also considered limitations introduced by Sentinel, including the potential for misclassification due to the use of administrative claims data. Other lessons learned for developing health plan-based clinical trials include using a single IRB, involving patient representatives in protocol design, and timing the start of the trial and mailing of materials around open enrollment and other health plan initiatives.
Learn more about CTTI’s other work to increase the appropriate use of real-world data sources and real-world evidence in clinical trials for regulatory submission.
Experts Explore Ways to Promote Use of Real-World Evidence in Clinical Trials: Latest CTTI Expert Meeting Summary Now
The use of real-world evidence (RWE)—derived from sources such as electronic health records (EHR) and claims data—has the potential to provide a more complete picture of patient experiences, reduce costs, and offer unique insights into important scientific questions. At the same time, there are relatively few examples to inform efforts to integrate RWE into clinical trials, as well as a lack of consensus among researchers about valid approaches for leveraging these data sources.
To address this issue, CTTI convened an expert meeting in June 2018 to discuss best practices and needed resources for advancing the use of RWE in randomized clinical trials. The meeting (see one-page summary) included investigators, patients, regulators, technology experts, sponsor representatives, and other groups.
While participants agreed that the use of RWE could be a major step forward in clinical trials, they stressed the importance of recognizing and planning for its limitations, including inconsistent data reliability and quality. They also agreed that direct interaction with participants and the integration of various real-world data sources is critical for improving the depth and breadth of available data.
As the next step in its Real-World Evidence work, CTTI will develop recommendations and resources for incorporating RWE into randomized trials for regulatory submission.
CTTI Celebrates Clinical Trials Day at SCT Annual Meeting
CTTI will commemorate Clinical Trials Day (which will be celebrated on May 21 this year) by leading a number of presentations at the Society for Clinical Trials (SCT) Annual Meeting May 20-23 in Portland, Ore. CTTI will discuss its findings on using mobile technologies for data capture, selecting and developing novel endpoints for use in clinical research, incorporating real-world evidence in randomized clinical trials, and more.
CTTI Executive Director Pamela Tenaerts will also share lessons learned since CTTI’s inception in 2007 and reflect on 10 years of transforming the clinical trials enterprise. See a full schedule of CTTI presentations below.
Poster: Selecting, Developing and Incorporating Technology-Derived Novel Endpoints into Clinical Trials
Date: Mon., May 21, 3:30-4:00pm
Related CTTI Project: MCT Novel Endpoints
Poster: One Decade of Impact. One Vision Ahead. Optimizing the Power of Public-Private Partnership: Lessons Learned from the Clinical Trials Transformation Initiative
Date: Tues., May 22, 3:30-4:00 p.m.
Poster: Use of Qualitative Data Analysis Software to Facilitate a Systematic Literature Review
Date: Tues., May 22, 10:15-10:45 a.m.
Related CTTI Project: MCT Novel Endpoints
Presentation 1: The Challenges and Opportunities of Mobile Technology: A Qualitative Examination of Investigators’ Experiences and Recommendations
Presentation 2: Mobile Technology and Clinical Trials: Patient Perspectives and Opportunities to Reduce the Burden of Participation
Date: Wed., May 23, 9:30-10:30 am
Presenter: Virginia Nido (Genentech – a member of the Roche Group)
Related CTTI Project: MCT Stakeholder Perceptions
Presentation: Designing Study Protocols When Mobile Devices Are Used for Data Capture: Recommendations from the Clinical Trials Transformation Initiative
Date: Wed., May 23, 9:30-10:30 am
Presenter: Tom Switzer (Genentech – a member of the Roche Group)
Related CTTI Project: MCT Mobile Technologies
Presentation: Understanding the Clinical Trial Enterprise’s Newest Trend: Incorporating Real-World Evidence into Randomized Clinical Trials
Date: Wed., May 23, 9:30-10:30 am
Presenter: Scott Evans (SCT)
Related CTTI Project: Real-World Data
Four Key Areas Where CTTI Has Transformed Clinical Trials
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.
CTTI Launches New Project to Accelerate Use of Real-World Data in Clinical Trials
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.