Public Web Conference Report: Stakeholder Engagement on ICH E6 Guideline for GCP
Author: Hannah Faulkner
CTTI to Release Resources for Designing and Running Master Protocols During Oct. 13 Webinar
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
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.
CTTI Paper Features Recommendations for Incorporating Patient and Site Perspectives in Digital Health Trials
Digital health technologies offer the potential to improve the conduct of clinical trials. If harnessed correctly, they can reduce patient burden, streamline operations, and optimize data collection. The key to unlocking these benefits is to ensure that patient and site perspectives are considered during the planning process. CTTI has released a new manuscript in Contemporary Clinical Trials Communications that features the first evidence-based set of recommendations for incorporating patient and site perspectives in digital health trials.
CTTI’s comprehensive recommendations for planning trials using digital health technologies offer advice across several research study topics, including:
- Engaging patients and sites in planning clinical trials using digital health technology
- Maximizing value and minimizing burden for study participants
- Addressing challenges for investigative sites
This comprehensive set of recommendations was developed by first conducting a survey of 193 potential research participants regarding their willingness to use digital health technology in clinical trials as well as their preferences and concerns. Site experiences and preferences were captured through qualitative interviews with 12 different investigators. CTTI then collated this information and conducted an expert meeting over two days. Attendees, including patients, investigators, regulators, sponsors, and technology experts, presented key findings and discussed strategies and implications.
Because patients and site personnel offer important perspectives on how best to incorporate digital health technology into a trial, CTTI recommends their input be taken into account early and often. Ensuring their engagement helps stakeholders incorporate digital health technologies in the most efficient way possible, which can help to advance clinical trials and accelerate the development of new treatment options.
Read the full manuscript.
CTTI Paper Offers Suggested Solutions for Improving Good Clinical Practice Training
A new CTTI paper, detailing its findings from a project designed to assess challenges and burdens associated with Good Clinical Practice (GCP) training, has published in Contemporary Clinical Trials Communications.
The paper, “More than a Box to Check: Research Sponsor and Investigator Perspectives on Making GCP Training Relevant,” outlines feedback on GCP training gleaned from interviews CTTI conducted with clinical investigators and research sponsors. While interview respondents recognized that GCP training addresses critical tasks necessary for the quality conduct of clinical trials, many found it burdensome and repetitive—one interviewee said the training was seen as “just another box to check off.”
CTTI’s paper also highlights respondents’ suggestions for navigating these challenges, noting a need for significant improvement in the design, content, presentation, and training of GCP guidelines. These findings, together with other evidence, informed CTTI’s Investigator Qualification recommendations for alleviating the burden of training and making it more engaging and applicable to real-world clinical research scenarios.
Navigating the New Normal: CTTI Announces Playbook on Best Practices for Conducting Trials During COVID-19
As the world adapts to the COVID-19 pandemic, CTTI is leading the charge to help the clinical trials ecosystem evolve and move forward. Since March 2020, CTTI conducted a series of initiatives to help the research community successfully navigate the challenges associated with adjusting trials that were underway when the pandemic hit. These initiatives and resulting best practices are captured in a new playbook, Best Practices for Conducting Trials During the COVID-19 Pandemic.
CTTI gathered experiences and learnings from across the clinical trials ecosystem via public surveys and discussions, and communicated these findings during two CTTI-hosted webinars. These efforts extrapolated best practices for conducting clinical trials with new FDA guidance on COVID-19, as well as solutions to help investigators shift to remote and virtual visits during the COVID-19 pandemic.
Through this initial work when the pandemic first hit, CTTI identified eight essential best practices on how to conduct clinical trials during the pandemic. These key points, fully outlined in the new COVID-19 playbook, recommend that stakeholders:
- Keep participants informed
- Perform outgoing risk-benefit assessment
- Communicate with IRBs and regulatory authorities
- Adjust new study starts and enrollment based on risk
- Pivot to remote study visits
- Switch to remote monitoring
- Be flexible
- Document everything with COVID-19 tags
The new document provides detailed information on how stakeholders can best integrate these important recommendations into their ongoing clinical trials while providing several additional resources to fully support these efforts. This comprehensive resource will help researchers adapt to the changing clinical trial landscape and continue to conduct successful studies during the pandemic.
New CTTI Project Aims to Increase the Use of Clinical Trial Endpoints Derived from Digital Technologies
While digital health technologies (DHT) offer clinical trial researchers the promise of more efficient and potentially accurate data, there are very few examples of digitally derived primary endpoints that can support regulatory labeling claims.
To address this issue, CTTI is conducting a new project that will build on previous novel endpoint work to create additional resources and recommendations to drive the use of digitally derived, functional outcomes as key endpoints in clinical trials to support regulatory decision-making.
Once the project is complete, stakeholders can look forward to resources such as:
- Best practice recommendations on the “standards of evidence” needed to qualify a DHT-derived novel endpoint
- Glossary of terms for digital health endpoints
- Summary of interview results
- Expert meeting summary
CTTI will conduct glossary term evaluations, literature reviews, and landscape assessments – as well as in-depth interviews and multi-stakeholder expert meetings – to collect data that will inform the new recommendations and resources.
These solutions will serve to increase the use of meaningful DHT-derived novel endpoints in clinical trials for labeling claims and help to advance the benefits of running digital health trials, including the capture of more meaningful and higher quality research data.