Post Trial Responsibilities: Continued Access

Principles

The MRCT Center’s Post-Trial Responsibilities: Continued Access to an Investigational Product outlines a principled and practical approach to identify the shared ethical responsibilities that can, in turn, guide action to provide continued access to an investigational product at the conclusion of a patient’s participation in a clinical trial.

The foundation of the MRCT Center’s work is grounded in 12 principles. The principles, accompanied by an analysis, should be read as a whole.

1. Research participants deserve consideration of continued access to a beneficial investigational product.
2. The responsibilities of post-trial, continued access of an investigational product to a trial participant (patient) after completion of a clinical trial are shared among all stakeholders: sponsor, investigator, site, healthcare provider, healthcare system, and the participant.
3. Provision of continued access is a bounded and limited responsibility of any one stakeholder
4. The responsibility to provide continued access to the investigational product is generally not influenced by whether the sponsor is a for-profit, not-for-profit, governmental agency, or sponsor-investigator, and whether the trial is conducted in a well- or low-resourced setting.
5. Provision of continued access must not inadvertently advantage some and harm others.
6. The plan to offer or not to offer continued access to an investigational product should be determined before a trial begins and appropriately communicated to investigators, ethics committees, and participants.
7.  If there is evidence of benefit exceeding risk in the trial population, and importantly in settings of unmet medical need, individual participants should be evaluated for continued access.
8. Generally, the informed consent document should include language related to continued access to the investigational product.
9. If continued access to an investigational product is offered, medical care, infrastructure, and long-term maintenance specifically necessary for the appropriate provision of the investigational product should be considered.
10. Continued access to an investigational product should always be provided under mechanisms that satisfy local regulatory requirements for investigational products
11. The sponsor is responsible for continuously assessing whether there is an ongoing unmet medical need for the investigational product during the clinical trial and product development program.
12.  For the health and safety of an individual participant, responsible transition from the investigational product to other appropriate care may be, and is often, necessary. The responsible transition of the participant to the marketed product following regulatory approval should also be anticipated and planned.

Post-Trial Responsibilities: A Shared Responsibility of Continued Access

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This image illustrates the shared responsibility of continued access throughout product development in an ideal situation, from planning to marketing to product availability. The work of the task force focused on challenging scenarios when this ideal situation does not happen.

What should sponsors consider when deciding whether or not to provide continued access?

The sponsor should apply interdependent criteria to determine whether continued access will be offered tostudy participants.

The MRCT Center has defined a set of interdependent criteria related to the study program that may lead to continued access, which may include but are not limited to:

INTERDEPENDENT CRITERIA

Program Level:

• Impact of discontinuation: The disease or condition under study is serious or life-threatening, and the research participant could be adversely impacted if access to the product were discontinued.
• Medical need: The investigational product addresses an unmet medical need in that no suitable therapeutic alternatives are available.
• No Access/Not Accessible: A physician cannot yet prescribe the product for the condition being studied.
• Research viability: The provision of continued access to the investigational product will not affect the viability of the research or the ability to complete the trial or other trials.
• Benefit/risk assessment: A positive overall study population benefit/risk assessment based on data analysis from first interpretable results or full study results.

Individual Participant Level:

In addition, the following criteria should be considered at completion of the trial:

• The eligible participant has completed the clinical trial protocol as intended.
• There is demonstrable evidence of benefit exceeding risk for an individual participant as determined by the investigator, in discussion with the participant and informed by the participant.

Sponsors and Researchers generally agree upon the criteria used to determine post-trial, continued access, the regulatory milestones, and the mechanisms used to provide continued access. The timing between a pivotal trial of an investigational product and its regulatory approval is variable, as is the timing to commercial milestones such as market availability and reimbursement. It is in these windows that decisions about the provision of continued access must be made. There are, however, complex decisions that require further analysis.

Regulatory Milestones:

1. Study planning
2. Ongoing clinical trials
3. Bridging the gap while awaiting a regulatory decision
4. Transition I: The investigational product is not approved
5. Transition II: The regulatory authority approves the investigational product

The Framework of Responsibility: Scenarios that Require Further Consideration is a list of considerations that organizations can utilize to make equitable and fair decisions related to continued access to an investigational medicine or significant-risk (SR) implanted device. These frameworks were designed for organizations developing investigational products and can be utilized to develop policy or guidance.

• Investigational Medicines Framework
• Investigational significant-risk, Implantable Device Framework – to be released in 2025

In November 2017, the MRCT Center published the Post-Trial Responsibilities: Continued Access to Investigational Medicines Guidance Document and Toolkit. This original framework outlined a case-based, principled, stakeholder approach to evaluate and guide the ethical responsibilities related to providing continued access to investigational medicine at the conclusion of a patient’s participation in a clinical trial. These resources have been used to develop policies and procedures at many global research organizations.

In 2022, the MRCT Center initiated the “PTR Taskforce” to update and add to the original resources. Utilization identified that the ethical principles and main consensus points remained valid. However, additional work was needed to advise on the practical application of the work. Throughout 2023 and the early months of 2024, the MRCT Center met monthly with the PTR task force to identify and develop updated tools and resources. The PTR task force developed a revised set of principles with associated analysis and a framework of responsibilities for continued access to investigational medicines. At the beginning of 2024, the work pivoted to the challenges of continued maintenance of investigational significant-risk (SR) implanted devices after a clinical trial. The MRCT Center, working with device experts, developed a device-specific framework of responsibilities reflecting the unique challenges of post-trial continued access to and maintenance of implanted SR devices. This work will be released in 2025.

ONGOING & FUTURE WORK

In 2025, the MRCT Center will focus on the challenges of continued access in lower- and middle-income countries. This work started in November of 2024 during a hybrid meeting of involved parties. Additional future work will focus on post-trial, continued access in Investigator-Initiated Trials (IITs) and analyzing the role of the Research Ethics Committee in assessing post-trial continued access to an investigational product.

Leadership:

Sarah White, MPH. Executive Director, MRCT Center

Karla Childers, BA, MSJ, MSBE. Co-Lead, Head of Bioethics-based Science & Technology Policy, Johnson & Johnson

Barbara Bierer, MD. Faculty Director, MRCT Center

Kayleigh To, MPH. Project Manager, MRCT Center

Task Force:

Dave Borasky, CIP, MPH. Vice President, Compliance Review Solutions, WCG IRB

Anthony Edmonds, MS. Senior Director, Global Medical Patient Access, Takeda

Sean Daly, Senior Director, Clinical Operations, Oncology, Takeda

Brandy Ellis, MBA, Participant/Patient Advocate

Christine Grady, MSN, PhD. Chief, Bioethics Head, Section on Human Subjects Research, NIH

Erika Hamilton, MD. Director of Breast Cancer and Gynecologic Cancer Research, Sarah Cannon Research Institute, ASCO

Donald Harvey, PharmD, FCCP, FHOPA, FASCO. Professor, Emory University School of Medicine, ASCO

Anna Kang, MPH, Principal Bioethics Leader, Roche-Genetech

Benjamin Rotz, Associate Vice President – Global Medical Policy, Strategy, and Operations, Eli Lilly and Company

Marjolein Willemen, MSc, PharmD, PhD. Medical Policy and External Collaborations Lead Novartis

Crispin Woolston, PhD. Global Head of Science Policy, Sanofi

Teri Pollastro, Participant/Patient Advocate

Device Experts:

Joy Domingo, MD. Medical Safety Officer, Johnson & Johnson

Elazer Edelman, SM, MD, PhD. Director, Center for Clinical Translational Research (CCTR), Edward J. Poitras Professor in Medical Engineering and Science Professor, Medicine, MIT, BWH & Harvard Medical School 

Saskia Hendriks, MD, PhD. Neuroethics Consultant, NIH

Richard Kuntz, MD. Formerly Chief Medical and Scientific Officer, Medtronic

Gabe Lázaro-Muñoz, PhD, JD. Assistant Professor, Harvard Medical School

Bruce Rosengard, MD, FACS, FRCS. Vice President of External Innovation, Johnson & Johnson

Paul Underwood, MD, FACC, FSCAI, RAC. President, Cardio MedSci.

The original project (2015-2017) was co-chaired by:

Carmen Aldinger, PhD, MPH, PMP. Project Manager, MRCT Center

Luann Van Campen, PhD, MA. Senior Advisor and Head of Bioethics, Eli Lilly & Company

Barbara E. Bierer, MD. Faculty Director, MRCT Center