Post-trial responsibilities in pragmatic clinical trials: Fulfilling the promise of research to drive real-world change.

While considerable scholarship has explored responsibilities owed to research participants at the conclusion of explanatory clinical trials, no guidance exists regarding responsibilities owed at the conclusion of a pragmatic clinical trial (PCT). Yet post-trial responsibilities in PCTs present distinct considerations from those emphasized in existing guidance and prior scholarship. Among these considerations include the responsibilities of the healthcare delivery systems in which PCTs are embedded, and decisions about implementation for interventions that demonstrate meaningful benefit following their integration into usual care settings-or deimplementation for those that fail to do so. In this article, we present an overview of prior scholarship and guidance on post-trial responsibilities, and then identify challenges for post-trial responsibilities for PCTs. We argue that, given one of the key rationales for PCTs is that they can facilitate uptake of their results by relevant decision-makers, there should be a presumptive default that PCT study results be incorporated into future care delivery processes. Fulfilling this responsibility will require prospective planning by researchers, healthcare delivery system leaders, institutional review boards, and sponsors, so as to ensure that the knowledge gained from PCTs does, in fact, influence real-world practice.

The ethical value of consulting community members in non-emergency trials conducted with waivers of informed consent for research.

There is growing interest in using embedded research methods, particularly pragmatic clinical trials, to address well-known evidentiary shortcomings afflicting the health care system. Reviews of pragmatic clinical trials published between 2014 and 2019 found that 8.8% were conducted with waivers of informed consent; furthermore, the number of trials where consent is not obtained is increasing with time. From a regulatory perspective, waivers of informed consent are permissible when certain conditions are met, including that the study involves no more than minimal risk, that it could not practicably be carried out without a waiver, and that waiving consent does not violate participants' rights and welfare. Nevertheless, when research is conducted with a waiver of consent, several ethical challenges arise. We must consider how to: address empirical evidence showing that patients and members of the public generally prefer prospective consent, demonstrate respect for persons using tools other than consent, promote public trust and investigator integrity, and ensure an adequate level of participant protections. In this article, we use examples drawn from real pragmatic clinical trials to argue that prospective consultation with representatives of the target study population can address, or at least mitigate, many of the ethical challenges posed by waivers of informed consent. We also consider what consultation might involve to illustrate its feasibility and address potential objections.

Single IRB Review and Local Context Considerations: A Scoping Review.

A leading concern about single IRB (sIRB) review for multisite studies, as is now required by federal policies, is whether and how sIRBs consider local context in their review. While several types of local context considerations have been proposed, there is no shared agreement among those charged with the ethics oversight of human subjects research as to the goals and content of local context review, nor the types of research studies for which sIRB review might be inappropriate. Through a scoping review of published scholarship, public comments, and federal guidance documents, we identified five assumed goals for local context review: protecting the rights and welfare of local participants; ensuring compliance with applicable laws and policies; assessing feasibility; promoting the quality of research; and promoting procedural justice. While a variety of content was proposed to be relevant, it was largely grouped into four domains: population/participant-level characteristics; investigator and research team characteristics; institution-level characteristics; and state and local laws. Proposed characteristics for exclusion from sIRB requirements reflected both protection- and efficiency-based concerns. These findings can inform ongoing efforts to assess the implications of policies mandating sIRB review, and when exceptions to those policies might be appropriate.

Hormonal Contraceptive Side Effects and Nonhormonal Alternatives on TikTok: A Content Analysis.

The use of hormonal contraceptives is decreasing in the United States alongside a growing interest in nonhormonal contraceptive options. Social media messaging may be contributing to this trend. TikTok thus offers a novel opportunity to understand how people share information about risks and alternatives for pregnancy prevention. To describe the availability and content of information about hormonal contraceptive side effects and nonhormonal contraceptive options on TikTok, we conducted a content analysis of 100 videos using the hashtags #birthcontrolsideeffects and #nonhormonalcontraception. We found that these videos were popular and often framed hormonal contraceptives and patient-provider interactions negatively, with users frequently discussing discontinuation of hormonal contraception and no plans for uptake of another contraceptive. When uptake of a new contraceptive method is mentioned, creators typically mention a fertility awareness-based method, which requires specialized knowledge to use safely and effectively. The risks and side effects of hormonal options were often overemphasized compared with the possible risks and side effects of nonhormonal options. This framing may suggest opportunities for providers and health educators to reassess how they counsel about contraceptive options. We conclude with recommendations for future research on TikTok and consider the policy implications of these findings.

Stakeholder perspectives on data sharing from pragmatic clinical trials: Unanticipated challenges for meeting emerging requirements.

Introduction: Numerous arguments have been advanced for broadly sharing de-identified, participant-level clinical trial data. However, data sharing in pragmatic clinical trials (PCTs) presents ethical challenges. While prior scholarship has described aspects of PCTs that raise distinct considerations for data sharing, there have been no reports of the experiences of those at the leading edge of data-sharing efforts for PCTs, including how these particular challenges have been navigated. To address this gap, we conducted interviews with key stakeholders, with a focus on the ethical issues presented by sharing data from PCTs. Methods: We recruited respondents using purposive sampling to reflect the range of stakeholder groups affected by efforts to expand PCT data sharing. Through semi-structured interviews, we explored respondents' experiences and perceptions about sharing de-identified, individual-level data from PCTs. An integrated approach was used to identify and describe key themes. Results: We conducted 40 interviews between April and September 2022. Five overarching themes emerged through analysis: (1) challenges in sharing data collected under a waiver or alteration of consent; (2) conflicting views regarding PCT patient-subject preferences for data sharing; (3) identification of respect-promoting practices beyond consent; (4) concerns about elevated risks or burdens from sharing PCT data; and (5) diverse views about the likely benefits resulting from sharing PCT data. Conclusion: Our data indicate unresolved tensions in how to fulfill the expectation to broadly share de-identified, individual-level data from PCTs, and suggest that those promulgating and implementing data-sharing policies must be sensitive to PCT-specific considerations. Future work could inform efforts to tailor data-sharing policy and practice to reflect the challenges presented by PCTs, including sharing experiences from trials that have successfully navigated these tensions.