Ruiz‐Palacios et al. — Safety and Efficacy of an Attenuated Vaccine against Severe Rotavirus Gastroenteritis

New England Journal of Medicine, 2006 · 10.1056/NEJMoa052434

HELD UP

In plain language

Ruiz-Palacios et al. (NEJM 2006) tested the oral rotavirus vaccine Rotarix (RIX4414) against an inert placebo in a trial of 63,225 infants, powered specifically for the safety endpoint of intussusception after an earlier rotavirus vaccine was withdrawn for that harm. Because Rotarix is an oral, non-adjuvanted vaccine, its placebo is a genuine inert comparator rather than an adjuvant or another vaccine. Intussusception occurred in 6 vaccine versus 7 placebo recipients within 31 days of any dose; recomputing gives a risk difference of about -0.31 per 10,000 and a risk ratio of 0.854, reproducing the paper's reported -0.32 per 10,000. The design can therefore support an absolute (vaccine-versus-nothing) safety inference, which almost no other product on the UK schedule can. The audit found no arithmetic or design problem: this is the schedule's true-placebo positive control.

Flags

None — the paper held up.

Method — the checks that were run

recompute intussusception risk — 6 vs 7 within 31 days across 63,225 infants -> risk difference approx -0.31/10,000, RR 0.854; reproduces the paper's -0.32/10,000.
classify comparator — Oral, non-adjuvanted vaccine vs inert placebo -> a genuine absolute-safety baseline, not an active comparator.

Next leads — where to look next

10.1056/NEJMoa1012952
Post-licensure (Mexico/Brazil) analysis reported a small transient intussusception signal in the first week after dose 1; the RCT was underpowered for that magnitude, so it tests the edge of this sound verdict.

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Audited by paper-forensics · claude-opus-4-8 · build 79245d004803 · 03 Aug 2026 · signed 4VLPoBn-HAO_… · the raw signed note ▸