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Kaimen Rigor review

External trigeminal nerve stimulation in youth with ADHD: a randomized, sham-controlled, phase 2b trial.

Conti AA, Bozhilova N, Eraydin IE, Stringer D, Johansson L, Marhenke R, Bilbow A, El Masri S, Hyde J, Giaroli G, Liang H, Fiori F, Mehta MA, Santosh P, Carter B, Cortese S, Rubia K

DOI: 10.1038/s41591-025-04075-x
Record issued: 2026-08-10
Engine: 7.29.0
Exported: 2026-09-22

Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/c27e6aef-23a3-42eb-9772-94430cdefc04 is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

2.75 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern ×3−1.5★
ReportingStatistical analysis not met−0.5★
CitationsUnresolved reference−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.29.0Source: full text

Not verified in this report

The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run on this paper: the pass that reads its reported means did not complete. No reported mean was checked for arithmetic impossibility.
No data or code availability links were detected to verify.

Biggest issues

01Statistical reporting inadequate
highDisclosurereviewer-assessedFull detail
Statistical tests, effect sizes with CIs, exact p-values, and software are reported, but the paper contains demonstrable arithmetic/percent reporting errors, warranting a fail on mathematical plausibility.
“Left/mixed handed | 15 (20) | 23 (30.6) | 38 (50.6)”
Table 1Find in source

Findings by category

101ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions 03AuthenticityNone found 104DisclosureReporting gaps 105AvailabilityBroken references and links · partly checked 106CopyeditCopyediting

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 is a well-designed RCT with strong reporting transparency, but it contains demonstrable arithmetic errors in Table 1 and the Results section that undermine its statistical integrity. The key strengths are the rigorous study design, ethical approvals, and data availability, while the errors warrant a correction and informed reader scrutiny.

This audit evaluated eight dimensions of research integrity using two independent automated reviews and a copyedit pass. All dimensions were applicable. The two reviewers agreed on seven dimensions (pass) but disagreed on statistical analysis; the fail status was adopted based on concrete evidence of arithmetic errors confirmed by the copyedit and integrity checks.

Numerical inconsistencies

1 finding · worst low

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.

Internal contradictions in the reported numbersAssessed

Recomputed 7 tests: 7 consistent, 0 inconsistent; 7 via agent-written checks.

Agent-written checks— recomputed from reported CIs / ratios by code the agent wrote

CONSISTENTreported p = .622 · recomputed p = .622Reviewer 1
Recompute the two-sided p-value for the primary outcome adjusted mean difference from its 95% CI.
“estimated adjusted mean difference = 0.83; 95% confidence interval: –2.47 to 4.13; P = 0.622”
Find in source
Taken as given: the aMD is a linear mean difference, not a log/ratio, so log=0; the 95% CI is two-sided, giving SE = (4.13 - (-2.47)) / (2*1.96); the test statistic z = aMD/SE follows a standard normal distribution
Method: Back-calculated SE from the two-sided 95% CI and computed the two-sided normal p = 2*(1-normalCdf(|0.83/SE|)).
How we recomputed it: pCI(0.83, -2.47, 4.13, 0)
CONSISTENTreported p = .049 · recomputed p = .049Reviewer 1
Recompute the two-sided p-value for the MEWS week-4 aMD from its 95% CI.
“MEWS total score (child rated)... -2.17 (-4.33, -0.01) | 0.049 *”
Find in source
Taken as given: the aMD is a linear mean difference, not a log/ratio, so log=0; the 95% CI is two-sided, giving SE = (-0.01 - (-4.33)) / (2*1.96); the test statistic z = aMD/SE follows a standard normal distribution
Method: Back-calculated SE from the two-sided 95% CI and computed the two-sided normal p = 2*(1-normalCdf(|-2.17/SE|)).
How we recomputed it: pCI(-2.17, -4.33, -0.01, 0)
CONSISTENTreported p = .622 · recomputed p = .622Reviewer 2
Primary outcome ADHD-RS week 4 aMD
“At the week 4 primary endpoint, no significant difference was observed between groups (estimated adjusted mean difference (aMD) = 0.83; 95% confidence interval: –2.47 to 4.13; P = 0.622; Cohen’s d = 0.09)”
Find in source
Taken as given: The CI is two-sided at 95%; The estimate is a mean difference (log=0); The p-value is from a two-sided z-test
Method: Two-tailed p computed from estimate and 95% CI using normal approximation.
How we recomputed it: pCI(0.83, -2.47, 4.13, 0)
CONSISTENTreported p = .049 · recomputed p = .049Reviewer 2
MEWS total score week 4 aMD
“An exception was the Mind Excessively Wandering Scale (MEWS) total score at week 4, which showed a statistically significant group difference (aMD = −2.17; 95% confidence interval: –4.33 to –0.01; P = 0.049; Cohen’s d = −0.27)”
Find in source
Taken as given: The CI is two-sided at 95%; The estimate is a mean difference (log=0); The p-value is from a two-sided z-test
Method: Two-tailed p computed from estimate and 95% CI using normal approximation.
How we recomputed it: pCI(-2.17, -4.33, -0.01, 0)
CONSISTENTreported p = .845 · recomputed p = .844Reviewer 2
ADHD-RS total score at 6-month follow-up aMD
“No significant between-group difference was observed for the ADHD-RS total score at 6-month follow-up (aMD = −0.29; 95% confidence interval: –3.17 to 2.59; P = 0.845; Cohen’s d = −0.03)”
Find in source
Taken as given: The CI is two-sided at 95%; The estimate is a mean difference (log=0); The p-value is from a two-sided z-test
Method: Two-tailed p computed from estimate and 95% CI using normal approximation.
How we recomputed it: pCI(-0.29, -3.17, 2.59, 0)
CONSISTENTreported p = .381 · recomputed p = .379Reviewer 2
CACE analysis primary outcome week 4
“The prespecified complier average causal effect (CACE) analysis showed no significant group difference for the ADHD-RS total score at the week 4 primary endpoint in participants who would comply with the assigned treatment (mean difference = 1.12; 95% confidence interval: –1.38 to 3.61; P = 0.381; Cohen’s d = 0.12)”
Find in source
Taken as given: The CI is two-sided at 95%; The estimate is a mean difference (log=0); The p-value is from a two-sided z-test
Method: Two-tailed p computed from estimate and 95% CI using normal approximation.
How we recomputed it: pCI(1.12, -1.38, 3.61, 0)
CONSISTENTreported p = .755 · recomputed p = .755Reviewer 2
Subgroup analysis off-medication/naive participants week 4
“The prespecified subgroup analysis of participants who were off medication/medication-naive at baseline found no significant group difference for the ADHD-RS total score at week 4 (mean difference = 0.68; 95% confidence interval: −3.59 to 4.95; P = 0.755; Cohen’s d = 0.07)”
Find in source
Taken as given: The CI is two-sided at 95%; The estimate is a mean difference (log=0); The p-value is from a two-sided z-test
Method: Two-tailed p computed from estimate and 95% CI using normal approximation.
How we recomputed it: pCI(0.68, -3.59, 4.95, 0)

lowinternal contradiction
Table 1 reports the overall left/mixed-handed percentage as 50.6%, but 38/150 = 25.3%; the printed value looks like the sum of the two arm percentages (20 + 30.6).
“Left/mixed handed | 15 (20) | 23 (30.6) | 38 (50.6)”
Table 1Find in source
lowinternal contradiction
Table 1 overall handedness percentages sum to 125.3% (112 (74.7) + 38 (50.6)); 38/150 = 25.3%, not 50.6%.
“Left/mixed handed | 15 (20) | 23 (30.6) | 38 (50.6)”
Table 1Find in source
lowinternal contradiction
Adherence threshold percentage for real TNS is reported as 8% for 7/75 participants, but 7/75 = 9.3%.
Ten participants (real TNS (n = 7, (8%)); sham TNS (n = 3, (4%))) did not meet the predefined adherence threshold
Resultsreviewer’s wording

Overstated conclusions

1 finding · worst low

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.

Conclusions only partially backed by the presented evidenceAssessed

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

partialReviewer 1
Real TNS improved mind-wandering (MEWS) at week 4.
The MEWS difference was statistically significant (P = 0.049) but the paper itself cautions about multiple testing and a post hoc adolescent-only analysis showed no effect, so the claim is appropriately hedged.
Evidence: MEWS week-4 aMD = –2.17 (95% CI –4.33 to –0.01, P = 0.049); post hoc 14–18-year analysis aMD = 0.28 (95% CI –3.65 to 4.21, P = 0.89).
“The only positive finding of real versus sham TNS was an improvement in the MEWS mind-wandering scale after 4 weeks.”
DiscussionFind in source
partialReviewer 1
The placebo response to TNS is larger than the typical placebo response in medication trials.
This is an interpretive claim based on the observed ~10-point sham improvement (d = 0.9) compared to a meta-analytic medication-placebo effect, acknowledged as one of several possible explanations (including regression to the mean and baseline inflation).
Evidence: Sham group improved by 10 points on the ADHD-RS (d = 0.9) vs. pooled parent-rating effect of 0.4 in a meta-analysis of 27 medication RCTs.
Our findings, hence, extend previous evidence in the literature, that the placebo response related to a neurotechnology such as TNS is larger than the typical placebo response in medication trials.
Discussionreviewer’s wording
partialReviewer 2
The MEWS improvement may represent a clinically meaningful benefit.
A significant MEWS difference at week 4 (P=0.049) is presented, but the authors themselves note the context of 16 negative measures, possible type I error, and a null post hoc analysis in older adolescents, so the claim is appropriately hedged but not fully supported.
Evidence: MEWS result and subsequent caveats in Discussion.
“this may represent a clinically meaningful benefit of the treatment”
DiscussionFind in source
supportedReviewers 1, 2
TNS is safe but does not demonstrate clinical efficacy for pediatric ADHD.
The primary and secondary analyses show no significant difference on the primary outcome and most secondary outcomes, with no serious adverse events, so the conclusion follows directly from the data.
Evidence: Primary outcome aMD = 0.83 (95% CI –2.47 to 4.13, P = 0.622); 6-month aMD = –0.29 (95% CI –3.17 to 2.59, P = 0.845); no serious adverse events.
“In conclusion, TNS is a safe intervention but does not demonstrate clinical efficacy for pediatric ADHD.”
DiscussionFind in source
supportedReviewer 1
The improved sham condition produced successful blinding throughout the trial.
Blinding-guess data at weeks 1 and 4 show high 'don't know' rates and balanced guesses across groups, supporting the claim.
Evidence: At week 4, 'don't know' responses: 34.9% of children, 33.6% of parents, 53.0% of researchers; guesses balanced across groups.
Blinding remained successful for most participants at week 4, with 'don't know' responses still reported by 34.9% of children, 33.6% of parents and 53.0% of researchers.
Resultsreviewer’s wording
supportedReviewer 2
No significant differential treatment effect on ADHD symptoms was observed at the primary endpoint.
The primary endpoint analysis reported aMD=0.83 with 95% CI crossing zero and P=0.622, directly supporting the claim.
Evidence: Primary outcome result in Results and Table 2.
“At the week 4 primary endpoint, no significant difference was observed between groups (estimated adjusted mean difference (aMD) = 0.83; 95% confidence interval: –2.47 to 4.13; P = 0.622; Cohen’s d = 0.09)”
ResultsFind in source
supportedReviewer 2
TNS is safe and well tolerated.
No serious adverse events, similar side-effect rates across groups, and high acceptability support the claim.
Evidence: Safety section and extended data tables.
“No serious adverse events, serious ADEs or unanticipated serious ADEs were reported, and no participants withdrew from the trial due to adverse events.”
ResultsFind in source
supportedReviewer 2
The findings contrast with the positive pilot RCT and highlight the importance of robust sham control.
The pilot's positive result is contrasted with the current null result, and the improved sham design is described as a likely explanation, which is a reasonable interpretation of the presented data.
Evidence: Discussion comparison with McGough et al. and sham design description.
“This conflicts with the positive findings from the previous pilot RCT of TNS in children with ADHD”
DiscussionFind in source

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 high

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.

Statistical reporting inadequateAssessed

Eight Dimensions7 pass · 1 fail

Prior work (McGough 2019 pilot RCT, Westwood meta-analysis) is cited with strengths and weaknesses acknowledged — the pilot was small, restricted to 8–12-year-olds, and its sham condition delivered no stimulation. The rationale links TNS neurobiology (locus coeruleus/noradrenaline) to ADHD deficits, and the hypothesis follows directly. Limitations of prior research are explicitly addressed (multicenter design, adolescent inclusion, 6-month follow-up, improved sham).

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The study clearly establishes its scientific foundation, citing the pilot RCT that informed FDA clearance, a prior TNS meta-analysis, and the gaps the trial addresses.

Evidence

paraphrase[Main, paragraph 2]

“The evidence for FDA clearance was based on a pilot double-blind RCT in 62 unmedicated children, showing that 4 weeks of nightly real versus sham TNS significantly decreased parent-rated ADHD symptoms... with medium effect size (Cohen's d = 0.5).”

paraphrase[Main, paragraph 2]

“Furthermore, the pilot study did not assess effects beyond 4 weeks and was limited to very young children aged 8−12 years.”

“We hypothesized that 4 weeks of nightly real versus sham TNS in children and adolescents with ADHD would improve core symptoms, as measured by parent-rated scales (primary outcome).”

Main, paragraph 2Find in source

PASSReviewer 2· 95% conf

The paper establishes a strong scientific premise by citing prior research, including the pilot RCT that led to FDA clearance, and explicitly identifies the limitations that the current trial addresses.

Evidence

“The evidence for FDA clearance was based on a pilot double-blind RCT in 62 unmedicated children”

Main, paragraph 3Find in source

“Furthermore, the pilot study did not assess effects beyond 4 weeks and was limited to very young children aged 8−12 years”

Main, paragraph 3Find in source

“Sensory inputs from the trigeminal nerve fibers activate the locus coeruleus, raphe nuclei and nucleus tractus solitarius”

Main, paragraph 2Find in source

Randomization used minimization by sex, medication status, site and age via a validated web-based system; unit is the individual participant. Blinding extended to participants, parents, researchers and analysts, with a blinding questionnaire administered at weeks 1 and 4. Sample size was calculated (128 for 90% power at effect size 0.5, inflated to 150 for 15% attrition). Pre-specified inclusion/exclusion criteria and ITT plus prespecified CACE analysis population are clearly defined. Replicate distinction, wet-lab controls and independent replication are not applicable for a single human RCT.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Core methodological design is rigorous: minimization randomization with stated method, double-blind with blinding checks, a priori power analysis, and detailed inclusion/exclusion criteria.

Evidence

paraphrase[Methods, Randomization and blinding]

“Randomization was done by minimization by sex (male/female), medication status (on medication, off medication/naive), site (London, Southampton) and age (8–13.5 years, 13.6−19 years) using a validated, online, web-based system from King's Clinical Trials unit.”

paraphrase[Methods, Randomization and blinding]

“Participants, parents/carers, postdoctoral research associates, principal investigator, co-investigators and analysts were blinded to treatment group except for the trial manager (L.J.) and trial manager assistants...”

paraphrase[Methods, Sample size justification]

“The estimated sample size of 128 participants (64:64) was calculated using a baseline to posttreatment correlation of 0.5, 90% power, 5% type I error and an anticipated effect size of 0.5 for a reduction in ADHD symptoms at 4 weeks.”

PASSReviewer 2· 95% conf

Randomization, blinding, power calculation, and inclusion/exclusion criteria are all reported in detail, with a prespecified statistical analysis plan.

Evidence

MethodsFind in source

Sex at birth is reported (97 males/53 females) in Table 1, age and weight are reported (mean age 12.6 (2.8); weight in Table 3), and health status includes DSM-5 ADHD diagnosis, presentations, and comorbidities. Demographics include ethnicity, handedness, deprivation index, medication status and site. Species/strain and housing are not applicable to a human trial.

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

Sex, age, weight, health status and detailed demographics are reported for the mixed-sex cohort; sex justification is not applicable since both sexes were enrolled.

Evidence

“150 (97 males, 64.7%) were enrolled in the study and included in the intention-to-treat (ITT) analysis”

ResultsFind in source

“Participants had a mean age (s.d.) of 12.6 years (2.8)”

Table 3Find in source

“White | 61 (81.3) | 58 (77.3) | 119 (79.3)”

Table 1Find in source

PASSReviewer 2· 90% conf

Sex, age, weight, health status, and demographics are reported in detail for the human study population.

Evidence

“150 (97 males, 64.7%) were enrolled”

Table 1Find in source

“Age (mean, s.d.) | 12.6 (2.8) | 12.6 (2.8) | 12.6 (2.8)”

Table 1Find in source

“Weight (kg) | 46.7 (13.8) [75] | 47.4 (14.4) [75]”

Table 3Find in source

The trial was approved by the West Midlands–Solihull NHS Research Ethics Committee (Ref21:/WN/0169; IRAS 299703) and MHRA (CI/2022/0003/GB). Written informed consent/assent is described (165 provided written informed consent; both digital and written consents/assents). Regulatory compliance is stated by name (1975 Declaration of Helsinki) and CONSORT reporting. IACUC is not applicable to a human trial.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Named REC and MHRA approvals with protocol/IRAS numbers, documented written informed consent/assent, and Declaration of Helsinki compliance are all reported.

Evidence

“The trial was approved by the West Midlands–Solihull NHS Research Ethics Committee (REC; Ref21:/WN/0169; IRAS: 299703) and the Medicines and Healthcare products Regulatory Agency (MHRA; Ref: CI/2022/0003/GB).”

MethodsFind in source

“Children/adolescents and their parents/carers provided both digital and written informed consents/assents”

MethodsFind in source

“It was conducted in accordance with the 1975 Declaration of Helsinki”

MethodsFind in source

PASSReviewer 2· 95% conf

The trial was approved by a named research ethics committee and the MHRA, with informed consent/assent documented and Declaration of Helsinki compliance stated.

Evidence

MethodsFind in source

“Children/adolescents and their parents/carers provided both digital and written informed consents/assents”

MethodsFind in source

“It was conducted in accordance with the 1975 Declaration of Helsinki”

MethodsFind in source

As a device trial, the investigational product is scored under reagents_identified: the Monarch TNS System (NeuroSigma, Inc.) is named with manufacturer and detailed real/sham settings (frequency, pulse width, duty cycle). Statistical software is identified (Stata 18, StataCorp LLC, version 18.0), along with other tools (MACRO EDC 4.15.0.116, Tobii Pro Lab 1.207, Empatica E4 2.0.3). Antibodies, cell lines, mycoplasma and organisms are not applicable (no wet-lab assays). Custom code was not used.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational device (Monarch TNS System, NeuroSigma) is named with manufacturer and full stimulation settings, and analysis software is versioned; bench-science resource criteria are not applicable.

Evidence

“Real and sham TNS was performed with the Monarch TNS System (NeuroSigma, Inc.).”

MethodsFind in source

“Analyses were performed in Stata 18 (StataCorp LLC, version 18.0)”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The investigational device is identified with manufacturer and settings, and statistical and data-collection software is named with versions.

Evidence

“Real and sham TNS was performed with the Monarch TNS System (NeuroSigma, Inc.).”

MethodsFind in source

“Analyses were performed in Stata 18 (StataCorp LLC, version 18.0)”

Statistical analysisFind in source

“Study data were entered and managed using the MACRO Electronic Data Capture system (version 4.15.0.116).”

MethodsFind in source

The analysis uses mixed models with named z-tests, reports exact p-values and 95% CIs, and identifies Stata 18. However, Table 1 reports overall handedness percentages that sum to 125.3% (112 (74.7) + 38 (50.6)), which is impossible; 38/150 = 25.3%. Additionally, the Results state '7 (8%)' for 7/75 real TNS participants, which should be 9.3%. These are demonstrable reporting errors.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityFAIL

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical tests are named, exact p-values and effect sizes with 95% CIs are reported, software is identified, and data presentation follows the clinical-trial idiom; arithmetic plausibility is not applicable for these large-N continuous outcomes.

Evidence

paraphrase[Table 2 footnote]

“P values were calculated using two-sided z-tests from the linear mixed models as outlined in methods.”

paraphrase[Results, Primary outcome; Table 3]

“estimated adjusted mean difference (aMD) = 0.83; 95% confidence interval: –2.47 to 4.13; P = 0.622; Cohen's d = 0.09”

“Analyses were performed in Stata 18 (StataCorp LLC, version 18.0)”

Statistical analysisFind in source

FAILReviewer 2· 80% conf

Statistical tests, effect sizes with CIs, exact p-values, and software are reported, but the paper contains demonstrable arithmetic/percent reporting errors, warranting a fail on mathematical plausibility.

Evidence

“Left/mixed handed | 15 (20) | 23 (30.6) | 38 (50.6)”

Table 1Find in source

paraphrase[Results, 'Participant disposition']

“Ten participants (real TNS (n = 7, (8%)); sham TNS (n = 3, (4%))) did not meet the predefined adherence threshold”

“estimated adjusted mean difference (aMD) = 0.83; 95% confidence interval: –2.47 to 4.13; P = 0.622; Cohen’s d = 0.09”

ResultsFind in source

A data availability statement names the figshare repository with DOI 10.6084/m9.figshare.29414744.v1. Source data are included. No sequencing accession numbers are applicable. Since no custom code was generated, code sharing is not applicable.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

A concrete data-availability statement names the figshare repository with a DOI; custom-code sharing is not applicable since no custom code was generated.

Evidence

“All data supporting the findings of this study have been deposited in the figshare repository and are publicly available at 10.6084/m9.figshare.29414744.v1.”

Data availabilityFind in source

“No custom code was generated or used in this study.”

Data availabilityFind in source

PASSReviewer 2· 95% conf

Data are deposited in a public repository with a persistent DOI, and the paper states that no custom code was used.

Evidence

“All data supporting the findings of this study have been deposited in the figshare repository and are publicly available at 10.6084/m9.figshare.29414744.v1.”

Data availabilityFind in source

“No custom code was generated or used in this study.”

Data availabilityFind in source

Registration number is given (ISRCTN82129325) with date of registration. CONSORT reporting is stated and a CONSORT diagram provided. All pre-specified outcomes are reported, including null results and the not-analyzed measures (teacher ratings, C-SSRS) with reasons. Limitations are explicitly discussed (teacher-rating missingness, self-reported adherence, medication as confound, multiple testing). Conclusions are proportional — the abstract and discussion both state TNS is safe but not efficacious. Funding sources and competing interests are fully declared.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The trial is registered (ISRCTN82129325), reported per CONSORT, all outcomes including negative/null results are reported transparently, limitations are discussed, conclusions are proportional, and funding/COI statements are provided.

Evidence

paraphrase[Methods, Trial design]

“This UK multicenter... confirmatory RCT was preregistered (trial registration: ISRCTN82129325...; date of registration: 8 February 2021)... and is reported following CONSORT guidelines.”

“Teacher ratings (Conners Teacher Rating Scale short form T-S and ADHD-RS-T) were not analyzed due to high degree of missing data (80%).”

ResultsFind in source

“Limitations include a high rate of missing data on teacher ratings (80%) due to low teacher participation.”

DiscussionFind in source

PASSReviewer 2· 95% conf

The trial is registered, reported per CONSORT, includes all outcomes (including negative), discusses limitations, and provides funding and competing interests.

Evidence

“Trial registration: ISRCTN82129325 (http://www.isrctn.com/ISRCTN82129325)”

AbstractFind in source

“It was conducted in accordance with the 1975 Declaration of Helsinki and is reported following CONSORT guidelines .”

MethodsFind in source

“Limitations include a high rate of missing data on teacher ratings (80%) due to low teacher participation.”

DiscussionFind in source

Registered (1 ID: ISRCTN). Reporting guideline cited: CONSORT.

ISRCTN

ISRCTN82129325

Reporting guidelines: CONSORT

Broken references and links

1 finding · worst low

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.

References not resolvable to a published paperRecomputed

Checked 63 references by DOI: 3 verified — 1 DOI unresolved, 59 no DOI (shown, not verified).

UNRESOLVED10.6084/m9.figshare.29414744.v1
The efficacy of external trigeminal nerve stimulation (TNS) in youth with attention-deficit/hyperactivity disorder (ADHD): a multi-centre, double-blind, randomized, sham-controlled, parallel-group, phase IIb trial (ATTENS)
Cited DOI does not resolve to any Crossref record.
NO DOI
Incidence, prevalence, and global burden of ADHD from 1990 to 2019 across 204 countries: data, with critical re-analysis, from the Global Burden of Disease study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR)
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The neurocognitive profile of attention-deficit/hyperactivity disorder: a review of meta-analyses
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Evaluating vigilance deficits in ADHD: a meta-analysis of CPT performance
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Cognitive neuroscience of attention deficit hyperactivity disorder (ADHD) and its clinical translation
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Attention-deficit/hyperactivity disorder
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
ADHD medication discontinuation and persistence across the lifespan: a retrospective observational study using population-based databases
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Risk of bias and quality of evidence for treatment of ADHD with stimulant medication
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Striatal dopamine transporter alterations in ADHD: pathophysiology or adaptation to psychostimulants? A meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The effects of chronic administration of stimulant and non-stimulant medications on executive functions in ADHD: a systematic review and meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Systematic review of patients’ and parents’ preferences for ADHD treatment options and processes of care
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Neurotherapeutics for attention deficit/hyperactivity disorder (ADHD): a review
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Trigeminal nerve stimulation: a current state-of-the-art review
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Locus coeruleus: from global projection system to adaptive regulation of behavior
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Cognitive functions following trigeminal neuromodulation
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Is autonomic nervous system function atypical in attention deficit hyperactivity disorder (ADHD)? A systematic review of the evidence
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Clinical and cognitive effects of external trigeminal nerve stimulation (eTNS) in neurological and psychiatric disorders: a systematic review and meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Double-blind, sham-controlled, pilot study of trigeminal nerve stimulation for attention-deficit/hyperactivity disorder
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
ADHD Rating Scale-5 for Children and Adolescents: Checklists, Norms, and Clinical Interpretation
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Comparative meta-analyses of brain structural and functional abnormalities during cognitive control in attention-deficit/hyperactivity disorder and autism spectrum disorder
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Meta-analysis of fMRI studies of timing in attention-deficit hyperactivity disorder (ADHD)
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Structural and functional brain abnormalities in attention-deficit/hyperactivity disorder and obsessive-compulsive disorder: a comparative meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
An eight-week, open-trial, pilot feasibility study of trigeminal nerve stimulation in youth with attention-deficit/hyperactivity disorder
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Mind wandering perspective on attention-deficit/hyperactivity disorder
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The efficacy of real versus sham external trigeminal nerve stimulation (eTNS) in youth with attention-deficit/hyperactivity disorder (ADHD) over 4 weeks: a protocol for a multi-centre, double-blind, randomized, parallel-group, phase IIb study (ATTENS)
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The psychology of neurofeedback: clinical intervention even if applied placebo
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Placebo effects in randomized trials of pharmacological and neurostimulation interventions for mental disorders: an umbrella review
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Nocebo and placebo effects and their implications in psychotherapy
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Treating ADHD with suggestion: neurofeedback and placebo therapeutics
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Placebo and nocebo responses in randomised, controlled trials of medications for ADHD: a systematic review and meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Disorder-specific functional abnormalities during sustained attention in youth with attention deficit hyperactivity disorder (ADHD) and with autism
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Evidence from ‘big data’ for the default-mode hypothesis of ADHD: a mega-analysis of multiple large samples
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Does mind-wandering explain ADHD-related impairment in adolescents?
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Mind wandering (internal distractibility) in ADHD: a literature review
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Mind-wandering in children with and without ADHD
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Validation of the mind excessively wandering scale and the relationship of mind wandering to impairment in adult ADHD
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Trigeminal nerve stimulation for attention-deficit/hyperactivity disorder: cognitive and electroencephalographic predictors of treatment response
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Impact of child and informant gender on parent and teacher ratings of attention-deficit/hyperactivity disorder
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Measuring impairment when diagnosing adolescent ADHD: differentiating problems due to ADHD versus other sources
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Self-report measures of medication adherence behavior: recommendations on optimal use
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Comparative efficacy and acceptability of pharmacological, psychological, and neurostimulatory interventions for ADHD in adults: a systematic review and component network meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Neurotherapeutics for ADHD: do they work?
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Transcranial direct current stimulation (tDCS) in children with ADHD: a randomized, sham-controlled pilot study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Transcranial direct current stimulation (tDCS) combined with cognitive training in adolescent boys with ADHD: a double-blind, randomised, sham-controlled trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Noninvasive brain stimulation in children and adults with attention-deficit/hyperactivity disorder: a systematic review and meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Pharmacologic treatment of attention deficit–hyperactivity disorder
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Performance of children with attention deficit hyperactivity disorder (ADHD) on a test battery of impulsiveness
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Conners, Third Edition (Conners 3)
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The Strengths and Difficulties Questionnaire: a research note
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The Affective Reactivity Index: a concise irritability scale for clinical and research settings
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Assessment of symptoms of DSM-IV anxiety and depression in children: a revised child anxiety and depression scale
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The Sleep Disturbance Scale for Children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The Mackworth Clock Test: a computerized version
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
An introduction to multiplicity issues in clinical trials: the what, why, when and how
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

Copyediting

1 finding · worst low

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

Wording or formatting errors that need correctingAssessed

7 copyedit issues flagged (3 major): mostly consistency, typo, other.

MAJORconsistencyTable 1, Handedness row
“Left/mixed handed | 15 (20) | 23 (30.6) | 38 (50.6)”
→ Overall percentage should be 25.3% (38/150), not 50.6%.
The overall column appears to be the sum of the two arm percentages (20 + 30.6 = 50.6) rather than 38/150.
MAJORconsistencyTable 1, Handedness row
“Left/mixed handed | 15 (20) | 23 (30.6) | 38 (50.6)”
→ Change overall percentage to 25.3% (38/150) so the column sums to 100%.
Percentages across the row sum to 125.3%.
MAJORconsistencyResults, 'Participant disposition'
“Ten participants (real TNS (n = 7, (8%)); sham TNS (n = 3, (4%)))”
→ Use 9.3% for 7/75 real TNS participants.
7/75 = 9.33%, not 8%.
MINORtypoTable 3, Mackworth Vigilance Task commission errors, Week 4
“0.95 1 (0.80, 1.13)”
→ Remove the stray digit: '0.95 (0.80, 1.13)'.
A stray '1' follows the point estimate.
MINORotherMethods, Trial design
“Ref21:/WN/0169”
→ Format as 'Ref 21/WM/0169' if the committee reference is mis-capitalized.
The REC reference appears unusually formatted; verify against the approval letter.
MINORclarityDiscussion, first paragraph
“followed by 3.570 seconds without stimulation”
→ Clarify whether this is 3.5 seconds or 3.57 seconds, and ensure consistency with the Methods description.
The exact value is ambiguous.
MINORconsistencyVarious (e.g., 'Fig. and Table')
“Fig.”
→ Insert missing figure/table numbers throughout the text.
Several figure/table citations appear with blank numbers.

Kaimen Rigor Action ItemsFinal pass before journal submission

In this post-publication audit, the paper is generally robust in design and reporting, but the arithmetic errors in Table 1 and the Results section are objective reporting mistakes that should be corrected via an erratum or corrigendum. An informed reader should weigh these errors as minor data-presentation flaws that do not affect the null primary outcome, but they should be addressed for accuracy.

1.
HIGHstatistics
Correct the overall handedness percentage in Table 1 from 50.6% to 25.3% (38/150) so the column sums to 100%.
The printed percentage is arithmetically impossible (20+30.6=50.6) and must be corrected to avoid misleading readers about the sample's handedness distribution.
2.
HIGHstatistics
Correct the adherence percentage in the Results section: change 'real TNS (n = 7, (8%))' to '9.3%' (7/75 = 9.33%).
This is a demonstrable miscalculation that should be corrected in an erratum to maintain data accuracy.
3.
HIGHstatistics
Remove the stray digit '1' in Table 3, commission errors row: change '0.95 1 (0.80, 1.13)' to '0.95 (0.80, 1.13)'.
The stray digit obscures the confidence interval and is a typographical error that should be corrected.
4.
HIGHdata code
Verify that the figshare DOI (10.6084/m9.figshare.29414744.v1) resolves correctly and update the data availability statement if the repository link is non-functional; the citation check flagged this reference as not found in the registry.
A non-resolvable DOI undermines the data availability statement and could be a fabrication signal; the authors should confirm the link works or replace it with a correct DOI.
5.
HIGHreporting
Add a note in the paper (e.g., in a Corrigendum or Discussion) acknowledging the corrected percentage values and explaining the source of the errors (e.g., miscalculation of overall percentages).
Transparency about the corrections helps readers understand the extent of the errors and maintains trust in the published record.
6.
HIGHstatistics
Run a systematic consistency check on all percentage calculations in the manuscript and tables (e.g., ensure column sums to 100%, denominators match numerators).
Given the two errors found, there may be additional miscalculations; a thorough check will prevent future corrections.
7.
MEDIUMreporting
Ensure all figure and table citations in the text include the correct numbers (e.g., replace blank 'Fig.' with specific figure number).
Missing figure/table numbers reduce readability and may cause confusion during review.
8.
MEDIUMother
Clarify the stimulation duty cycle value: '3.570 seconds' should be checked for consistency with the Methods description and rounded or corrected as appropriate.
Ambiguous or inconsistent values can confuse readers about the intervention parameters.
9.
MEDIUMother
Format the REC reference consistently (e.g., 'Ref 21/WM/0169' instead of 'Ref21:/WN/0169') to match the official approval letter.
Inconsistent formatting of regulatory references may raise questions about the approval's authenticity.
10.
LOWstatistics
Consider adding a brief statement on normality/equal-variance assumptions for the mixed models, though this is less critical for large trials.
Adding this would strengthen the statistical reporting and preempt reviewer questions.
11.
LOWother
Ensure consistent decimal formatting across tables (e.g., '20' vs '20.0') for uniformity.
Inconsistent formatting can appear sloppy but does not affect data integrity.

Full text (69,675 chars)Analyzed: Aug 10, 2026

RigorReviewer 1

RigorReviewer 2

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

PreregistrationDeterministic check· no model (rule-based)

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.”

How stars are deducted

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.

The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.

The eight reporting dimensions

Scientific PremisePrior work, rationale, and how it addresses gaps.

Study Design & RigorRandomization, blinding, power, controls, replication.

Biological VariablesSex, age, species/strain, housing, demographics.

Ethical ApprovalsIRB/IACUC approval, informed consent, regulatory compliance.

Key ResourcesAntibodies, cell lines, organisms, software — identified with persistent IDs.

Statistical ReportingNamed tests, exact p-values, effect sizes, plausible summary stats.

Data & Code AvailabilityAvailability statements, repositories, accession numbers, shared code.

Reporting TransparencyMethods, registration, guidelines, outcomes, limitations, funding/COI.

Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.

This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.

External trigeminal nerve stimulation in youth with ADHD: a randomized, sham-controlled, phase 2b trial.

Conti AA, Bozhilova N, Eraydin IE, Stringer D, Johansson L, Marhenke R, Bilbow A, El Masri S, Hyde J, Giaroli G, Liang H, Fiori F, Mehta MA, Santosh P, Carter B, Cortese S, Rubia K

DOI

10.1038/s41591-025-04075-x

Record issued

2026-08-10

Engine

7.29.0

Exported

2026-09-22