Low concentration atropine eye drops and progression of myopia in children: multicentre placebo controlled, double masked, randomised trial in the UK (CHAMP-UK).
Azuara-Blanco A, Logan NS, McConnell E, Kearney S, Kirk G, Jones S, McDowell C, Murphy L, O'Hanlon G, McFarland M, Painter S, Muthusamy B, Nabili S, Preston J, Flitcroft I, Loughman J, Mackey D, Lee S, Dahlmann-Noor A, Congdon N, Hogg RE, Hammond CJ, Saunders K, Allen PM, Strang N, Clarke M
- DOI
- 10.1136/bmj-2025-086698
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- 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/9df7d526-6b07-4e74-a820-c5d799daf938 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern ×3−1.5★
- ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
- ClaimsTreatment effect not shown to be clinically meaningful−0.5★
- ReportingData & code availability partially met−0.25★
- No data or code availability links were detected to verify.
- 01Efficacy rests on an unvalidated surrogate endpoint
The primary outcome is spherical equivalent refractive error (SER), a surrogate for myopia progression. The paper does not demonstrate target engagement at the tested dose (no PK/PD data) and does not cite validated evidence linking SER to the clinical outcome of myopia-related visual impairment. The claim of efficacy rests on this surrogate without establishing a validated surrogate-to-clinical-outcome link.
“The primary outcome was spherical equivalent refractive error of both eyes measured by autorefractor under cycloplegia after two years.”
- 02Treatment effect not shown to be clinically meaningful
The reported effect size is a mean difference of 0.33 D in SER, which is small relative to the normal range of myopia progression and lacks an anchor to a minimal clinically important difference. The paper acknowledges the effect is small and does not provide a clinically meaningful threshold for this difference.
“The results of the CHAMP-UK trial indicate that atropine 0.01% eye drops were well tolerated and reduced the rate of myopia progression in children in a UK population, although the effect was small.”
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-conducted and well-reported randomised controlled trial with rigorous design, clear ethical approvals, and appropriate statistical methods. The main weakness is the incomplete data availability statement and lack of code sharing, which limits reproducibility. Minor copyedit issues (typos in tables) should be corrected.
Both reviewers independently scored all eight dimensions and agreed on every status; no divergence to reconcile. The statistics verification recomputed 5 tests, all consistent, but coverage is limited to tests with test statistics/CI; other reported statistics were not machine-verified. The citation check found no retracted or unresolved references.
Numerical inconsistencies
1 finding · worst lowValues 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 5 tests: 5 consistent, 0 inconsistent; 5 via agent-written checks.
- CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1Primary outcome mean difference (ITT) p-value from CI
“mean difference 0.33 D, 95% confidence interval (CI) 0.17 to 0.49 D, P<0.001”
Taken as given: The CI is a 95% confidence interval for the mean difference.; The estimate is 0.33 and the CI is 0.17 to 0.49.; The p-value is two-sided.Method: Recomputed p-value from the estimate and 95% CI using the normal approximation.How we recomputed it: pCI(0.33, 0.17, 0.49, 0) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1Axial length mean difference (ITT) p-value from CI
“mean difference 0.14 mm (95% CI 0.07 to 0.21, P<0.001)”
Taken as given: The CI is a 95% confidence interval for the mean difference.; The estimate is 0.14 and the CI is 0.07 to 0.21.; The p-value is two-sided.Method: Recomputed p-value from the estimate and 95% CI using the normal approximation.How we recomputed it: pCI(0.14, 0.07, 0.21, 0) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2Primary outcome mean difference and CI from GEE
“mean difference 0.33 D, 95% confidence interval (CI) 0.17 to 0.49 D, P<0.001”
Taken as given: The estimate is 0.33 and the 95% CI is 0.17 to 0.49.; The CI is two-sided at 95%.; The estimate is on a linear scale (not log).Method: Recomputed p-value from the estimate and 95% CI using the normal approximation.How we recomputed it: pCI(0.33, 0.17, 0.49, 0) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2Axial length mean difference and CI from GEE
“mean difference 0.14 mm (95% CI 0.07 to 0.21, P<0.001)”
Taken as given: The estimate is 0.14 and the 95% CI is 0.07 to 0.21.; The CI is two-sided at 95%.; The estimate is on a linear scale (not log).Method: Recomputed p-value from the estimate and 95% CI using the normal approximation.How we recomputed it: pCI(0.14, 0.07, 0.21, 0) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2Pupil diameter mean difference and CI from GEE
“pupil diameter, which was greater in the atropine group (0.36 mm, 95% CI 0.17, 0.55, P<0.001)”
Taken as given: The estimate is 0.36 and the 95% CI is 0.17 to 0.55.; The CI is two-sided at 95%.; The estimate is on a linear scale (not log).Method: Recomputed p-value from the estimate and 95% CI using the normal approximation.How we recomputed it: pCI(0.36, 0.17, 0.55, 0)
- lowinternal contradictionIn Table 5, the per protocol analysis for severity of myopia lists '3.00 D or more' without a minus sign, inconsistent with the intention-to-treat row and the definition of severity.
Severity of myopia: | 3.00 D or more | −0.43 (0.65); n=41 | −0.74 (0.60); n=24 | 0.27 (−0.11 to 0.65) | 0.65
Table 5reviewer’s wording - lowinternal contradictionTable 1 reports White ethnicity as 136 (701) for the atropine group, which is an impossible percentage (701%). This appears to be a typo for 71%.
“White | 136 (701) | 71 (73) | 207 (72)”
Table 1Find in source - lowinternal contradictionIn Table 5, per protocol analysis, severity of myopia subgroup is labeled '3.00 D or more' instead of '−3.00 D or more'.
Severity of myopia: | 3.00 D or more | −0.43 (0.65); n=41 | −0.74 (0.60); n=24 | 0.27 (−0.11 to 0.65) | 0.65
Table 5reviewer’s wording
Overstated conclusions
3 findings · worst highConclusions 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.
- Efficacy rests on an unvalidated surrogate endpointAssessed
- Treatment effect not shown to be clinically meaningfulAssessed
- Conclusions only partially backed by the presented evidenceAssessed
6 major claims checked against the paper's own evidence: 2 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.
- partialReviewer 1The findings suggest that a low concentration atropine eye drop product would be a worthwhile addition to currently available optical interventions for the treatment of myopia in children in the UK.The trial shows efficacy, but the claim of 'worthwhile addition' involves policy and cost considerations beyond the trial's scope.Evidence: Discussion and policy implications.
“The findings suggest that a low concentration atropine eye drop product would be a worthwhile addition to currently available optical interventions for the treatment of myopia in children in the UK”
What this study addsFind in source - partialReviewer 2The effect size in refractive error observed in our study is similar to other trials conducted primarily on Chinese populations evaluating low concentrations of atropine.The paper compares its effect size to the Cochrane review's pooled estimate (0.25 D) and notes similarity, but the claim of similarity to Chinese population trials is not directly evidenced with specific comparisons.Evidence: Discussion comparing to Cochrane review and other studies.
“The effect size in refractive error observed in our study is similar to other trials conducted primarily on Chinese populations evaluating low concentrations of atropine.”
DiscussionFind in source - supportedReviewers 1, 2Low concentration atropine (0.01%) eye drops significantly reduced progression of myopia compared with placebo in children in the UK.The primary outcome showed a statistically significant mean difference of 0.33 D (95% CI 0.17 to 0.49, P<0.001), supporting the claim.Evidence: Primary outcome result in abstract and results section.
“Low concentration atropine (0.01%) eye drops significantly reduced progression of myopia and were well tolerated compared with placebo in children in the UK.”
AbstractFind in source - supportedReviewers 1, 2Atropine eye drops were well tolerated compared with placebo.No differences in adverse events or tolerability measures were found, and no serious adverse events were related to treatment.Evidence: Results section on adverse events and tolerability.
“no differences in frequency of adverse events or in tolerability measures. No serious adverse events were related to the trial drugs.”
AbstractFind in source - supportedReviewers 1, 2Changes in central axial length were significantly less in the atropine group versus placebo group.The secondary outcome showed a mean difference of 0.14 mm (95% CI 0.07 to 0.21, P<0.001), supporting the claim.Evidence: Secondary outcome result in abstract and results section.
“Changes in central axial length were significantly less in the atropine group versus placebo group: mean difference 0.14 mm (95% CI 0.07 to 0.21, P<0.001).”
AbstractFind in source - supportedReviewers 1, 2Prespecified subgroup analyses did not show differences according to age, ethnicity, sex, or severity of myopia.Subgroup analyses showed no statistically significant interaction terms, supporting the claim.Evidence: Table 5 and results section.
“Prespecified subgroup analyses did not show differences according to age, ethnicity, sex, or severity of myopia.”
AbstractFind in source
Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.
- INADEQUATESurrogate endpointThe primary outcome is spherical equivalent refractive error (SER), a surrogate for myopia progression. The paper does not demonstrate target engagement at the tested dose (no PK/PD data) and does not cite validated evidence linking SER to the clinical outcome of myopia-related visual impairment. The claim of efficacy rests on this surrogate without establishing a validated surrogate-to-clinical-outcome link.
“The primary outcome was spherical equivalent refractive error of both eyes measured by autorefractor under cycloplegia after two years.”
- INADEQUATEEffect sizeThe reported effect size is a mean difference of 0.33 D in SER, which is small relative to the normal range of myopia progression and lacks an anchor to a minimal clinically important difference. The paper acknowledges the effect is small and does not provide a clinically meaningful threshold for this difference.
“The results of the CHAMP-UK trial indicate that atropine 0.01% eye drops were well tolerated and reduced the rate of myopia progression in children in a UK population, although the effect was small.”
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 a Cochrane review and multiple studies on atropine for myopia, acknowledging uncertainties and gaps in European populations. The rationale for the trial is clearly linked to the need for effective myopia control in the UK. The paper explicitly discusses limitations of previous studies, such as small sample sizes and lack of objective adherence measures, and addresses them in the current design.
“A recent Cochrane review found that high concentration atropine (≥0.5%) may be the most effective treatment option, but the side effects (photophobia, blurred vision at near reading distance, and allergic reactions) render it unsuitable for routine clinical interventions to control myopia.”
“In the CHAMP-UK (Childhood Atropine for Myopia Progression in the UK) study we evaluated the efficacy, safety, and mechanism of action of low concentration atropine (0.01%) in UK children with myopia aged 6 to 12 years.”
“Limitations of previously published studies include smaller sample sizes and a lack of an objective measure of eye drop use, with typically calendar review and parental report used to record adherence to eye drop use.”
“A recent Cochrane review found that high concentration atropine (≥0.5%) may be the most effective treatment option, but the side effects (photophobia, blurred vision at near reading distance, and allergic reactions) render it unsuitable for routine clinical interventions to control myopia.”
“In the CHAMP-UK (Childhood Atropine for Myopia Progression in the UK) study we evaluated the efficacy, safety, and mechanism of action of low concentration atropine (0.01%) in UK children with myopia aged 6 to 12 years.”
“Limitations of previously published studies include smaller sample sizes and a lack of an objective measure of eye drop use, with typically calendar review and parental report used to record adherence to eye drop use.”
Randomization was computer-generated using a minimisation algorithm, with allocation concealed. Blinding was double-masked for participants and investigators. A detailed sample size calculation was provided. Inclusion/exclusion criteria were pre-specified. The analysis population (ITT and per-protocol) and missing data handling were defined. Controls (placebo) were appropriate. Independent replication is not applicable for a single pivotal trial.
“Randomisation (2:1) was computer generated using a minimisation algorithm to ensure balanced allocation of participants across the two treatment groups.”
“Investigators (chief, principal, and co-investigators), study monitors, and study participants were all masked throughout the study.”
“With a standard deviation (SD) of 0.7, an intraclass correlation coefficient between the two eyes of 0.9, and a variation inflation factor of 1.9, we determined that we would need 228 participants (456 eyes).”
“Randomisation (2:1) was computer generated using a minimisation algorithm to ensure balanced allocation of participants across the two treatment groups.”
“Investigators (chief, principal, and co-investigators), study monitors, and study participants were all masked throughout the study.”
“Considering a dropout rate of 15% and that 10% of recruited children could be Chinese, we increased the number required to a total of 289 participants: 193 in the atropine group and 96 in the placebo group, to detect this difference in the non-Chinese UK population with 90% power.”
Sex is reported for all participants (56% girls). Age, weight, and height are reported in Table 1. Demographics including ethnicity are detailed. Since both sexes are enrolled, sex_justified is not applicable. Species/strain and housing conditions are not applicable for a human trial.
“161 (56%) were girls”
“Mean (SD) age (years) | 9.3 (1.7) | 9.3 (1.7) | 9.3 (1.7)”
“White | 136 (701) | 71 (73) | 207 (72)”
“161 (56%) were girls”
“Mean (SD) age (years) | 9.3 (1.7) | 9.3 (1.7) | 9.3 (1.7)”
“White | 136 (701) | 71 (73) | 207 (72)”
The study was approved by the Office for Research Ethics Committees Northern Ireland (reference 18/NI/0164). Informed consent is implied through the recruitment process ('After parental consent had been obtained'). Regulatory compliance is stated via adherence to the European Clinical Trials Directive and Good Clinical Practice.
“CHAMP-UK (Childhood Atropine for Myopia Progression in the UK) was reviewed and approved by the Office for Research Ethics Committees Northern Ireland (reference 18/NI/0164).”
“After parental consent had been obtained, children were screened and, if eligible, enrolled and randomised.”
“Serious adverse events related to the use of the study drugs in the trial were reported in accordance with the guidance from the European Clinical Trials Directive 2001/20/EC”
“CHAMP-UK (Childhood Atropine for Myopia Progression in the UK) was reviewed and approved by the Office for Research Ethics Committees Northern Ireland (reference 18/NI/0164).”
“After parental consent had been obtained, children were screened and, if eligible, enrolled and randomised.”
“Serious adverse events related to the use of the study drugs in the trial were reported in accordance with the guidance from the European Clinical Trials Directive 2001/20/EC”
The study drug is identified as preserved atropine sulfate 0.01% eye drops, developed and supplied by Stockport Pharmaceuticals. The placebo is described with the same preservative and pH. Statistical software (Stata 15.1) is identified. Other bench resources are not applicable as this is a clinical trial.
“The intervention group was assigned to receive preserved atropine sulfate 0.01% eye drops once daily at bedtime in both eyes for two years.”
“The study drug was developed and supplied by Stockport Pharmaceuticals”
“Analyses were performed with Stata Statistical Software, version 15.1 (StataCorp, College Station, TX).”
“The intervention group was assigned to receive preserved atropine sulfate 0.01% eye drops once daily at bedtime in both eyes for two years.”
“Each site used the same type of autorefractor throughout the study (Grand Seiko Binocular Auto-refractor/Keratometer WR-5100 K, WAM-5500 or Shin-Nippon Accuref K-900; Grand Seiko, Hiroshima, Japan).”
“Analyses were performed with Stata Statistical Software, version 15.1 (StataCorp, College Station, TX).”
The primary analysis used GEE with 95% CIs, and p-values are reported exactly (e.g., P<0.001). Effect sizes are reported with CIs. Statistical software is identified. Data presentation includes per-group n and dispersion. Mathematical plausibility checks were not possible for all values due to continuous outcomes and model-based estimates, but no obvious errors were found.
“We compared the atropine and control groups using generalised estimating equations and 95% confidence intervals (CIs) to allow for the correlation between eyes within a participant.”
“mean difference 0.33 D, 95% confidence interval (CI) 0.17 to 0.49 D, P<0.001”
“mean difference 0.14 mm (95% CI 0.07 to 0.21, P<0.001)”
“We compared the atropine and control groups using generalised estimating equations and 95% confidence intervals (CIs) to allow for the correlation between eyes within a participant.”
“mean difference 0.33 D, 95% confidence interval (CI) 0.17 to 0.49 D, P<0.001”
“Analyses were performed with Stata Statistical Software, version 15.1 (StataCorp, College Station, TX).”
The data availability statement is incomplete in the provided text (cut off). It likely states 'available on reasonable request' but lacks a concrete mechanism. No repository deposit or accession numbers are mentioned. Code sharing is not applicable as no custom code is described.
“The code used to analyse the data in the paper ca”
“The code used to analyse the data in the paper ca”
The trial is registered (ISRCTN99883695, NCT03690089). Methods are detailed enough for replication. Limitations are discussed. Conclusions are proportional to the evidence. Funding and competing interests are declared. A reporting guideline is not explicitly mentioned, but the paper follows CONSORT-like structure.
“Trial registration ISRCTN registry ISRCTN99883695, ClinicalTrials.gov NCT03690089”
“A limitation of the current study is that as it is an efficacy trial, with adherence assessed by MEMS device, the generalisability of these findings to non-trial settings without the advantage of objective monitoring of adherence is unknown.”
“Funding: National Institute for Health and Care Research Efficacy and Mechanism Evaluation (project 15/48/59).”
“Trial registration ISRCTN registry ISRCTN99883695, ClinicalTrials.gov NCT03690089”
“A limitation of the current study is that as it is an efficacy trial, with adherence assessed by MEMS device, the generalisability of these findings to non-trial settings without the advantage of objective monitoring of adherence is unknown.”
“Funding: National Institute for Health and Care Research Efficacy and Mechanism Evaluation (project 15/48/59).”
Registered (2 IDs: ClinicalTrials.gov, ISRCTN). No reporting guideline cited.
Broken references and links
None found · partly checkedReferences 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 51 references by DOI: 47 verified — 4 no DOI (shown, not verified).
- NO DOISPECS 2030No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAtropine reduces experimental myopia and eye enlargement via a nonaccommodative mechanismNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe Hong Kong progressive lens myopia control study: study design and main findingsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPriority 10 Sight Loss and Vision PSP Refractive Error and Motility. Can we precent myopia?No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
Copyediting
5 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 5 minor suggestions below.
5 copyedit issues flagged: mostly consistency, typo, clarity.
- MINORtypoTable 1, Ethnicity row“136 (701)”→ Should be 136 (71)Percentage appears to be a typo.
- MINORconsistencyTable 5, Per protocol analysis, Severity of myopia“3.00 D or more”→ Should be −3.00 D or moreMissing minus sign.
- MINORconsistencyTable 5, Per protocol analysis, Sex row“−0.35 (0.630; n=48”→ Should be −0.35 (0.63); n=48Missing closing parenthesis.
- MINORclarityData availability statement“The code used to analyse the data in the paper ca”→ Complete the sentence.Statement is truncated.
- MINORconsistencyTable 5, Per protocol analysis, Sex: Boy“−0.35 (0.630; n=48”→ Should be −0.35 (0.63); n=48Missing closing parenthesis.
The published work is robust and trustworthy, with minor reporting gaps. An informed reader should weigh the incomplete data availability statement and the absence of code sharing as limitations to reproducibility. The copyedit typos (e.g., 701% in Table 1) are minor but should be corrected in any erratum.
- 1.HIGHcopyeditCorrect the impossible percentage in Table 1, Ethnicity row: change '136 (701)' to '136 (71)'.A percentage of 701% is an obvious typo that undermines data credibility.
- 2.HIGHcopyeditFix the missing minus sign in Table 5, Per protocol analysis, Severity of myopia: change '3.00 D or more' to '−3.00 D or more'.The severity threshold is negative in myopia; the missing minus sign is an internal inconsistency.
- 3.HIGHdata codeComplete the data availability statement in the manuscript to specify a concrete access route, such as a repository or a data access committee, with conditions and timeframe.The current statement is truncated and does not meet clinical trial data-sharing standards.
- 4.HIGHdata codeDeposit de-identified aggregate data or a data dictionary in a public repository (e.g., Dryad, Zenodo) and provide a persistent identifier.Enhances transparency and reproducibility while respecting participant privacy.
- 5.HIGHdata codeProvide the analysis code in a public repository (e.g., GitHub, Zenodo) with a DOI, as the current statement is truncated and no code link is given.Code sharing is essential for reproducibility of the statistical analyses.
- 6.MEDIUMreportingAdd a statement referencing the CONSORT reporting guideline and provide the checklist as supplementary material.CONSORT is expected for randomised controlled trials and improves reporting completeness.
- 7.MEDIUMcopyeditFix the missing closing parenthesis in Table 5, Per protocol analysis, Sex row: change '−0.35 (0.630; n=48' to '−0.35 (0.63); n=48'.The current formatting is inconsistent and may confuse readers.
- 8.LOWotherClarify in the data availability statement that individual participant data are not publicly available due to privacy, and describe the process for requesting access.Provides transparency about data access limitations.
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.
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.
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.