Arguments for expanding clinical trials data sharing often involve two claims related to the interests of research participants. The first claim is that expanded sharing of analyzable research datasets honors the contribution of trial participants, recognizing the risks and burdens they assumed in the interest of generating socially valuable knowledge by making full use of the data generated as a result of their contributions (Ohman et al. 2017). Second, that data sharing is consistent with the preferences and expectations of trial participants.

These two claims are both challenged for trials conducted with waivers or alterations of consent (Morain et al. 2022). While ethical arguments support the use of waivers or alterations for some PCTs, the use of waivers or alterations challenges the presumption that sharing data from a PCT advances the interests or preferences of patient-participants, who may not have voluntarily assumed the risks and burdens related to the initial research activity, much less any additional privacy risks related to downstream sharing of research data. Additionally, as described in Patient Perspectives on Data Sharing, little is known about whether patients enrolled in PCTs do, in fact, prefer and/or expect their data to be shared, particularly for trials conducted with waivers or alterations of informed consent.

An additional challenge when considering data sharing for PCTs conducted under a waiver or alteration is that existing policy guidance for clinical trials data sharing and related scholarship, developed for explanatory clinical trials, has heavily emphasized the role of informed consent to fulfill the ethical obligation to respect those whose data are shared. Yet if informed consent is not obtained for the initial research activity, it clearly cannot serve as the means by which to demonstrate respect for subsequent uses of the resulting research data.

While these challenges complicate decisions about sharing data from PCTs conducted under a waiver of informed consent, they do not make it necessarily impermissible to share data from PCTs conducted under a waiver or alteration of informed consent. However, they suggest the need for investigators and health systems to consider additional ways to fulfill the ethical obligation of respecting patient-participants when sharing their data from PCTs. Recent ethics scholarship has suggested several ways to respect patient-participants in PCTs using waivers or alterations of informed consent, including engaging patients and communities in research design and execution and improving transparency to patients about research activities and resulting findings (Morain et al. 2022). Further work is needed to test these and other strategies and their impacts on respect for PCT patient-participants.

Sharing results with participants

The preceding sections have focused on ethical and regulatory considerations when sharing individual-level data, such as to advance transparency and reproducibility, or to facilitate additional research. However, an additional ethical consideration relating to sharing data is sharing aggregate results research participants. While there has been growing appreciation of the importance of sharing aggregate results of clinical trials with research participants, such as via summary-level, lay-friendly summaries of research findings, this practice has not been examined in the context of pragmatic clinical trials, which have special features that may complicate the ethics and logistics of sharing aggregate results.

A manuscript from the NIH Pragmatic Trials Collaboratory Ethics and Regulatory Core summarizes the ethical arguments for sharing aggregate results and describe the features of pragmatic trials that may raise logistical and other barriers to disclosure (Morain et al. 2024). They also discuss the important role healthcare system partners play in sharing results from pragmatic trials.

The authors offer the following recommendations:

• Sharing aggregate results with research participants should be the default, and decisions not to share should be justified
• Planning for sharing aggregate results should begin early in the planning of the trial
• The healthcare care systems in which the trial is embedded should be key partners in decisions about what and how to share
• Proactive sharing of results from a pragmatic trial that was conducted under a waiver or alteration of consent, including an explanation for why consent was not obtained in the study, can promote trust in the investigators and their healthcare system partners