Table 1.

Ethical considerations in pragmatic trials and in pragmatic trials for pain.

Ethical consideration in pragmatic trials	Application to pain trials and potential solutions
Do trials require the same ethical and regulatory oversight as efficacy trials if they test ‘usual practice’ and established interventions? This dilemma is known as the “research/treatment distinction.” Some authors purport that this distinction blurs in pragmatic trials, reducing the need for ethical oversight.41,92 Conversely, if routine clinical practice or aspects thereof are changed to implement the trial, ethical assessment is required.	Most pragmatic trials in pain will impose additional requirements on patients and medical personnel (such as additional outcome collection),71 for which ethical approval should be obtained. Targeted recruitment of potentially vulnerable people is also common in pain research,2,71 requiring careful ethical assessment. Ethical approval can be streamlined for all other aspects of a trial. For example, interventions may not require detailed review if they are not modified for the trial or are not directed at patients.12
Is consent required in trials that test “usual practice” and established interventions that are known to be safe? According to the principle of patient autonomy, voluntary informed consent is required for human involvement in any experimentation. If only regarding consent as necessary to inform about added risks of experimentation, consent may be waived or simplified in pragmatic trials between low-risk interventions for which there is equipoise. This is, however, controversial and defining “low risk” is challenging108,132; also controversial is the need for disclosure of study methodology, including randomization.58	Consent can be waived or simplified under certain circumstances, many of which may apply to pragmatic trials of pain research.19,58,90,132 Especially noninvasive nonpharmacological interventions are believed to hold little medical risk, and streamlining of consent has been called for.41,92 These interventions are often studied in pragmatic pain trials.71 Risk assessments in pragmatic pain trials should consider patient subgroups with different risk profiles, eg, depending on comorbidities or levels of health literacy.132 Risk/benefit assessments may have to include consideration of other undesirable effects from testing and implementing nonefficacious interventions and low-value care, such as nocebo, behavioral, and socioeconomic effects.72
How can pragmatic trials promote justice and equity in trial research? Pragmatic trials are often considered opportunities to involve people in research that are not usually participants and to conduct research relevant to minority groups. However, involvement of such groups may also require additional methods to protect potentially vulnerable participants.132,179 Pragmatic trials, often embedded within health systems, also risk perpetuating their existing structural injustices.2	Ali et al.2 proposed strategies for addressing injustices and inequities in pragmatic pain research. Also, see Kelsey et al.95 Strategies involve*  Consideration of socioeconomic trial context  Effective and equitable stakeholder engagement  Broad criteria for participating centers  Recruitment of underserved and vulnerable populations even if additional monitoring may be required  Flexibility and tailoring of interventions to subgroups  Accessible data collection methods  Digital tools for equitable trial participation  Promotion of diversity within the research team itself

The first column is largely based on Goldstein et al.⁵⁸

^*Detailed recommendations relating to these points are referred to throughout this article.