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Stewardship Prompts to Improve Antibiotic Selection for Urinary Tract Infection: The INSPIRE Randomized Clinical Trial.

Name: Αlpha¹ Rigor Record — Stewardship Prompts to Improve Antibiotic Selection for Urinary Tract Infection: The INSPIRE Randomized Clinical Trial.
Item: Stewardship Prompts to Improve Antibiotic Selection for Urinary Tract Infection: The INSPIRE Randomized Clinical Trial.
Rating: 96
Author: Αlpha¹

Gohil SK, Septimus E, Kleinman K, Varma N, Avery TR, Heim L, Rahm R, Cooper WS, Cooper M, McLean LE, Nickolay NG, Weinstein RA, Burgess LH, Coady MH, Rosen E, Sljivo S, Sands KE, Moody J, Vigeant J, Rashid S, Gilbert RF, Smith KN, Carver B, Poland RE, Hickok J, Sturdevant SG, Calderwood MS, Weiland A, Kubiak DW, Reddy S, Neuhauser MM, Srinivasan A, Jernigan JA, Hayden MK, Gowda A, Eibensteiner K, Wolf R, Perlin JB, Platt R, Huang SS

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Αlpha¹ Rigor Review — 1.25★ (Critical), 0 critical, 5 high issues for “Stewardship Prompts to Improve Antibiotic Selection for Urinary Tract Infection: The INSPIRE Randomized Clinical Trial.”

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Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · August 16, 2026

Αlpha¹ Rigor Review

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 ×3−1.5★
ClaimsOverstated claim ×2−1★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★
ReportingData & code availability partially met−0.25★

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

Not verified in this report

No data or code availability links were detected to verify.

Problems surfaced6 types

Numerical inconsistencies1

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

Overstated conclusions3

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
Conclusions overstated beyond the evidenceAssessed

Data authenticity concerns1

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.

Other integrity concernAssessed

Reporting gaps1

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.

Data/code availability incompleteAssessed

This Αlpha¹ Rigor Review uses AI 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-designed cluster-randomized trial with rigorous methodology, clear reporting, and appropriate statistical analysis. The main weakness is the vague data availability statement, which lacks a concrete access route. Minor reporting gaps include lack of explicit blinding description and retrospective trial registration.

Both reviewers classified the study as interventional, and I adopt that. The evaluation covered the full text, including methods, results, and supplements referenced. Non-applicable criteria (e.g., blinding, species/strain, reagents) were excluded from scoring. The statistics verification covered only a subset of tests; the rest are unverified but not flagged.

7 major claims checked against the paper's own evidence: 2 not fully backed by the presented evidence (unsupported or overstated).

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

Recomputed 3 tests: 3 consistent, 0 inconsistent; 3 via agent-written checks.

3 integrity concerns flagged (0 high).

Reporting

Eight Dimensions7 pass · 1 warn

The introduction cites prior studies on UTI burden, antibiotic overuse, and stewardship strategies, and acknowledges gaps (e.g., few studies address empiric selection before culture results). The rationale for using patient-specific MDRO risk estimates to guide empiric therapy is clearly articulated. Limitations of prior work are implicitly addressed by the novel risk-based prompt approach.

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 prior work cited and a logical rationale linking the problem of antibiotic overuse to the intervention.

Evidence

paraphrase[Introduction, paragraph 1-2]

“Few studies have addressed reducing unnecessary extended-spectrum antibiotic use among hospitalized patients with UTI before culture results return.”

paraphrase[Introduction, paragraph 2]

“Successfully identifying patients with low risk for MDRO UTI could reduce empiric extended-spectrum antibiotic exposure.”

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise with prior work cited and a logical rationale linking the problem of antibiotic overuse to the intervention.

Evidence

paraphrase[Introduction, paragraph 1-2]

“Few studies have addressed reducing unnecessary extended-spectrum antibiotic use among hospitalized patients with UTI before culture results return.”

paraphrase[Introduction, paragraph 2]

“Successfully identifying patients with low risk for MDRO UTI could reduce empiric extended-spectrum antibiotic exposure.”

paraphrase[Introduction, paragraph 2]

“Paraphrase: The introduction notes that prior stewardship efforts focused on diagnostic stewardship and de-escalation, but not on empiric selection, which this study addresses.”

Randomization method is described (1:1 ratio within matched pairs using Mahalanobis distance). Unit of randomization is the hospital (cluster). Blinding is not applicable in this pragmatic trial; the paper does not mention blinding, but it is not required for this design. Power analysis is reported (97% power to detect 12.5% difference). Inclusion/exclusion criteria are pre-specified (noncritically ill adults, UTI discharge codes, exclusions for prison and early ICU transfer). Outlier handling is addressed through sensitivity analyses and pre-specified analysis populations. Controls are the routine stewardship group. Independent replication is not applicable for a single pivotal trial.

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsN/A

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: cluster randomization with pairing, pre-specified outcomes, power analysis, and appropriate statistical methods.

Evidence

paraphrase[Methods, Randomization]

“Hospitals were randomized in a 1:1 ratio to routine care or the intervention group... Randomization was performed within these pairs.”

paraphrase[Methods, Trial Outcomes]

“The study had 97% power (95% CI, 91%-99%) to detect a 12.5% difference in extended-spectrum days of therapy between the intervention and routine stewardship groups during the first 3 days”

PASSReviewer 2· 95% conf

The cluster-randomized design is rigorous with adequate randomization, blinding considerations, power analysis, and pre-specified outcomes.

Evidence

paraphrase[Methods, Randomization]

“Randomization was performed within these pairs.”

paraphrase[Methods, Trial Outcomes]

“The study had 97% power (95% CI, 91%-99%) to detect a 12.5% difference in extended-spectrum days of therapy between the intervention and routine stewardship groups during the first 3 days”

absence[Methods, Study Design and Intervention]

Blinding is not explicitly described.

Sex is reported for all groups (e.g., 30.5% male overall). Age is reported as mean (SD) and in age bands. Demographics include race/ethnicity, insurance type, and Elixhauser comorbidity counts. Since both sexes are enrolled, sex justification is not applicable. 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

Demographic and clinical characteristics are thoroughly reported, including age, sex, race, and comorbidities.

Evidence

direct quote[Abstract, Results]

“the mean (SD) age was 69.4 (17.9) years, 30.5% were male”

paraphrase[Table 1]

“Male 10,739 (30.5) ... Female 24,382 (69.2)”

PASSReviewer 2· 90% conf

Demographic and clinical characteristics are well reported, including sex, age, and comorbidities.

Evidence

direct quote[Abstract, Results]

“the mean (SD) age was 69.4 (17.9) years, 30.5% were male”

direct quote[Methods, Data Collection]

“Race and ethnicity were included as collected in the HCA electronic health record to address population diversity and generalizability.”

paraphrase[Abstract, Results]

“the median Elixhauser Comorbidity Index count was 4 (IQR, 2-5)”

The paper states that the Harvard Pilgrim Health Care Institute IRB provided centralized oversight with reliance agreements, and informed consent was waived. This satisfies both IRB approval and consent handling. Regulatory compliance is implied by adherence to CONSORT and mention of national guidance, though not explicitly named as a framework; however, the IRB statement is adequate.

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 approval and consent waiver are clearly documented.

Evidence

paraphrase[Methods, Hospital Recruitment and Study Cohort Definition]

“The Harvard Pilgrim Health Care Institute Institutional Review Board provided centralized oversight, with reliance agreements and operational committee approvals from all participating hospitals. Individual informed consent was waived.”

PASSReviewer 2· 95% conf

Ethical approval and consent waiver are clearly documented.

Evidence

paraphrase[Methods, Hospital Recruitment and Study Cohort Definition]

direct quote[Methods, Hospital Recruitment and Study Cohort Definition]

“Individual informed consent was waived.”

direct quote[Abstract, Trial Registration]

“ClinicalTrials.gov Identifier: NCT03697096”

The intervention is a CPOE prompt system, not a drug or device; the paper describes the algorithm and its components. Statistical software is identified (SAS 9.4, R 4.0.0). No antibodies, cell lines, or organisms are used, so those criteria are not applicable. The CPOE algorithm is described in detail, and the risk model is referenced.

Sub-criteria

mycoplasma testingN/A

reagents identifiedN/A

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational product (CPOE prompts) and software are adequately identified; no bench reagents are used.

Evidence

direct quote[Methods, Statistical Analysis]

“All analyses were performed using SAS (version 9.4; SAS Institute) or R (version 4.0.0; R Project for Statistical Computing).”

PASSReviewer 2· 85% conf

The investigational product (CPOE prompt) is described, and software tools are identified.

Evidence

direct quote[Methods, Statistical Analysis]

“All analyses were performed using SAS (version 9.4; SAS Institute) or R (version 4.0.0; R Project for Statistical Computing).”

paraphrase[Methods, Study Design and Intervention]

“The CPOE algorithm and prompt were activated when extended-spectrum antibiotics were ordered in a non-ICU location for an indication of UTI within 72 hours of admission”

Tests are named (generalized linear mixed-effects models, proportional hazards models). Assumptions are handled by design (clustering, pre-specified models). Exact p-values are reported (e.g., P < .001). Effect sizes with 95% CIs are provided for primary and secondary outcomes. Software is identified. Data presentation includes per-group n and rates; individual data points are not expected for a large trial. Mathematical plausibility checks: the reported percentages and counts appear consistent; no arithmetic errors detected.

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 and effect sizes with CIs.

Evidence

paraphrase[Abstract, Results]

“the group using CPOE prompts had a 17.4% (95% CI, 11.2%-23.2%) reduction in empiric extended-spectrum days of therapy (rate ratio, 0.83 [95% CI, 0.77-0.89]; P < .001).”

PASSReviewer 2· 90% conf

Statistical methods are appropriate and well-described, with exact p-values and effect sizes with CIs.

Evidence

paraphrase[Methods, Statistical Analysis]

“Outcomes were assessed using generalized linear mixed-effects models to assess differences between the baseline and intervention periods.”

paraphrase[Abstract, Results]

“P < .001”

paraphrase[Abstract, Results]

“17.4% (95% CI, 11.2%-23.2%) reduction”

The paper states 'Data Sharing Statement: See Supplement 3.' This is a placeholder, not a concrete access route. No repository or accession numbers are provided. Since this is a clinical trial with patient data, managed access is acceptable, but the statement lacks specifics. Code sharing is not mentioned.

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositNOT REPORTED

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

Data availability statement is present but vague; no repository deposit or code sharing.

Evidence

paraphrase[End of paper]

“Data Sharing Statement: See Supplement 3.”

WARNReviewer 2· 80% conf

Data availability statement is present but vague, and no code is shared.

Evidence

paraphrase[End of paper]

“Data Sharing Statement: See Supplement 3.”

absence[Data Sharing Statement]

No repository deposit is mentioned.

absence[Data Sharing Statement]

No code sharing is mentioned.

Trial registration is provided (NCT03697096). CONSORT guidelines are referenced. All pre-specified outcomes are reported, including safety outcomes. Limitations are explicitly discussed. Conclusions are proportional to the evidence. Funding and conflicts of interest are disclosed.

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· 90% conf

Reporting is transparent: trial registered, CONSORT referenced, limitations discussed, conclusions proportional, funding and COI disclosed.

Evidence

direct quote[Abstract, Trial Registration]

“Trial Registration ClinicalTrials.gov Identifier: NCT03697096”

paraphrase[Discussion, Limitations]

“There are several limitations to this study. First, because the prompts were designed to conservatively identify low-risk patients...”

PASSReviewer 2· 95% conf

The trial is registered, follows CONSORT, reports all outcomes, discusses limitations, and provides funding/COI statements.

Evidence

direct quote[Abstract, Trial Registration]

“ClinicalTrials.gov Identifier: NCT03697096”

paraphrase[Methods, Hospital Recruitment and Study Cohort Definition]

“Results are reported according to CONSORT guidelines.”

direct quote[Discussion, Limitations]

“There are several limitations to this study.”

4 copyedit issues flagged: mostly consistency, typo, clarity.

Checked 35 references by DOI: 32 verified — 3 no DOI (shown, not verified).

Reproducibility

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

The published work is robust and credible, with strong methodology and transparent reporting. An informed reader should weigh the vague data sharing statement and the retrospective registration as minor limitations, but neither undermines the validity of the findings. No erratum is warranted based on the identified issues.

1.
HIGHdata code
Replace the placeholder 'Data Sharing Statement: See Supplement 3' with a concrete statement specifying a managed-access platform (e.g., YODA, Vivli) or a data-access committee with conditions and timeframe.
A vague data sharing statement is a reporting gap that limits reproducibility and is a common reviewer concern.
2.
HIGHdata code
Add a statement about code availability, even if it is 'available on request', to clarify whether analysis scripts are shared.
Code sharing is not mentioned, and providing it would enhance reproducibility.
3.
HIGHreporting
Clarify the blinding status of outcome assessors in the Methods section, even if the intervention is unblinded to clinicians.
Reviewer 2 flagged blinding as inadequately reported; a brief statement would resolve this.
4.
HIGHreporting
Temper the claim that the intervention could reduce unnecessary antibiotics in up to 200,000 US adults annually, as this extrapolation is not directly demonstrated by the trial.
The claim audit flagged this as overstated; the conclusion should be limited to what the trial directly shows.
5.
HIGHreporting
Temper the claim that the intervention is a viable strategy to reduce extended-spectrum antibiotics in up to 200,000 adults annually, as it extrapolates beyond the study population.
The claim audit flagged this as overstated; the conclusion should be limited to what the trial directly shows.
6.
MEDIUMreporting
Add a note in the Methods or Discussion acknowledging that trial registration was retrospective (submitted after the study start date).
The integrity check flagged this; transparency about registration timing is important for readers.
7.
MEDIUMreporting
Consider providing a CONSORT flow diagram in the main text to improve transparency of participant flow.
Reviewer 2 suggested this; it would enhance reporting completeness.
8.
MEDIUMstatistics
Include a note on the handling of missing data for the primary outcome in the statistical analysis section.
Reviewer 2 suggested this; it would clarify the analysis approach.
9.
MEDIUMreporting
Specify the version of the MEDITECH EHR system used, as it may affect generalizability.
Reviewer 2 suggested this; it would improve reproducibility.
10.
MEDIUMreporting
Provide more detail on the validation of the MDRO risk prediction model, including discrimination and calibration metrics.
Reviewer 2 suggested this; it would strengthen the methods.
11.
MEDIUMreporting
Consider reporting the number of patients who were excluded due to ICU transfer within 2 days, to clarify the cohort definition.
Reviewer 2 suggested this; it would improve transparency.
12.
LOWcopyedit
Add a comma after 'Nickolay' in the author list for consistency with other authors.
Minor formatting inconsistency flagged by copyedit.
13.
LOWcopyedit
Use consistent number formatting: change '27 907' to '27,907' in the Results section.
Inconsistent number formatting flagged by copyedit.
14.
LOWcopyedit
Consider moving the sentence 'The a priori statistical analytic plan is provided in Supplement 1' to the beginning of the Statistical Analysis section for clarity.
Minor organizational suggestion from copyedit.

Full text (55,265 chars)Analyzed: Aug 16, 2026

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Stewardship Prompts to Improve Antibiotic Selection for Urinary Tract Infection: The INSPIRE Randomized Clinical Trial.

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DOI

10.1001/jama.2024.6259

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Issued Aug 16, 2026Engine 7.39.0

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