Clinical trials are vital to advancing medical knowledge and care, yet participation can impose significant financial burdens on participants and their familiesโfrom travel and time away from work to uncovered medical and ancillary expenses.
This webinar examined the sources and impact of these costs and highlighted emerging strategies to reduce financial hardship for research volunteers. Presenters also introduced tools, checklists, and other resources developed through the EACT Project, a collaborative forum advancing financial neutrality in clinical research participation.
Long-term follow-up (LTFU) studies of gene therapy recipients are crucial for understanding the overall benefit-risk profile of these innovative products. However, LTFU studies are challenging to design, conduct, and execute, and pose significant burdens on both patients and sponsors.
In September 2024, the MRCT Center launched an LTFU Working Group. The committee comprises patients, as well as representatives from patient advocacy organizations, industry sponsors, academic medical centers, clinical research organizations, and human oversight protection organizations, each bringing diverse perspectives and complementary scientific, medical, regulatory, and ethical expertise.
On November 4, 2025, the MRCT Center released theย Toolkit for Supporting the Design, Conduct, and Reporting of Long-Term Follow-Up Studies as a draft for public comment. The Toolkit provides practical guidance regarding best practices for LTFU studies for both investigational and approved gene therapies. It aims to balance the generation of critical long-term safety and efficacy data with the need to reduce burdens placed on participants, caregivers, sponsors, and investigators.
This webinar introduced the Toolkitโs ๐๐๐ฟ๐๐ฐ๐๐๐ฟ๐ฒ ๐ฎ๐ป๐ฑ ๐ฐ๐ผ๐ป๐๐ฒ๐ป๐๐, including: ๐น ๐๐๐ถ๐ฑ๐ถ๐ป๐ด ๐ฃ๐ฟ๐ถ๐ป๐ฐ๐ถ๐ฝ๐น๐ฒ๐ ๐น ๐๐ผ๐ป๐๐ถ๐ฑ๐ฒ๐ฟ๐ฎ๐๐ถ๐ผ๐ป๐ ๐ฎ๐ป๐ฑ ๐ฅ๐ฒ๐ฐ๐ผ๐บ๐บ๐ฒ๐ป๐ฑ๐ฎ๐๐ถ๐ผ๐ป๐ ๐น ๐๐ผ๐ผ๐ธ๐ถ๐ป๐ด ๐๐ผ๐ฟ๐๐ฎ๐ฟ๐ฑ
It also highlighted additional practical resources: ๐น ๐๐ฒ๐ ๐ฑ๐ฒ๐๐ถ๐ด๐ป ๐ฒ๐น๐ฒ๐บ๐ฒ๐ป๐๐ of LTFU studies for FDA-approved gene therapies ๐น ๐๐ป๐๐ฒ๐ฟ๐ป๐ฎ๐๐ถ๐ผ๐ป๐ฎ๐น ๐ฟ๐ฒ๐ด๐๐น๐ฎ๐๐ผ๐ฟ๐ ๐ด๐๐ถ๐ฑ๐ฎ๐ป๐ฐ๐ฒ ๐น ๐๐น๐ผ๐๐๐ฎ๐ฟ๐ถ๐ฒ๐ ๐ฎ๐ป๐ฑ ๐ฏ๐ฎ๐ฐ๐ธ๐ด๐ฟ๐ผ๐๐ป๐ฑ ๐ถ๐ป๐ณ๐ผ๐ฟ๐บ๐ฎ๐๐ถ๐ผ๐ป on types of LTFU studies
๐ ๐ผ๐ฑ๐ฒ๐ฟ๐ฎ๐๐ผ๐ฟ: Carolyn Riley Chapman, PhD MS โ Lead Investigator, Brigham and Womenโs Hospital; Member of the Faculty, Harvard Medical School
๐ฃ๐ฎ๐ป๐ฒ๐น๐ถ๐๐๐: Durhane Wong-Rieger, PhD – President and CEO, Canadian Organization for Rare Disorders Barbara Isquith Arone, MS โ Vice President, Medical Affairs Category Lead, IQVIA Patrick Cullinan, PhD โ Head of Medical Writing and Transparency, Adverum Biotechnologies
On October 30, the MRCT Center hosted a webinar on Applied Health Literacy: Using Teach-Back in Conversations About Clinical Research. The session focused on how the Teach-Back method can improve participant understanding, support safe and equitable clinical research, and strengthen communication throughout the research process. The recording, slides, and a list of resources discussed during the session are provided below.
Overview
The webinar reviewed the essential elements of the Teach-Back method and discussed how study teams can simplify complex information, confirm understanding, and foster dialogue with participants and caregivers during recruitment, informed consent, and ongoing study engagement. Presenters emphasized the role of Teach-Back in enhancing clarity, reducing burden, and supporting participant-centered, high-quality research.
Speakers
Mary Ann Abrams, MD, MPH โ Physician and Health Literacy Expert, Nationwide Childrenโs Hospital; Assistant Professor of Pediatrics, The Ohio State University College of Medicine
Published in:ย International Journal of Technology Assessment in Health Care
Abstract: In this scoping review detailing the challenges of assessing new technologies for use in children, authors Nora Hutchinson, Lauren Otterman, Elisa Koppelman, Barbara E. Bierer, and colleagues highlight the substantial difficulties in incorporating children within the population-wide health technology assessment (HTA) system, as well as the uncertainty accompanying pediatric HTAs due to data constraints, lack of guidance and/or variation in guidance, between HTA bodies.
Hutchinson N, Otterman L, Bain PA, Koppelman E, Bierer BE. A Scoping Review of Challenges in Pediatric Health Technology Assessments with a Focus on Pharmaceutical Interventions.ย International Journal of Technology Assessment in Health Care. Published online 2025:1-34. doi:10.1017/S0266462325103188
October 22:ย In the articleย โCharacteristics of long-term follow-up studies for gene therapies registered on ClinicalTrials.gov,โ published inย Gene Therapy,ย co-authorsย Carolyn Chapman, Emina Berbic, Ava Glazier, and Barbara Biererย report a descriptive study of key characteristics of LTFU gene therapy study protocols registered inย ClinicalTrials.gov. The analysis enabled a better understanding of how registered LTFUย studies are currently designed and stimulated ideas for improvement. Most notably, the results suggest a lack of harmonization in how safety outcomes are monitored and reported across LTFU studies. Standardization and/orย harmonization of data and outcome reporting may increase the scientific value of these studies.
Chapman, C.R., Glazier, A., Berbiฤ, E. et al. Characteristics of long-term follow-up studies for gene therapies registered on ClinicalTrials.gov. Gene Ther (2025). https://doi.org/10.1038/s41434-025-00571-4
Please join us on Tuesday, November 18, 2025, from 12:00 pm โ 1:00 pm ET for the second webinar in our Digital Twins and Synthetic Data series, focusing on practical use cases in clinical research. This session will explore how digital twins and synthetic data are being used to enhance the efficiency of clinical trials, including reducing the size of control arms, enhancing Bayesian statistical analysis, supporting single-arm trials, and optimizing the design of future trials. Dr. Daniele Bertolini of Unlearn.ai will share examples and reflect on lessons learned from deploying these tools across various therapeutic areas. The session will include a moderated discussion and audience Q&A.
Topic: Whatโs Mine Is Mine and Whatโs Yours Is Mine: Data Ownership and Sovereignty
This meeting is open to sponsors of the MRCT Center Bioethics Collaborative and select invited guests. For more information about the Bioethics Collaborative and how to become a sponsor, click here.
Topic: Research Interrupted: Clinical Trial Termination and Withdrawal of Consent
Abstract: Withdrawal from research participation is widely acknowledged as foundational to ethical research, yet it comes with costs, including the loss of data and delays in completing valuable research. Historically, withdrawing from research has been conceived as an all-or-nothing decision, regardless of whether that decision is made by the participant or the research team. However, this assumption precludes the possibility that individuals may be willing to continue contributing to the research in other ways, even if they are not willing to participate in all aspects of a study. While access to public records (e.g., National Death Index) may allow follow-up data collection, it is rare, at the time of withdrawal, for studies to seek individuals’ permission to continue other forms of data collection, such as access to medical records or interaction with a personal care provider. Are there risks to offering more fine-grained options for monitoring and continued data collection to subjects who express a desire to withdraw? Could it be construed as unduly pressuring participants or interfering with the right to withdraw? What would the ethical parameters of such an approach be? How would these discussions need to be approached, and what would the informed consent process at enrollment need to say about it?
Transitioning from individual rights to systemic issues, it becomes evident that there are also ethical concerns surrounding trial termination generally, particularly when study closure is premature or occurs for reasons not envisaged at study launch. Currently, there is a lack of ethical guidelines, standardized protocols, and attention to or analysis of trial closure. Reasons for terminations are often inadequately documented, and procedures for closing a trial are inadequate. This raises questions about the obligations of researchers and sponsors to trial participants and the data, especially when trials are terminated for non-scientific reasons (e.g., business priorities). The recent abrupt withdrawal of NIH funding left an estimated 74,000 participants stranded and prevented those studies from producing robust knowledge and scientific benefits, which are generally needed to justify the assumption of risks for participants. Further, early closures due to seemingly preventable reasons, such as lack of participant accrual, remain common, and academic institutions routinely close protocols when an investigator leaves (or loses interest) without accountability to the research, data, or currently enrolled (or completed) participants. A framework for trial termination, emanating from use cases and experience, is needed.
This meeting is open to sponsors of the MRCT Center Bioethics Collaborative and select invited guests. For more information about the Bioethics Collaborative and how to become a sponsor, click here.
This webinar focused on how to responsibly integrate AI into the design, conduct, and oversight of clinical research, introducing two rapidly evolving applications:
Digital twins โ simulated models of individual patients designed to predict disease trajectories and treatment responses, with the potential to enhance statistical power, optimize design, and reduce the number of participants assigned to control arms.
Synthetic data โ artificially generated datasets that mirror the statistical properties of verified clinical data, with potential use in trial design, conduct, analysis, and regulatory submissions.
Long-term follow-up (LTFU) studies are essential to assess the benefitโrisk profile of gene therapies. Yet they are difficult to design and carry out, placing burdens on both participants and sponsors.
In September 2024, the MRCT Center convened a working group on LTFU studies for gene therapies. The group includes patients and representatives from pharmaceutical companies, clinical research organizations, academic medical centers, institutional review board oversight, and patient advocacy organizations.
This webinar will introduce a Toolkit for Supporting the Design and Conduct of Long-Term Follow-Up Studies for Gene Therapies, which is being released as a draft for public comment. Members of the working group will share their perspectives on the Toolkitโs development and discuss next steps. The session will conclude with audience questions and discussion.
Key Topics:
An overview of the draft Toolkit for Long-Term Follow-Up Studies in Gene Therapies
