Nirsevimab versus placebo for medically attended RSV lower respiratory tract infection in infants

Registration and administrative information (PROSPERO field set)

Risk of bias (RoB-2)

Variant:

Unit assessed: —

Assessor 1: (anthropic family). Assessor 2: (openai family).

Overall judgement per trial

Inter-assessor agreement

This assessment is DUAL — two assessors from different model families, the second asked blind. The agreement rate is withheld pending adjudication. Both readers were given this review’s decision rule; an earlier version of this sentence said the blinding had withheld it, and that was wrong. What the 10 domain comparison(s) show is a reading difference that runs in OPPOSITE directions by domain — on domains 1 to 3 the second assessor more often declines to judge at all, and on domains 4 and 5 it more often judges low. A single agreement rate averages those two behaviours into one number that describes neither. Both assessors’ per-result judgements are shown in the table above, unadjudicated, and neither is this review’s finding. No adjudication has been performed, so this review holds no final risk-of-bias judgement for these results.

References

Included studies

• Phase 2b — https://clinicaltrials.gov/study/NCT02878330
• MELODY — https://clinicaltrials.gov/study/NCT03979313

Regulatory documents

Methods and guidance

Sources

Visual abstract

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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 9f355bac034f9402), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — visual-abstract.eps, 4 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — visual-abstract.tiff, 27,685 KB.

Projected from the canonical object, so it carries the same k, the same pooled estimate and the same interval as the paper and cannot drift from them. The interval is drawn to scale against the no-difference line, which it EXCLUDES: 0.177 to 0.385, with no difference at 1.

Risk of bias, both assessors

⬇ SVG (vector) 4 KB

Only the vector format is offered for this figure, by choice: it is line art — discrete marks, glyphs and labels — which SVG reproduces exactly at any size, so a raster would add weight without adding fidelity. The build was able to rasterise; it was asked not to.

Every cell carries BOTH independent cross-family assessments and they are not reconciled: showing one column would be a reconciliation presented as an observation. Glyph as well as colour, so the panel survives greyscale printing and colour-blind reading. A trial with no judgement is shown as a row of not-assessed markers rather than omitted, so a gap in the assessment cannot be mistaken for a clean assessment. Agreement as measured: {'per domain agreed': 10, 'per domain total': 10, 'per domain rate pct': 100.0, 'overall agreed': 0, 'overall total': 2, 'overall is derived': True, 'recomputed from the stored judgements': True, 'why recomputed': 'The stored disagreement tallies were frozen as text and 12 of 22 no longer match the judgements in the object -- a later guidance pass moved 51 the randomisation process judgements and the tallies were never recomputed. This is derived from what the object holds now.'}.

GOSH

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Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — gosh.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — gosh.tiff, 5,537 KB.

Deliberately not drawn. Every subset meta-analysis of 2 trials is 3 points; a cloud that small cannot show the multimodality GOSH exists to reveal, and a reader would take the picture as evidence of its absence.

Trial-sequential analysis

⬇ SVG (vector) 1 KB ⬇ PNG 3500x650 87 KB

All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 25ed9800fdf56614), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — tsa.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — tsa.tiff, 6,665 KB.

TSA boundaries depend entirely on a target information size that must be pre-specified. This review's protocol registers none, so any boundary drawn here would be a parameter chosen after seeing the data -- which is the practice TSA exists to protect against.

Meta-regression

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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: e35ec93bbc9a1c10), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — bubble.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — bubble.tiff, 5,537 KB.

The protocol pre-specifies no moderator, and at k = 2 a meta-regression would be fitted on 2 points. Not drawn rather than drawn with a caveat: a bubble plot invites reading a slope, and there is no slope here that any reader should read.

Summary of findings

1. This certainty rating is PENDING, not rated. It rests on a risk-of-bias judgement that this review has not finalised: two assessors read every contributing result independently, they disagree, and no adjudication has been performed, so this review holds no final risk-of-bias judgement for these results. Cochrane rates certainty per outcome by aggregating the risk-of-bias judgements of the results contributing to it, so a certainty rating cannot be more final than the risk-of-bias assessment it reads. The rating this object currently records, and the steps behind it, are shown below as the work so far rather than as this review's answer. No level is published for this outcome -- not the recorded one, not a more cautious one, and not a midpoint -- because choosing one would be the judgement that has not been made.

Reproducibility artifact

This page CANNOT be rebuilt from what is recorded here: no canonical object is recorded and no registered commit is recorded. Each figure on the Analysis tab downloads as an SVG carrying exactly the values shown.

Other recorded qualifications

Statements this review records about the limits of what it establishes, which are not shown elsewhere on this page. They are reproduced from the object verbatim and are not summarised.

Paper

Each statement below cites the record it came from; those sources are listed at the end of every section. Where the record holds nothing, the section says so by name rather than being left out, so a procedure that was not carried out can be told from one that simply was never mentioned.

Title

Nirsevimab versus placebo for medically attended RSV lower respiratory tract infection in infants¹

Abstract

Question. In Nirsevimab versus placebo for medically attended RSV lower respiratory tract infection in infants, what is the effect on versus placebo on medically attended RSV lower respiratory tract infection?¹

Methods. estimates were pooled under a random-effects model with the REML estimator; risk of bias was assessed with RoB 2 (Cochrane risk-of-bias tool for randomized trials); and certainty was rated with GRADE, following the Cochrane Handbook chapter 14. Randomised evidence starts HIGH and is rated down with reasons.²

Results. Medically attended RSV lower respiratory tract infection: risk ratio 0.261 (0.177 to 0.385) across 2 trials; 1 of these pooled outcome(s) carries a stated qualification -- a referral or a recorded finding -- given in full in Results and not reproduced here; and no statistical heterogeneity was detected (I-squared 0%), though heterogeneity cannot be reliably assessed with two trials.³

Introduction

Background. This review asks: In Nirsevimab versus placebo for medically attended RSV lower respiratory tract infection in infants, what is the effect on versus placebo on medically attended RSV lower respiratory tract infection? It pools 2 randomised trials, against placebo. The outcome pooled is medically attended RSV lower respiratory tract infection. Every count and denominator behind those estimates is read as follows. Registry throughout. Counts and denominators read from ClinicalTrials.gov posted results.¹

Methods — search

Primary trials. No bibliographic search for primary trials was run. The 2 included trials were identified by reading named registrations on 2026-08-18. All three seeded registrations read on 2026-08-18 including arm types and posted results. Published syntheses. PubMed E-utilities esearch + esummary, executed 2026-08-21. Query as executed: (nirsevimab[tiab] OR MEDI8897[tiab]) and (meta-analysis[pt] OR "systematic review"[pt] OR meta-analysis[tiab] OR "pooled"[tiab] or melody[tiab]). It matched 39 record(s), of which 39 were retrieved and 39 read; 1 appraised.¹

Methods — synthesis

For medically attended RSV lower respiratory tract infection, a random-effects model was fitted with the REML estimator.¹

Risk of bias was assessed with RoB 2 (Cochrane risk-of-bias tool for randomized trials) , following . 2 result-level assessments were made.²

A ceiling applies to every risk-of-bias judgement in this review; it is stated with the assessment itself rather than summarised here.³

Certainty of evidence was rated with GRADE, following the Cochrane Handbook chapter 14. Randomised evidence starts HIGH and is rated down with reasons., following . 1 pooled outcome(s) were rated. No domain is rated UP. Rating up applies to observational evidence; these are randomised trials starting HIGH.⁴

Results

The pooled risk ratio for medically attended RSV lower respiratory tract infection was 0.261 (0.177 to 0.385) across 2 trials, against placebo.¹

Noted on this pool. A published systematic review of this agent included six randomised trials (n = 12,086) where this pool carries two. Lien et al., Pediatrics and Neonatology 2026, PMID 41314935, reports RSV-related hospitalisation at OR 0.19 (0.13 to 0.30) and severe RSV infection at OR 0.23 (0.12 to 0.44). Those are different outcomes on a different scale from this pool's medically attended RSV lrti risk ratio of 0.2605 (0.1766 to 0.3845), so no discrepancy is claimed -- the point is the trial count. A published synthesis of this question included 6 trials where this pool carries 2. Source: Lien et al., Pediatrics and Neonatology 2026, PMID 41314935, six randomised trials totalling 12,086 participants. Which trials are absent is not established. The published abstract names none of its included studies and no included-study table was read, so this is a difference in stated counts and nothing more. It is not a claim that 4 specific trials were missed, and nobody here has identified them. The review's abstract names none of its six trials and no included-study table was read, so the four trials this object does not carry are counted and not identified. Naming them would require reading the review. The estimate above is computed from the trials this object carries and is not withdrawn or altered by this note. What a reader is owed is the scope: a larger evidence base on this question exists in the literature, and whether this review's search should be widened is a decision that has not been made.²

The trials' results were closely consistent with one another: I-squared, the share of the variation between them that is more than chance alone would produce, was 0%; the estimated variance of the true effects between trials (tau-squared) was 0, the heterogeneity test statistic Q was 0.0876, on degrees of freedom 1.³

What this does not establish: Not that either trial is free of bias -- no risk-of-bias assessment is recorded. Not anything about the excluded open-label trial, which reports a large effect on its own terms and is excluded on comparator type, not on quality. Not RSV hospitalisation or mortality, neither of which is the pooled endpoint. Not reliability at k=2 -- see Hartung-Knapp.⁴

The full model output for every pooled outcome -- the call, the estimator, the heterogeneity statistics and the back-transformed interval -- is stored verbatim on this review object at `results.by_outcome.<outcome>.r_output.verbatim`. It is not reproduced as an Extended data section in this article; an earlier version of this sentence said it was, and no such section exists.⁵

Risk of bias in the included results

Risk of bias was assessed with RoB 2 at the level of each reported result, by two assessors reading independently. Their judgements differ on 2 of the 2 results and no adjudication has been performed, so this review holds no final risk-of-bias judgement for these results. Assessor 1 recorded: 2 at some concerns. Assessor 2 recorded: 2 at no information. Both are shown in the risk-of-bias table; neither is the review's finding. The per-domain judgements behind them are recorded with the extracted data.¹

Certainty of the evidence

Certainty was rated with GRADE, following the Cochrane Handbook chapter 14. Randomised evidence starts HIGH and is rated down with reasons..¹

No domain is rated UP. Rating up applies to observational evidence; these are randomised trials starting HIGH.²

This certainty rating is pending, not rated. It rests on a risk-of-bias judgement that this review has not finalised: two assessors read every contributing result independently, they disagree, and no adjudication has been performed, so this review holds no final risk-of-bias judgement for these results. Cochrane rates certainty per outcome by aggregating the risk-of-bias judgements of the results contributing to it, so a certainty rating cannot be more final than the risk-of-bias assessment it reads. The rating this object currently records, and the steps behind it, are shown below as the work so far rather than as this review's answer. No level is published for this outcome -- not the recorded one, not a more cautious one, and not a midpoint -- because choosing one would be the judgement that has not been made.³

MODERATE certainty. The single downgrade is for two unjudgeable risk-of-bias domains that the registry does not carry -- not for inconsistency, indirectness or imprecision, none of which the evidence supports downgrading.⁴

Comparison with published syntheses

Published syntheses were identified as follows. PubMed E-utilities, executed 2026-08-21. Query, counts and per-record disposition in ssot/nirsevimab-infant-rsv-review/appraisal/the screen of published syntheses.json.¹

Limitations

What this review does not give a clinician: the number of events in each arm, any absolute effect or number needed to treat and any measure of harm. A relative effect cannot be turned into the benefit or the risk facing one patient without them, so this review can support a judgement about what these trials found and not a judgement about what to do.¹

Note on registration

No PROSPERO registration or protocol record is held on this object. That is not the same as knowing this review was not registered, and neither claim is made. It is recorded here as an absence so that a reader does not have to infer it from silence.¹

References

Figures

Trial characteristics

Not reported in this record

The items below were not written because the record does not hold what they would be composed from. They are named here so that an absence is not mistaken for an omission.