At least 3 factors related to the pragmatic features of pragmatic clinical trials present challenges for assessing and managing collateral findings.

First, some pragmatic trials are conducted with waivers or alterations of informed consent. (See the Consent, Disclosure, and Non-Disclosure chapter of the Living Textbook.) While a waiver or alteration of consent in a pragmatic trial may be justified on ethical and regulatory grounds, it may complicate decisions related to the ethical management of collateral findings. This is because individuals in the trial may not have known they were enrolled in a pragmatic trial and, therefore, could not have considered the potential that they might receive information about their health that emerged from the trial (Morain et al 2020). This means that, unlike solutions identified in prior guidance for managing incidental and secondary findings, informed consent processes will have limited value as a policy solution, as individuals may not have had the opportunity ahead of time to consider and declare their preferences for receiving additional information related to their health.

Second, collateral findings in pragmatic trials may be identified by researchers who have no prior relationship to the patient-subjects for whom the collateral findings may have clinical relevance. In some cases, the researchers who discover the collateral findings might even be at a different institution from the one where the patient-subjects received their clinical care. The indirectness of this relationship between researcher and patient-subject may influence the nature of the responsibility of researchers (and/or their institutions) to disclose collateral findings in pragmatic trials, as well as their responsibility for subsequent management of those findings, including clinical follow-up (Morain et al 2022). It also may shape practical considerations related to disclosure, including decisions about how to provide relevant health information to individuals and processes for subsequent clinical follow-up (Morain et al 2020).

Third, pragmatic trials are often implemented at a large scale, with respect to both the number of sites and the number of individuals enrolled. The scale of many pragmatic trials has implications for management of collateral findings, as disclosure and follow-up could require considerable effort and costs by healthcare systems and the clinicians working within them (Morain et al 2020; Morain et al 2022).