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Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.

Name: Kaimen Rigor review — Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.
Item: Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.
Rating: 96
Author: Alpha1

Jackson DJ, Wechsler ME, Jackson DJ, Bernstein D, Korn S, Pfeffer PE, Chen R, Saito J, de Luíz Martinez G, Dymek L, Jacques L, Bird N, Schalkwijk S, Smith D, Howarth P, Pavord ID, SWIFT-1 and SWIFT-2 Investigators, SWIFT-1 Investigators, SWIFT-2 Investigators

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Kaimen Rigor review — 4.75★ (Strong), 0 critical, 2 high issues for “Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.”

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This rigor review was examined and confirmed by Alpha1 Editorial · August 16, 2026

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Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.

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DOI

10.1056/NEJMoa2406673

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.

Paper source

Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.

Read full text

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Links back to this Kaimen Rigor review.

Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 16, 2026

Kaimen Rigor review

Kaimen Rigor reviewed

4.75 / 5

Strong — minor issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

ReportingData & code availability partially met−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Not verified in this report

The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 32 reported means were read, and their group size is not stated where the values are printed (this source has no machine-readable table structure). These checks need the count the mean was averaged over, so none was performed.
Declared data/code links were not checked for liveness or content.

Findings by category

01ArithmeticNone found 02OverreachNone found 03AuthenticityNone found 104DisclosureReporting gaps 05AvailabilityNone found · partly checked 06Copyedit4 minor suggestions

This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

The paper reports two well-designed, rigorously conducted phase 3 trials with clear scientific rationale, detailed methods, and transparent reporting. The main weakness is the vague data availability statement and minor reporting gaps (statistical software, informed consent, reporting guideline).

Both reviewers classified the study as interventional, and I adopted that. The evaluation covered all eight dimensions; species/strain/housing and cell line sub-criteria were not applicable for this human trial. The statistics verification checked only 4 tests (all consistent); other reported statistics were not machine-verified.

Numerical inconsistencies

None found

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Checked — nothing surfaced.

Recomputed 4 tests: 4 consistent, 0 inconsistent; 4 via agent-written checks.

Overstated conclusions

None found

Conclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.

Checked — nothing surfaced.

4 major claims checked against the paper's own evidence: all adequately supported.

Efficacy claim is anchored to an adequate endpoint and a meaningful effect.

Data authenticity concerns

None found

An adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.

Checked — nothing surfaced.

Reporting gaps

1 finding · worst medium

Required detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.

Data/code availability incompleteAssessed

Eight Dimensions7 pass · 1 warn

The introduction cites multiple prior studies (references 1-19) establishing the role of IL-5 in eosinophilic asthma, the efficacy of shorter-acting anti-IL-5 biologics, and the phase 1 data for depemokimab. The rationale linking the need for less frequent dosing to improved patient quality of life is logically presented. Limitations of prior therapies (dosing frequency) are acknowledged and addressed by the study design.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise with extensive prior work and a logical rationale for the study.

Evidence

paraphrase[Introduction, paragraph 1-3]

“In 2009, proof-of-concept trials showed that the anti–interleukin-5 antibody mepolizumab reduced the frequency of exacerbations in patients who had a sputum eosinophil count of more than 3% and a history of exacerbations.”

paraphrase[Introduction, paragraph 4]

“Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5, which potentially enables effective 6-month dosing intervals for patients with asthma.”

absence[Introduction]

Limitations of prior work are not explicitly discussed as such.

PASSReviewer 2· 95% conf

The paper clearly establishes the scientific premise by citing prior work on interleukin-5 biology, anti-IL-5 therapies, and the rationale for depemokimab's ultra-long-acting design.

Evidence

paraphrase[Introduction, paragraphs 1-3]

“Interleukin-5 is responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils... In 2009, proof-of-concept trials showed that the anti–interleukin-5 antibody mepolizumab reduced the frequency of exacerbations...”

paraphrase[Introduction, paragraph 4]

“Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5, which potentially enables effective 6-month dosing intervals for patients with asthma.”

paraphrase[Discussion, paragraph 3]

“Our findings regarding depemokimab represent a potential advance in patient quality of life because therapies that have a reduced dosing frequency are associated with a lower patient-reported treatment burden...”

Randomization method (RandAll NG, block size six, stratified by ICS dose) and unit (patient) are reported. Blinding is described (trial staff, patients, investigators unaware). Power analysis is referenced but details are in the supplementary appendix. Inclusion/exclusion criteria are detailed. Outlier handling is addressed via the full analysis population definition and exclusion of sites for GCP violations. Controls (placebo) are appropriate. Independent replication is inherent in the two replicate trials.

Sub-criteria

controlsADEQUATE

power analysisINADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The trial design is rigorous with adequate randomization, blinding, and prespecified analysis populations.

Evidence

paraphrase[Methods, Treatments and Randomization]

“The randomization schedule was generated with the use of RandAll NG software and was performed by means of interactive-response technology with a block size of six.”

“Trial staff members, patients, and investigators were unaware of trial-group assignments.”

MethodsFind in source

paraphrase[Methods, Statistical Analysis]

“Additional details about the statistical models, sample-size determination, interim analyses, handling of missing data, and pooled analysis are provided in the Supplementary Appendix.”

PASSReviewer 2· 95% conf

The study design is rigorous: randomized, double-blind, placebo-controlled, with adequate randomization, blinding, and pre-specified inclusion/exclusion criteria.

Evidence

paraphrase[Methods, Treatments and Randomization]

“The randomization schedule was generated with the use of RandAll NG software and was performed by means of interactive-response technology with a block size of six.”

“Trial staff members, patients, and investigators were unaware of trial-group assignments.”

MethodsFind in source

paraphrase[Methods, Patients]

“Key eligibility criteria were an age of at least 12 years, an asthma diagnosis by a physician at least 2 years earlier, a blood eosinophil count of at least 300 cells per microliter during the previous 12 months...”

Table 1 provides detailed baseline demographics: age (mean and distribution), sex, race, asthma duration, inhaled glucocorticoid dose, eosinophil counts, IgE levels, FEV1, and exacerbation history. Sex is reported for both sexes (mixed-sex study, so sex_justified is not applicable). Age and weight are reported. Species/strain/housing are not applicable for a human trial. Demographics are comprehensive.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Demographic and clinical characteristics are well reported, including sex, age, and key disease characteristics.

Evidence

“Female sex — no. (%) 144 (58) 79 (60) 160 (63) 81 (63)”

Table 1Find in source

“Distribution — no. (%) 12–17 yr 3 (1) 5 (4) 12 (5) 10 (8)”

Table 1Find in source

PASSReviewer 2· 95% conf

Demographic and clinical characteristics are well-reported, including age, sex, race, eosinophil counts, lung function, and comorbidities.

Evidence

“Female sex — no. (%) 144 (58) 79 (60) 160 (63) 81 (63)”

Table 1Find in source

“Age Mean 54.1±13.8 53.6±14.9 53.6±16.0 51.2±16.6”

Table 1Find in source

“Peripheral-blood eosinophil count — no. (%) ≥150 cells/μl at screening 224 (90) 123 (93) 219 (87) 118 (92)”

Table 1Find in source

The paper states that the trials were conducted in accordance with the Declaration of Helsinki and ICH-GCP guidelines. It explicitly mentions that the institutional review board or ethics committee at each site approved the trial protocol. Informed consent is implied by the ethical framework but not explicitly stated; however, for a phase 3 trial conducted under ICH-GCP, informed consent is standard and the statement of ethical compliance is sufficient. Regulatory compliance is stated.

Sub-criteria

iacuc statementN/A

informed consentINADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Ethics approval and consent are adequately reported.

Evidence

“The institutional review board or ethics committee at each site approved the trial protocol (available at NEJM.org) and any other relevant documents.”

MethodsFind in source

paraphrase[Methods, Trial Design and Oversight]

“The two trials were conducted in accordance with consensus ethical principles derived from international guidelines, including the Declaration of Helsinki and the Council for International Organizations of Medical Sciences, applicable International Council for Harmonisation Good Clinical Practice guidelines, and all applicable laws and regulations.”

absence[Methods]

Informed consent is not explicitly described in the main text.

PASSReviewer 2· 95% conf

Ethical approvals are adequately reported: the trials were conducted in accordance with the Declaration of Helsinki and ICH-GCP, with IRB/ethics committee approval at each site.

Evidence

“The institutional review board or ethics committee at each site approved the trial protocol (available at NEJM.org) and any other relevant documents.”

MethodsFind in source

paraphrase[Methods, Trial Design and Oversight]

absence[Methods, Trial Design and Oversight]

Informed consent is not explicitly mentioned.

Depemokimab is identified as a 100 mg subcutaneous dose administered at weeks 0 and 26, supplied in a prefilled syringe. Placebo is described as matching. The randomization software (RandAll NG) is named. Statistical software is not explicitly named in the main text but is likely detailed in the Supplementary Appendix. Antibodies, cell lines, mycoplasma, and organisms are not applicable for this clinical trial. Reagents are not applicable beyond the investigational product.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational product (depemokimab) is adequately identified, and statistical software is named.

Evidence

“Patients underwent randomization in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg) or placebo subcutaneously at week 0 and week 26, in addition to standard care.”

MethodsFind in source

“The randomization schedule was generated with the use of RandAll NG software”

MethodsFind in source

PASSReviewer 2· 95% conf

The investigational product (depemokimab) is identified with dose and regimen; placebo is described; software tools are identified.

Evidence

“Patients underwent randomization in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg) or placebo subcutaneously at week 0 and week 26, in addition to standard care.”

MethodsFind in source

“The randomization schedule was generated with the use of RandAll NG software”

MethodsFind in source

absence[Methods, Statistical Analysis]

Statistical software is not identified in the main text.

The primary analysis uses a generalized linear model with negative binomial distribution, covariates are listed, and an offset is included. The hierarchical testing procedure is described. Exact p-values are reported for the primary endpoints (P<0.001). Effect sizes with 95% CIs are reported for primary and secondary endpoints. Software is not identified in the main text. Data presentation includes per-group Ns, CIs, and Kaplan-Meier curves. Mathematical plausibility checks: the reported exacerbation counts (120 vs 150 in SWIFT-1, 153 vs 167 in SWIFT-2) are plausible given the rates and person-years.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedNOT REPORTED

assumptions verifiedINADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical methods are appropriate and well-described, with exact p-values and confidence intervals for primary and key secondary endpoints.

Evidence

paraphrase[Methods, Statistical Analysis]

“We analyzed the primary end point using a generalized linear model that assumed a negative binomial distribution with covariates of trial group, baseline dose of inhaled glucocorticoids (medium or high), exacerbation history (2, 3, or ≥4 events), geographic region, and baseline prebronchodilator percent of the predicted FEV 1 with an offset of log e (total number of years in the trials).”

paraphrase[Results, Primary End Point]

“for a rate ratio of 0.42 (95% CI, 0.30 to 0.59) (P<0.001) in SWIFT-1”

absence[Methods, Statistical Analysis]

Statistical software for analysis is not named.

PASSReviewer 2· 95% conf

Statistical methods are well-described: negative binomial model for the primary endpoint, hierarchical testing for multiplicity, and exact p-values reported for primary endpoints.

Evidence

paraphrase[Methods, Statistical Analysis]

“We analyzed the primary end point using a generalized linear model that assumed a negative binomial distribution with covariates of trial group, baseline dose of inhaled glucocorticoids (medium or high), exacerbation history (2, 3, or ≥4 events), geographic region, and baseline prebronchodilator percent of the predicted FEV1 with an offset of loge(total number of years in the trials).”

paraphrase[Results, Primary End Point]

“In SWIFT-1, the annualized rate of exacerbations over 52 weeks was significantly lower... (P<0.001)... In SWIFT-2... (P<0.001).”

“Rate ratio (95% CI) 0.42 (0.30 to 0.59)”

Table 2Find in source

The paper states 'A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.' This is a vague statement that does not specify a concrete access route or repository. For a clinical trial, managed access via a platform would be adequate, but the statement here is insufficient. No code sharing is reported. The trial is registered at ClinicalTrials.gov (NCT04719832 and NCT04718103), which provides some transparency.

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositNOT REPORTED

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

A data sharing statement is mentioned but not detailed in the main text; no repository or accession numbers are provided.

Evidence

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

End of articleFind in source

WARNReviewer 2· 90% conf

A data sharing statement is mentioned but not detailed in the main text; no repository deposit or code sharing is reported.

Evidence

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

ReferencesFind in source

absence[Throughout paper]

No repository deposit is mentioned.

absence[Throughout paper]

No code sharing is mentioned.

Methods are detailed enough for replication. The trials are registered at ClinicalTrials.gov with numbers NCT04719832 and NCT04718103. A reporting guideline is not explicitly referenced but NEJM typically requires CONSORT. All pre-specified outcomes are reported, including negative results (SGRQ). Limitations are discussed in the Discussion. Conclusions are proportional to the evidence. Funding (GSK) and conflicts of interest are disclosed.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The manuscript is transparent with trial registration, detailed methods, and discussion of limitations.

Evidence

“SWIFT-1 and SWIFT-2 ClinicalTrials.gov numbers, NCT04719832 and NCT04718103.”

AbstractFind in source

paraphrase[Discussion]

“A further limitation of these trials is that SWIFT-1 was initiated during the coronavirus disease 2019 pandemic, which potentially had an effect on the overall rate of exacerbations and the ability to conduct routine lung-function testing.”

absence[Methods]

Reporting guideline is not explicitly mentioned.

PASSReviewer 2· 95% conf

Reporting is transparent: methods are detailed, the trial is registered, limitations are discussed, conclusions are proportional, and funding/COI are disclosed.

Evidence

“(Funded by GSK; SWIFT-1 and SWIFT-2 ClinicalTrials.gov numbers, NCT04719832 and NCT04718103.)”

AbstractFind in source

paraphrase[Discussion, paragraph 4]

“A further limitation of these trials is that SWIFT-1 was initiated during the coronavirus disease 2019 pandemic, which potentially had an effect on the overall rate of exacerbations...”

“Supported by GSK. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.”

End of main textFind in source

Registered (2 IDs: ClinicalTrials.gov). No reporting guideline cited.

Broken references and links

None found · partly checked

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.

Checked 31 references by DOI: 1 verified — 30 no DOI (shown, not verified).

Copyediting

4 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 4 minor suggestions below.

4 copyedit issues flagged: mostly typo, consistency, clarity.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is robust and methodologically sound. An informed reader should weigh the minor reporting gaps (data availability, statistical software, informed consent) as transparency issues, not validity threats. No erratum is warranted based on the verified statistics or citation checks.

1.
HIGHdata code
Replace the vague data sharing statement in the main text with a concrete description of the access mechanism (e.g., via GSK's data sharing portal or Vivli) and conditions.
The current statement does not specify how readers can access the data, which is a transparency gap for a data-driven clinical trial.
2.
HIGHstatistics
Name the statistical software and version (e.g., SAS 9.4) in the Statistical Analysis section.
Reproducibility requires knowing the software used for analysis; the paper only names the randomization software.
3.
MEDIUMethics
Add an explicit statement that informed consent was obtained from all participants (or describe a waiver) in the Ethics section.
Informed consent is a standard ethical requirement and its absence from the main text is a minor reporting gap.
4.
MEDIUMreporting
Explicitly state adherence to the CONSORT reporting guideline in the Methods section.
Referencing the reporting guideline improves transparency and reader confidence in the trial reporting.
5.
MEDIUMstatistics
Provide the sample-size calculation details (effect size, alpha, power) in the main text or ensure they are clearly presented in the Supplementary Appendix.
The main text only references the supplementary appendix; key parameters should be accessible to readers.
6.
MEDIUMstatistics
Clarify how outliers were handled in the statistical analysis (e.g., sensitivity analyses excluding extreme values).
The analysis population definition addresses data integrity, but explicit outlier handling is not described.
7.
LOWcopyedit
Fix the extra parenthesis in the Abstract: change '0.46 (95% confidence interval [CI]), 0.36 to 0.58)' to '0.46 (95% CI, 0.36 to 0.58)'.
Typographical error in the abstract could confuse readers.
8.
LOWcopyedit
Fix the typo in the Results, Subgroup Analyses: change '0.58 (95% CI, 0.43 for 0.78)' to '0.58 (95% CI, 0.43 to 0.78)'.
Incorrect preposition in the CI range is a typographical error.
9.
LOWcopyedit
Clarify the Table 2 footnote about the pooled analysis handling of SWIFT-1's low event count for hospitalization/ED exacerbations.
The footnote explains the omission but could be clearer about the pooled analysis methodology.

Full text (47,126 chars)Analyzed: Aug 16, 2026

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Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.

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DOI

10.1056/NEJMoa2406673

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Record fingerprint

b15435b57fa6cc28d3036839672e7eeb9ab9f685b1c79f46d458eee78e7d5f4e

Verify via API

Issued Aug 16, 2026Engine 7.39.0

Alpha1 assesses methodological rigor, not the importance of the findings. See how we calibrate →

Kaimen Rigor review

Kaimen Rigor reviewed

4.75 / 5

Strong — minor issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

ReportingData & code availability partially met−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Not verified in this report

The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 32 reported means were read, and their group size is not stated where the values are printed (this source has no machine-readable table structure). These checks need the count the mean was averaged over, so none was performed.
Declared data/code links were not checked for liveness or content.

Findings by category

01ArithmeticNone found 02OverreachNone found 03AuthenticityNone found 104DisclosureReporting gaps 05AvailabilityNone found · partly checked 06Copyedit4 minor suggestions

Numerical inconsistencies

None found

Checked — nothing surfaced.

Recomputed 4 tests: 4 consistent, 0 inconsistent; 4 via agent-written checks.

Overstated conclusions

None found

Checked — nothing surfaced.

4 major claims checked against the paper's own evidence: all adequately supported.

Efficacy claim is anchored to an adequate endpoint and a meaningful effect.

Data authenticity concerns

None found

Checked — nothing surfaced.

Reporting gaps

1 finding · worst medium

Data/code availability incompleteAssessed

Eight Dimensions7 pass · 1 warn

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise with extensive prior work and a logical rationale for the study.

Evidence

paraphrase[Introduction, paragraph 1-3]

paraphrase[Introduction, paragraph 4]

“Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5, which potentially enables effective 6-month dosing intervals for patients with asthma.”

absence[Introduction]

Limitations of prior work are not explicitly discussed as such.

PASSReviewer 2· 95% conf

The paper clearly establishes the scientific premise by citing prior work on interleukin-5 biology, anti-IL-5 therapies, and the rationale for depemokimab's ultra-long-acting design.

Evidence

paraphrase[Introduction, paragraphs 1-3]

paraphrase[Introduction, paragraph 4]

“Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5, which potentially enables effective 6-month dosing intervals for patients with asthma.”

paraphrase[Discussion, paragraph 3]

Sub-criteria

controlsADEQUATE

power analysisINADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The trial design is rigorous with adequate randomization, blinding, and prespecified analysis populations.

Evidence

paraphrase[Methods, Treatments and Randomization]

“The randomization schedule was generated with the use of RandAll NG software and was performed by means of interactive-response technology with a block size of six.”

“Trial staff members, patients, and investigators were unaware of trial-group assignments.”

MethodsFind in source

paraphrase[Methods, Statistical Analysis]

“Additional details about the statistical models, sample-size determination, interim analyses, handling of missing data, and pooled analysis are provided in the Supplementary Appendix.”

PASSReviewer 2· 95% conf

The study design is rigorous: randomized, double-blind, placebo-controlled, with adequate randomization, blinding, and pre-specified inclusion/exclusion criteria.

Evidence

paraphrase[Methods, Treatments and Randomization]

“The randomization schedule was generated with the use of RandAll NG software and was performed by means of interactive-response technology with a block size of six.”

“Trial staff members, patients, and investigators were unaware of trial-group assignments.”

MethodsFind in source

paraphrase[Methods, Patients]

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Demographic and clinical characteristics are well reported, including sex, age, and key disease characteristics.

Evidence

“Female sex — no. (%) 144 (58) 79 (60) 160 (63) 81 (63)”

Table 1Find in source

“Distribution — no. (%) 12–17 yr 3 (1) 5 (4) 12 (5) 10 (8)”

Table 1Find in source

PASSReviewer 2· 95% conf

Demographic and clinical characteristics are well-reported, including age, sex, race, eosinophil counts, lung function, and comorbidities.

Evidence

“Female sex — no. (%) 144 (58) 79 (60) 160 (63) 81 (63)”

Table 1Find in source

“Age Mean 54.1±13.8 53.6±14.9 53.6±16.0 51.2±16.6”

Table 1Find in source

“Peripheral-blood eosinophil count — no. (%) ≥150 cells/μl at screening 224 (90) 123 (93) 219 (87) 118 (92)”

Table 1Find in source

Sub-criteria

iacuc statementN/A

informed consentINADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Ethics approval and consent are adequately reported.

Evidence

“The institutional review board or ethics committee at each site approved the trial protocol (available at NEJM.org) and any other relevant documents.”

MethodsFind in source

paraphrase[Methods, Trial Design and Oversight]

absence[Methods]

Informed consent is not explicitly described in the main text.

PASSReviewer 2· 95% conf

Ethical approvals are adequately reported: the trials were conducted in accordance with the Declaration of Helsinki and ICH-GCP, with IRB/ethics committee approval at each site.

Evidence

“The institutional review board or ethics committee at each site approved the trial protocol (available at NEJM.org) and any other relevant documents.”

MethodsFind in source

paraphrase[Methods, Trial Design and Oversight]

absence[Methods, Trial Design and Oversight]

Informed consent is not explicitly mentioned.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational product (depemokimab) is adequately identified, and statistical software is named.

Evidence

“Patients underwent randomization in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg) or placebo subcutaneously at week 0 and week 26, in addition to standard care.”

MethodsFind in source

“The randomization schedule was generated with the use of RandAll NG software”

MethodsFind in source

PASSReviewer 2· 95% conf

The investigational product (depemokimab) is identified with dose and regimen; placebo is described; software tools are identified.

Evidence

“Patients underwent randomization in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg) or placebo subcutaneously at week 0 and week 26, in addition to standard care.”

MethodsFind in source

“The randomization schedule was generated with the use of RandAll NG software”

MethodsFind in source

absence[Methods, Statistical Analysis]

Statistical software is not identified in the main text.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedNOT REPORTED

assumptions verifiedINADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical methods are appropriate and well-described, with exact p-values and confidence intervals for primary and key secondary endpoints.

Evidence

paraphrase[Methods, Statistical Analysis]

paraphrase[Results, Primary End Point]

“for a rate ratio of 0.42 (95% CI, 0.30 to 0.59) (P<0.001) in SWIFT-1”

absence[Methods, Statistical Analysis]

Statistical software for analysis is not named.

PASSReviewer 2· 95% conf

Statistical methods are well-described: negative binomial model for the primary endpoint, hierarchical testing for multiplicity, and exact p-values reported for primary endpoints.

Evidence

paraphrase[Methods, Statistical Analysis]

“We analyzed the primary end point using a generalized linear model that assumed a negative binomial distribution with covariates of trial group, baseline dose of inhaled glucocorticoids (medium or high), exacerbation history (2, 3, or ≥4 events), geographic region, and baseline prebronchodilator percent of the predicted FEV1 with an offset of loge(total number of years in the trials).”

paraphrase[Results, Primary End Point]

“In SWIFT-1, the annualized rate of exacerbations over 52 weeks was significantly lower... (P<0.001)... In SWIFT-2... (P<0.001).”

“Rate ratio (95% CI) 0.42 (0.30 to 0.59)”

Table 2Find in source

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositNOT REPORTED

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

A data sharing statement is mentioned but not detailed in the main text; no repository or accession numbers are provided.

Evidence

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

End of articleFind in source

WARNReviewer 2· 90% conf

A data sharing statement is mentioned but not detailed in the main text; no repository deposit or code sharing is reported.

Evidence

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

ReferencesFind in source

absence[Throughout paper]

No repository deposit is mentioned.

absence[Throughout paper]

No code sharing is mentioned.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The manuscript is transparent with trial registration, detailed methods, and discussion of limitations.

Evidence

“SWIFT-1 and SWIFT-2 ClinicalTrials.gov numbers, NCT04719832 and NCT04718103.”

AbstractFind in source

paraphrase[Discussion]

absence[Methods]

Reporting guideline is not explicitly mentioned.

PASSReviewer 2· 95% conf

Reporting is transparent: methods are detailed, the trial is registered, limitations are discussed, conclusions are proportional, and funding/COI are disclosed.

Evidence

“(Funded by GSK; SWIFT-1 and SWIFT-2 ClinicalTrials.gov numbers, NCT04719832 and NCT04718103.)”

AbstractFind in source

paraphrase[Discussion, paragraph 4]

“A further limitation of these trials is that SWIFT-1 was initiated during the coronavirus disease 2019 pandemic, which potentially had an effect on the overall rate of exacerbations...”

“Supported by GSK. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.”

End of main textFind in source

Registered (2 IDs: ClinicalTrials.gov). No reporting guideline cited.

Broken references and links

None found · partly checked

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.

Checked 31 references by DOI: 1 verified — 30 no DOI (shown, not verified).

Copyediting

4 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 4 minor suggestions below.

4 copyedit issues flagged: mostly typo, consistency, clarity.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
HIGHdata code
Replace the vague data sharing statement in the main text with a concrete description of the access mechanism (e.g., via GSK's data sharing portal or Vivli) and conditions.
The current statement does not specify how readers can access the data, which is a transparency gap for a data-driven clinical trial.
2.
HIGHstatistics
Name the statistical software and version (e.g., SAS 9.4) in the Statistical Analysis section.
Reproducibility requires knowing the software used for analysis; the paper only names the randomization software.
3.
MEDIUMethics
Add an explicit statement that informed consent was obtained from all participants (or describe a waiver) in the Ethics section.
Informed consent is a standard ethical requirement and its absence from the main text is a minor reporting gap.
4.
MEDIUMreporting
Explicitly state adherence to the CONSORT reporting guideline in the Methods section.
Referencing the reporting guideline improves transparency and reader confidence in the trial reporting.
5.
MEDIUMstatistics
Provide the sample-size calculation details (effect size, alpha, power) in the main text or ensure they are clearly presented in the Supplementary Appendix.
The main text only references the supplementary appendix; key parameters should be accessible to readers.
6.
MEDIUMstatistics
Clarify how outliers were handled in the statistical analysis (e.g., sensitivity analyses excluding extreme values).
The analysis population definition addresses data integrity, but explicit outlier handling is not described.
7.
LOWcopyedit
Fix the extra parenthesis in the Abstract: change '0.46 (95% confidence interval [CI]), 0.36 to 0.58)' to '0.46 (95% CI, 0.36 to 0.58)'.
Typographical error in the abstract could confuse readers.
8.
LOWcopyedit
Fix the typo in the Results, Subgroup Analyses: change '0.58 (95% CI, 0.43 for 0.78)' to '0.58 (95% CI, 0.43 to 0.78)'.
Incorrect preposition in the CI range is a typographical error.
9.
LOWcopyedit
Clarify the Table 2 footnote about the pooled analysis handling of SWIFT-1's low event count for hospitalization/ED exacerbations.
The footnote explains the omission but could be clearer about the pooled analysis methodology.

Full text (47,126 chars)Analyzed: Aug 16, 2026