Language: English

Meeting Summary

Presented on: September 8, 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: Research in rare diseases presents several ethical challenges, which have, to date, been under-explored. Decisions about whether to initiate rare disease research in the first place can be complicated by economic realities, given that the eventual market for rare disease therapies may be quite limited. How should companies and research funders generally balance economic and feasibility considerations with the needs of rare patient groups? Other challenges characterize the conduct of rare disease research. Some of these involve issues related to privacy and confidentiality. The smaller the patient population, the easier it may be to identify participants and individuals within clinical trial datasets, even when efforts are made to protect privacy. Others involve how to be fair toward rare disease patients eager to participate in research, which include determining where to run trials and provide fair access. Finally, determining the scope of post-trial obligations toward rare disease populations, and what is owed to rare disease patients who appear to benefit from therapies that lack efficacy in wider populations, can be complicated. How should sponsors and other research stakeholders think about these issues?     

Meeting Summary

Presented on: December 8, 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: Rigorous evaluation of investigational therapies often requires the presence of a control group that will not receive the therapy under evaluation. In active-controlled studies, people in the control arm receive a currently available treatment, but in some cases, they receive a placebo from which they are not likely to benefit. Furthermore, clinical research for certain conditions, such as rare neurological or genetic disorders, places increasing demands on all participants, including those in the control arm, for invasive and burdensome procedures. For example, in studies where a drug is delivered intrathecally to participants in an active arm over multiple cycles, participants in the control arm may also be asked to undergo serial lumbar puncture and placebo injections directly into the spinal canal, to maintain the blind or provide a baseline for safety and/or biomarker assessments. 

How much risk and burden is too much to ask individuals in these studies to accept— particularly those in control arms who will receive a placebo or otherwise fail to benefit? How should we think about the difference, if any, between active and placebo control arms on this issue? If intrusive elements of designs are truly indispensable to the research, should the IRB and research ethics community be willing to adjust their tolerance for risk? Are there practical mitigation strategies that can help? Do studies that include vulnerable populations, such as children and those unable to consent for themselves, demand heightened concern or a different analysis? Who decides what level of risk is acceptable? And what role, if any, should the perspectives of patient communities play in helping to set those limits? The December BC will aim to address these and related topics. 

Meeting Summary

Presented on: March 10, 2026

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: 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.