Language: English

Long-Term Follow-Up for Gene Therapies: Key Deliverables and the Path Forward 

Video

Presented on: October 22, 2025, at the MRCT Center Annual Symposium

Long-Term Follow-Up (LTFU) studies are critical for understanding the long-term safety and risk/benefit profile of innovative cell and gene therapies. Study participants, patients, treating clinicians, companies, regulators, payers, and society-at-large all derive different value from LTFU studies. However, these studies present unique challenges due to their unprecedented duration. For sponsors, they are challenging and expensive to design, conduct, and operationalize. For patients, LTFU participation can be burdensome in terms of time, expense, and opportunity costs.

In this recorded panel, which was held during the MRCT Center’s Annual Symposium in October 2025, Dr. Carolyn Chapman describes the aims of the Center’s LTFU Working Group, which was launched in September 2024 and benefited from the perspectives of 25 members from outside the Center.  Dr. Chapman also previews the release of the LTFU Toolkit, which was collaboratively developed by the Working Group. The Toolkit offers practical guidance to support best practices for LTFU studies for both investigational and approved gene therapies.

In this session, Dr. Chapman leads a discussion with three distinguished industry leaders on a variety of issues addressed in the LTFU Toolkit. These include integrating decentralized elements to reduce burden, refining endpoint selection, harmonizing data for interoperability across LTFU studies, and minimizing loss to follow-up through participant engagement and clear communication. They also highlight the need for flexibility in LTFU study designs to meet evolving patient needs, and the importance of keeping new and current participants informed about protocol changes and any key findings. Looking ahead, the group calls for ongoing dialogue on data harmonization and sharing, results transparency, and innovative approaches to streamline the collection of long-term safety information.

𝗠𝗼𝗱𝗲𝗿𝗮𝘁𝗼𝗿:
Carolyn Riley Chapman, PhD, MS – Lead Investigator, Brigham and Women’s Hospital; Member of the Faculty, Harvard Medical School

Panelists:

  • Pamela Tenaerts, MD, MBA, Chief Medical Officer, Medable
  • Daniel Kavanagh, PhD, RAC – Senior Scientific Advisor, Gene Therapy, Vaccines, & Biologics, WCG
  • Lara Gehl, Executive Director, Global Trial Management – Bristol Myers Squibb
2026_LTFU-Toolkit-Version02_01-23-2026Download
Webinar: November 4, 2025
2025-11-04 LTFU Toolkit release webinar_finalDownload
Cell and Gene Therapies
Patient-Centered Long-Term Follow-Up for Gene Therapies
Innovative Approaches for Gene Therapy Long-Term Follow-Up

Toolkit for Supporting the Design, Conduct, and Reporting of Long-Term Follow-Up Studies for Gene Therapies

Toolkit

Released on: January 23, 2026

Long-term follow-up (LTFU) studies of gene therapy (GT) 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 comprised 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 the Toolkit for Supporting the Design, Conduct, and Reporting of Long-Term Follow-Up Studies for Gene Therapies as v1, a draft for public comment. Building upon regulatory authorities’ LTFU guidance, the Toolkit is comprehensive, providing background information, practical resources, and recommendations to support best practices for LTFU studies for both investigational and approved gene therapies—balancing the generation of critical long-term safety and efficacy data with the need to reduce burdens placed on participants, caregivers, sponsors, and investigators. The Toolkit also explores ideas for how LTFU studies could be improved in the future, raising questions that the field should discuss and address.

On January 23, 2026, the MRCT Center released version 2.0 of the Toolkit for Supporting the Design, Conduct, and Reporting of Long-Term Follow-Up Studies, which was revised and improved based on feedback received on the first version, released as a draft for public comment.  Most notably, the updated Toolkit v2.0 includes two new resources, an Executive Summary and a Patient Resource, which have also been released as standalone versions.  Some revisions were also made to existing sections of the Toolkit. Additions included new charts in the Investigational or Approved GTs subsection of the Types of LTFU studies section. Three more GTs were included in the table of key design elements of LTFU studies for GTs that have received FDA approval. We also made edits to the stakeholder group table, language concerning assent, and added language to clarify that informed consent for GTs should include the provision of available information on the product’s long-term safety and/or efficacy (i.e., updates to informed consent in or beyond the LTFU study may be necessary).

The Toolkit enables easy navigation to various sections and subsections via multiple clickable, interactive toolbars. The sections are as follows, with the core elements in bold font:

  • Executive Summary (new in v2.0)
  • Introduction and Background
  • Types of LTFU studies for GTs
  • Flowcharts
  • Guiding Principles
  • Considerations and Recommendations for the Design, Conduct, and Reporting of LTFU Studies for GTs
  • Looking Forward
  • Key Design Elements of LTFU Studies for FDA-approved GTs
  • Regulatory Guidance Relating to LTFU of GTs
  • Patient Resource: Long-Term Follow-Up Studies After Gene Therapy (new in v2.0)
  • Compiled Glossary of Scientific LTFU-Related Terminology
  • Easy-to-Understand (Accessible) LTFU-Related Definitions from the MRCT Center’s Clinical Research Glossary
  • Appendices
  • List of Acronyms and Abbreviations Used
  • References Cited

Please email us at mrct@bwh.harvard.edu with any questions or suggestions regarding the Toolkit.

2026_LTFU-Toolkit-Version02_01-23-2026Download

Navigation Highlights

The Toolkit incorporates several interactive features designed to support intuitive navigation and ease of use:

  • Clickable Table of Contents for rapid access to major sections and subsections.
  • Right-hand vertical navigation bar on every page, enabling quick movement between tools within the document.
  • Interactive table of LTFU study types, mirrored by color-coded tabs that remain clickable throughout the associated pages.
  • Secondary navigation bar at the top of each page within the Considerations & Recommendations section. This feature highlights your location within the nine subsections, allows you to jump directly between subsections by clicking the dots, and includes a grey diamond icon that returns you to the full list of subsections.
Long-Term Follow-Up for Gene Therapies: Toolkit Release
MRCT Center Annual Symposium: Panel 3 – Cell and Gene Therapies Long-Term Follow-Up (LTFU).
Panelists:
Pamela Tenaerts, MD, MBA, Chief Medical Officer, Medable
Daniel Kavanagh, PhD, RAC – Senior Scientific Advisor, Gene Therapy, Vaccines, & Biologics, WCG
Lara Gehl, Executive Director, Global Trial Management – Bristol Myers Squibb
𝗠𝗼𝗱𝗲𝗿𝗮𝘁𝗼𝗿:
Carolyn Riley Chapman, PhD, MS – Lead Investigator, Brigham and Women’s Hospital; Member of the Faculty, Harvard Medical School
Patient-Centered Long-Term Follow-Up for Gene Therapies
Innovative Approaches for Gene Therapy Long-Term Follow-Up
Cell and Gene Therapies

Public Comments submitted to TEHDAS2 on targeted issues related to the European Health Data Space

Public Comment

Comments provided on: November 30, 2025

Comments provided to: TEHDAS2, coordinated by the Finnish Innovation Fund SITRA

Description:The MRCT Center and Vivli co-host an ongoing, invite-only forum focused on the European Health Data Space (EHDS), bringing together stakeholders to track developments and coordinate responses. The MRCT Center submitted responses to three TEHDAS2 guidance documents offered for public consultation to Health Data Access Bodies:

  1. GUIDELINE FOR HEALTH DATA ACCESS BODIES ON DATA MINIMISATION, PSEUDONYMISATION, ANONYMISATION AND SYNTHETIC DATA 
  2. DRAFT GUIDELINE FOR HEALTH DATA ACCESS BODIES ON IMPLEMENTING OPT-OUT FROM THE SECONDARY USE OF HEALTH DATA
  3. DRAFT GUIDELINE FOR HEALTH DATA ACCESS BODIES ON IMPLEMENTING THE OBLIGATION OF NOTIFYING THE NATURAL PERSON ON A SIGNIFICANT FINDING FROM THE SECONDARY USE OF HEALTH DATA
TEHDAS2 public consultation on Draft guideline for Health Data Access Bodies on data minimisation, pseudonymisation, anonymisation and synthetic dataDownload
TEHDAS2 public consultation on draft guideline for Health Data Access Bodies on implementing opt-outDownload
TEDHAS2 comments secondary useDownload

Medical Need or Market Opportunity: Setting Research Priorities

Meeting Summary

Presented on: March 10, 2025

This meeting was presented to the Bioethics Collaborative. The Bioethics Collaborative is a forum to propose, share, and discuss ethical challenges in multi-national clinical trials. Meetings convene individuals from academia, industry, patient/participant groups, ethics committees, government, and others.

Abstract: Since funding and other resources for clinical research are limited, decisions must be made about which research projects to pursue, which not to pursue, and how to prioritize among the studies that are chosen. The principle of “unmet medical need” is often acknowledged as a guiding consideration in this context, and there have been calls for community input into prioritization and the choice of the study question. Further, addressing unmet medical needs, particularly in the context of the global burden of disease, is important for public health but may not, and likely will not, maximize market opportunity or financial profits – a dynamic that is particularly salient for private industry sponsors. Should prioritization then rest solely or principally with the funder? How should such entities balance economic obligations toward shareholders with the public good?

One salient principle of distributive justice is “prioritarianism,” the idea that research that stands to benefit the worse-off or those who are already underprivileged should be given priority over research that stands to benefit people in better situations: the well-being of the most disadvantaged is prioritized. Even prior to this, however, questions arise over how to understand the expected goods of research, who the beneficiaries might be, and how the well-being of different possible beneficiary groups should be measured. Further downstream, issues arise over who should engage in prioritization decisions, and in particular, whether the research community should rely solely on high-level, centralized prioritization mechanisms (e.g., industry sponsors, NIH, non-profit funders), or whether individual institutions, local communities, and/or patients and their allies might have some role to play in ensuring that studies are appropriately prioritized at a local level. How should these various voices be heard, should they be represented, and how can—or should—balance be achieved, and if so, what processes should be considered? The March Bioethics Collaborative will seek to address these and other issues in connection with the ethics of research priority-setting.  

Download the Meeting Summary
Bioethics Collaborative Summary_March 2025Download

Therapeutic Misconception Revisited

Meeting Summary

Presented on: June 4, 2025

This meeting was presented to the Bioethics Collaborative. The Bioethics Collaborative is a forum to propose, share, and discuss ethical challenges in multi-national clinical trials. Meetings convene individuals from academia, industry, patient/participant groups, ethics committees, government, and others.

Abstract: The lines between research and care continue to blur. Pragmatic research studies comparing accepted therapies are increasingly embedded seamlessly into clinical practice. More and more, participation in research deemed promising is offered to patients before standard therapies are exhausted, sometimes as a first-line option. While the concept of “therapeutic misconception”—in very broad strokes, the tendency for individuals to misapply attributes of clinical care to research—has been a mainstay of research ethics for over 40 years, these developments provide an occasion, and perhaps even an urgent need, to revisit it and related topics. How exactly should we understand the therapeutic misconception and what it involves, particularly in cases where the line between research and care really is vague and hard to determine? Even more basically, how should we understand the relationship between research and care in the first place? Are concerns over therapeutic misconception still important, or do they perhaps reflect naïve understandings of research and care and the relation between them–particularly in cases where current options are limited? 

Download the Meeting Summary
June 2025 Bioethics Collaborative SummaryDownload

Biannual Global Meeting of The Joint Task Force For Clinical Trial Competency: December 2025

Proceedings and Presentations

Proceedings from: Joint Task Force for Clinical Trial Competency Biannual Global Meeting on December 10, 2025, a virtual meeting.

The Joint Task Force for Clinical Trial Competency (JTF), anchored at the MRCT Center, develops and disseminates standards and practices for the global clinical research workforce. By fostering a cohesive and collaborative approach, the JTF ensures that professionals have the competencies to conduct clinical trials ethically and effectively.

Our international team of investigators, educators, and clinical research professionals has developed and/or utilizes a framework that defines the knowledge, skills, and attitudes necessary for conducting safe, ethical, and high-quality clinical research.

The meeting featured five presentations demonstrating real-world implementation of the JTF Framework:

  • From Translation to Transformation: Advancing Clinical Research Competencies in Pakistan through the Urdu JTF Framework
  • Designing Experiential Learning with a Focus on JTF Competencies at North Carolina Central University
  • Applying JTF Competencies in a Master’s-Level Clinical Data Science Program
  • Professional Development of the Clinical Research Workforce in New Zealand Public Hospitals
  • Advancing Professional Standards and Recognition for Australian Clinical Trials Professionals

On-demand Recording on YouTube (with timestamps)

Note: The recording includes timestamps for each of the five presentations.

Meeting Summary
Compiled Slide Deck

Compiled Slides

2025-12-10 JTF Biannual Global Mtg Dec 10Download

Meeting Summary

2026-01-05b JTF December 10 Biannual Full SummaryDownload

Mitigating Financial Toxicity for Participants in Clinical Trials: Best Practice Considerations & Recommendations for Sponsors

Webinar

Presented on: December 9, 2025

Hosted by the MRCT Center, in collaboration with Equitable Access to Clinical Trials (EACT), a project convened by LUNGevity Foundation.

Clinical trials are vital to advancing medical knowledge and care, yet participation can impose significant financial burdens on participants and their families—from 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.

Panelists

Moderator
Dr. Barbara Bierer, Faculty Director, MRCT Center

A Framework for AI Adoption and Oversight in Clinical Research
2025-12-09_EACT_MRCT-Webinar-PresentationDownload

EACT Project Resources

Financially challenged and underinsured populations

Interpretation and Application of ICH E6(R3): Good Clinical Practice Guideline

Training Material

Released in: October 2025

Designed and developed by: The MRCT Center, an International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) training partner

Good Clinical Practice (GCP) is an international, ethical, scientific, and quality standard for the conduct of trials that involve human participants. The MRCT Center developed and designed this course in collaboration with the ICH E6(R3) Expert Working Group (EWG). This course consists of 5 modules introducing and explaining the key concepts of the E6(R3) guideline. This training is intended for anyone involved in the conduct of an interventional clinical trial. The course links will take the learner to the ICH Training Library website. Courses are free for all registrants.

Currently available is:

Module 1: Introduction and Foundational Concepts, published in October 2025

Over the next few months, the following modules will be released as they become available:

Module 2: Responsibilities and Oversight

Module 3: Data Governance

Module 4: Informed Consent, published in January 2026

Module 5: Essential Records

View the MRCT Center Training Catalog, including Module 1 and Module 4

Ethical, Legal, and Social Issues (ELSI) in Human Somatic Gene Therapy Clinical Research: A Scoping Review

Publication

Presented on: November 14, 2025

Published in: Human Gene Therapy

Carolyn Chapman, Mena Shaikh, Ava Glazier, Andrew Creamer, and Barbara Bierer published Ethical, Legal, and Social Issues (ELSI) in Human Somatic Gene Therapy Clinical Research: A Scoping Review in Human Gene Therapy. Dozens of gene therapies have been approved, and hundreds more are in development, prompting the need to better characterize the ethical, legal, and social implications (ELSI) of this emerging therapeutic class. The authors conducted a scoping review to map these issues across the literature, identifying themes related to risk–benefit assessment, engagement and communication, justice and access, ethical trial design, and the influence of financial and regulatory decision-making. The article also discusses potential approaches to address these ELSI as gene-therapy research expands.

View article

Ethical, Legal, and Social Issues (ELSI) in Human Somatic Gene Therapy Clinical Research: A Scoping Review

Carolyn Riley Chapman, Mena Shaikh, Ava Glazier, Andrew Creamer, and Barbara E. Bierer Human Gene Therapy 202536:21-22, 1387-1404

AI Digital Twins and Synthetic Data: Practical Use Cases for Clinical Research

Webinar

Presented on: November 18, 2025

This webinar focused on real-world examples and lessons learned from deploying synthetic data and digital twins across therapeutic areas.

Key Topics:

  • Reducing the size of control arms 
  • Enhancing Bayesian statistical analysis 
  • Supporting single-arm trials 
  • Optimizing the design of future trials 

Panelist: Daniele Bertolini, Machine Learning Scientist at Unlearn.ai.

Moderator: Barbara Bierer, Faculty Director at the MRCT Center

A Framework for AI Adoption and Oversight in Clinical Research
2025-11-18 Use Cases DigiTwins and SynData_CombinedDownload
AI Digital Twins and Synthetic Data: Application to Clinical Trials
Framework for Review of Clinical Research Involving AI
A Framework for AI Adoption and Oversight in Clinical Research