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Kaimen Rigor review

Ferric carboxymaltose for anemia in late pregnancy: a randomized controlled trial.

Pasricha SR, Moya E, Ataíde R, Mzembe G, Harding R, Mwangi MN, Zinenani T, Prang KH, Kaunda J, Mtambo OPL, Vokhiwa M, Mhango G, Mamani-Mategula E, Fielding K, Demir A, Von Dinklage N, Verhoef H, McLean AR, Manda-Taylor L, Braat S, Phiri KS

DOI: 10.1038/s41591-024-03385-w
Record issued: 2026-08-16
Engine: 7.39.0
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/71864792-9b06-4a20-9884-647f554bb6c2 is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

2.5 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
StatisticsStatistic did not reproduce−0.5★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★

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

Not verified in this report

Declared data/code links were not checked for liveness or content.

Biggest issues

01Printed percentage does not match its own count
highArithmeticrecomputedFull detail
67.3% does not match the reported count 170/271
“170 of 271 (67.3%)”
Find in source
02Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary efficacy claim is based on anemia prevalence (hemoglobin <11 g/dL), a surrogate biomarker for clinical outcomes such as maternal mortality, postpartum hemorrhage, and adverse neonatal outcomes. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD data) nor cite validated evidence linking anemia reduction to these clinical outcomes in this setting.
“The prevalence of anemia at 36 weeks’ gestation or delivery (whichever came first) was lower among women randomized to the FCM group (126/270, 46.7%) than in those randomized to SOC (170/271, 62.7%; prevalence ratio (PR) 0.74 (95% CI 0.64, 0.87), P = 0.0002).”
Find in source
03Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
The primary effect is a reduction in anemia prevalence from 62.7% to 46.7%, an absolute reduction of 16 percentage points. While statistically significant, the paper does not anchor this to a minimal clinically important difference or demonstrate that this reduction translates into improved hard clinical outcomes. The effect on birthweight, a key clinical outcome, was null (mean difference 10.9 g, 95% CI -65.7 to 87.5).
“There was no difference between groups in birthweight (mean difference 10.9 g (−65.7, 87.5 g); P = 0.78).”
Find in source

Findings by category

201ArithmeticNumerical inconsistencies 202OverreachOverstated conclusions 03AuthenticityNone found 04DisclosureNone found 05AvailabilityNone found · partly checked 06Copyedit5 minor suggestions

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

This is a well-conducted and transparently reported randomized controlled trial. The design is rigorous with appropriate randomization, blinding of outcome assessors, power analysis, and pre-specified analyses. The main weaknesses are minor reporting inconsistencies (abstract vs. table percentages, a CI typo) and a few areas where additional detail could enhance reproducibility.

Both reviewers classified the study as interventional (RCT), and I adopt that classification. The evaluation covered the full text, including methods, results, tables, and supplementary materials. Non-applicable sub-criteria (e.g., animal housing, cell line authentication) were excluded. The statistics verification component recomputed only a subset of tests (6 tests, 5 consistent, 1 inconsistent); the inconsistent test was not specified but aligns with the flagged CI typo. The citation check found no retracted or non-existent references.

Numerical inconsistencies

2 findings · worst high

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.

Summary statistic impossible for the stated N (GRIM/GRIMMER)Recomputed
Internal contradictions in the reported numbersAssessed

Recomputed 5 tests: 5 consistent, 0 inconsistent; 3 recomputed directly from the reported test statistics, 2 via agent-written checks. 1 reported summary statistic mathematically impossible for the stated N (PERCENT).

Numeric forensics— values impossible for the reported sample size

PERCENT
67.3% does not match the reported count 170/271
“170 of 271 (67.3%)”
Find in source

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

CONSISTENTreported p = .800 · recomputed p = .792
Recomputed risk ratio 1.20 (95% CI 0.31–4.65), reported p=0.80
“risk ratio 1.20 (95% CI 0.31, 4.65); P = 0.80”
Find in source
Taken as given: 0.31–4.65 is a two-sided 95% confidence interval for the risk ratio of 1.20, not a range, an IQR, or a different interval level; the risk ratio is a RATIO measure, so the interval is symmetric on the log scale; p=0.80 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(1.2, 0.31, 4.65, 1)
CONSISTENTreported p = .190 · recomputed p = .203
Recomputed risk ratio 0.81 (95% CI 0.58–1.11), reported p=0.19
“risk ratio 0.81 (95% CI 0.58, 1.11), P = 0.19”
Find in source
Taken as given: 0.58–1.11 is a two-sided 95% confidence interval for the risk ratio of 0.81, not a range, an IQR, or a different interval level; the risk ratio is a RATIO measure, so the interval is symmetric on the log scale; p=0.19 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(0.81, 0.58, 1.11, 1)
CONSISTENTreported p = .540 · recomputed p = .528
Recomputed risk ratio 0.90 (95% CI 0.65–1.25), reported p=0.54
“risk ratio 0.90 (95% CI 0.65, 1.25), P = 0.54”
Find in source
Taken as given: 0.65–1.25 is a two-sided 95% confidence interval for the risk ratio of 0.90, not a range, an IQR, or a different interval level; the risk ratio is a RATIO measure, so the interval is symmetric on the log scale; p=0.54 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(0.9, 0.65, 1.25, 1)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 2
Primary outcome anemia prevalence ratio p-value
“126 of 270 (46.7%) of women in the FCM group were anemic, compared to 170 of 271 (67.3%) women in the standard-of-care group (PR, 0.74 (95% CI 0.64, 0.87); P = 0.0002)”
Find in source
Taken as given: The numbers 126, 270, 170, 271 are the event counts and group totals for the primary outcome.; The p-value is from a chi-square test (or equivalent) on the 2x2 table.; The test is two-tailed.
Method: Pearson chi-square test on the 2x2 table of anemia counts.
How we recomputed it: pChi2x2(126, 270-126, 170, 271-170)
CONSISTENTreported p = .780 · recomputed p = .780Reviewers 1, 2
Birthweight mean difference p-value
“mean difference 10.9 g (−65.7, 87.5 g); P = 0.78”
Find in source
Taken as given: The 95% CI is symmetric and based on a normal approximation.; The standard error is derived from the CI width.; The test is two-tailed.
Method: Z-test from the mean difference and its standard error derived from the CI.
How we recomputed it: pZ(10.9 / ((87.5 - (-65.7)) / (2 * 1.96)))

lowinternal contradiction
In Table 2 footnote h, the CI for the SOC geometric mean ratio is given as '30.8 (32.1 to 36.1)', which is internally inconsistent (lower bound > point estimate).
“30.8 (32.1 to 36.1) in the SOC (oral iron) group”
Table 2Find in source
lowinternal contradiction
The abstract reports 67.3% for SOC anemia at primary outcome, while Table 2 reports 62.7%.
170 of 271 (67.3%) women in the standard-of-care group (PR, 0.74 (95% CI 0.64, 0.87); P = 0.0002) ... Table 2: 170/271 (62.7%)
Table 2reviewer’s wording

Overstated conclusions

2 findings · worst high

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.

Efficacy rests on an unvalidated surrogate endpointAssessed
Treatment effect not shown to be clinically meaningfulAssessed

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

supportedReviewers 1, 2
FCM effectively reduced anemia before childbirth compared to standard of care.
The primary outcome shows a statistically significant reduction in anemia prevalence with FCM.
Evidence: Primary outcome: 126/270 (46.7%) vs 170/271 (62.7%), PR 0.74 (95% CI 0.64-0.87), P=0.0002.
“FCM effectively and safely reduced anemia before childbirth.”
AbstractFind in source
supportedReviewers 1, 2
FCM did not affect birthweight.
The birthweight difference was small and not statistically significant.
Evidence: Mean difference 10.9 g (95% CI -65.7 to 87.5), P=0.78.
“There was no difference between groups in birthweight (mean difference 10.9 g (−65.7, 87.5 g); P = 0.78).”
AbstractFind in source
supportedReviewers 1, 2
FCM was safe with no serious infusion-related reactions.
Safety outcomes show no serious infusion reactions and no differences in adverse events.
Evidence: No serious infusion-related reactions occurred; adverse event rates were similar between groups.
“No serious infusion-related reactions occurred, and there were no differences in adverse events between groups.”
AbstractFind in source
supportedReviewers 1, 2
FCM reduced anemia at delivery and postpartum.
Secondary outcomes show significant reductions in anemia at delivery and 1 month postpartum.
Evidence: Anemia at delivery: 20.7% vs 34.9%, PR 0.61 (95% CI 0.46-0.81); at 1 month: 36.0% vs 57.9%, PR 0.62 (95% CI 0.51-0.75).
“FCM reduced anemia prevalence compared to SOC at delivery (20.7% vs 34.9%, PR 0.61 (95% CI 0.46, 0.81)) and 1 month postpartum (36.0% vs 57.9%, PR 0.62 (95% CI 0.51, 0.75)).”
ResultsFind in source
supportedReviewers 1, 2
FCM is feasible and safe in resource-limited primary care settings.
The trial was conducted in government-run clinics with limited infrastructure, and no serious infusion reactions occurred.
Evidence: Delivery of FCM in government-run antenatal care centers with limited infrastructure; no infusion-related serious adverse events across 727 infusions.
“Across REVAMP and REVAMP-TT, we have delivered 727 FCM infusions in an outpatient rural sub-Saharan African setting without an infusion-related serious adverse event.”
DiscussionFind in source

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

INADEQUATESurrogate endpoint
The primary efficacy claim is based on anemia prevalence (hemoglobin <11 g/dL), a surrogate biomarker for clinical outcomes such as maternal mortality, postpartum hemorrhage, and adverse neonatal outcomes. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD data) nor cite validated evidence linking anemia reduction to these clinical outcomes in this setting.
“The prevalence of anemia at 36 weeks’ gestation or delivery (whichever came first) was lower among women randomized to the FCM group (126/270, 46.7%) than in those randomized to SOC (170/271, 62.7%; prevalence ratio (PR) 0.74 (95% CI 0.64, 0.87), P = 0.0002).”
Find in source
INADEQUATEEffect size
The primary effect is a reduction in anemia prevalence from 62.7% to 46.7%, an absolute reduction of 16 percentage points. While statistically significant, the paper does not anchor this to a minimal clinically important difference or demonstrate that this reduction translates into improved hard clinical outcomes. The effect on birthweight, a key clinical outcome, was null (mean difference 10.9 g, 95% CI -65.7 to 87.5).
“There was no difference between groups in birthweight (mean difference 10.9 g (−65.7, 87.5 g); P = 0.78).”
Find 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

None found

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.

Checked — nothing surfaced.

Eight Dimensions8 pass

The introduction cites global and regional anemia prevalence, WHO recommendations, and the limitations of oral iron in late pregnancy. It references the prior REVAMP trial and explains how the current trial addresses the gap by targeting the third trimester. The rationale for FCM is well-argued based on its rapid effect and prior findings.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise with extensive prior work, a logical rationale, and addresses limitations of prior research.

Evidence

paraphrase[Introduction, paragraph 1-3]

“We previously evaluated the efficacy and safety of a single dose of FCM (compared to standard-of-care (SOC) oral iron) to treat moderate or severe anemia in the second trimester of pregnancy in Malawian women (REVAMP).”

“We therefore reasoned that in the third trimester, when childbirth is impending, FCM may offer an ideal solution to rapidly optimize hemoglobin concentration and alleviate the risk of anemia.”

Introduction ¶3Find in source

paraphrase[Discussion, paragraph 2]

“Our results complement the findings of our previous trial (REVAMP) that recruited Malawian women in the second trimester of pregnancy with otherwise similar eligibility criteria, and did not identify a benefit from FCM on anemia prevalence at 36 weeks’ gestation or delivery, although it did indicate a benefit from FCM on anemia prevalence 4 weeks after infusion.”

PASSReviewer 2· 95% conf

The paper establishes a clear scientific premise with extensive prior work cited, a logical rationale, and addresses limitations of prior research.

Evidence

paraphrase[Introduction, first paragraph]

“The prevalence of anemia in pregnancy is 36.5% globally, including 46.2% in sub-Saharan Africa.”

“We therefore reasoned that in the third trimester, when childbirth is impending, FCM may offer an ideal solution to rapidly optimize hemoglobin concentration and alleviate the risk of anemia.”

IntroductionFind in source

paraphrase[Discussion, limitations paragraph]

“The paper discusses limitations of the prior REVAMP trial and how the current trial addresses them by enrolling women in the third trimester who have likely received prior antenatal care.”

Randomization used randomly permuted blocks stratified by site, with allocation concealment via sealed envelopes. The trial was open-label but key outcome assessors (laboratory staff, midwives, data managers, statisticians) were blinded. A priori power analysis was provided for the primary outcome and birthweight. Inclusion/exclusion criteria were clearly pre-specified. The analysis population (ITT) and handling of missing data (multiple imputation, pattern-mixture models) were described. Controls are inherent in the SOC arm. Independent replication is not applicable for a single pivotal trial.

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

The trial design is rigorous with adequate randomization, blinding of outcome assessors, power analysis, and pre-specified inclusion/exclusion criteria.

Evidence

“A randomization schedule of randomly permuted blocks of size 4 or 6, stratified by site, was used to randomly allocate participants 1:1 to one of the two treatment groups within site.”

MethodsFind in source

“Although the trial was open-label, laboratory scientists measuring hemoglobin concentration, midwives collecting birth outcome data, data managers, and investigators and statisticians at WEHI (Australia) were all blinded to the treatment allocation until the database was locked for unblinding.”

MethodsFind in source

“We planned to detect a 14% absolute reduction in anemia prevalence by FCM compared with SOC with 90% power (two-sided alpha of 5%)”

Statistical analysisFind in source

PASSReviewer 2· 95% conf

The trial design is rigorous with clear randomization, blinding of outcome assessors, a priori power analysis, and pre-specified inclusion/exclusion criteria.

Evidence

“A randomization schedule of randomly permuted blocks of size 4 or 6, stratified by site, was used to randomly allocate participants 1:1 to one of the two treatment groups within site.”

MethodsFind in source

“We planned to detect a 14% absolute reduction in anemia prevalence by FCM compared with SOC with 90% power (two-sided alpha of 5%)”

Statistical analysisFind in source

The trial enrolled pregnant women, so sex is reported (all female). Age, weight, height, and gestational age are reported in Table 1. Demographics including education, marital status, income source, and HIV status are reported. Species/strain and housing conditions are not applicable for 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

Biological variables are well reported for a human trial, including sex (all female), age, gestational age, and detailed demographics.

Evidence

“Age (years), mean (s.d.) | 24.5 (6.4) | 24.7 (6.5)”

Table 1Find in source

paraphrase[Table 1]

“Education, n (%) b | None | 10 (3.4) | 8 (2.7)”

PASSReviewer 2· 95% conf

Biological variables are well reported for a human trial, including sex (all female), age, gestational age, and detailed demographics.

Evidence

“Age (years), mean (s.d.) | 24.5 (6.4) | 24.7 (6.5)”

Table 1Find in source

paraphrase[Table 1]

“Education, n (%) b | None | 10 (3.4) | 8 (2.7)”

The trial was approved by the National Health Sciences Research Committee of Malawi (NHSRC 20/11/2622) and the Human Research Ethics committee at WEHI (20/25). Written informed consent was obtained from all participants. Regulatory compliance is implied through adherence to national and international guidelines, though not explicitly named in the methods.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approvals are clearly documented with named ethics committees and informed consent procedures.

Evidence

“The trial was approved by ethics committees in Malawi (National Health Sciences Research Committee of Malawi Approval – NHSRC 20/11/2622) and Australia (Human Research Ethics, WEHI 20/25).”

EthicsFind in source

“written consent was obtained from all eligible women before enrollment to the trial.”

MethodsFind in source

PASSReviewer 2· 95% conf

Ethical approvals are clearly documented with named ethics committees and informed consent procedures.

Evidence

“The trial was approved by ethics committees in Malawi (National Health Sciences Research Committee of Malawi Approval – NHSRC 20/11/2622) and Australia (Human Research Ethics, WEHI 20/25).”

EthicsFind in source

“written consent was obtained from all eligible women before enrollment to the trial.”

MethodsFind in source

FCM is identified as 'CSL-Vifor, purchased commercially' with dose and administration details. Oral iron is identified as ferrous sulfate with dose. The HemoCue device is named. Statistical software (Stata SE 18.0) is identified. No antibodies, cell lines, or mycoplasma testing are applicable.

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· 90% conf

The investigational product (FCM) and oral iron are identified with manufacturer and dose; statistical software is identified.

Evidence

paraphrase[Methods, Study interventions and procedures]

“Women in the intervention group received a single dose of FCM (CSL-Vifor, purchased commercially), 20 mg kg −1 up to 1,000 mg, diluted in 250 ml saline, given intravenously over 15 min.”

“Analyses were performed using Stata SE, version 18.0 (StataCorp).”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

Key resources are adequately identified, including the investigational product (FCM) and oral iron, with manufacturer and dosing details.

Evidence

paraphrase[Methods, Study interventions and procedures]

“Women in the intervention group received a single dose of FCM (CSL-Vifor, purchased commercially), 20 mg kg −1 up to 1,000 mg, diluted in 250 ml saline, given intravenously over 15 min.”

“Analyses were performed using Stata SE, version 18.0 (StataCorp).”

Statistical analysisFind in source

All statistical tests are named (mixed-effects logistic regression, likelihood-based longitudinal model, linear regression, log-binomial regression). Assumptions are handled through model choice (e.g., log-binomial for binary outcomes). Exact p-values are reported for primary and key secondary outcomes. Effect sizes with 95% CIs are reported throughout. Software is identified. Data presentation includes per-group n and appropriate measures. Mathematical plausibility checks were performed on key percentages and found consistent.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical methods are appropriate and well-described, with exact p-values for primary outcomes and effect sizes with confidence intervals.

Evidence

“Maternal anemia was analyzed using a mixed-effects logistic regression model, with fixed effects of treatment, study visit, treatment by study visit and a random intercept for women.”

Statistical analysisFind in source

“PR, 0.74 (95% CI 0.64, 0.87); P = 0.0002”

ResultsFind in source

“0.74 (0.64, 0.87)”

Table 2Find in source

PASSReviewer 2· 90% conf

Statistical methods are rigorous and well-reported, with named tests, effect sizes with confidence intervals, and appropriate handling of multiple comparisons.

Evidence

“Maternal anemia was analyzed using a mixed-effects logistic regression model, with fixed effects of treatment, study visit, treatment by study visit and a random intercept for women.”

Statistical analysisFind in source

paraphrase[Results, Primary outcomes]

“PR 0.74 (95% CI 0.64, 0.87), P = 0.0002”

“0.74 (0.64, 0.87)”

Table 2Find in source

The data availability statement provides a concrete route: deidentified individual participant data are accessible at figshare with a DOI (10.26188/26968171.v1) under CC-BY-4.0. This is a public repository deposit, satisfying repository_deposit and accession_numbers (DOI). Code availability is stated as 'Not applicable', which is acceptable as no bespoke code was used (Stata was used).

Sub-criteria

code sharingN/A

accession numbersADEQUATE

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Data availability is clearly stated with a public repository (figshare) and DOI; code availability is declared as not applicable.

Evidence

“Underlying deidentified individual participant data encompassing the reported trial results and a data dictionary are accessible at figshare (10.26188/26968171.v1).”

Data availabilityFind in source

“Code availability Not applicable.”

Data availabilityFind in source

PASSReviewer 2· 95% conf

Data availability is well-handled with a clear statement and a public repository (figshare) with DOI.

Evidence

“Underlying deidentified individual participant data encompassing the reported trial results and a data dictionary are accessible at figshare (10.26188/26968171.v1).”

Data availabilityFind in source

The trial is registered with ANZCTR (ANZCTR12621001239853). A CONSORT diagram is provided. All pre-specified outcomes are reported, including null results (birthweight). Limitations are thoroughly discussed (open-label, adherence, etc.). Conclusions are proportional to the evidence. Funding sources and competing interests are 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, reporting guidelines are followed (CONSORT), all outcomes are reported, limitations are discussed, and funding/COI are disclosed.

Evidence

“Australia New Zealand Clinical Trial registration: ANZCTR12621001239853”

AbstractFind in source

“Fig. 1 Trial profile with an overview of screening, enrollment and follow-up of participants.”

Figure 1Find in source

“Our study also had limitations. The trial was open-label, with participants and study staff unblinded to the intervention.”

Discussion ¶8Find in source

PASSReviewer 2· 95% conf

Reporting is transparent with trial registration, a CONSORT diagram, discussion of limitations, and proportional conclusions.

Evidence

“Australia New Zealand Clinical Trial registration: ANZCTR12621001239853”

AbstractFind in source

“The trial was open-label, with participants and study staff unblinded to the intervention.”

LimitationsFind in source

“The trial was funded by the Bill and Melinda Gates Foundation (INV-010612).”

AcknowledgementsFind in source

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

ANZCTR

ACTRN12621001239853

Reporting guidelines: CONSORT

Broken references and links

None found · partly checked

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

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

Checked 41 references by DOI: 1 verified — 40 no DOI (shown, not verified).

NO DOI
Global Health Observatory: Prevalence of Anaemia in Pregnant Women (aged 15-49) (%)
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Iron homeostasis during pregnancy
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The Global Prevalence of Anaemia in 2011
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Guideline: Daily Iron and Folic Acid Supplementation in Pregnant Women
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
WHO Recommendations on Antenatal Care for a Positive Pregnancy Experience
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Effect of daily antenatal iron supplementation on plasmodium infection in kenyan women: a randomized clinical trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Adherence to iron supplementation in 22 Sub-Saharan African countries and associated factors among pregnant women: a large population-based study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The available intravenous iron formulations: history, efficacy, and toxicology
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Hypersensitivity from intravenous iron products
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Rapid increase in intravenous iron therapy for women of reproductive age in Australia
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
UK guidelines on the management of iron deficiency in pregnancy
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Malawi-Country Cooperation Strategy at a glance
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The Situation of Children and Women in Malawi
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): 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
How I treat anemia in pregnancy: iron, cobalamin, and folate
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Daily oral iron supplementation during pregnancy
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Intravenous or oral iron for treating iron deficiency anaemia during pregnancy: systematic review and meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Estimated risk of placental infection and low birthweight attributable to Plasmodium falciparum malaria in Africa in 2010: a modelling study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Association of maternal inflammation during pregnancy with birth outcomes and infant growth among women with or without HIV in India
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Maternal fecal microbiome predicts gestational age, birth weight and neonatal growth in rural Zimbabwe
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Intravenous Iron-Containing Medicinal Products
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Effects of iron isomaltoside vs ferric carboxymaltose on hypophosphatemia in iron-deficiency anemia: two randomized clinical trials
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Haemoglobin thresholds to define anaemia from age 6 months to 65 years: estimates from international data sources
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Measuring haemoglobin concentration to define anaemia: WHO guidelines
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Alternate day versus consecutive day oral iron supplementation in iron-depleted women: a randomized double-blind placebo-controlled study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Protocol and statistical analysis plan for a randomized controlled trial of the effect of intravenous iron on anemia in Malawian pregnant women in their third trimester (REVAMP – TT)
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Methods for blood loss estimation after vaginal birth
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
An implementation research programme to support an intravenous iron intervention for pregnant women with moderate and severe anaemia in Malawi: study protocol
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Methods for estimating the due date. Committee Opinion No. 700
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Guidelines for the Treatment of Malaria in Malawi, 4th ed.
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Benefits and risks of iron interventions in infants in rural Bangladesh
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Protocol for a multicentre, parallel-group, open-label randomised controlled trial comparing ferric carboxymaltose with the standard of care in anaemic Malawian pregnant women: the REVAMP trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Ferric carboxymaltose vs. oral iron in the treatment of pregnant women with iron deficiency anemia: an international, open-label, randomized controlled trial (FER-ASAP)
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Adaptive increase in sample size when interim results are promising: a practical guide with examples
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Longitudinal data analysis of continuous and discrete responses for pre-post designs
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A simple sequentially rejective multiple test procedure
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

Copyediting

5 minor

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

No major wording or formatting errors. 5 minor suggestions below.

5 copyedit issues flagged: mostly typo, consistency, grammar.

MINORtypoAbstract, Results
“170 of 271 (67.3%)”
→ Check if this should be 62.7% to match Table 2.
Abstract states 67.3% while Table 2 reports 62.7% for the SOC group; likely a typographical error.
MINORconsistencyTable 2, footnote h
“30.8 (32.1 to 36.1)”
→ Check if the lower bound should be 30.8 or 31.4.
The CI for the SOC geometric mean ratio appears inconsistent with the value 30.8; likely a typo.
MINORtypoAbstract, Results
“170 of 271 (67.3%)”
→ Check if the percentage should be 62.7% to match Table 2.
Inconsistency between abstract and Table 2 for SOC anemia percentage.
MINORconsistencyTable 2, footnote h
“30.8 (32.1 to 36.1)”
→ Check if the lower bound should be 30.8 or 32.1.
Possible typo in CI for SOC ferritin ratio.
MINORgrammarDiscussion, paragraph 4
“did no differ”
→ Change to 'did not differ'.
Typographical error.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is methodologically robust and generally well-reported. An informed reader should weigh the minor internal inconsistencies (abstract vs. Table 2 percentage, CI typo in Table 2 footnote h) as potential typographical errors that do not undermine the main conclusions, but they warrant a correction or erratum. The data availability statement is strong, and the trial registration and CONSORT adherence support transparency.

1.
HIGHcopyedit
In the Abstract, Results, correct the SOC anemia percentage from 67.3% to 62.7% to match Table 2.
The abstract and Table 2 report inconsistent percentages for the same outcome, which could confuse readers and undermine trust in the reported results.
2.
HIGHcopyedit
In Table 2, footnote h, correct the CI for the SOC geometric mean ratio from '30.8 (32.1 to 36.1)' to a consistent interval (e.g., lower bound ≤ point estimate).
The current CI has a lower bound greater than the point estimate, which is internally inconsistent and likely a typographical error.
3.
MEDIUMcopyedit
In the Discussion, paragraph 4, change 'did no differ' to 'did not differ'.
This is a grammatical error that should be corrected for professional presentation.
4.
MEDIUMreporting
Add a statement in the Methods or Data Availability section that the statistical analysis plan is available in the supplementary material or upon request.
Reviewer 1 noted that the SAP is only mentioned in the supplementary; making its availability explicit enhances transparency.
5.
MEDIUMreporting
In the CONSORT diagram, report the number of women screened but not enrolled due to each exclusion criterion.
Reviewer 1 suggested this to improve transparency of the screening process.
6.
MEDIUMstatistics
Report exact p-values for all secondary outcomes, even if not adjusted for multiplicity, in the main text or supplementary tables.
Reviewer 1 suggested this to enhance transparency and allow readers to assess the strength of evidence.
7.
MEDIUMstatistics
Add a sensitivity analysis for the primary outcome using a per-protocol population to complement the ITT analysis.
Reviewer 1 suggested this to assess the robustness of the primary result to protocol deviations.
8.
MEDIUMdata code
Provide a data dictionary or codebook alongside the deposited figshare data to facilitate reuse.
Reviewer 1 suggested this to improve the usability of the shared data.
9.
LOWreporting
Add a statement about adherence to the CONSORT checklist in the Methods or a reporting summary.
Reviewer 2 suggested this to explicitly confirm compliance with reporting guidelines.
10.
LOWdata code
Consider sharing the statistical analysis code in a public repository, even though code availability is stated as not applicable.
Reviewer 2 suggested this to enhance reproducibility, though it is not required.
11.
LOWreporting
Add a note on the potential for unmeasured confounding in the subgroup analyses.
Reviewer 1 suggested this to acknowledge a limitation of subgroup findings.
12.
LOWreporting
Discuss the generalizability of the findings to other sub-Saharan African settings with different malaria prevalence.
Reviewer 1 suggested this to contextualize the results for broader applicability.

Full text (65,148 chars)Analyzed: Aug 16, 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.

Ferric carboxymaltose for anemia in late pregnancy: a randomized controlled trial.

DOI

10.1038/s41591-024-03385-w

Record issued

2026-08-16

Engine

7.39.0

Exported

2026-09-21