Empirical research related to the ethics of pragmatic clinical trials: A scoping review

Pragmatic clinical trials (PCTs) offer insights into real-world intervention effectiveness, but they may involve challenging ethical issues. Empirical ethics research may inform deliberations about them.

We conducted a scoping review of empirical ethics research related to PCTs. This involved searching in PubMed and Embase, charting findings, and analyzing themes to identify trends and gaps.

Eighty-two publications were included, which examined a vast number of issues encompassing 22 themes. The five most prominent were: consent/disclosure; risk assessment; trust and transparency; burdens, barriers, and costs; and engagement. Written consent is often impractical, prompting interest in opt-out or general notification approaches. Challenges in risk assessment include variability in defining minimal risk, thereby complicating regulatory determinations for the appropriateness of particular participant protections and communicating research risks. Trust-building practices, such as result-sharing and data-use disclosure, can foster confidence. Stakeholder engagement can address logistical barriers, improve recruitment, and align research with participant needs. Time, financial, and regulatory burdens are significant obstacles to implementing PCTs.

There has been progress in understanding many ethical issues encountered in PCTs, including appropriately navigating alternatives to obtaining written informed consent, trust-building, and the operational role of stakeholder engagement. However, critical gaps remain, with research concentrated in Western contexts and reliant on surveys and hypothetical scenarios, limiting generalizability and real-world insights. Addressing these gaps with geographically inclusive studies, innovative methods, and nested empirical work will be important for more comprehensively understanding the ethical issues in PCTs and developing appropriate approaches to mitigating them.