A critical look at the evolution of randomized controlled trials: new and old ethical issues

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Curr Opin Immunol. 2026 Mar 16;100:102758. doi: 10.1016/j.coi.2026.102758. Online ahead of print.

ABSTRACT

The traditional randomized controlled trial (RCT), a most valuable tool of evidence-based medicine, is rapidly evolving into new forms. The main reason behind this evolution is the basic explanatory nature of RCT and the related need for real-world data to help with daily medical care. The marked progress in data accumulation in technology is a driving element. The many forms of RCT with pragmatic elements are the main outcome of this evolution. Another, this time we consider a devolutionary form of RCT is the safety outcome trial (SOT) with primary outcomes of irreversible harm. In this review we discuss the various ethical issues involved in this evolution and devolution under the principles of the Belmont Report. We find the utilization of pragmatic elements in SOTs with primary outcomes of irreversible harm particularly worrisome.

PMID:41844068 | DOI:10.1016/j.coi.2026.102758

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