Statistical, Methods, and Reproducibility Review

This guide supports structured questions; it does not replace a statistician, methodologist, domain expert, or independent reanalysis. Sources reviewed on 2026-10-01, with source-specific verification limits, are recorded in assets/source_ledger.csv.

Evidence hierarchy for the review

Use, in order:

1. The stated research question and target population
2. Protocol, registration, analysis plan, and amendments
3. Reported design and data-generating process
4. Methods, code, tables, figures, supplements, and repository records
5. Applicable primary method or regulatory guidance
6. Current reporting guidance
7. Target venue policy

Do not reject a method merely because another method is more familiar. Explain the estimand, assumption, error, or interpretation at stake.

Core review sequence

1. Define what is being estimated

Write down:

• Unit of inference
• Population
• Intervention, exposure, test, or predictors
• Comparator or reference condition
• Outcome and time horizon
• Target effect, association, accuracy, or predictive performance
• Intercurrent events, censoring, and missing observations where relevant

Then trace whether design, data collection, analysis, result, and claim target the same quantity.

For applicable clinical trials, ICH E9(R1) provides a framework for estimands and sensitivity analyses. It is not a universal rule for every study.

2. Reconstruct the design

Identify:

• Prospective, retrospective, cross-sectional, longitudinal, experimental, or observational structure
• Recruitment or sampling frame
• Experimental/observational unit
• Pairing, nesting, clustering, repeated measures, sites, batches, and time
• Allocation, concealment, blinding, matching, or weighting
• Primary and secondary outcomes
• Prespecified versus exploratory analyses

If the design cannot be reconstructed, first request missing reporting. Do not label the design invalid solely because details are absent.

3. Trace every denominator

Reconcile:

• Eligible, enrolled, assigned, treated/exposed, followed, measured, and analyzed units
• Outcome-specific denominators
• Exclusions before and after allocation or measurement
• Missing values and reasons
• Complete-case, imputed, weighted, or model-based analysis populations
• Figure, table, abstract, text, and supplement totals

Report the exact mismatch and locations; do not infer why counts differ.

4. Assess analysis–design alignment

Ask whether the method accounts for:

• Outcome scale and distribution
• Pairing and repeated measures
• Clustering and multilevel structure
• Unequal follow-up, censoring, or competing events
• Sampling weights or matched designs
• Baseline adjustment and prespecified covariates
• Multiplicity and outcome hierarchy
• Model tuning and validation
• Missingness assumptions

The name of a statistical test is not enough. The report should state inputs, model form, uncertainty method, software/version, and relevant diagnostics.

5. Assess estimates and interpretation

Prefer:

• Effect or performance estimates with units
• Compatible uncertainty intervals
• Absolute as well as relative quantities when decision-relevant
• Exact denominators and analysis sets
• Assumption and sensitivity context
• Clinical, biological, policy, or practical relevance distinct from statistical compatibility

The ASA’s six p-value principles include:

• A p-value is about incompatibility with a specified model, not the probability a hypothesis is true.
• Threshold crossing alone should not determine scientific conclusions.
• Transparent reporting of all relevant analyses is required.
• Statistical significance does not measure effect size or importance.
• A p-value alone is not a good measure of evidence.

SAMPL provides concise biomedical statistical reporting guidance. Apply it as reporting guidance, not a universal analysis recipe.

Topic-specific checks

Sample size and precision

Look for:

• Prospective calculation or precision rationale
• Target effect or interval width
• Variance, event rate, prevalence, or accuracy assumptions
• Type I error, power, sidedness, and multiplicity when applicable
• Design effect, clustering, attrition, noncompliance, and missingness
• Model complexity and effective sample size
• Simulation details for complex designs

Do not request observed/post hoc power as a remedy for an imprecise result. Examine the estimate and uncertainty.

Randomized trials

Check:

• Allocation sequence and concealment
• Prespecified estimand and analysis population
• Protocol/registry/outcome consistency
• Baseline adjustment and stratification factors
• Intercurrent events, adherence, treatment switching, and missing data
• Harms and unintended effects
• Sensitivity and supplementary analyses
• Non-inferiority/equivalence margin and interpretation if relevant

Use CONSORT 2025 and SPIRIT 2025 for reporting. Use ICH E9/E9(R1) only when its scope and decision context fit.

Observational causal analyses

Check:

• Causal question and target contrast
• Time zero, eligibility, treatment/exposure assignment, follow-up, and outcome timing
• Confounder rationale and measurement timing
• Positivity/overlap
• Exchangeability and consistency assumptions
• Missingness, censoring, selection, and measurement error
• Model specification and balance diagnostics
• Sensitivity to unmeasured confounding or alternative specifications

Avoid judging causal identification from adjusted versus unadjusted p-values.

Diagnostic accuracy

Check:

• Intended use, setting, and participant spectrum
• Index test and reference standard
• Threshold prespecification
• Blinding and timing
• Indeterminate/missing results
• Verification and incorporation bias
• Two-by-two denominators and uncertainty
• External applicability

STARD/STARD-AI describe reporting; use an appropriate risk-of-bias framework separately.

Prediction models

Check:

• Intended use, prediction time, outcome, and target population
• Data source and participant flow
• Predictor availability at intended use
• Missing-data and preprocessing leakage
• Sample size relative to outcome information and complexity
• Internal validation and optimism correction
• Independent evaluation and dataset shift
• Calibration, discrimination, decision utility, and uncertainty
• Hyperparameter tuning separated from evaluation
• Reproducible model specification and preprocessing
• Subgroup performance tied to plausible use and harms

TRIPOD+AI replaces TRIPOD 2015 for regression and machine-learning prediction model reporting. STARD-AI is more appropriate when diagnostic accuracy of an index test is the primary aim.

Systematic reviews and meta-analyses

Check:

• Protocol and registration
• Eligibility criteria and information sources
• Reproducible search dates and strategies
• Duplicate screening/extraction processes or justified alternatives
• Risk-of-bias assessment
• Effect measure and synthesis model
• Heterogeneity and prediction intervals when appropriate
• Dependence among estimates
• Small-study and reporting biases
• Certainty assessment, if claimed
• Transparent deviations and unavailable data

PRISMA 2020 assesses reporting. Do not substitute PRISMA coverage for review-conduct appraisal.

Clustered and longitudinal data

Check:

• Level of assignment, measurement, and inference
• Within-cluster/subject correlation
• Number and distribution of clusters
• Small-cluster corrections where needed
• Time structure, nonlinear change, and irregular measurement
• Informative visit, dropout, or censoring processes
• Cluster-level versus individual-level covariates

Repeated observations do not increase independent sample size one-for-one.

Multiplicity

Identify the inferential family before recommending adjustment:

• Multiple primary outcomes
• Multiple intervention arms or contrasts
• Repeated time points
• Subgroups and interactions
• Interim analyses
• High-dimensional features
• Model selection

Possible responses include hierarchical testing, family-wise control, false-discovery control, multilevel modeling, transparent exploratory labeling, or emphasis on estimates and uncertainty. The remedy depends on the claim and decision rule.

Missing data

Check:

• Missingness by group, variable, outcome, and time
• Reasons and relation to intercurrent events
• Information used by imputation or weighting
• Number of imputations and pooling when applicable
• Compatibility of imputation and analysis models
• Uncertainty propagation
• Sensitivity to plausible departures from assumptions

Avoid demanding one preferred technique without considering the estimand and missingness process.

Reproducibility review

Materials and provenance

Check:

• Stable identifiers for datasets, samples, models, protocols, and materials
• Raw-to-processed provenance
• Exclusion and transformation records
• Versioned analysis inputs and outputs
• Repository accession numbers
• Data dictionary, units, and coding
• Domain metadata standard where applicable

Legacy domain standards and their current status are summarized in references/reporting_standards.md.

Code and computational environment

Check:

• Executable code for central analyses when sharing is permitted
• Dependency versions or lock/environment file
• Operating-system or hardware requirements that affect results
• Random seeds and nondeterminism
• Parameter, configuration, and model checkpoints
• Run order and instructions
• Tests or validation of custom code
• License and access restrictions

Code availability does not prove that the code generated the reported result. Provenance and a reproducible run record are separate evidence.

Data and access

Open sharing may be limited by consent, privacy, indigenous/community governance, security, contracts, or licensing. A useful statement should identify:

• What exists
• Where it is held
• Who can request access
• Criteria and process
• Expected timeline
• Restrictions and rationale
• Whether code or synthetic/aggregate alternatives are available

Do not request disclosure that would violate ethics, law, consent, or governance.

Independent reproduction

Claim independent reproduction only if the reviewer actually:

1. Obtained authorized inputs.
2. Recorded versions and environment.
3. Ran documented commands.
4. Preserved content hashes or equivalent provenance.
5. Compared prespecified outputs.
6. Recorded deviations and failures.

A static consistency audit is not reproduction.

When to request specialist review

Escalate when a central conclusion depends on methods outside competence, including:

• Complex adaptive, Bayesian, causal, survival, multilevel, spatial, or longitudinal methods
• High-dimensional omics or multiple-testing procedures
• Diagnostic, prediction, or AI evaluation
• Survey weighting or complex sampling
• Economic modeling
• Meta-analysis with dependent effects or network structure
• Unfamiliar qualitative or mixed-methods methodology
• Image forensics, biosecurity, privacy, or domain-specific ethics

Say what expertise is needed and which claim depends on it. Do not mask uncertainty with an automated score.

Using the local checklist

Copy assets/statistical_reproducibility_template.json, record evidence locations without pasting manuscript prose into report fields, and run:

python3 scripts/audit_statistics_reproducibility.py local-checklist.json

Statuses:

• verified_present
• partly_documented
• missing
• not_assessed
• not_applicable with rationale

The tool reports item IDs and counts. It does not calculate merit, rerun analyses, or certify reproducibility.