CTTI News

Report Now Available: ICH E6 Guideline for Good Clinical Practice (GCP) – Update on Progress

Posted on by Hannah Faulkner

The report of the public web conference on “ICH E6 Guideline for Good Clinical Practice (GCP) – Update on Progress,” organized by International Council for Harmonisation (ICH) and convened by the Clinical Trials Transformation Initiative (CTTI), is now available.  The web conference, which consisted of identical meetings at different times on May 18 & 19 to accommodate a global audience, reached more than 5100 attendees.

The ICH E6 Expert Working Group (EWG) members, who are updating the guideline, presented a video wherein they shared the ICH guideline development process and the approach to updating ICH E6  The video was followed by presentations on the vision and goals for updating the ICH E6 guideline and on lessons learned from public input and stakeholder feedback on the ICH E6 revision process.  In the final session, EWG members discussed the draft principles, which were published in April.  Key stakeholders closed the web conference by sharing their visions and aspirations for clinical trials.

Check out the recording and the slide decks for each day of the web conference to learn more from the presenters.

For additional information on updating the ICH E6, please refer to the following materials:

 

 

CTTI Announces New Executive Director Sally Okun

Posted on by Hannah Faulkner

Today, CTTI proudly announced its new Executive Director: Sally Okun, a seasoned thought leader in clinical research, care, and policy.

“Sally’s wealth of experience, distinct perspective, and passion for driving change uniquely position her as the ideal leader for CTTI at this particular time,” said Mark McClellan, chair of CTTI’s executive committee and director of the Duke-Margolis Center for Health Policy. “Throughout her career, she has brought the patient voice to many audiences in the public and private sectors in the U.S. and globally, and also emphasized the critical importance of evidence generation in clinical research – principles that strongly align with the fabric of CTTI and where we are headed with our Transforming Trials 2030 vision.”

Okun most recently served as the Vice President for Policy & Ethics at PatientsLikeMe where, among many efforts, she supported the development of the company’s emerging social contract for the conduct of biomedical and multi-omics research through its initiative DigitalMe™ and led a newly established Ethics and Compliance Advisory Board comprised of external members representing patients, consumers, law, ethics, and cybersecurity. Prior to PatientsLikeMe, Okun, a registered nurse, practiced as a palliative and end-of-life care specialist for nearly three decades and contributed to multiple clinical, research, and educational projects in that specialty area.

“Now, more than ever, is the time to challenge our thinking, test our assumptions, and push the boundaries in the clinical trials space – all with the goal of making significant advancements and improvements in research to benefit patients,” said Okun. “I am honored and excited to lead CTTI during this time of its ambitious Transforming Trials 2030 vision, which focuses on shaping the future of clinical trials from the patient perspective – that, I believe, is where real transformation must begin.”

Announced earlier this year, Transforming Trials 2030 is CTTI’s bold vision that clinical trials by 2030 be: 1) patient-centered and easily accessible, 2) fully integrated into health processes, 3) designed with a quality approach, 4) maximally leverage available data, and 5) improve population health.

“I am most excited about the impact that CTTI can have when it achieves the first vision of Transforming Trials 2030 – to make clinical trials patient-centric and easily accessible,” said Okun. “We can only accomplish this vision if we are on the journey together with patients.”

“Sally’s fresh perspective and passion for driving change will be invaluable for CTTI,” said John Alexander, Duke co-chair of CTTI and a senior faculty member at the Duke Clinical Research Institute. “She will bring a lot of innovative ideas and new focus to the initiative as we think about transforming trials and we get from where we are today, to where we want to be in 2030.”

“Sally is a well-respected thought leader across research, care, and policy. She will bring an important and comprehensive perspective to CTTI,” added Khair ElZarrad, FDA co-chair of CTTI and acting director of the Office of Medical Policy (OMP) at FDA’s Center for Drug Evaluation and Research (CDER). “She is well-suited to lead CTTI during this time of ambitious and critical work to transform clinical trials in a rapidly changing ecosystem.”

In her new role as CTTI Executive Director, Okun will work closely with the executive committee, steering committee, and staff to develop and implement strategies to accomplish CTTI’s mission and Transforming Trials 2030 vision. She will also orchestrate efforts to effectively engage all interested stakeholders to improve the conduct of clinical trials.

Recording Now Available: “Next Steps for Obtaining Novel Endpoint Reliability & Acceptance” Webinar

Posted on by Hannah Faulkner

A recording of CTTI’s public webinar on “Next Steps for Obtaining Novel Endpoint Reliability & Acceptance” is now available.

During the webinar, presenters Lindsay Kehoe (CTTI) and Alicia Staley (Medidata) discussed CTTI’s current work to obtain reliability and acceptance of meaningful, digitally derived novel endpoints – a project that builds on CTTI’s existing novel endpoint development recommendations and resources from 2017. They also provided:

  • Highlights from a recent Expert Meeting of leaders and stakeholders from across the clinical trials ecosystem
  • Insights from in-depth interviews with sponsors
  • A preview of the forthcoming set of CTTI novel endpoint recommendations and resources

This webinar built on recent webinars by DiMe, which focused on the best resources currently available for using digitally derived endpoints, and TransCelerate, which demonstrated key considerations and challenges for developing novel digital endpoints through a hypothetical case study.

“As the novel endpoints space continues to evolve, CTTI, DiMe, and TransCelerate are committed to working together to help stakeholders across the clinical trials enterprise evolve with it,” said Kehoe. “By encouraging greater collaboration and innovation among technology companies, academic investigators, patients, regulators, and trial sponsors and sites, we can accelerate progress to the benefit of everyone involved.”

For more on CTTI’s work around Novel Endpoints, please visit CTTI’s website.

CTTI Holds Meeting to Refresh and Enhance Decentralized Clinical Trials Recommendations

Posted on by Hannah Faulkner

The Clinical Trials Transformation Initiative (CTTI) held a two-day multi-stakeholder expert meeting on Aug. 25-26 to discuss best practices on conducting research in remote and virtual settings, including lessons learned from the COVID-19 pandemic. The insights gathered will be used to refresh CTTI’s 2018 Decentralized Clinical Trials (DCT) recommendations and ensure that they offer the most current information for planning and operationalizing DCT solutions (i.e., remote and virtual visits, using local labs and healthcare providers, and direct-to-participant shipping).

During the meeting, relevant experts and key stakeholders—including investigators, patients, regulators, technology experts, sponsor representatives, and other groups—CTTI and attendees exchanged knowledge, insights, and current solutions for using DCT solutions in clinical trials.

They also identified some important themes and identified opportunities to increase adoption of DCT solutions moving forward:

  • Design with Purpose. The design of DCTs must prioritize patient safety and data quality. DCT elements should only be incorporated into study design where they are appropriate to the purpose of the study.
  • Engage Everyone. It’s important to engage all stakeholders in DCT protocol design and implementation.
  • Think Ahead, Early On. Careful planning and consideration from the earliest stages of study and program design is essential.
  • Invest in Quality. DCTs are often not the cheapest or easiest solution, but they can be the most impactful in terms of making trials more patient-centered and getting the best data.
  • Where to Focus Next. Communication, collaboration, and regulatory guidance are critical for broader adoption of DCT solutions.

CTTI is now updating its recommendations and will make them available by early 2022 to help accelerate the adoption of DCT solutions in clinical trials going forward.

CTTI to Host 10/5 Webinar on “Next Steps for Obtaining Novel Endpoint Reliability & Acceptance”

Posted on by Hannah Faulkner

On Oct. 5 at noon ET, the Clinical Trials Transformation Initiative (CTTI) will host a public webinar on “Next Steps for Obtaining Novel Endpoint Reliability & Acceptance” – the third in a series of webinars on using novel digitally derived endpoints in clinical trials for medical product development from CTTI, Digital Medicine Society (DiMe), and TransCelerate.

Presenters Lindsay Kehoe, CTTI, and Alicia Staley, Medidata, will discuss CTTI’s current work to obtain reliability and acceptance of meaningful, digitally derived novel endpoints – a project that builds on its existing novel endpoint development recommendations and resources from 2017.

Attendees will hear:

  • Highlights from a recent Expert Meeting of leaders and stakeholders from across the clinical trials ecosystem
  • Insights from in-depth interviews with sponsors
  • A preview of the forthcoming set of CTTI novel endpoint recommendations and resources.

This webinar builds on recent webinars by DiMe, which focused on the best resources currently available for using digitally derived endpoints, and TransCelerate, which demonstrate key considerations and challenges for developing novel digital endpoints through a hypothetical case study.

“As the novel endpoints space continues to evolve, CTTI, DiMe and TransCelerate are committed to working together to help stakeholders across the clinical trials enterprise evolve with it,” said Kehoe. “By encouraging greater collaboration and innovation among technology companies, academic investigators, patients, regulators and trial sponsors and sites, we can accelerate progress to the benefit of everyone involved.”

Register to attend “Next Steps for Obtaining Novel Endpoint Reliability & Acceptance” today.

CTTI Holds Meeting to Advance Novel, Digitally Derived Endpoints in Clinical Trials

Posted on by Hannah Faulkner

Despite the increased use of digital health technologies (DHTs) in trials over the past several years, few examples of a digitally-derived primary endpoint exist today. Working to fill this gap, CTTI held an “Obtaining Novel Endpoint Reliability & Acceptance” Expert Meeting on July 27-28 to inform its new recommendations and resources for driving novel endpoint acceptance.

Attendees discussed challenges and potential solutions to advancing the practical use of novel, digitally derived endpoints in clinical trials. They also uncovered and agreed on some important common themes:

  • The Time is Now. Digitally derived endpoints have the ability to capture information that is more reflective of how patients feel and function in their day-to-day lives – but many factors hinder their acceptance. Collaborative partnerships and solutions that increase the understanding and use of DHT-derived endpoints are needed to make this happen.
  • Fit-for-Purpose is a Must. DHT-derived endpoints need to be based on the specific context of use and validly measure a concept of interest in a way that is accurate, interpretable, and not misleading.
  • “Meaningful” in More than One Way. To develop a DHT-derived endpoint, have the community – including patients and clinicians – discuss what constitutes “meaningful” change. A meaningful measure should show treatment benefit as well as clinical benefit.
  • Engage Early and Often. Engage patients, investigative site personnel, and the FDA early and often when planning; involve biostatisticians and data scientists, as appropriate, in decisions regarding protocol design, data collection, analysis, and interpretation
  • Validate, Validate, Validate. It’s important to remember that validating a device is a separate, yet parallel, process from validating the clinical measure. It is also especially important to demonstrate analytical validation of DHT algorithms within the specific patient populations.

This meeting and its findings, part of CTTI’s Novel Endpoint Acceptance project, will help expand CTTI’s 2017 Novel Endpoint work, which produced a set of recommendations, flowchart, detailed steps, and many other resources for developing novel endpoints.

For a preview of CTTI’s expanded set of novel endpoints recommendations and resources, register to attend its Oct. 5 “Next Steps for Obtaining Novel Endpoint Reliability & Acceptance” webinar.

FDA, CTTI Accepting Applications for Patient Engagement Collaborative (PEC)

Posted on by Hannah Faulkner

The FDA and CTTI are currently accepting applications from patient advocates interested in becoming members of the Patient Engagement Collaborative (PEC). The PEC is an ongoing, collaborative forum that brings the patient community and regulators together to discuss ways to increase patient engagement in medical product development and regulatory discussions at the FDA.

Applicants will be selected based on their ability to meaningfully contribute to the PEC, represent and express the patient voice for their constituency, work in a constructive manner with involved stakeholders, and understand and navigate the clinical research ecosystem.

Successful applicants will include:

 

  • Patients who have personal disease experience
  • Caregivers who support patients, such as a family member or friend, and who have personal disease experience through this caregiver role
  • Representatives from patient groups who, through their role in the patient group, have direct or indirect disease experience

PEC members will be expected to participate in working meetings two to four times per year, either in-person (in the Washington D.C. area) or virtually. Given the ongoing COVID-19 pandemic, meetings will be conducted virtually and may resume in-person when it is safe to do so. Additional meetings may be organized as needed, and currently include monthly, one-hour teleconferences.

Interested applicants are encouraged to complete and submit the online form no later than 11:59 p.m. ET on August 23, 2021. Those who are unable to submit an application electronically are encouraged to call the FDA’s Office of Patient Affairs at 301-796-8460 to arrange for a mail submission.

Please review the related Federal Register notice for important information about the application process.

New Case Studies Reveal Real-World Experience with Quality by Design (QbD)

Posted on by Hannah Faulkner

Organizations are gaining experience using CTTI’s Quality by Design (QbD) recommendations to design and conduct better clinical trials. CTTI today announced four new QbD case studies, adding to its robust QbD toolkit. Three of the case studies are also now featured in CTTI’s recently-announced Building Better Clinical Trials: A Case Study Exchange resource.

The case studies provide an in-depth look at real-word implementation of QbD principles by:

  • Alexion, a biopharmaceutical company focused on developing medicines for rare diseases, applied QbD principles early in study design to build a streamlined, simple protocol for a global Phase III trial on a tight timeline.
  • An investigator at the Duke Clinical Research Institute applied QbD principles to thoughtfully and strategically design a 1,000 patient, multicenter trial that can be largely executed remotely.
  • The Medicines Company (now part of Novartis), a small pharma company that applied QbD principles with two collaborators to plan a 5-year trial that is already seeing faster-than-expected recruitment.
  • University of Oxford’s Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU) followed a QbD approach in planning and conducting a streamlined, mail-based trial that enrolled over 15,000 participants.

QbD is not a checklist, rather it is a common sense approach in which stakeholders consider: (1) what aspects of a trial are critical to generating reliable data and providing appropriate protection of research participants (“critical to quality” factors); and, (2) what strategies and actions will effectively and efficiently support quality in these critical areas.

These new case studies not only describe the critical-to-quality factors for each trial, and how they were addressed, but also provide tangible strategies and examples for how other organizations can implement such an approach.

This news comes on the heels of CTTI announcing:

  • New resources for the adoption of a QbD approach – including a QbD Maturity Model, Metrics Framework, Implementation Guide, and Documentation Tool – at the end of 2020; and
  • Building Better Clinical Trials: A Case Study Exchange, announced in March 2021; three of the case studies announced today will be included in this resource.

Want to be featured on Building Better Clinical Trials: A Case Study Exchange?

If you are part of an organization that has used any of CTTI’s recommendations or tools and would like to be featured on the site, we may be able to include your story.

By sharing your experience, you can showcase your organization’s success while providing helpful information that will benefit other organizations and facilitate collaboration and knowledge sharing across the research community.

Please reach out to Karisa Merrill to learn more.

New CTTI Project to Explore the Challenges Preventing Timely and Complete ClinicalTrials.gov Reporting

Posted on by Hannah Faulkner

Timely and complete registration and results reporting of clinical trial information is an important part of keeping patients, providers, researchers, and the public informed about clinical trials. The Food and Drug Administration Amendments Act of 2007 (FDAAA) requires that the responsible party for an applicable clinical trial register and submit results information for the trial to the ClinicalTrials.gov databank to promote transparency and accountability, in an effort to limit duplicity and encourage others to build on results. Despite the importance of this goal, public reporting has suggested that not all clinical trials are registered in a timely manner or have incomplete results.

To address this problem, CTTI is launching a new project to identify the challenges that lead to late registration and incomplete or missing results information for applicable clinical trials. The project will use in-depth stakeholder interviews and surveys to identify and explore the key challenges to timely submission of clinical trial information and identify potential solutions. The project will explore factors other than those related to the ClinicalTrials.gov platform and is intended to be complementary to the National Library of Medicine’s ClinicalTrials.gov Modernization initiative.

CTTI will use this data to develop informed best practices for responsible parties and other stakeholders. The findings from this project may also provide potential ways to support responsible parties in meeting the registration and results reporting requirements.

CTTI Updates DCT Recommendations in Response to COVID-19

Posted on by Hannah Faulkner

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.