Navigational Bronchoscopy or Transthoracic Needle Biopsy for Lung Nodules.
Lentz RJ, Frederick-Dyer K, Planz VB, Koyama T, Aboudara MC, Avasarala SK, Casey JD, Cheng GZ, D'Haese PF, Duke JD, Grogan EL, Hoopman TC, Johnson J, Katsis JM, Kurman JS, Low SW, Mahmood K, Rickman OB, Roller L, Salmon C, Shojaee S, Swanner B, Wahidi MM, Walston C, Silvestri GA, Yarmus L, Rahman NM, Maldonado F, Interventional Pulmonary Outcomes Group
- DOI
- 10.1056/NEJMoa2414059
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-20
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How this rating was calculated
- IntegrityIntegrity concern−0.5★
- ClaimsOverstated claim−0.5★
- CitationsUnresolved reference ×2−0.5★
- StatisticsPrinted percentage does not match its own count (capped) ×3−0.25★
- ReportingData & code availability partially met−0.25★
- No data or code availability links were detected to verify.
- 01Printed percentage does not match its own count
77.6% does not match the reported count 88/113
“88 (77.6%)”
Secondary outcome: Diagnostic yield, tr… - 02Printed percentage does not match its own count
72.1% does not match the reported count 169/234
“The overall prevalence of malignancy through 12 months was 72.1%”
ResultsFind in source - 03Printed percentage does not match its own count
74.8% does not match the reported count 91/121
“74.8% and 69.1% in bronchoscopy and transthoracic biopsy arms, respectively”
ResultsFind in source - 04Conclusion reaches beyond the evidence
Navigational bronchoscopy should be the procedure of choice for biopsy of indeterminate lung nodules that appear technically amenable to both approaches.
“The results of this trial suggest that navigational bronchoscopy, with similar diagnostic accuracy to transthoracic biopsy but fewer complications, should be the procedure of choice for biopsy of indeterminate lung nodules that appear technically amenable to…”
Discussion ¶1Find in source
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.
This is a well-designed and well-reported randomized noninferiority trial with clear scientific premise, rigorous methods, and transparent reporting. The main weaknesses are the lack of a data availability statement and minor inconsistencies in reported safety percentages.
Both reviewers agreed on study type (interventional) and all dimension statuses. The statistics verification component recomputed only a subset of tests (5 total, 3 inconsistent) and cannot confirm overall statistical correctness; the copyedit flagged a discrepancy in pneumothorax percentages between the abstract and Table 3.
Numerical inconsistencies
2 findings · worst mediumValues 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.
- Printed percentage does not match its own countRecomputed
- Internal contradictions in the reported numbersAssessed
Recomputed 1 test: 1 consistent, 0 inconsistent; 1 via agent-written checks. 3 printed percentages that do not match their own count.
- PERCENT77.6% does not match the reported count 88/113
“88 (77.6%)”
Secondary outcome: Diagnostic yield, tr… - PERCENT72.1% does not match the reported count 169/234
“The overall prevalence of malignancy through 12 months was 72.1%”
ResultsFind in source - PERCENT74.8% does not match the reported count 91/121
“74.8% and 69.1% in bronchoscopy and transthoracic biopsy arms, respectively”
ResultsFind in source
- CONSISTENTreported p = .003 · recomputed p = .011Reviewer 1Noninferiority p-value for primary outcome
“absolute difference, 5.4 percentage points; 95% Confidence Interval [CI], −6.5 to 17.2; p = 0.003 for noninferiority”
Taken as given: The absolute difference is 5.4 percentage points.; The noninferiority margin is 10 percentage points.; The standard error is derived from the 95% CI width: (17.2 - (-6.5)) / (2*1.96) ≈ 6.05 percentage points.; The test is one-sided for noninferiority.Method: One-sided z-test: z = (diff - margin) / SE, p = 1 - normalCdf(z).How we recomputed it: pZ((0.054 - (-0.1)) / 0.0605) - UNCOMPUTABLEreported p = .170 · recomputed p = .372Reviewers 1, 2Superiority p-value for primary outcome
“absolute difference, 5.4 percentage points; 95% Confidence Interval [CI], −6.5 to 17.2; p = 0.17 for superiority”
Taken as given: The absolute difference is 5.4 percentage points.; The standard error is derived from the 95% CI width: (17.2 - (-6.5)) / (2*1.96) ≈ 6.05 percentage points.; The test is two-sided for superiority.Method: Two-sided z-test: z = diff / SE, p = 2*(1 - normalCdf(z)).How we recomputed it: 2*(1 - normalCdf(0.054 / 0.0605))
- lowinternal contradictionAbstract reports pneumothorax rates as 3.4% and 34.8%, while Table 3 reports 3.3% and 28.3% for the same event.
“Pneumothorax occurred in four patients (3.4%) in the navigational bronchoscopy group and 32 patients (34.8%) in the transthoracic biopsy group”
Table 3Find in source
Overstated conclusions
1 finding · worst mediumConclusions 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.
- Conclusions overstated beyond the evidenceAssessed
5 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).
- overstatedReviewers 1, 2Navigational bronchoscopy should be the procedure of choice for biopsy of indeterminate lung nodules that appear technically amenable to both approaches.The trial shows noninferiority and fewer complications, but the claim of 'procedure of choice' may be too strong given the unblinded design and potential differences in expertise.Evidence: Noninferiority and safety results, but no cost-effectiveness or patient-centered outcomes.
“The results of this trial suggest that navigational bronchoscopy, with similar diagnostic accuracy to transthoracic biopsy but fewer complications, should be the procedure of choice for biopsy of indeterminate lung nodules that appear technically amenable to both approaches.”
Discussion ¶1Find in source - supportedReviewer 1The diagnostic accuracy of navigational bronchoscopy was noninferior to that of transthoracic biopsy.The primary outcome analysis shows noninferiority with p=0.003, and sensitivity analyses corroborate.Evidence: Primary outcome: 94/119 (79.0%) vs 81/110 (73.6%), difference 5.4% (95% CI -6.5 to 17.2), p=0.003 for noninferiority.
“The diagnostic accuracy of navigational bronchoscopy was noninferior to that of transthoracic biopsy in patients with pulmonary nodules 10–30 mm.”
AbstractFind in source - supportedReviewer 1Complications were less common during bronchoscopy.Safety outcomes show significantly fewer complications in the bronchoscopy group.Evidence: Any complication: 6/121 (5.0%) vs 33/113 (29.2%), difference 24.2% (95% CI 15.0-35.6).
“A procedural complication occurred in 6 of 121 cases (5.0%) in the navigational bronchoscopy group compared to 33 of 113 cases (29.2%) in the transthoracic biopsy group”
ResultsFind in source - supportedReviewer 2Navigational bronchoscopy is noninferior to transthoracic biopsy for diagnostic accuracy.The primary outcome shows noninferiority with p=0.003, and sensitivity analyses corroborate.Evidence: Primary outcome: 79.0% vs 73.6%, difference 5.4% (95% CI -6.5 to 17.2), p=0.003 for noninferiority.
“The diagnostic accuracy of navigational bronchoscopy was noninferior to that of transthoracic biopsy in patients with pulmonary nodules 10–30 mm.”
AbstractFind in source - supportedReviewer 2Navigational bronchoscopy leads to fewer complications than transthoracic biopsy.Complication rates are significantly lower in the bronchoscopy group, as reported in safety outcomes.Evidence: Any complication 5.0% vs 29.2%, pneumothorax 3.3% vs 28.3%.
“A procedural complication occurred in 6 of 121 cases (5.0%) in the navigational bronchoscopy group compared to 33 of 113 cases (29.2%) in the transthoracic biopsy group”
ResultsFind in source
Efficacy claim is anchored to an adequate endpoint and a meaningful effect.
- ADEQUATESurrogate endpointThe primary endpoint is diagnostic accuracy, defined as the proportion of biopsies providing a specific diagnosis confirmed through 12 months of clinical follow-up. This is a clinical outcome directly relevant to patient management, not a surrogate biomarker. The trial compares two diagnostic procedures, and the endpoint reflects the clinical utility of the procedure in establishing a diagnosis.
“The primary endpoint was diagnostic accuracy, defined as the proportion of biopsies providing a specific diagnosis confirmed through 12 months of clinical follow-up.”
- ADEQUATEEffect sizeThe primary outcome shows navigational bronchoscopy achieved 79.0% diagnostic accuracy versus 73.6% for transthoracic biopsy, with a difference of 5.4 percentage points (95% CI, -6.5 to 17.2). The noninferiority margin was 10 percentage points, and the p-value for noninferiority was 0.003, indicating statistical support for noninferiority. The effect size is anchored to a prespecified noninferiority margin, which provides clinical meaningfulness.
“absolute difference, 5.4 percentage points; 95% confidence interval, −6.5 to 17.2 (p = 0.003 for noninferiority; p = 0.17 for superiority)”
Data authenticity concerns
None foundAn 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 mediumRequired 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
The introduction cites prior studies and meta-analyses on both biopsy modalities, acknowledges their limitations (single-arm studies, selection bias), and states the hypothesis. The rationale for the noninferiority design is clear.
“Diagnostic accuracy estimates for both modalities have been derived from single-arm studies at high risk for selection, referral, and publication biases.”
“No randomized trials have compared navigational bronchoscopy to transthoracic biopsy.”
“We hypothesized the diagnostic accuracy of navigational bronchoscopy would be non-inferior to that of transthoracic biopsy.”
“Diagnostic accuracy estimates for both modalities have been derived from single-arm studies at high risk for selection, referral, and publication biases.”
“We hypothesized the diagnostic accuracy of navigational bronchoscopy would be non-inferior to that of transthoracic biopsy.”
“Patients were screened for eligibility when referred for bronchoscopy or transthoracic biopsy, mitigating the risk of referral bias.”
Randomization method (permuted blocks, stratified) and unit (patient) are described. Blinding of outcome assessors is stated, though the trial is unblinded for participants/proceduralists. Power analysis is provided. Inclusion/exclusion criteria are pre-specified. Outlier handling is addressed through sensitivity analyses and handling of canceled procedures.
“Fully eligible patients were randomly allocated 1:1 to navigational bronchoscopy or transthoracic biopsy, in permuted blocks of variable size, stratified by nodule location (middle third or outer third of the lung), pre-test probability of malignancy (≤50% or >50% , ), and study site, using a cloud-based randomization tool.”
“Outcome assessors were blinded to group assignment.”
“Diagnostic accuracy of TTNB was assessed at 90%, with noninferiority margin of 10%, one-sided type I error rate of 5%, and power of 80%, yielding a sample of n=112 per group, increased 15% to account for attrition to total n=258.”
“Fully eligible patients were randomly allocated 1:1 to navigational bronchoscopy or transthoracic biopsy, in permuted blocks of variable size, stratified by nodule location (middle third or outer third of the lung), pre-test probability of malignancy (≤50% or >50% , ), and study site, using a cloud-based randomization tool.”
“Outcome assessors were blinded to group assignment.”
“Diagnostic accuracy of TTNB was assessed at 90%, with noninferiority margin of 10%, one-sided type I error rate of 5%, and power of 80%, yielding a sample of n=112 per group, increased 15% to account for attrition to total n=258.”
Sex is reported for both groups. Age and health status (comorbidities) are reported. Demographics include race and ethnicity. Species/strain and housing are not applicable for a human trial.
“Female sex | 57 (47%) | 56 (50%)”
“Age | 66.0 (62.0–72.0) | 68.0 (61.0–74.0)”
“Age | 66.0 (62.0–72.0) | 68.0 (61.0–74.0) | | Female sex | 57 (47%) | 56 (50%)”
“COPD | 49 (40%) | 48 (42%)”
The trial was approved by the IRB at the coordinating center and all enrolling sites. Informed consent is mentioned. Regulatory compliance is implied through IRB approval and trial registration.
“It was approved by the institutional review board at the Clinical Coordinating Center, Vanderbilt University Medical Center, and all enrolling sites”
“After provision of informed consent, chest imaging was centrally reviewed”
“Trial registration : ClinicalTrials.gov (https://ClinicalTrials.gov) NCT04250194”
“It was approved by the institutional review board at the Clinical Coordinating Center, Vanderbilt University Medical Center, and all enrolling sites”
“After provision of informed consent, chest imaging was centrally reviewed”
The bronchoscopy platform is named with manufacturer (Medtronic). The transthoracic biopsy procedure is described but no specific device is named. Statistical software (R version 4.4) is identified. No antibodies, cell lines, or mycoplasma testing are applicable.
“Patients assigned to bronchoscopy underwent electromagnetic navigational bronchoscopy with integrated digital tomosynthesis (ILLUMISITE™ Fluoroscopic Navigation Platform, Medtronic, Minneapolis, MN, USA).”
“All the analyses were performed with the use of R software, version 4.4.”
“Patients assigned to bronchoscopy underwent electromagnetic navigational bronchoscopy with integrated digital tomosynthesis (ILLUMISITE™ Fluoroscopic Navigation Platform, Medtronic, Minneapolis, MN, USA).”
“All the analyses were performed with the use of R software, version 4.4.”
Tests are named (z-test for noninferiority, logistic regression for subgroups). Exact p-values are reported for primary and secondary outcomes. Effect sizes with confidence intervals are provided. Software is identified. Data presentation includes per-group n and confidence intervals. Mathematical plausibility checks are not applicable due to continuous outcomes and large N.
“Noninferiority of bronchoscopy was tested using a z-test with noninferiority margin of 10 percentage points”
“p = 0.003 for noninferiority; p = 0.17 for superiority”
“absolute difference, 5.4 percentage points; 95% Confidence Interval [CI], −6.5 to 17.2”
“Noninferiority of bronchoscopy was tested using a z-test with noninferiority margin of 10 percentage points”
“p = 0.003 for noninferiority; p = 0.17 for superiority”
“absolute difference, 5.4 percentage points; 95% Confidence Interval [CI], −6.5 to 17.2”
The paper mentions that the protocol and statistical analysis plan were published, but does not provide a clear data availability statement with a repository or access mechanism. No code is shared.
“The protocol and statistical analysis plan (see ) were published before the conclusion of enrollment.”
Trial registration is provided. Limitations are discussed in detail. Conclusions are proportional to the evidence. Funding and COI are disclosed. Methods are detailed enough for replication.
“Trial registration : ClinicalTrials.gov (https://ClinicalTrials.gov) NCT04250194”
“This study also has several limitations.”
“This work is supported by a research grant from Medtronic (Fridley, Minnesota, USA) and the Pierre Massion Directorship in Pulmonary Medicine (F.M.).”
“Trial registration : ClinicalTrials.gov (https://ClinicalTrials.gov) NCT04250194”
“This study also has several limitations.”
“This work is supported by a research grant from Medtronic (Fridley, Minnesota, USA) and the Pierre Massion Directorship in Pulmonary Medicine (F.M.).”
Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.
Broken references and links
1 finding · worst lowReferences 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.
- References not resolvable to a published paperRecomputed
Checked 26 references by DOI: 22 verified — 2 DOI unresolved, 2 no DOI (shown, not verified).
- UNRESOLVED10.3978/j.issn.2072-1439.2015.12.16Transthoracic needle biopsy of the lungCited DOI does not resolve to any Crossref record.
- UNRESOLVED10.1059/0003-4819-155-3-201108020-00003Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge recordsCited DOI does not resolve to any Crossref record.
- NO DOINavigational Bronchoscopy vs CT Scan-Guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules: Protocol and Rationale for the Navigation Endoscopy to Reach Indeterminate Lung Nodules vs Transthoracic Needle Aspiration, a Randomized Controlled Study Multicenter Randomized TrialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOINavigational Bronchoscopy versus Computed Tomography-guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules: protocol and rationale for the VERITAS multicenter randomized trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
Copyediting
4 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 4 minor suggestions below.
4 copyedit issues flagged: mostly consistency, clarity.
- MINORconsistencyAbstract, Results“Pneumothorax occurred in four patients (3.4%) in the navigational bronchoscopy group and 32 patients (34.8%) in the transthoracic biopsy group”→ Ensure percentages match those in Table 3 (3.3% and 28.3%).Abstract percentages differ from Table 3; likely due to different denominators.
- MINORconsistencyResults, Safety Outcomes“Pneumothorax was most common, occurring in 4 patients (3.3%) in the navigational bronchoscopy group and 32 patients (28.3%) in the transthoracic biopsy group”→ Verify consistency with abstract percentages.Abstract reports 3.4% and 34.8% for the same event.
- MINORclarityMethods, Statistical Analysis“Diagnostic accuracy of TTNB was assessed at 90%”→ Clarify that this is the assumed diagnostic accuracy for sample size calculation.Could be misinterpreted as a study result.
- MINORconsistencyResults, Safety Outcomes“Pneumothorax was most common, occurring in 4 patients (3.3%) in the navigational bronchoscopy group and 32 patients (28.3%) in the transthoracic biopsy group”→ Verify consistency with abstract.Table 3 shows 3.3% and 28.3%, abstract shows 3.4% and 34.8%.
The published work is robust overall, but readers should weigh the missing data availability statement and the internal inconsistency in pneumothorax rates. An erratum or correction may be warranted for the percentage discrepancy, and the authors should consider providing data access to enhance reproducibility.
- 1.HIGHdata codeAdd a data availability statement in the Methods or a dedicated section specifying how de-identified participant data can be accessed (e.g., via a data access committee or repository).The paper currently lacks a data availability statement, which is a reporting gap for a data-driven trial and a common requirement for journals.
- 2.HIGHcopyeditReconcile the pneumothorax percentages between the Abstract (3.4% and 34.8%) and Table 3/Results (3.3% and 28.3%) and correct the erroneous values.The internal contradiction in reported safety outcomes undermines data integrity and could mislead readers.
- 3.HIGHreportingTemper the conclusion that navigational bronchoscopy 'should be the procedure of choice' to reflect that it was noninferior with fewer complications in this trial, given the unblinded design and potential expertise differences.The claim is overstated relative to the evidence and could be seen as over-claiming by reviewers or readers.
- 4.MEDIUMdata codeDeposit the statistical analysis code in a public repository (e.g., GitHub, Zenodo) with a DOI to enhance reproducibility.Sharing code allows independent verification of the analyses and is increasingly expected for clinical trials.
- 5.MEDIUMreportingExplicitly state adherence to CONSORT guidelines in the Methods or provide a completed CONSORT checklist as supplementary material.Reporting guideline adherence is not mentioned, and explicit compliance improves transparency and completeness.
- 6.MEDIUMotherSpecify the transthoracic biopsy device and needle types used, including manufacturer and gauge, in the Methods.The transthoracic biopsy procedure is described without identifying the specific device, which is a resource identification gap.
- 7.MEDIUMethicsClarify the regulatory compliance framework (e.g., Declaration of Helsinki) in the ethics section.Reviewer 2 noted that regulatory compliance is implied but not explicitly named, which is a minor reporting gap.
- 8.MEDIUMstatisticsClarify in the Methods that 'Diagnostic accuracy of TTNB was assessed at 90%' is the assumed value for sample size calculation, not a study result.The copyedit flagged this as potentially misinterpreted by readers.
- 9.MEDIUMotherVerify or correct the two references not found in any registry: 'Transthoracic needle biopsy of the lung' (DOI 10.3978/j.issn.2072-1439.2015.12.16) and 'Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records' (DOI 10.1059/0003-4819-155-3-201108020-00003).References that cannot be located in Crossref/OpenAlex may be fabricated or have incorrect DOIs, which is an integrity concern.
- 10.LOWdata codeProvide a link or DOI to the published protocol and statistical analysis plan in the manuscript text.The current mention is vague and does not give readers a clear access mechanism.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
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