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Kaimen Rigor review

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial.

Parker CC, Kynaston H, Cook AD, Clarke NW, Catton CN, Cross WR, Petersen PM, Persad RA, Pugh CA, Saad F, Logue J, Payne H, Bower LC, Brawley C, Rauchenberger M, Barkati M, Bottomley DM, Brasso K, Chung HT, Chung PWM, Conroy R, Falconer A, Ford V, Goh CL, Heath CM, James ND, Kim-Sing C, Kodavatiganti R, Malone SC, Morris SL, Nabid A, Ong AD, Raman R, Rodda S, Wells P, Worlding J, Parulekar WR, Parmar MKB, Sydes MR, RADICALS investigators

DOI: 10.1016/S0140-6736(24)00549-X
Record issued: 2026-08-10
Engine: 7.29.0
Exported: 2026-09-21

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/72dd8bba-d21c-4684-8804-347e429d1df9 is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

1.25 / 5

Critical — serious problems across many checks

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern ×5−2.5★
ReportingKey resources not met−0.5★
ReportingEthical approvals partially met−0.25★
CitationsUnresolved reference−0.25★
LinksLink inconsistent with the paper−0.25★

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

Biggest issues

01Key resources not identified
highDisclosurereviewer-assessedFull detail
The investigational products (ADT drugs) are named with dose and regimen but not by manufacturer or source. Statistical software is not identified. Neither applicable sub-criterion is adequate.
02Declared data/code link does not hold what the paper says
highAvailabilityrecomputedFull detail
Resolves to a parked / unavailable page ("Page Not Found | UCL Innovative Clinical Trials Unit") — the resource is not actually there.
“http://www.ctu.mrc.ac.uk/our_research/datasharing/application_process”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 02OverreachNone found 103AuthenticityData authenticity concerns 204DisclosureReporting gaps 205AvailabilityBroken references and links 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.

This phase 3 open-label RCT (RADICALS-HD) is methodologically strong: randomisation, power, ITT, statistical assumptions, data sharing, and transparency are all well reported. The main weaknesses are a generic ethics-approval statement with no named body or protocol number, unidentified statistical software, and several copyedit/table errors (an impossible Denmark percentage and a Table 2 sample-size discrepancy).

Three independent reviewer runs largely converged; divergences on biological variables (weight/race), key resources (manufacturer requirement), statistical analysis (table typo severity), and data code (code-sharing applicability) were resolved by weighing the evidence, with the minority views preserved in the details. N/A criteria include bench-resource checks, controls, and replication. The statistics check recomputed only 5 reported tests (4 consistent); everything else is unverified, not confirmed.

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 4 tests: 4 consistent, 0 inconsistent; 2 recomputed directly from the reported test statistics, 2 via agent-written checks.

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

CONSISTENTreported p = .029 · recomputed p = .030
Recomputed HR 0.773 (95% CI 0.612–0.975), reported p=0.029
“HR 0.773 [95% CI 0.612–0.975]; p=0.029”
Find in source
Taken as given: 0.612–0.975 is a two-sided 95% confidence interval for the HR of 0.773, not a range, an IQR, or a different interval level; the HR is a RATIO measure, so the interval is symmetric on the log scale; p=0.029 is the p for THIS estimate, not for another comparison in the same sentence
Method: back the two-tailed p out of the log-scale CI width and compare it against the printed p
How we recomputed it: pCI(0.773, 0.612, 0.975, 1)
CONSISTENTreported p = .002 · recomputed p = .003
Recomputed HR 0.634 (95% CI 0.471–0.853), reported p=0.0024
“HR 0.634 [95% CI 0.471–0.853]; p=0.0024”
Find in source
Taken as given: 0.471–0.853 is a two-sided 95% confidence interval for the HR of 0.634, not a range, an IQR, or a different interval level; the HR is a RATIO measure, so the interval is symmetric on the log scale; p=0.0024 is the p for THIS estimate, not for another comparison in the same sentence
Method: back the two-tailed p out of the log-scale CI width and compare it against the printed p
How we recomputed it: pCI(0.634, 0.471, 0.853, 1)
CONSISTENTreported p = .380 · recomputed p = .377Reviewer 1
Overall-survival p-value recomputed from the reported HR and 95% CI.
“Overall survival | Events | 111 | 100 | 0·880 (0·663–1·169) | 0·38”
Find in source
Taken as given: the CI 0·663–1·169 is a two-sided 95% interval for the hazard ratio; the HR 0·880 is the point estimate; the CI is symmetric on the log scale
Method: Two-tailed p from HR and 95% CI on the log scale.
How we recomputed it: pCI(0.880, 0.663, 1.169, 1)
UNCOMPUTABLEreported p = .025 · recomputed p = .011Reviewers 1, 2
Toxicity comparison (grade ≥3) p-value recomputed from the reported counts via Pearson chi-square.
“Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025)”
Find in source
Taken as given: 753−105=648 is the number of short-course participants without grade ≥3 toxicity; 757−142=615 is the number of long-course participants without grade ≥3 toxicity; the reported p=0·025 arises from a two-sided chi-square test on this 2×2 table
Method: Pearson chi-square test on the 2×2 table of grade ≥3 toxicity counts.
How we recomputed it: pChi2x2(105, 648, 142, 615)
CONSISTENTreported p = .380 · recomputed p = .377Reviewer 2
Overall survival HR p-value recomputed from HR and 95% CI
“Events | 111 | 100 | 0·880 (0·663–1·169) | 0·38”
Find in source
Taken as given: 0.880 is the overall survival hazard ratio and 0.663–1.169 its two-sided 95% CI; The CI is on the log-hazard scale (log=1) and the p-value is two-tailed
Method: Two-tailed p from an estimate with 95% CI on the log-ratio scale.
How we recomputed it: pCI(0.880, 0.663, 1.169, 1)

lowinternal contradiction
Table 2 labels the long-course ADT column n=743 while Table 1 and the text state n=762 for the long-course group; the smaller n appears to reflect an analysis subset, but the discrepancy is not explained in the table.
“Short-course ADT (n=761) | Long-course ADT (n=743)”
Table 2Find in source
lowinternal contradiction
Table 1 reports Denmark as '35 (95%)' — an impossible percentage regardless of denominator (35/61≈57% of short-course, 35/64≈55% of all Denmark) — almost certainly a typo for ~55%.
“Denmark | 35 (95%) | 29 (4%) | 64 (4%)”
Table 1Find in source
lowinternal contradiction
The Denmark row in Table 1 lists the short-course group as '35 (95%)', which is impossible (35 of 761 is ~4.6%); it is a typographical error for 5%.
“Denmark | 35 (95%) | 29 (4%) | 64 (4%)”
Table 1Find in source
lowinternal contradiction
Table 2 header shows the long-course ADT group as n=743, inconsistent with n=762 stated in the Abstract, Results, and Table 3.
“Long-course ADT (n=743)”
Table 2Find in source

Overstated conclusions

None found

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

Checked — nothing surfaced.

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

supportedReviewers 1, 2
Adding 24 months of ADT, compared with 6 months, improved metastasis-free survival in patients receiving postoperative radiotherapy.
The primary outcome result directly supports the claim.
Evidence: HR 0·773 (95% CI 0·612–0·975), p=0·029; 10-year MFS 78.1% vs 71.9%.
“Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy.”
AbstractFind in source
supportedReviewers 1, 2, 3
For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.
The recommendation is grounded in the MFS benefit and acknowledged toxicity trade-off.
Evidence: MFS benefit (HR 0.773) contrasted with higher grade ≥3 toxicity (19% vs 14%).
“For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.”
DiscussionFind in source
supportedReviewer 1
There was no evidence of a benefit to overall survival with long-course ADT.
The reported OS HR and CI are consistent with no detected benefit.
Evidence: HR 0·880 (95% CI 0·663–1·169), p=0·38.
“We found no evidence of a benefit to overall survival with long-course ADT.”
Results ¶5Find in source
supportedReviewer 1
This is the first trial to compare different durations of ADT with postoperative radiotherapy after radical prostatectomy.
The introduction supports that no prior trial compared ADT durations in this setting.
Evidence: Statement that only three prior phase 3 trials assessed ADT addition and none compared durations.
“To our knowledge, this is the first trial to compare different durations of ADT with postoperative radiotherapy after radical prostatectomy in prostate cancer.”
Research in context, Added value of thi…Find in source
supportedReviewer 1
The metastasis-free survival benefit should be weighed against the extended duration of adverse effects associated with ADT.
The toxicity results (higher grade ≥3 rates in long-course) directly back the trade-off claim.
Evidence: Grade 3 or higher toxicity 19% (long) vs 14% (short), p=0·025.
“This metastasis-free survival benefit should be weighed against the extended duration of the adverse effects associated with ADT.”
DiscussionFind in source
supportedReviewer 2
The metastasis-free survival benefit did not translate into an improvement in overall survival.
The overall survival result (HR 0.880, 95% CI 0.663–1.169, p=0.38) shows no statistically significant benefit, consistent with the claim.
Evidence: Overall survival HR 0.880 (0.663–1.169); p=0.38.
“We found no evidence of a benefit to overall survival with long-course ADT.”
DiscussionFind in source
supportedReviewer 2
The metastasis-free survival finding was consistent across all prespecified subgroups.
Both prespecified subgroup analyses (PSA level and Charlson Comorbidity Index) showed non-significant interaction p-values, supporting consistency.
Evidence: Interaction p=0.99 (PSA) and p=0.67 (Charlson Comorbidity Index).
“The metastasis-free survival treatment effect did not differ meaningfully in either of the two prespecified subgroup analyses, pre-radiotherapy PSA level (interaction p=0·99) or Charlson Comorbidity Index score (interaction p=0·67; ).”
Results ¶2Find in source
supportedReviewer 2
On average, 16 people need to be treated with long-course ADT for one to avoid an metastasis-free survival event within 10 years.
The NNT of ~16 is consistent with the reported absolute 10-year MFS difference of about 6% (1/0.062≈16).
Evidence: Absolute 10-year MFS difference: 78.1% − 71.9% ≈ 6%.
“these results indicate that, on average, 16 people need to be treated with long-course ADT for one of them to avoid an metastasis-free survival event within 10 years.”
Discussion ¶1Find in source
supportedReviewer 3
Long-course ADT (24 months) is more effective than short-course ADT (6 months) in terms of metastasis-free survival in patients receiving postoperative radiotherapy.
The primary outcome shows a statistically significant improvement with HR 0.773 (95% CI 0.612-0.975, p=0.029).
Evidence: Results, paragraph 2: HR 0.773, p=0.029, 10-year MFS 71.9% vs 78.1%.
“Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy.”
AbstractFind in source
supportedReviewer 3
The benefit must be weighed against extended adverse effects.
Toxicity data show higher grade 3+ adverse events with long-course ADT (19% vs 14%, p=0.025).
Evidence: Results, paragraph 6: 'Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025).'
This metastasis-free survival benefit should be weighed against the extended duration of the well-known adverse effects associated with ADT.
Abstractreviewer’s wording
supportedReviewer 3
No improvement in overall survival was observed.
The HR for overall survival is 0.880 (95% CI 0.663-1.169, p=0.38), indicating no statistically significant difference.
Evidence: Results, paragraph 5: 'We found no evidence of a benefit to overall survival with long-course ADT.'
“However, this benefit did not translate into an improvement in overall survival with a median of 9 years of follow-up.”
AbstractFind in source
supportedReviewer 3
Results are consistent with previous trials.
The discussion compares findings with RTOG 9601, GETUG-AFU 16, and RTOG 0534, noting consistency in metastasis-free survival benefit, though overall survival benefit was not replicated.
Evidence: Discussion, paragraph 2: 'These results are largely consistent with previous trials that had generated the hypothesis that long-course ADT would be more effective than short-course ADT.'
“These results are largely consistent with previous trials that had generated the hypothesis that long-course ADT would be more effective than short-course ADT.”
Discussion ¶2Find in source

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

ADEQUATESurrogate endpoint
The primary endpoint is metastasis-free survival, a composite of distant metastasis or death from any cause, which is a hard clinical outcome rather than a biomarker or mechanistic proxy. The paper does not rely on a surrogate for the efficacy claim; it directly measures a clinical event.
“The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause.”
Find in source
ADEQUATEEffect size
The reported effect is a hazard ratio of 0.773 (95% CI 0.612–0.975) for metastasis-free survival, with an absolute improvement in 10-year metastasis-free survival from 71.9% to 78.1% (6.2 percentage points). The paper anchors this as clinically meaningful by stating that 16 people need to be treated with long-course ADT to avoid one metastasis-free survival event within 10 years.
“10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. ... on average, 16 people need to be treated with long-course ADT for one of them to avoid an metastasis-free survival event within 10 years.”
Find in source

Data authenticity concerns

1 finding · worst low

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.

Data look implausibly cleanAssessed

5 integrity concerns flagged (0 high).

lowdata too clean
The percentage for Denmark in Table 1 is listed as 35 (95%) for short-course ADT, which is clearly a typo (should be approximately 5%). This does not affect the study validity but indicates a data presentation error.
35 (95%)
Table 1reviewer’s wording

Reporting gaps

2 findings · 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.

Key resources not identifiedAssessed
Ethics/consent reporting incompleteAssessed

Eight Dimensions6 pass · 1 warn · 1 fail

The introduction cites three key phase 3 trials (RTOG 0534, GETUG-AFU 16, RTOG 9601) and notes that no previous trial compared different ADT durations in the postoperative setting. The hypothesis that long-course ADT would be more effective is logically derived from prior evidence. Limitations of prior research, such as the lack of duration comparisons, are explicitly addressed. All three sub-criteria are met.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise, cites relevant prior trials (RTOG 0534, GETUG-AFU 16, RTOG 9601), and derives a testable hypothesis from them.

Evidence

“Radiotherapy is also commonly used after radical prostatectomy, but only three phase 3 randomised controlled trials in this setting have assessed the addition of ADT, and none have compared different durations of ADT.”

Introduction ¶2Find in source

“In developing the RADICALS-HD trial in 2006, we hypothesised that long-course ADT would be more effective than short-course ADT in people receiving postoperative radiotherapy.”

Introduction ¶3Find in source

“Subgroup analysis of RTOG 9601 found that the overall survival benefit from long-course bicalutamide was restricted to those with a higher PSA level at the time of salvage radiotherapy.”

Discussion ¶4Find in source

PASSReviewer 2· 90% conf

The paper clearly establishes prior evidence (RTOG 0534, GETUG-AFU 16, RTOG 9601, ICECaP) and a logical rationale for comparing long-course versus short-course ADT, noting that no prior trial compared ADT durations in this setting.

Evidence

“only three phase 3 randomised controlled trials in this setting have assessed the addition of ADT, and none have compared different durations of ADT”

Introduction ¶1Find in source

“we hypothesised that long-course ADT would be more effective than short-course ADT in people receiving postoperative radiotherapy”

Introduction ¶2Find in source

PASSReviewer 3· 100% conf

The scientific premise is well-established: prior trials of ADT with radiotherapy in prostate cancer are cited, the rationale for comparing ADT durations in the postoperative setting is clearly explained, and limitations of prior work are acknowledged.

Evidence

“In people receiving salvage radiotherapy after radical prostatectomy, the addition of short-course (4–6 months) ADT has been shown in the RTOG 0534 randomised controlled trial to reduce disease progression and in the GETUG-AFU 16 randomised controlled trial to improve metastasis-free survival.”

Introduction ¶1Find in source

“In developing the RADICALS-HD trial in 2006, we hypothesised that long-course ADT would be more effective than short-course ADT in people receiving postoperative radiotherapy.”

Introduction ¶2Find in source

paraphrase[Introduction, paragraph 1]

“The paper notes that only three phase 3 trials assessed adding ADT to postoperative radiotherapy, and none compared different durations.”

The trial uses central randomisation with minimisation and stratification. The power analysis is described and updated appropriately. The primary analysis is ITT. Inclusion/exclusion criteria are listed. Blinding is not performed and is stated as open-label, but no rationale is provided; this is a minor inadequacy. All other applicable sub-criteria are adequate. Overall, 5 of 6 applicable criteria are adequate, exceeding the 60% threshold.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsINADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Core design elements for a human RCT are all reported: central minimisation randomisation, patient-level randomisation unit, open-label design clearly stated, a priori power analysis, pre-specified eligibility criteria, and ITT analysis.

Evidence

“Randomisation was achieved centrally by the method of minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned ADT type.”

MethodsFind in source

“The allocated treatment was open label.”

MethodsFind in source

“The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72).”

AbstractFind in source

PASSReviewer 2· 90% conf

Centralised minimisation randomisation with stratification is described, the open-label design is disclosed, a formal power calculation is given, and eligibility/inclusion-exclusion criteria are pre-specified; ITT analysis is stated.

Evidence

MethodsFind in source

“The allocated treatment was open label.”

MethodsFind in source

“this revised design had 80% power with two-sided 5% α to detect an increase in 10-year metastasis-free survival from 75% to 81% (HR 0·72)”

Statistical analysisFind in source

PASSReviewer 3· 95% conf

The study design is rigorous with central randomisation, a pre-specified power analysis, ITT analysis, and clear inclusion/exclusion criteria. The open-label design is stated but not justified, which is a minor shortfall.

Evidence

MethodsFind in source

“Based on 300 metastasis-free survival events from the 1523 participants, this revised design had 80% power with two-sided 5% α to detect an increase in 10-year metastasis-free survival from 75% to 81% (HR 0·72).”

Statistical analysisFind in source

“The allocated treatment was open label.”

MethodsFind in source

Sex is uniformly male (prostate cancer), a disease-specific single-sex cohort that needs no further justification. Median age (65 years, IQR 60–69) and comorbidity (Charlson Comorbidity Index) are reported; weight is not applicable for this human trial. Demographics are incomplete because the paper states 'Data on race and ethnicity were not collected', a gap transparently discussed in the limitations. Two of three applicable criteria are adequate.

Sub-criteria

demographicsINADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 70% conf

Age, health status (Charlson Comorbidity Index), and disease characteristics are reported; sex is inherent to the prostate-cancer population. Race/ethnicity were not collected, which the authors transparently disclose as a limitation.

Evidence

“The median age of participants was 65 years (IQR 60–69)”

Results ¶1Find in source

“Data on race and ethnicity were not collected.”

Discussion ¶1Find in source

“Two prespecified subgroup analyses were planned, by pre-radiotherapy PSA level and by Charlson Comorbidity Index score.”

Statistical analysisFind in source

PASSReviewer 2· 80% conf

Age and comorbidity (Charlson index) are reported, and the all-male cohort is inherent to prostate cancer; however, race and ethnicity data were not collected, which the authors acknowledge.

Evidence

“The median age of participants was 65 years (IQR 60–69)”

Results ¶1Find in source

“Data on race and ethnicity were not collected.”

Results ¶1Find in source

WARNReviewer 3· 85% conf

Age is reported, but weight and detailed health status are not fully reported. Race and ethnicity data were not collected. Sex is implied by the disease but not explicitly stated. Only 1 of 3 applicable sub-criteria is adequate.

Evidence

paraphrase[Results, paragraph 1]

“The median age of participants was 65 years (IQR 60–69).”

“Data on race and ethnicity were not collected.”

Results ¶1Find in source

absence[Not found]

Weight is not reported.

The paper states 'Appropriate ethical review was in place for each participating country (appendix p 8)' but does not name the specific ethics committee or provide a protocol number. Written informed consent is clearly documented. No explicit mention of adherence to a regulatory framework such as the Declaration of Helsinki is present. Thus, 1 of 3 applicable sub-criteria is adequate.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementINADEQUATE

regulatory complianceNOT REPORTED

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 70% conf

Informed consent is clearly reported, but the ethics-approval statement is vague ('Appropriate ethical review was in place for each participating country (appendix p 8)') with no named approving body or protocol number in the main text, and no explicit regulatory-compliance framework is named.

Evidence

“Appropriate ethical review was in place for each participating country (appendix p 8).”

MethodsFind in source

“All participants gave written informed consent.”

MethodsFind in source

absence[Methods]

No named regulatory/compliance framework is stated.

WARNReviewer 2· 75% conf

Informed consent is documented and a general statement of ethical review is given, but no named ethics body or protocol number appears in the text and no explicit regulatory-compliance statement is present.

Evidence

“Appropriate ethical review was in place for each participating country (appendix p 8)”

MethodsFind in source

“All participants gave written informed consent.”

MethodsFind in source

WARNReviewer 3· 95% conf

Informed consent is adequately reported, but the ethics approval statement is vague (no named body or protocol number), and regulatory compliance (e.g., Declaration of Helsinki) is not explicitly stated. Not all applicable criteria are adequate.

Evidence

“Appropriate ethical review was in place for each participating country (appendix p 8).”

MethodsFind in source

“All participants gave written informed consent.”

MethodsFind in source

absence[Not found]

No specific regulatory framework is cited.

The paper describes the ADT agents (GnRH analogue, bicalutamide, degarelix) with dose and schedule, but does not name the manufacturer or source. Software used for statistical analysis is not mentioned. Both applicable sub-criteria are inadequate or not reported, resulting in a fail.

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedNOT REPORTED

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 70% conf

The investigational products (GnRH analogue, bicalutamide, degarelix) are named with dose and regimen, but the statistical analysis software is not identified.

Evidence

“daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix”

MethodsFind in source

absence[Methods, Statistical analysis]

Statistical analysis software is not identified.

FAILReviewer 2· 70% conf

The investigational ADT agents are named with dosing, but no manufacturer/source is given (deliberately 'local choice'), and the statistical software is not identified, leaving no applicable resource criterion fully reported.

Evidence

“using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix”

MethodsFind in source

absence[Methods, Statistical analysis]

Statistical software not identified

FAILReviewer 3· 85% conf

The investigational products (ADT drugs) are named with dose and regimen but not by manufacturer or source. Statistical software is not identified. Neither applicable sub-criterion is adequate.

Evidence

paraphrase[Methods, Procedures]

“ADT was given with local choice of a subcutaneous gonadotrophin-releasing hormone analogue, supplemented by 3 weeks of an oral anti-androgen... daily oral bicalutamide monotherapy 150 mg or monthly subcutaneous degarelix.”

absence[Not found]

Statistical software is not identified.

The log-rank test and Cox regression are specified. The Grambsch–Therneau test is used to verify proportional hazards. Exact p-values (e.g., p=0.029) and HR with 95% CIs are provided. Data are presented with KM curves and risk tables. Software is not named. 6 of 7 applicable sub-criteria are adequate, exceeding the pass threshold.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedNOT REPORTED

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 80% conf

Statistical tests are named, proportional-hazards assumptions are tested, exact p-values and effect estimates with 95% CIs are reported, and per-group n and KM/forest presentations are given. Only the statistical software is not identified.

Evidence

paraphrase[Methods, Statistical analysis]

“The Grambsch–Therneau test was used to test the proportional hazards assumption, with restricted mean survival time becoming the primary estimate of effect if non-proportional hazards were detected.”

“HR 0·773 [95% CI 0·612–0·975]; p=0·029”

Results ¶4Find in source

“Metastasis-free survival events were reported for 313 patients, including 174 in the short-course ADT group and 139 in the long-course ADT group”

Results ¶3Find in source

WARNReviewer 2· 70% conf

Statistical tests, exact p-values, effect sizes with CIs, and data presentation are strong, but the software is not identified and a table contains a demonstrable percentage error (Denmark 35 [95%]).

Evidence

“HR 0·773 [95% CI 0·612–0·975]; p=0·029”

Results ¶2Find in source

“The Grambsch–Therneau test was used to test the proportional hazards assumption”

Statistical analysisFind in source

“Denmark | 35 (95%) | 29 (4%) | 64 (4%)”

Table 1Find in source

PASSReviewer 3· 95% conf

Statistical tests are named, assumptions are tested (proportional hazards), exact p-values and effect sizes with CIs are reported, and data presentation is appropriate for a clinical trial. The only missing element is software identification, which is not critical.

Evidence

paraphrase[Methods, Statistical analysis]

“The statistical significance of differences between groups was evaluated with the log-rank test, stratified by randomisation minimisation factors. Effect estimates were obtained from Cox regression models... The Grambsch–Therneau test was used to test the proportional hazards assumption.”

paraphrase[Results, paragraph 2]

“Metastasis-free survival was improved in patients allocated to long-course ADT compared with short-course ADT (HR 0·773 [95% CI 0·612–0·975]; p=0·029).”

absence[Not found]

Statistical software is not identified.

The data_availability_statement is concrete: data are held at the MRC Clinical Trials Unit at UCL, shared under controlled access, with an email address, a formal application process, and review by the trial team and independent researchers. This is reported_and_adequate for identifiable individual-patient data. repository_deposit and accession_numbers are not applicable (patient-level privacy; no sequencing/imaging data produced), and code_sharing is not applicable (no bespoke analysis code described). The single applicable criterion is adequate, so the dimension passes.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

A clear controlled-access data-sharing route is described via the MRC CTU at UCL with a named contact, formal application process, and review criteria; repository/accession/code are not applicable to identifiable patient-level trial data.

Evidence

“Requests for data can be made at any time and can be initiated by email to mrcctu. datareleaserequest@ucl.ac.uk or via our website. There is a formal application process, whereby the request will undergo review by the trial team, as well as independent researchers”

Data availabilityFind in source

PASSReviewer 2· 85% conf

A concrete managed-access data-sharing route is described with a formal application process, appropriate for identifiable individual-patient data.

Evidence

“The RADICALS trial data are held at the MRC Clinical Trials Unit at University College London (UCL), which encourages optimal use of data by using a controlled access approach to data sharing.”

Data availabilityFind in source

“There is a formal application process, whereby the request will undergo review by the trial team, as well as independent researchers, to ensure that the proposed research is both ethical and has a strong scientific rationale.”

Data availabilityFind in source

WARNReviewer 3· 85% conf

A detailed data sharing statement is provided with a controlled access mechanism. Code sharing is not addressed. Repository deposit and accession numbers are not applicable. One of two applicable criteria is adequate.

Evidence

paraphrase[Data sharing section]

“Requests for data can be made at any time and can be initiated by email to mrcctu.datareleaserequest@ucl.ac.uk or via our website. There is a formal application process...”

absence[Not found]

Code sharing is not mentioned.

The trial is registered with ISRCTN and ClinicalTrials.gov. The methods provide sufficient detail for replication. Primary and secondary outcomes are reported, including non-significant results. Limitations are extensively discussed. Conclusions are measured. Funding sources and conflicts of interest are fully disclosed. No reporting guideline is referenced, but 6 of 7 applicable criteria are adequate.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 80% conf

Methods are detailed, the trial is registered (ISRCTN40814031, NCT00541047), outcomes are transparently reported with disclosed omissions, limitations are extensively discussed, conclusions are proportional, and funding/COI are fully disclosed. Only an explicit reporting-guideline (CONSORT) reference is absent.

Evidence

“The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov (https://clinicaltrials.gov/) , NCT00541047”

AbstractFind in source

“An additional secondary outcome of treatment failure, defined as PSA progression when on ADT, was not well reported by sites and is not presented.”

MethodsFind in source

absence[Whole manuscript]

A named reporting guideline (CONSORT) is not referenced.

PASSReviewer 2· 80% conf

Methods are detailed, the trial is registered, limitations are thoroughly discussed, conclusions are measured, and funding/COI are declared; however, no reporting guideline (CONSORT) is cited and two pre-specified secondary outcomes were not presented.

Evidence

“This study is registered with the ISRCTN registry, ISRCTN40814031, and with ClinicalTrials.gov (https://clinicaltrials.gov/) , NCT00541047 .”

MethodsFind in source

“An additional secondary outcome of treatment failure, defined as PSA progression when on ADT, was not well reported by sites and is not presented.”

MethodsFind in source

PASSReviewer 3· 95% conf

Methods are complete, the trial is registered, all outcomes are reported (including negative results), limitations are discussed, conclusions are proportional, and funding/COI are disclosed. The only missing element is a reference to a reporting guideline (e.g., CONSORT).

Evidence

paraphrase[Methods, Study design and participants]

“This study is registered with the ISRCTN registry, ISRCTN40814031, and with ClinicalTrials.gov, NCT00541047.”

paraphrase[Discussion, paragraph 5]

“RADICALS-HD also has several limitations. Based on the recent results from the RADICALS-RT trial, and the ARTISTIC meta-analysis, postoperative radiotherapy is now typically given in the salvage, rather than the adjuvant, setting.”

paraphrase[Funding and Declaration of interests sections]

“Funding sources (Cancer Research UK, MRC, Canadian Cancer Society) and detailed conflicts of interest for all authors are provided.”

Registered (3 IDs: ClinicalTrials.gov, ISRCTN, PROSPERO). No reporting guideline cited.

ClinicalTrials.gov

NCT00541047

ISRCTN

ISRCTN40814031

PROSPERO

CRD42022325769

Broken references and links

2 findings · worst high

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.

Data/code link contradicts the paperRecomputed
References not resolvable to a published paperRecomputed

Checked 17 references by DOI: 16 verified — 1 DOI unresolved.

UNRESOLVED10.5281/zenodo.6586525
RADICALS trial statistical analysis plan
Cited DOI does not resolve to any Crossref record.

4 data/code links checked; 4 live; 1 resolved to content that does not match the paper.

datahttp://www.ctu.mrc.ac.uk/our_research/datasharingLIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttp://www.ctu.mrc.ac.uk/our_research/datasharing/application_processLIVEINCONSISTENTHTTP 200
Resolves to a parked / unavailable page ("Page Not Found | UCL Innovative Clinical Trials Unit") — the resource is not actually there.
datahttps://www.mrcctu.ucl.ac.uk/media/1811/radicals-protocol-version-60-14-dec-2018_signed.pdfLIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttps://clinicaltrials.gov/LIVEHTTP 200
Resolves, but the content could not be matched to the paper.

Copyediting

1 finding · worst low

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

Wording or formatting errors that need correctingAssessed

8 copyedit issues flagged (3 major): mostly consistency, grammar, punctuation.

MAJORconsistencyTable 1, Denmark row, short-course ADT column
“Denmark | 35 (95%) | 29 (4%) | 64 (4%)”
→ Change '35 (95%)' to '35 (5%)'; 35/761 ≈ 4.6%.
As printed, 95% is impossible for a single country's share of one arm; clearly a typo for 5%.
MAJORconsistencyTable 1, Country row
“Denmark | 35 (95%) | 29 (4%) | 64 (4%)”
→ Change '35 (95%)' and '29 (4%)' to the correct percentages (approximately 55% and 45% of the 64 Denmark participants).
35/64 = 54.7% and 29/64 = 45.3%; 95% cannot be correct for any reasonable denominator.
MAJORconsistencyTable 2, column header
“Long-course ADT (n=743)”
→ Reconcile with the n=762 stated in the Abstract, Results, and Table 3, or footnote the analysis denominator.
The long-course ADT group is consistently n=762 elsewhere; n=743 in the Table 2 header is unexplained.
MINORgrammarMethods, Statistical analysis
“Events rates as specified times were taken from Kaplan–Meier survival functions.”
→ Change 'Events rates' to 'Event rates'.
Subject-verb agreement/typo.
MINORpunctuationData sharing section
“mrcctu. datareleaserequest@ucl.ac.uk”
→ Remove the space: 'mrcctu.datareleaserequest@ucl.ac.uk'.
Line-break artifact in the email address.
MINORtypoTable 1, Denmark row
“35 (95%)”
→ 35 (5%)
The percentage for short-course ADT in Denmark appears to be a typo; 35/761 ≈ 4.6%, likely intended as 5%.
MINORconsistencyTable 1, Ireland row
“1 (<1%)”
→ 1 (<1%)
Consistent with other entries, but note that 1/761 ≈ 0.1%, so <1% is correct.
MINORclarityAbstract, Methods
“Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system.”
→ No change needed, but consider splitting long sentence for readability.
Minor stylistic suggestion.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is robust in its core design, analysis, and transparency; an informed reader should weigh the unresolved ethics-approval detail (appendix pointer instead of a named body), the missing statistical software identification, and the two table errors (Denmark percentage, Table 2 n=743 vs n=762), which warrant an erratum or correction. Independent re-analysis is not required based on the checks performed, but the corrections should be issued.

1.
HIGHcopyedit
Correct the Table 1 Denmark row: change '35 (95%)' to '35 (5%)' (35/761 ≈ 4.6%) and reconcile '29 (4%)' to the correct percentage of the 64 Denmark participants (~45%).
The printed '95%' is an impossible percentage for a single country's share of one arm and is a demonstrable data-presentation error that a reader will catch.
2.
HIGHcopyedit
Reconcile the Table 2 column header 'Long-course ADT (n=743)' with the n=762 stated in the Abstract, Results, and Table 3, or footnote the analysis denominator.
The internal contradiction between n=743 and n=762 for the same group is an unexplained inconsistency that undermines table credibility.
3.
HIGHethics
Name the specific research ethics committees/IRBs that approved the trial and provide approval/protocol numbers in the main text (or explicitly cite the details in appendix p 8), and add a regulatory-compliance statement (e.g., 'conducted in accordance with the Declaration of Helsinki' or ICH-GCP).
The current generic statement ('Appropriate ethical review was in place for each participating country') is inadequate for a published trial and leaves an applicable ethics criterion unmet.
4.
HIGHreporting
Identify the statistical analysis software and version (e.g., Stata/SAS/R) used for all analyses in the Statistical analysis section.
The statistical software is not identified anywhere, which is a reproducibility gap for a data-driven trial.
5.
HIGHreporting
Specify the source/manufacturer of the GnRH analogue and other ADT products, or state where the 'local choice' product list is documented, to satisfy investigational-product identification.
Two reviewers flagged the missing manufacturer/source as a resource-identification gap; naming the drugs alone is borderline adequate.
6.
HIGHreporting
Reference the CONSORT reporting guideline and note the location of the CONSORT checklist in the Methods or as supplementary material.
The manuscript otherwise follows CONSORT-style reporting (Figure 1 flow) but does not cite the guideline, a minor transparency gap.
7.
HIGHother
Verify or correct the reference 'RADICALS trial statistical analysis plan' (DOI 10.5281/zenodo.6586525), which was not found in any registry.
A reference that cannot be located in Crossref/OpenAlex may be fabricated or mis-cited; it should be confirmed against the actual Zenodo record or corrected.
8.
MEDIUMcopyedit
Fix the email address in the Data sharing section: remove the space in 'mrcctu. datareleaserequest@ucl.ac.uk' to make it 'mrcctu.datareleaserequest@ucl.ac.uk'.
The line-break artifact in the email address would prevent readers from contacting the data custodian.
9.
MEDIUMcopyedit
Fix the grammatical error in the Statistical analysis section: change 'Events rates' to 'Event rates'.
Minor subject-verb agreement/typo in the Methods text.
10.
MEDIUMreporting
Provide a brief rationale for the open-label design (e.g., 'blinding was not feasible due to differing injection schedules and durations') in the Randomisation and masking section.
One reviewer flagged the lack of justification for the open-label design; a one-sentence rationale improves completeness.
11.
MEDIUMreporting
Disclose the fate of the treatment-failure and PROMs secondary outcomes more fully in the Discussion or a supplement table, beyond the one-line note in Methods.
Strengthens complete outcome reporting and answers the reviewer concern that two pre-specified outcomes were not presented.
12.
LOWdata code
Add a statement on the planned disposition of analysis code (e.g., 'available from the MRC CTU on request') in the Data sharing section.
Clarifies whether the custom analysis code is obtainable, addressing a reviewer's data-code concern.
13.
LOWother
Note in the limitations that race/ethnicity data were not collected and that weight/BMI were not reported, and consider collecting these in future analyses.
The demographics gap is already acknowledged; explicitly noting weight/BMI would fully address the age_weight_health criterion.

Full text (49,033 chars)Analyzed: Aug 10, 2026

RigorReviewer 1

RigorReviewer 2

RigorReviewer 3

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

ReproducibilityLink verification (liveness + content)· no model (rule-based)

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.

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial.

DOI

10.1016/S0140-6736(24)00549-X

Record issued

2026-08-10

Engine

7.29.0

Exported

2026-09-21