15-strain live biotherapeutic product or same donor fecal microbiota transplant for recurrent Clostridioides difficile infection: a randomized phase 1b trial.
Bethlehem L, Bartu L, Marke G, Mar P, Feldman S, Eggers J, Ruprecht C, Britton GJ, Aggarwala V, Bongers G, Li Z, Yang N, Hohmann EL, Mogno I, Faith JJ, Grinspan A
- DOI
- 10.1038/s41591-026-04442-2
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-20
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/0bdd60b2-c893-4e3f-83d4-2650c0ef4482 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern ×2−1★
- ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
- ClaimsTreatment effect not shown to be clinically meaningful−0.5★
- ReportingStudy design partially met−0.25★
- ReportingStatistical analysis partially met−0.25★
- 01Efficacy rests on an unvalidated surrogate endpoint
The primary efficacy claim is prevention of recurrent C. difficile infection (rCDI) at 8 weeks, which is a clinical outcome. However, the trial is a phase 1b with small sample size (N=18) and the primary endpoint is safety, not efficacy. The efficacy outcome is recurrence of CDI, which is a clinical event, but the trial is not powered for efficacy and the claim of 'similar efficacy' is based on a small number of events. The surrogate issue arises because the paper also emphasizes engraftment of bacterial strains as a secondary outcome and uses it to support the efficacy claim, but engraftment is a surrogate for clinical benefit. The paper does not provide validated evidence linking engraftment to prevention of rCDI recurrence, and target engagement at the tested dose is not established in terms of a dose-response for clinical outcome. The efficacy claim rests on a small clinical trial with a surrogate (engraftment) used to infer efficacy.
“For secondary outcomes of efficacy and engraftment, recurrent Clostridioides difficile infection was prevented eight weeks after dosing in seven out of nine LBP patients, similar to eight out of nine FMT patients.”
- 02Treatment effect not shown to be clinically meaningful
The reported effect size for the primary efficacy outcome is the prevention of rCDI recurrence at 8 weeks: 7/9 (78%) for LBP and 8/9 (89%) for FMT. This is a small sample size and the difference between groups is not statistically tested. The effect size is not anchored to a minimal clinically important difference, and the small number of events (3 recurrences total) makes the effect size imprecise. The paper does not provide a confidence interval for the difference or a statistical comparison. The effect size is presented as 'similar' but without formal statistical support or clinical meaningfulness anchor.
“recurrent Clostridioides difficile infection was prevented eight weeks after dosing in seven out of nine LBP patients, similar to eight out of nine FMT patients.”
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 1b RCT comparing a defined 15-strain LBP (MTC01) with FMT from the same donor is methodologically sound in its premise, ethics, resource description, data/code availability, and reporting transparency. The main weaknesses are the open-label design, small feasibility-based sample size (18 total, not the planned 15/group), and some statistical reporting gaps (threshold p-values, unverified assumptions, post-hoc analyses).
Both reviewers classified the study as interventional (RCT), and I adopt that. The statistics verification covered only 2 tests (1 consistent, 0 inconsistent) due to limited reporting of test statistics/df; most model-based estimates remain unverified. The citation check found no retracted or unresolved references. The integrity check flagged two low-severity internal contradictions (arm order, AE relatedness) that do not change the overall assessment.
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 1 test: 1 consistent, 0 inconsistent; 1 via agent-written checks.
- CONSISTENTreported p = .004 · recomputed p = <.001Reviewers 1, 2Check p-value for high dose MTC01 vs high dose FMT engraftment difference (β=3.9, 95% CI [1.8,6.0])
“High dose MTC01 had the highest overall number of the 15 strains colonized even when compared with high dose FMT (β = 3.9, 95%CI [1.8,6.0], p=0.004; ).”
Taken as given: The estimate is a linear regression coefficient (not a ratio).; The 95% CI is two-sided.; The p-value is two-sided.Method: Recomputed p-value from the estimate and 95% CI using the normal approximation (pCI).How we recomputed it: pCI(3.9, 1.8, 6.0, 0) - UNCOMPUTABLEreported p = .019 · recomputed p = .006Reviewers 1, 2Check p-value for low dose MTC01 vs high dose FMT engraftment difference (β=-3.2, 95% CI [-5.5,-0.9])
“Low dose MTC01 had the fewest number of strains colonized suggesting a likely dose effect in the LBP recipients (β = −3.2, 95%CI [−5.5,−0.9], p=0.019; linear mixed effects model compared to high dose FMT).”
Taken as given: The estimate is a linear regression coefficient.; The 95% CI is two-sided.; The p-value is two-sided.Method: Recomputed p-value from the estimate and 95% CI using the normal approximation (pCI).How we recomputed it: pCI(-3.2, -5.5, -0.9, 0)
- lowinternal contradictionThe abstract states '18 of 20 screened patients met eligibility and were randomized equally to one of four arms: low dose FMT (N=4), high dose FMT (N=5), low dose MTC01 (N=4), or high dose MTC01 (N=5)' but the results section says 'Twenty subjects were assessed for eligibility with 18 patients dosed (5 high dose FMT, 4 low dose FMT, 5 high dose MTC01, 4 low dose MTC01) and 2 screen failures.' The order of arms differs but the counts are consistent.
18 of 20 screened patients met eligibility and were randomized equally to one of four arms: low dose FMT (N=4), high dose FMT (N=5), low dose MTC01 (N=4), or high dose MTC01 (N=5) ... Twenty subjects were assessed for eligibility with 18 patients dosed (5 high dose FMT, 4 low dose FMT, 5 high dose MTC01, 4 low dose MTC01) and 2 screen failures.
Abstractreviewer’s wording - lowinternal contradictionThe paper states 'no treatment-related adverse events across all four groups' but Table 1 lists adverse events such as C. difficile and diarrhea in MTC01 groups. The text explains these were considered unrelated, but the table does not indicate relatedness.
“no treatment-related adverse events across all four groups”
Table 1Find in source
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
8 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 manufacturing platform is accessible and can accelerate LBP development.The paper provides protocols and regulatory documentation, but the claim of 'accelerate' is not directly tested; it is a reasonable inference.Evidence: Provision of IND, MBRs, and protocols.
“Here we show how an accessible platform to produce human-grade LBPs could accelerate LBP development.”
AbstractFind in source - partialReviewer 2The LBP seed approach allows for the highest population diversity across recipients.The paper shows MTC01 recipients do not cluster as closely with the donor as FMT recipients, but the claim about population diversity is speculative.Evidence: Beta diversity analysis shows MTC01 recipients only partially approach donor microbiota.
“If maintaining microbial population diversity across the human population is a priority , the LBP seed approach with the smallest possible effective community allows for the highest population diversity across recipients as they are not all colonized by nearly identical communities.”
DiscussionFind in source - supportedReviewer 1In vitro manufactured LBP MTC01 has similar efficacy and engraftment to FMT from the same donor.The paper reports similar recurrence rates (7/9 vs 8/9) and high engraftment for both, supporting the claim.Evidence: Recurrence rates and engraftment data in Results.
“recurrent Clostridioides difficile infection was prevented eight weeks after dosing in seven out of nine LBP patients, similar to eight out of nine FMT patients.”
AbstractFind in source - supportedReviewer 1MTC01 strains have higher engraftment frequencies than non-MTC01 strains from the same donor.The post-hoc analysis shows significantly higher engraftment for MTC01 strains, supporting the claim.Evidence: Wilcoxon test results with p-values.
We find the 15 MTC01 strains have significantly higher engraftment frequencies compared to non-MTC01 strains both when administered by FMT or by LBP (FMT median difference=0.67, 95%CI=[0.20,0.87], p=1.1×10−7 ; LBP median difference=0.92, 95% CI=[0.79,0.93], p=4.7×10−11 ; Wilcoxon test; ).
Resultsreviewer’s wording - supportedReviewer 1In vitro manufactured strains colonize human recipients similarly to the same strains from the native human gut.Engraftment data show similar colonization for MTC01 and FMT, supporting the claim.Evidence: Engraftment results.
“we find in vitro manufactured monocultures colonize human recipients similarly to the same bacterial strains cultivated in a human gut with similar efficacy and safety in the treatment of rCDI”
DiscussionFind in source - supportedReviewer 2In vitro manufactured bacteria have similar efficacy and engraftment to the same microbes derived from their native human colon environment for FMT administration.The paper presents data showing similar recurrence rates and engraftment between MTC01 and FMT, supporting the claim.Evidence: Recurrence rates: 7/9 for LBP vs 8/9 for FMT; engraftment data showing high and durable colonization for both.
“recurrent Clostridioides difficile infection was prevented eight weeks after dosing in seven out of nine LBP patients, similar to eight out of nine FMT patients.”
AbstractFind in source - supportedReviewer 2The manufacturing platform is cost- and space-efficient and can accelerate LBP development.The paper provides detailed manufacturing protocols and demonstrates successful production of MTC01, supporting the claim.Evidence: Detailed description of the platform, manufacturing timelines, and release data.
“We developed a novel cost- and space-efficient platform for manufacturing human-grade LBPs for clinical trials.”
IntroductionFind in source - supportedReviewer 2Selecting strains with high FMT engraftment frequencies leads to high LBP engraftment.The post-hoc analysis shows MTC01 strains have higher engraftment frequencies than non-MTC01 strains, supporting the claim.Evidence: Wilcoxon test results: FMT median difference=0.67, p=1.1×10−7; LBP median difference=0.92, p=4.7×10−11.
“We find the 15 MTC01 strains have significantly higher engraftment frequencies compared to non-MTC01 strains both when administered by FMT or by LBP”
ResultsFind in source
Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.
- INADEQUATESurrogate endpointThe primary efficacy claim is prevention of recurrent C. difficile infection (rCDI) at 8 weeks, which is a clinical outcome. However, the trial is a phase 1b with small sample size (N=18) and the primary endpoint is safety, not efficacy. The efficacy outcome is recurrence of CDI, which is a clinical event, but the trial is not powered for efficacy and the claim of 'similar efficacy' is based on a small number of events. The surrogate issue arises because the paper also emphasizes engraftment of bacterial strains as a secondary outcome and uses it to support the efficacy claim, but engraftment is a surrogate for clinical benefit. The paper does not provide validated evidence linking engraftment to prevention of rCDI recurrence, and target engagement at the tested dose is not established in terms of a dose-response for clinical outcome. The efficacy claim rests on a small clinical trial with a surrogate (engraftment) used to infer efficacy.
“For secondary outcomes of efficacy and engraftment, recurrent Clostridioides difficile infection was prevented eight weeks after dosing in seven out of nine LBP patients, similar to eight out of nine FMT patients.”
- INADEQUATEEffect sizeThe reported effect size for the primary efficacy outcome is the prevention of rCDI recurrence at 8 weeks: 7/9 (78%) for LBP and 8/9 (89%) for FMT. This is a small sample size and the difference between groups is not statistically tested. The effect size is not anchored to a minimal clinically important difference, and the small number of events (3 recurrences total) makes the effect size imprecise. The paper does not provide a confidence interval for the difference or a statistical comparison. The effect size is presented as 'similar' but without formal statistical support or clinical meaningfulness anchor.
“recurrent Clostridioides difficile infection was prevented eight weeks after dosing in seven out of nine LBP patients, similar to eight out of nine FMT patients.”
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
2 findings · worst highRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Statistical reporting gaps (tests, assumptions, effect sizes)Assessed
- Study-design details incomplete (controls, blinding, power)Assessed
The introduction cites prior FMT and LBP trials, acknowledges limitations of undefined fecal products, and justifies the need for defined LBPs. The hypothesis that strains with high engraftment frequencies will improve LBP efficacy is logically derived from prior observations. The paper also addresses limitations of prior research by directly comparing the same strains in FMT and LBP forms.
“These shared donor-derived FMT and donor-isolated LBP drug products allowed us to compare the safety, efficacy, and engraftment of the same strains manufactured in vitro with the full spectrum donor sourced FMT fecal slurry at two matched doses.”
“We developed a novel cost- and space-efficient platform for manufacturing human-grade LBPs for clinical trials.”
“fecal-based drugs have little to no overlap in strain composition across the varied donors used in their production – , and therefore the efficacy and safety of such products represent an average across many microbial compositions resulting in uncertainty for individual product batches.”
Randomization method (block randomization) and unit (individual participant) are reported. The trial is open-label, which is stated but not justified. A power analysis is mentioned but not detailed (no effect size, alpha, or power). Inclusion/exclusion criteria are pre-specified. Outlier handling is not explicitly addressed. Controls are inherent (FMT comparator). Independent replication is not applicable for a single trial.
“In this open label trial, patients were block randomized (fixed block size = 4) without stratification to receive either high dose FMT, low dose FMT, high dose MTC01, or low dose MTC01.”
“The study was open label with no concealment of the randomization from the clinical team.”
“An original sample size of 15 subjects per group was selected based off feasibility of manufacturing and the size of prior exploratory studies to assess safety and microbiome engraftment in rCDI.”
“In this open label trial, patients were block randomized (fixed block size = 4) without stratification to receive either high dose FMT, low dose FMT, high dose MTC01, or low dose MTC01.”
“The study was open label with no concealment of the randomization from the clinical team.”
“An original sample size of 15 subjects per group was selected based off feasibility of manufacturing and the size of prior exploratory studies to assess safety and microbiome engraftment in rCDI. The study set in the present analysis are the first 18 patients dosed.”
Sex is reported (15 females, 3 males) and justified by higher incidence in females. Age (median 59.5) and health status (comorbidities listed) are reported. Demographics include race/ethnicity (Hispanic/not-Hispanic). Species/strain and housing conditions are not applicable.
“hispanic | 2 (40%) | 0 (0%) | 1 (20%) | 0 (0%)”
The paper states IRB approval (Icahn School of Medicine IRB, STUDY-23-00563) and that all participants provided written informed consent. Regulatory compliance is implied through IND submission and FDA interactions.
“Ethical approval was obtained from the (Icahn School of Medicine IRB, STUDY-23-00563), and all participants provided written informed consent prior to enrolment.”
“Patients were consented at Mount Sinai Hospital under IRB STUDY-23–00563”
“all participants provided written informed consent prior to enrolment.”
MTC01 strains are identified by species and source; manufacturing details are extensive. FMT is described with donor and processing. Software (Strainer, Metaphlan4, R packages) is named with versions. Antibodies, cell lines, and mycoplasma testing are not applicable.
“Drug candidate “Microbiome Translational Center drug 01” (MTC01) is composed of 15 obligate anaerobe bacterial strains isolated from a single FMT donor (D283)”
“Linear mixed effects models, using the lme4 R package”
Tests (linear mixed effects, Wilcoxon) are named. Assumptions are not explicitly verified. Exact p-values are sometimes given (e.g., p=0.004) but also thresholds (p<1.0×10−8). Effect sizes with CIs are reported. Software is identified. Data presentation includes individual data points in figures. Mathematical plausibility checks were not possible for most statistics.
“High dose MTC01 had the highest overall number of the 15 strains colonized even when compared with high dose FMT (β = 3.9, 95%CI [1.8,6.0], p=0.004; ).”
Data availability statement names a repository (PRJNA1322507) for metagenomic data and mentions supplementary materials. Code is available on GitHub. Individual clinical metadata are in supplementary tables. Managed access is not needed as data are not identifiable.
“Custom code used for strain tracking is available at GitHub ( https://github.com/jeremiahfaith/strainer2 ).”
“Metagenomic sequencing data are available at PRJNA1322507 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1322507)”
“Custom code used for strain tracking is available at GitHub ( https://github.com/jeremiahfaith/strainer2 ).”
Trial registration (NCT05911997) is provided. Methods are comprehensive. CONSORT checklist is mentioned. All outcomes are reported. Limitations are discussed (manufacturing time, endoscopic delivery). Conclusions are proportional. Funding and competing interests are stated.
“ClinicalTrials.gov (http://ClinicalTrials.gov) identifier: NCT05911997”
“A key limitation to the manufacturing process used here is the time restriction of only manufacturing two strains per week, which could be prohibitive to produce very large consortia.”
“ClinicalTrials.gov (http://ClinicalTrials.gov) identifier: NCT05911997”
“A key limitation to the manufacturing process used here is the time restriction of only manufacturing two strains per week”
Registered (1 ID: ClinicalTrials.gov). Reporting guideline cited: CONSORT.
Broken references and links
None foundReferences 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.
Checked — nothing surfaced.
Checked 70 references by DOI: 65 verified — 5 no DOI (shown, not verified).
- NO DOIFecal Microbiota for Transplantation: Safety Alert - Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic OrganismsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIFecal Microbiota for Transplantation: Safety Communication- Risk of Serious Adverse Reactions Due to Transmission of Multi-Drug Resistant OrganismsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEarly Clinical Trials with Live Biotherapeutic Products: Chemistry, Manufacturing, and Control InformationNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIstrainer2 algorithm for detecting bacterial strains inside metagenomesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIFitting Linear Mixed-Effects Models Using lme4No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
2 data/code links checked; 2 live.
- dataBioProjectLIVEHTTP 200https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1322507Resolves to BioProject (data repository).
- codeGitHubLIVEHTTP 200https://github.com/jeremiahfaith/strainer2Resolves to GitHub (code repository).
Copyediting
6 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 6 minor suggestions below.
6 copyedit issues flagged: mostly typo, consistency, clarity.
- MINORtypoAbstract“recurrent Clostridioides difficile infection was prevented eight weeks after dosing in seven out of nine LBP patients, similar to eight out of nine FMT patients.”→ Consider rephrasing for clarity: 'recurrent Clostridioides difficile infection was prevented at eight weeks after dosing in seven of nine LBP patients, similar to eight of nine FMT patients.'Minor wording.
- MINORconsistencyResults, Phase-1b clinical trial“The median patient age was 59.5 with 15 females and 3 males”→ Ensure consistency with Table 2 which shows 15 females and 3 males.Consistent.
- MINORclarityOnline Methods, Statistical analyses“number _ MTC 01 _ strains _ detected ~ baseline _ drugDose + ( 1 | patient _ id )”→ Format the model formula clearly, e.g., using LaTeX or a code block.Formatting.
- MINORconsistencyAbstract“18 of 20 screened patients met eligibility and were randomized equally to one of four arms: low dose FMT (N=4), high dose FMT (N=5), low dose MTC01 (N=4), or high dose MTC01 (N=5)”→ Consider reordering the arms consistently (e.g., low dose FMT, high dose FMT, low dose MTC01, high dose MTC01) throughout the paper.The order of arms varies between the abstract and the results section.
- MINORtypoResults, Phase-1b clinical trial“Bifididobacterium pseudocatenulatum”→ Change to 'Bifidobacterium pseudocatenulatum'.Typographical error in the species name.
- MINORclarityMethods, Statistical analyses“number _ MTC 01 _ strains _ detected ~ baseline _ drugDose + ( 1 | patient _ id )”→ Use a more readable notation, e.g., 'number_MTC01_strains_detected ~ baseline_drugDose + (1|patient_id)'.The model notation is difficult to read due to spaces and underscores.
The published work is robust in its core design, ethics, and data sharing, but an informed reader should weigh the open-label design, the small feasibility-based sample size, and the threshold-only p-values when interpreting efficacy claims. The minor internal inconsistencies (arm order, AE relatedness) and the species-name typo are cosmetic and do not warrant an erratum, but the lack of a formal power analysis and assumption checks are worth noting in any independent re-analysis.
- 1.HIGHrigorAdd a formal a priori power analysis with effect size, alpha, and power to the Methods section, or explicitly justify the final sample size of 18 patients relative to the original 15-per-group target.The current power analysis is feasibility-based and the final sample size deviates from the stated target, which weakens the statistical foundation for efficacy claims.
- 2.HIGHrigorProvide a rationale for the open-label design and describe any blinding measures for outcome assessors, or acknowledge the potential bias in the Discussion.The open-label design with no concealment is a known source of bias that should be explicitly justified or mitigated.
- 3.HIGHstatisticsReport exact p-values for all statistical tests instead of threshold-only values (e.g., p<1.0×10−8) in the Results section.Threshold-only p-values reduce transparency and prevent readers from assessing the strength of evidence.
- 4.HIGHstatisticsAdd a statement on verification of statistical assumptions (e.g., normality, homoscedasticity) for the linear mixed effects models in the Methods.Assumption checks are currently not reported, which is a standard expectation for model-based analyses.
- 5.HIGHstatisticsClarify how outliers were handled in the statistical analyses, or explicitly state that no outliers were excluded.Outlier handling is not explicitly described, and readers need to know whether any data points were excluded and why.
- 6.HIGHreportingClarify the post-hoc nature of the engraftment frequency comparison and its exploratory status in the Methods or Results.Some analyses appear post-hoc; pre-registering or labeling them as exploratory improves transparency.
- 7.MEDIUMreportingInclude a CONSORT flow diagram in the main text (currently only mentioned in supplementary).A CONSORT flow diagram is a standard reporting element for RCTs and improves completeness.
- 8.MEDIUMreportingAdd a note in Table 1 indicating whether each adverse event was considered treatment-related, to reconcile with the text stating 'no treatment-related adverse events'.The current table lists AEs without relatedness, creating an apparent contradiction with the text.
- 9.MEDIUMreportingStandardize the order of trial arms (low dose FMT, high dose FMT, low dose MTC01, high dose MTC01) consistently across the Abstract and Results.The arm order differs between the abstract and results, which is a minor consistency issue that could confuse readers.
- 10.MEDIUMcopyeditFix the typo 'Bifididobacterium pseudocatenulatum' to 'Bifidobacterium pseudocatenulatum' in the Results section.The species name is misspelled, which is a factual error in a scientific name.
- 11.MEDIUMdata codeProvide exact version numbers for all software used (e.g., R version, lme4 version) in the Methods.Exact software versions are needed for reproducibility.
- 12.MEDIUMdata codeConsider depositing the full de-identified clinical dataset in a repository with managed access to enhance reproducibility.While supplementary tables are provided, a managed-access repository would strengthen data sharing for a clinical trial.
- 13.LOWcopyeditRephrase the abstract sentence 'recurrent Clostridioides difficile infection was prevented eight weeks after dosing in seven out of nine LBP patients' to 'prevented at eight weeks after dosing in seven of nine LBP patients' for clarity.Minor wording improvement for readability.
- 14.LOWcopyeditFormat the model formula 'number _ MTC 01 _ strains _ detected ~ baseline _ drugDose + ( 1 | patient _ id )' using readable notation (e.g., LaTeX or code block).The current formatting is difficult to read due to spaces and underscores.
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.