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. 2025 Feb;22(1):109-115.
doi: 10.1177/17407745241284798. Epub 2024 Oct 15.

Are pragmatism and ethical protections in clinical trials a zero-sum game?

Hayden P Nix  1 , Charles Weijer  2   3   4 , Monica Taljaard  5   6
Affiliations

Are pragmatism and ethical protections in clinical trials a zero-sum game?

Hayden P Nix et al. Clin Trials. 2025 Feb.

Abstract

Background: Randomized controlled trials with pragmatic intent aim to generate evidence that directly informs clinical decisions. Some have argued that the ethical protection of informed consent can be in tension with the goals of pragmatism. But the impact of other ethical protections on trial pragmatism has yet to be explored.

Purpose: In this article, we analyze the relationship between additional ethical protections for vulnerable participants and the degree of pragmatism within the PRagmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) domains of trial design.

Methods: We analyze three example trials with pragmatic intent that include vulnerable participants.

Conclusion: The relationship between ethical protections and trial pragmatism is complex. In some cases, additional ethical protections for vulnerable participants can promote the pragmatism of some of the PRECIS-2 domains of trial design. When designing trials with pragmatic intent, researchers ought to look for opportunities wherein ethical protections enhance the degree of pragmatism.

Keywords: Pragmatic trials; critical care; geriatrics; psychiatry; research ethics; vulnerability.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.W. receives consulting income from Cardialen, Eli Lilly & Company. H.P.N. is a co-author of the published PRiVII Trial protocol and is a member of the research team coordinating the trial. M.T. has no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
PRECIS-2 diagrams of the PRiVII Trial, corresponding to rigorous capacity assessments (dotted line), brief capacity assessments (dashed line), and using records of clinical decision-making capacity (solid line). This figure is based on the PRECIS-2 diagram in the published trial protocol.
Figure 2.
Figure 2.
PRECIS-2 diagrams of the Chlorhexidine Bath Trial, corresponding to exclusion of surgical patients (dashed line) and inclusion of surgical patients with additional chlorhexidine baths provided by nursing staff (solid line). This PRECIS-2 diagram was verified by the Principal Investigator of the Chlorhexidine Bath Trial.
Figure 3.
Figure 3.
PRECIS-2 diagrams of the ED to EPI Trial, corresponding to prepaid cell phones not used in the trial but used in practice (dashed line); prepaid cell phones used in the trial but not in practice (dotted line); and prepaid cell phones used in the trial and in practice (solid line). This PRECIS-2 diagram was verified by the Principal Investigator of the ED to EPI Trial.
See this image and copyright information in PMC

References

    1. Schwartz D, Lellouch J. Explanatory and pragmatic attitudes in therapeutic trials. J Chron Dis 1967; 20: 637–648. - PubMed
    1. Loudon K, Trweek S, Sullivan F, et al. The PRECIS-2 tool: designing trials that are fit for purpose. BMJ 2015; 350: h2147. - PubMed
    1. Ford I, Norrie J. Pragmatic trials. N Engl J Med 2016; 375: 454–463. - PubMed
    1. Kim SH. Ethical issues in pragmatic trials of “standard-of-care” interventions in learning health care systems. Learn Health Syst 2017; 2: e10045. - PMC - PubMed
    1. Pletcher MJ, Lo B, Grady D. Informed consent in randomized quality improvement trials: a critical barrier for learning health systems. JAMA Intern Med 2014; 174(5): 668–670. - PubMed

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