mcpbeat

Meta Analysis

aperivue/meta-analysis

Systematic review and meta-analysis pipeline for medical research. Covers protocol registration (PROSPERO), search strategy, screening, data extraction, risk of bias assessment (QUADAS-2/ROBINS-I), statistical synthesis (bivariate/HSROC for DTA, random-effects for intervention), and PRISMA-compliant reporting. Supports both DTA and intervention meta-analyses.

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Install

one command, takes just this skill from the repository
npx skills add https://github.com/Aperivue/medsci-skills --skill meta-analysis

The instruction itself

27 sections, as written by the author

Meta-Analysis Skill

You are helping a medical researcher conduct a systematic review and meta-analysis.

You support the full pipeline from protocol development to submission-ready manuscript,

with specialized support for diagnostic test accuracy (DTA) meta-analyses.

Communication Rules

  • Communicate with the user in their preferred language.
  • All output documents, code, and checklists in English.
  • Medical terminology always in English.

Reference Files

Built-in References (${CLAUDE_SKILL_DIR}/references/)

  • PROSPERO template: ${CLAUDE_SKILL_DIR}/references/PROSPERO_template.md -- field-by-field guide with word limits, pitfalls checklist
  • ICMJE COI guide: ${CLAUDE_SKILL_DIR}/references/icmje_coi_guide.md -- batch generation, python-docx pitfalls, form structure
  • R templates: ${CLAUDE_SKILL_DIR}/references/r_templates.md
  • Checklists: ${CLAUDE_SKILL_DIR}/references/checklists/
  • PRISMA_DTA.md -- 27-item checklist
  • QUADAS2.md -- 4 domains + signalling questions
  • ROBINS_I.md -- 7 domains + pre-assessment + synthesis recommendation
  • RoB2.md -- 5 domains + signalling questions + overall judgment
  • PROBAST.md -- 4 domains + AI extension + validation studies
  • NOS.md -- Cohort (8 items) + Case-control (8 items) + star interpretation
  • JBI_Case_Series.md -- 10-item critical appraisal checklist for case series
  • Phase 9 Co-author Circulation: ${CLAUDE_SKILL_DIR}/references/phase9_circulation.md -- thread continuity, attachment scope, recipient structure, 7-day window
  • Phase 10 Self-Audit Recovery: ${CLAUDE_SKILL_DIR}/references/phase10_recovery.md -- trigger conditions, 12-step rebuild sprint, PROSPERO amendment, re-circulation framing
  • Data integrity checklist: ${CLAUDE_SKILL_DIR}/references/data_integrity_checklist.md -- DI-1~DI-9 extraction/synthesis guardrails (prior anonymized MA projects)
  • Review orchestration: ${CLAUDE_SKILL_DIR}/references/review_orchestration.md -- RO-1~RO-5 circulation discipline (extends phase9_circulation.md)
  • Submission package drift: ${CLAUDE_SKILL_DIR}/references/submission_package_drift.md -- multi-journal folder hygiene, DO_NOT_EDIT_HERE gate, _build.sh pattern
  • Post-submission release ops: ${CLAUDE_SKILL_DIR}/references/post_submission_release_ops.md -- Zenodo DOI gating, tag-cleanup gates, reject-retarget versioning
  • Empirical peer-review lessons: ${CLAUDE_SKILL_DIR}/references/empirical_lessons.md -- 16 accumulated SR-MA peer-review / submission lessons (2026-05/06) that drive the Phase 4 extraction-form schema, Phase 4c QC, and Phase 8 submission gates. Load before designing the extraction form and before submission.

Built-in Templates (${CLAUDE_SKILL_DIR}/templates/)

  • Extraction Form v2 (templates/extraction_form_v2.md) -- dual-extractor schema with source_page_ref, source_verbatim_quote, cohort_source, overlap_flag_reviewer1/2, sample_n_dta_pool vs sample_n_prognostic_pool columns. Required for SR-MA targeting high-impact radiology / medical AI journals.
  • Supplementary 8-file Checklist (templates/supplementary_8file_checklist.md) -- S1-S8 mandatory package (PRISMA, PROSPERO, search strategy, exclusion list, extraction table, per-study x per-domain RoB, subgroup forests, sensitivity / publication bias) with a submission-gate bash check.

Built-in Scripts (${CLAUDE_SKILL_DIR}/scripts/)

  • screening_reconcile.py -- Phase 3f ID-set screening reconciliation.
  • check_pool_consistency.py -- pool-composition / PRISMA count consistency.
  • cohort_overlap_check.py -- shared-database cohort-overlap detection.
  • extract_assist.py -- Phase 4 AI-assisted extraction *suggestions* (page ref + verbatim quote, AI_SUGGESTED/needs_review); human-confirm then dta_extraction_qc.py. Challenge card: scripts/extract_assist_challenge/.
  • dta_extraction_qc.py -- 2x2 cell ↔ source sens/spec QC on the confirmed extraction CSV.

Meta-Analysis Types

| Type | RoB Tool | Statistical Model | Reporting Guideline |

|------|----------|-------------------|-------------------|

| DTA (diagnostic test accuracy) | QUADAS-2 | Bivariate / HSROC | PRISMA-DTA |

| Intervention (treatment effect) | RoB 2 (RCT) / ROBINS-I (NRSI) | Random-effects (DL/REML) | PRISMA 2020 |

| Prognostic (prediction model) | QUIPS / PROBAST | Random-effects | PRISMA 2020 |

| Observational (prevalence/association) | NOS / JBI | Random-effects | MOOSE |

Auto-detect type from the research question or accept user specification.


Workflow Phases

Phase 1: Protocol Development

Goal: Produce a PROSPERO-ready protocol document.

  • Structure the research question:
  • DTA: PIRD (Population, Index test, Reference standard, Diagnosis)
  • Intervention: PICO (Population, Intervention, Comparator, Outcome)
  • Define eligibility criteria:
  • Study design (cross-sectional DTA, cohort, RCT, etc.)
  • Population characteristics
  • Index test / intervention specifics
  • Comparator / reference standard
  • Outcome measures (Se/Sp for DTA; effect size for intervention)
  • Exclusion criteria with justification
  • Plan the search:
  • Minimum 3 databases: PubMed, Embase, and Cochrane CENTRAL (add Scopus, Web of Science as needed)
  • Draft Boolean search strategy using PIRD/PICO components
  • Grey literature plan (conference abstracts, trial registries)
  • Language restrictions (state explicitly)
  • Date range with justification
  • Plan RoB assessment:
  • Select tool based on type (see table above)
  • State number of independent assessors (minimum 2)
  • Plan for disagreement resolution (consensus, third reviewer)
  • Plan synthesis:
  • DTA: bivariate random-effects model (Reitsma) or HSROC (Rutter & Gatsonis)
  • Intervention: random-effects (DerSimonian-Laird or REML)
  • Heterogeneity assessment plan
  • Subgroup / sensitivity analysis plan
  • Publication bias assessment plan
  • Generate PROSPERO registration document:
  • Read ${CLAUDE_SKILL_DIR}/references/PROSPERO_template.md for field-by-field guidance
  • Generate all fields with word counts (stay within limits per field)
  • Structure: title, review question, PICO, searches, data collection, outcomes, synthesis, subgroups, stage, affiliation
  • Registration-ID format gate. A PROSPERO ID is CRD42 + 9 digits (14 characters total), e.g. CRD42024500001. Validate any ID that appears in the manuscript or registration doc with grep -oE 'CRD42[0-9]+' and assert a 14-character length / ^CRD42\d{9}$ — a 15-character ID (a stray digit) is a transcription error a reviewer will check against the live record.
  • Review-type selection. Pick the *least-wrong* portal review type for the actual design and state any portal constraint in the protocol. A descriptive single-arm proportion synthesis is not an "Intervention review"; choosing "Intervention review" only to satisfy a portal field contradicts a later GRADE / effect-certainty statement. Whatever certainty language the protocol commits to (GRADE vs "evidence statements only") must match the manuscript verbatim — a guideline-style "we recommend" is not licensed by a descriptive review type.
  • For mixed designs (comparative + single-arm): explicitly address comparator for both arms
  • For RoB: map tool to study design (NOS for comparative, JBI for case series → select "Other" in form)
  • Output: Markdown + DOCX (via pandoc) for copy-paste into PROSPERO web form
  • Append Common Pitfalls Checklist (HTML entities, word limits, stage constraint)
  • Save to project 7_Submission/ or equivalent directory

Phase 2: Search Strategy

Goal: Develop and validate reproducible search strategies.

  • Build search blocks from PIRD/PICO:
  • Population block (MeSH + free text)
  • Index test / Intervention block
  • Comparator / Reference standard block (optional)
  • Study design filter (if applicable)
  • Combine with Boolean operators:
  • Within blocks: OR
  • Between blocks: AND
  • Execute search per database using /search-lit:
  • PubMed: MeSH + free text
  • Embase: Emtree + free text
  • Additional databases as specified in protocol
  • Report search per PRISMA-S (Rethlefsen et al. 2021, PMID:33499930):

Save search strategies as a structured document, one section per database,

with date of search, number of results, and any limits applied.

  • Merge and deduplicate: Combine all database results into a single spreadsheet.

Deduplicate by DOI first, then PMID. Save raw counts for PRISMA flow.

Phase 3: Screening & Selection

Goal: Systematic title/abstract and full-text screening with two independent reviewers.

3a. Round 1 — initial title/abstract screening (single reviewer). Define the exclusion codes

from the protocol (E1=Not target population, E2=Not intervention, E3=Ineligible type, E4=Non-human,

E5=Duplicate). Mark every record INCLUDE / EXCLUDE / MAYBE with a reason code → round1_{date}.tsv.

3b. Round 2 — dual independent title/abstract screening. A second independent reviewer (or AI

as a *documented* second-pass tool with human verification) re-screens all R1 records. Compute

Cohen's κ and report it in Methods. round2_tag = INCLUDE / EXCLUDE / MAYBE, where MAYBE means

disagreement or either reviewer flagged uncertainty → round2_tag, round2_reason columns.

3c. Round 3 — adjudication of disagreements (first reviewer). Build the R3 sheet with all MAYBE

records first, then INCLUDE records for a brief confirmation pass. The first reviewer independently

adjudicates each row (round3_decision, plus round3_reason only when overturning R2). Optional

AI-assisted pre-screening can compress the effort — but AI suggestions are not decisions: the

reviewer independently confirms or overturns every one. Template, sort priority, and the required

Methods boilerplate are in the reference file.

3d. Round 4 — full-text screening. Retrieve full texts for round3_decision = INCLUDE (use

/fulltext-retrieval), apply the full-text exclusion codes (F1=No extractable outcome, F2=No

comparative data, F3=Cannot separate target population, F4=Inadequate sample/follow-up,

F5=Full-text unavailable), with two independent reviewers, Cohen's κ, and consensus or a third

reviewer for disagreements. Flag comparative studies for priority extraction.

3e. PRISMA flow. Track counts at every stage (R1 → R2 → R3 → R4 → final included); generate the

diagram with /make-figures once the numbers are final.

3f. Post-consensus count reconciliation gate (MANDATORY before Phase 5 write-up). Reconcile the

counts from the raw ID sets, never from prose summaries, and record the canonical totals in one

source-of-truth file:

python "${CLAUDE_SKILL_DIR}/scripts/screening_reconcile.py" \
  --screening 2_Screening/fulltext_screening.tsv \
  --consensus 2_Screening/consensus_decisions.tsv \
  --table1 6_Tables/table1_studies.csv \
  --output 2_Screening/screening_consensus.json

Downstream stages consume screening_consensus.json for counts and ID sets; the Markdown consensus

document remains the human explanation. Three hard rules:

  • List the narrative-only IDs explicitly. The highest-yield red flag is a numeric claim ("10

narrative-only studies") that does not match the enumerable set (A ∪ C) \ B \ T.

  • No "N → M" transition without ID receipts. "k rose from 30 to 32 after FLAG consensus" must

cite the added/removed IDs. A transition claim with no enumerable ID set is a P0 and blocks

the Phase 5 hand-off.

  • STAGE_TRANSFER_LOSS is a P0. Exit 1 when a record is included at screening but **absent

from the consensus artifact altogether** — no adjudication was ever recorded. An exclusion is a

decision; silence is a gap. Never let it settle into narrative-only (why: reference file).

The set algebra, the reconciliation-table template, and the precedent (a manuscript shipped 32/10/46

where the ID sets said 24/2/54, with four artifacts echoing the same unreconciled prose total) are

in the reference file.

3f.5 Pool composition lock (MANDATORY at adjudication freeze). Once 3f passes, freeze the pool

into a single source-of-truth YAML that every downstream artifact can be checked against:

cp "${CLAUDE_SKILL_DIR}/templates/FINAL_POOL_LOCK.yaml.template" 2_Data/FINAL_POOL_LOCK.yaml
# fill counts + UID lists from 3f, compute the SHA-256 over the sorted UID list,
# and COMMIT THE LOCK before any Phase 4 extraction
  • Never re-derive k included from the extraction TSV at manuscript build time — always

reference final_pool_n from the lock.

  • Aggregate patient/lesion totals are locked too, not just study counts. Distinguish

arm-separable from both-arm rows: a study contributing one arm must not have its

full-cohort count folded into a pooled total. A hand-carried headline total that does not

re-derive from the locked per-study values is a P0.

  • A late post-freeze change to the pool is a formal PROSPERO amendment: file it, re-freeze as

FINAL_POOL_LOCK_v2.yaml, and propagate to every artifact.

Read on demand:

| File | Read it when | Cost if read blindly |

|---|---|---|

| references/phase3_screening_detail.md | you are executing a screening round, using AI pre-screening, or a reconciliation/lock gate fired | ~3,600 tokens; the round procedures are needed one round at a time, not all at invocation |

Phase 4: Data Extraction

Goal: Create standardized extraction forms and extract 2x2 or effect-size data.

4.0 Entry gate (MANDATORY) — pool composition lock ↔ adjudication TSV. Before any extraction

work begins, confirm the round-3 adjudication TSV and FINAL_POOL_LOCK.yaml (Phase 3f.5) agree on

which UIDs are included:

python "${CLAUDE_SKILL_DIR}/scripts/check_pool_consistency.py" \
    --lock 2_Data/FINAL_POOL_LOCK.yaml \
    --adjudication-tsv 2_Screening/round3_adjudication.tsv \
    --decision-col round3_decision --uid-col uid \
    --include-labels "INCLUDE,INCLUDE_MIXED" \
    --out qc/pool_consistency.json

The gate fails closed: any UID disagreement blocks extraction. Resolve by re-freezing the lock

with the corrected UID set (and propagating downstream) or by correcting a mis-labelled TSV row. Do

NOT proceed with a mismatch — the extraction matrix will not align with the locked pool, and the

drift surfaces as a fabrication-grade red flag at peer review.

> Failure-mode cross-refreferences/data_integrity_checklist.md DI-1~DI-5 are mandatory

> during extraction (2x2 arm-swap, KM audit trail, methodology mismatch, PRISMA 5-way drift,

> single-source k).

Extraction form. For an SR-MA targeting high-impact radiology / medical AI journals use

${CLAUDE_SKILL_DIR}/templates/extraction_form_v2.md — its dual-extractor, source-page-reference,

and verbatim-quote columns are what close the 2x2 cell-swap and cohort-overlap blind spots. The

DTA and intervention field lists are in the reference file.

AI-drafted starting document — treat as hallucination-suspect. If a mentor or collaborator

shared an AI-drafted study list, 2x2 set, or effect estimates (*even* flagged "for reference

only"): save it with a _DO_NOT_USE_VERBATIM suffix and re-verify every N, denominator, event

count, OR/CI, and author/year against the source PDF. Trust hierarchy: **source PDF + own analysis

stdout > the mentor's direct text > the attached AI draft** — never promote a draft up that ladder.

Procedure and precedent: reference file.

4b. Special cases (KM reconstruction, composite exposure). When studies report outcomes only as

Kaplan-Meier curves, or the intervention is a composite of techniques, load

${CLAUDE_SKILL_DIR}/references/phase4_km_composite.md for the WebPlotDigitizer → IPDfromKM

procedure (cite Guyot et al. 2012, doi:10.1186/1471-2288-12-9) and the 4-path composite-exposure

decision tree. Pre-specify a sensitivity analysis excluding composite-exposure studies.

Cross-verification (≥2 independent reviewers). Report inter-reviewer agreement (% or Cohen's

κ) at title/abstract and full-text stages. Verify denominator consistency — **the denominator may

differ across outcomes within one study**, so for each outcome back-calculate event ÷ denominator

and confirm it reproduces the paper's reported percentage. Distinguish KM-curve estimates from raw

event counts and record the data source (Table / KM / text). Log every consensus decision in

{project}/consensus_log.md, then lock the dataset; later changes need a dated justification.

4c. Extraction QC & cohort overlap. After dual-extractor consensus, run both before locking:

# 2x2 cell integrity: validates TP/FN/TN/FP against source-reported sens/spec (catches arm-swap)
python3 "${CLAUDE_SKILL_DIR}/scripts/dta_extraction_qc.py" \
  --input 2_Extraction/extraction.csv --tolerance 0.02 \
  --out 2_Extraction/qc/dta_extraction_qc.tsv

# cohort overlap: shared public DB / same institution+period / same first author ±2y
python3 "${CLAUDE_SKILL_DIR}/scripts/cohort_overlap_check.py" \
  --input 2_Extraction/studies.csv --enrich \
  --out 2_Extraction/qc/cohort_overlap.md

Any FLAG_SWAP / FLAG_MISMATCH requires third-reviewer adjudication before Phase 6. **A

confirmed flag is not resolved until the extraction form itself is edited** — a flag corrected only

in a review note silently re-enters synthesis, so re-run the QC and confirm zero open flags before

locking. HIGH-confidence overlap pairs require a Limitations acknowledgment plus a sensitivity

analysis excluding one of the pair. Cross-links: /peer-review Phase 2A P1 + P2.

Read on demand:

| File | Read it when | Cost if read blindly |

|---|---|---|

| references/phase4_extraction_detail.md | building the extraction form, an AI draft was shared, you want the optional extract_assist.py scaffolding, or a QC flag fired | ~4,700 tokens; a clean dual-extraction with no AI draft needs none of it |

| references/phase4_km_composite.md | studies report only KM curves, or the exposure is composite | ~2,200 tokens |

Phase 5: Risk of Bias Assessment

Goal: Guide structured RoB assessment with the appropriate tool.

Select tool based on meta-analysis type (see table above), then read the corresponding checklist:

| Tool | Checklist File |

|------|---------------|

| QUADAS-2 (DTA) | ${CLAUDE_SKILL_DIR}/references/checklists/QUADAS2.md |

| RoB 2 (RCT) | ${CLAUDE_SKILL_DIR}/references/checklists/RoB2.md |

| ROBINS-I (NRSI) | ${CLAUDE_SKILL_DIR}/references/checklists/ROBINS_I.md |

| PROBAST (Prediction) | ${CLAUDE_SKILL_DIR}/references/checklists/PROBAST.md |

| NOS (Observational) | ${CLAUDE_SKILL_DIR}/references/checklists/NOS.md |

| JBI (Case Series) | ${CLAUDE_SKILL_DIR}/references/checklists/JBI_Case_Series.md |

For AI/ML prediction models, also apply PROBAST+AI extensions.

Output: Summary table + traffic light plot (use /make-figures).

Phase 6: Statistical Synthesis

Goal: Execute meta-analysis and generate publication-ready outputs.

> Failure-mode cross-refreferences/data_integrity_checklist.md DI-6/DI-7/DI-9 are the consistency gate (CSV ↔ script ↔ prose; single-source k; 3-way numeric reconciliation before Stage 4).

IMPORTANT: Always use R for meta-analysis (packages: meta, metafor, mada).

See ${CLAUDE_SKILL_DIR}/references/r_templates.md for full code templates.

| Analysis family | Primary tool | Key output |

|-----------------|-------------|-----------|

| DTA | mada::reitsma() (bivariate) | Pooled Se/Sp + SROC with confidence/prediction regions |

| Intervention | meta::metagen() / meta::metabin() | Pooled OR/RR, I², Egger's test, leave-one-out |

| Dual (comparative + single-arm) | metabin + metaprop | PRIMARY vs SECONDARY per pre-specified protocol |

Load-on-demand: Read ${CLAUDE_SKILL_DIR}/references/phase6_statistical_synthesis.md

for the full R code templates, the dual-approach decision table (comparative vs

single-arm), practical cautions (method.tau, HK CI, zero-cell correction),

publication-bias test power, sensitivity-analysis menu, and error-handling rules.

Phase 6b: Post-Analysis Source Fidelity Audit (MANDATORY)

Goal: Catch numerical hallucinations that survived the forward pipeline (CSV → .R → manuscript).

Precedent failure pattern — treat this as a lived near-miss, not hypothetical:

> In a revision-era comparative meta-analysis, a safety outcome was reported as "3/45 vs

> 0/56, p=0.085." The primary-source Table actually recorded "0/45 vs 1/56, p=0.37" —

> direction reversed. The extraction CSV was correct; the R script's Fisher exact

> matrix() was hand-typed after a column in the source Table was misread. Internal

> consistency checks passed because every downstream artifact (Abstract, Discussion,

> Table, forest caption) echoed the same wrong number. The reversal was caught only on

> a second-pass audit with random extraction sampling against the primary paper.

Non-negotiable rules:

  • No hand-typed numerical matrices when a CSV exists.
  • Use read.csv(...) + subset / filter. Never copy a 2x2 table from a paper's Table into

matrix(c(...), ...) by eye.

  • If hand entry is truly unavoidable (e.g., text-only extraction), the matrix, c(), or

data.frame line MUST carry a comment citing the exact CSV row + column OR the exact

primary-source Table/Page coordinate. Example:

     # source: data_extraction_final.csv row <N> (<first-author> <year>), cols <event_arm1>=0, <event_arm2>=1
     # verified against primary source Table <X>, page <P>
     fisher.test(matrix(c(0, 45, 1, 55), nrow = 2, byrow = FALSE))
  • Comparative-arm subsets are a separate consensus-log row.
  • When one study's arm-specific values (e.g., one arm of a multi-arm study) are used in a

comparative analysis while the full cohort of that study appears elsewhere,

extraction_consensus_log.md must carry an explicit row for the arm-specific values.

Pooled totals and arm-specific values MUST NOT share a row.

  • Random 3-claim back-check before closing Phase 6.
  • After the forest/funnel/subgroup outputs stabilize, randomly sample 3 numerical claims

from the Results section of the draft manuscript and trace each back to (a) the R output

log and (b) the original paper's Table/Figure.

  • Record the back-check as a small table in peer_review_<vN>_internal.md:

| Claim (manuscript line) | R output file:line | Primary source (paper, Table/Fig, page) | Match? |

|---|---|---|---|

  • A single mismatch is a P0 blocker — do not advance to Phase 7 until resolved.
  • Revision-introduced numbers must be tagged.
  • Any new number added after v1 — including numbers produced by a new comparative / subgroup /

sensitivity script — MUST be wrapped inline as [VERIFY-CSV] in the manuscript until the

Phase 2.5a audit in /self-review clears it.

  • Sensitivity analyses must be recomputed on the modified data, not copied.
  • When you add a sensitivity / leave-one-out / erosion / alternative-model analysis, every

reported effect size (Cohen's dz/f, AUC, OR, HR, β, sens/spec, ICC) MUST be re-derived from

the modified dataset. If a sensitivity-table effect size is **identical to the primary

analysis to two decimals across ≥4 values**, the recomputation almost certainly did not run

and the primary values were transcribed — re-run the script on the modified data.

  • The underlying means/SDs/counts will change even when the effect size looks similar; if the

effect sizes are byte-identical while the inputs differ, that is the tell. Probability of ≥4

independent values coinciding to 2 decimals by chance is ≈ (0.01)^4 — essentially zero.

  • Precedent: a revision-era sensitivity analysis (1-voxel erosion) reported 8 effect-size values

(Cohen's dz + f across 4 VOIs) byte-identical to the primary tables while the means/SDs

differed — the erosion analysis had not actually been recomputed. Caught only by external QC.

  • A "fixed" / "resolved" audit note requires re-run evidence, not a claim.
  • When a prior audit note records a number as fixed, resolved, or corrected, that status is

only valid if it carries the re-run evidence: a timestamp and the relevant stdout / output-file

line showing the corrected value, or the commit that changed it. A bare "fixed in v10" with no

re-run artifact does NOT clear the finding — re-run the script and attach the output.

  • The forward pipeline can echo a stale value through every artifact while an audit note claims it

was fixed (e.g., a major-comparison N still reading the old total after a "fixed" note). The

outcome-denominator cross-check (/self-review Phase 2.5b, the cohort-arithmetic / pool-lock

assertions) must pass against the *current* outputs before any "fixed" status is accepted.

When this phase triggers: every time Phase 6 outputs change (first draft, revision, reviewer-

requested re-analysis). Not optional on "minor" re-runs — the precedent reversal above

occurred inside a "minor" revision-era re-analysis.

Phase 7: GRADE / Certainty of Evidence

Goal: Assess certainty of the body of evidence.

For DTA meta-analysis, apply GRADE-DTA framework:

  • Risk of bias (from QUADAS-2)
  • Indirectness (applicability concerns)
  • Inconsistency (heterogeneity)
  • Imprecision (wide CIs, small sample)
  • Publication bias

For intervention meta-analysis, apply standard GRADE.

Output: Summary of Findings table.

Phase 8: Reporting & Manuscript

Goal: Generate PRISMA-compliant manuscript sections.

> Failure-mode cross-refreferences/submission_package_drift.md — apply the _build.sh pattern + DO_NOT_EDIT_HERE gate when staging multi-journal submission folders.

  • Check reporting compliance: Use /check-reporting with PRISMA-DTA or PRISMA 2020
  • Write manuscript: Use /write-paper with meta-analysis type selected
  • Figures: Use /make-figures for:
  • PRISMA flow diagram
  • Forest plots (paired for DTA)
  • SROC curve (DTA)
  • Funnel plot
  • RoB summary (traffic light plot)
  • Tables:
  • Characteristics of included studies
  • 2x2 data per study (DTA)
  • RoB assessment results
  • Summary of findings / GRADE table
  • Supplementary & analysis-code pre-submission gate (run before Phase 9 circulation and before portal upload). Presence of the 8-file package (Empirical Lesson 5) is necessary but not sufficient — each item must also be reviewer-ready:
  • De-scaffold: strip internal-QC / tool artifacts before bundling — raw /check-reporting output ("Assessed by: <tool>", JSON blocks, "READY FOR SUBMISSION" verdicts, action-item lists), search-development planning docs (decision logs, expected-yield estimates, [Check on execution] placeholders, version-history dev notes), and stale version stamps. Ship a clean PRISMA 2020 checklist (27-item / 42-subitem table only) and an executed-method search-strategy doc, not the working drafts.
  • Blind: supplementary goes to reviewers — remove author names/initials and sibling-project cross-references ("Designed by: <name>", "identical to a sibling review"). Same standard as the blinded manuscript.
  • Cross-consistency with the manuscript: every supplementary number must match the main text — PRISMA counts, pool k/N, the Cochrane/CENTRAL search description, RoB counts. A supplement that says "Cochrane — NOT SEARCHED" while Methods report a confirmatory CENTRAL search is a contradiction reviewers catch.
  • Submitted analysis code must reproduce and be self-contained: run it from a clean copy of the bundle. It must (a) read the bundled locked dataset (not an out-of-bundle path) and write to the working directory, and (b) regenerate every pool reported in the results table. A hard-coded study-id subset that drifts from the manuscript (e.g., a pool computed over k=7 while the manuscript reports k=9) is a P0 — fix and re-run; never ship stale code or stale figures derived from it.
  • Run a supplementary-only review pass — the manuscript self-review/panel does not see the supplement; mirror /self-review Phase 2.5c–2.5d (reference + cross-reference QC) over the supplementary files.

Phase 9: Co-author Circulation

Goal: Standardized pre-submission circulation of the manuscript to co-authors and

senior methodologist / reviewer, with a bounded review window and a controlled attachment

scope.

Trigger: Phase 8 is complete, and the draft has cleared Phase 6b source-fidelity

audit.

Summary: Reply to the prior-version email thread to preserve In-Reply-To continuity

(v1 → v2 → v3 tracked in one place). Attach the manuscript body with figures inline and,

for v≥2, a change summary — exclude graphical abstract, cover letter, COI forms, and

supplementary until the target journal is confirmed. TO = corresponding author + one

senior methodologist; CC = remaining co-authors. Set a 7-day deadline (5 business days +

weekend). Ask the corresponding author for target-journal preference, reviewer candidates,

and cover-letter framing.

Load-on-demand procedural detail (thread continuity, attachment scope rationale,

size-to-method table, journal-undetermined framing, response-tracking log):

${CLAUDE_SKILL_DIR}/references/phase9_circulation.md.

> Failure-mode cross-refreferences/review_orchestration.md RO-1~RO-5 (dual-rating completeness, defensive-tone bias audit, response-matrix numeric tracking, 2nd-reviewer availability blocking).


Phase 10: Self-Audit Recovery (v{N} → v{N+1} sprint)

Goal: When an audit uncovers a structural data or protocol-application error,

withdraw the current version, rebuild, and re-circulate with a transparent audit trail.

Catching the error yourself before a journal reviewer does is the principal trust-building

move in this phase.

Trigger conditions (any one):

| # | Trigger | Source |

|---|---------|--------|

| T1 | Extraction CSV ↔ primary source disagreement for a cell feeding a pooled/subgroup estimate or reported proportion | Phase 6b audit |

| T2 | Included/excluded study violates the pre-specified criteria on re-read | Protocol review |

| T3 | Hand-typed numerical literal in the analysis script traces to a wrong value | Phase 6b audit |

| T4 | PROSPERO protocol ↔ delivered analysis disagreement on outcome, subgroup, or eligibility | Protocol ↔ analysis diff |

| T5 | Dual-reviewer consensus record ↔ locked dataset disagreement on inclusion | Consensus log diff |

Non-negotiable rule: if the trigger fires after Phase 9 circulation but before

journal submission, withdraw the current version within 24 hours. Reviewer discovery is

a strictly worse failure mode than self-withdrawal.

Sprint outline (12 steps): (10.1) audit log at qc/audit_vN_to_vNplus1.md

(10.2) CSV re-verification with [VERIFY-CSV] tagging → (10.3) fresh script re-run

(fixed seed, logged) → (10.4) manuscript auto-sync (grep for v{N} residue) → (10.5)

supplementary regeneration (consensus log, RoB, GRADE/SoF, PRISMA flow) → (10.6) figure

regeneration via /make-figures → (10.7) change summary with delta table → (10.8)

PROSPERO amendment (application correction, not criteria change) → (10.9) re-circulation

in the Phase 9 thread with the "On re-review" framing → (10.10) anti-patterns to avoid

(hide-and-submit, "minor revision" reframe, cover-letter-only disclosure) → (10.11) post-

submission escalation path → (10.12) post-recovery loop (Phase 9 restart; tighten Phase

6b if a second sprint is needed).

Load-on-demand procedural detail (exact audit-log fields, delta-table template,

amendment language template, re-circulation paragraph template, anti-pattern rationale):

${CLAUDE_SKILL_DIR}/references/phase10_recovery.md.

> Failure-mode cross-refreferences/post_submission_release_ops.md Gate 4 covers reject/revise Zenodo versioning, tag-cleanup gate, and re-target workflow (avoid "new version" misuse on re-target).


Failure Modes (prior MA projects, anonymized)

Failure patterns observed across three prior MA projects (anonymized). Each topical reference extends the phase it cross-references above — consult alongside phase procedural docs, not in isolation.

| Domain | Phase span | Load-on-demand reference |

|---|---|---|

| Data integrity (2x2 arm-swap, KM audit, methodology mismatch, PRISMA 5-way drift, single-source k) | Phase 3 → 6 | references/data_integrity_checklist.md (DI-1~DI-9) |

| Review orchestration (2nd-reviewer blocking, dual-rating completeness, defensive-tone audit, response-matrix tracking) | Phase 9 circulation (extends phase9_circulation.md) | references/review_orchestration.md (RO-1~RO-5) |

| Submission package drift (multi-journal folder hygiene, DO_NOT_EDIT_HERE gate, build artifact vs master) | Phase 8 → submission | references/submission_package_drift.md |

| Post-submission release ops (Zenodo DOI timing, tag-cleanup gate, reject-retarget versioning) | Submission → Phase 10 | references/post_submission_release_ops.md |

Automation hooks (invoke at the phase listed)

| When | Script | Gate |

|---|---|---|

| Phase 3f reconciliation (before Phase 5 write-up) | python3 ${CLAUDE_SKILL_DIR}/scripts/check_exclusion_code_validity.py --protocol 0_Protocol/protocol.md --screening 2_Screening/*.tsv --strict | validates each applied exclusion code against the *registered* eligibility criteria: CODE_CONTRADICTS_ELIGIBILITY (a code excludes a design the protocol includes — the bulk study-loss defect no arithmetic/inter-rater gate can see), CODE_NOT_REGISTERED (off-protocol code), CODE_RENUMBERED (same code, two meanings). Challenge card: scripts/check_exclusion_code_validity_challenge/. |

| Phase 4 kickoff (before first extraction row) | python3 ${CLAUDE_SKILL_DIR}/../../scripts/extraction_consensus_log_init.py --output 2_Data/extraction_consensus_log.md | DI-1: creates standalone consensus log so comparative arm-specific rows are never folded into R-script comments. |

| Phase 3f reconciliation + every revision touching PRISMA numbers | python3 ${CLAUDE_SKILL_DIR}/../../scripts/prisma_5way_consistency.py --ssot prisma.yaml | DI-6: 5-surface drift check (abstract / main text / flow figure / supplement / CSV) against YAML SSOT. Non-zero exit blocks Phase 5 writeup. |

| Phase 8 pre-submission + every journal retarget | bash ${CLAUDE_SKILL_DIR}/../../scripts/tag_cleanup_gate.sh | DI-8: fails if VERIFY-CSV/TODO/FIXME/XXX survive in 7_Manuscript, supplement, SUBMISSION, etc. |

| Phase 8 on first build per journal (--record), then before every re-submission (--verify) | python3 ${CLAUDE_SKILL_DIR}/../../scripts/verify_package_integrity.py --record --journal <name> then --verify --journal <name> | SPD: checksum-based drift detection between master manuscript and built SUBMISSION/{journal}/ folder. Journal-editable files (cover letter, response, MANIFEST, DO_NOT_EDIT_HERE.md) are auto-excluded. |

All four scripts are repo-shipped as of 2026-04 (FOLLOWUPS P10). Non-zero exit = gate failure; resolve before proceeding to the next phase.


Empirical Lessons (peer-review cycles)

Sixteen accumulated SR-MA peer-review / submission lessons (2026-05 and 2026-06) — the

drivers behind the Phase 4 extraction-form schema, the Phase 4c QC scripts, and the Phase 8

submission gates. To keep this entry point lean they live load-on-demand in

${CLAUDE_SKILL_DIR}/references/empirical_lessons.md. **Load that file when designing the

extraction form (before Phase 4) and before submission (Phase 8)** — it covers dual-extractor

2x2 integrity, cohort-overlap clustering, small-k subgroup caution, the supplementary 8-file

bar, PROSPERO ID format, AI-disclosure presence, recompute-don't-copy sensitivity analyses,

outcome harmonization, heterogeneous-RoB κ, survival-specific concerns, supplement blinding /

de-scaffolding, self-contained reproducible analysis scripts, sidecar re-sync, methodological

+ software citations, wide-table PDF rendering, and submission-portal journal-identity checks.


DTA-Specific Pitfalls (Always Check)

| Pitfall | Problem | Solution |

|---------|---------|----------|

| Separate pooling of Se/Sp | Ignores correlation | Use bivariate/HSROC model |

| Ignoring threshold effect | False heterogeneity | Check Spearman correlation, SROC plot |

| Standard funnel plot for DTA | Inappropriate | Use Deeks' funnel plot |

| I-squared only for heterogeneity | Doesn't capture threshold effect | Use prediction region on SROC |

| Missing GRADE | Common omission in DTA MA | Apply GRADE-DTA. If <4 studies, assess each domain narratively and state the limitation explicitly |

| Partial verification bias | Inflates sensitivity | Assess in QUADAS-2 Flow & Timing domain |

| Unevaluable results excluded | Biases accuracy estimates | Report intent-to-diagnose analysis |


Small Study Considerations

When the number of included studies is small (< 10):

  • Bivariate/HSROC model may not converge -- consider univariate random-effects as fallback
  • Publication bias tests are underpowered -- state this limitation
  • Subgroup/meta-regression analysis not recommended
  • Wide prediction regions expected -- emphasize uncertainty in conclusions
  • Consider narrative synthesis as alternative/complement

Skill Interactions

| When | Call | Purpose |

|------|------|---------|

| Need literature search | /search-lit | PubMed/Semantic Scholar search with verified citations |

| Need statistical code | /analyze-stats | Execute R/Python analysis scripts |

| Need figures | /make-figures | PRISMA flow, forest plots, SROC, funnel plots |

| Need reporting check | /check-reporting | PRISMA-DTA / PRISMA 2020 compliance (includes Step 4c registration / amendment timing) |

| Need manuscript writing | /write-paper | Full IMRAD manuscript generation |

| Need self-review | /self-review | Pre-submission quality check |

| Self-audit recovery entrypoint (Phase 10) | /write-paper Step 7.4a | Recovery branch for polish pipelines that surface structural audit failures |

| /sync-submission SR-MA gate | /sync-submission | Before submission, verify supplementary package matches all 8 files in templates/supplementary_8file_checklist.md (PRISMA, PROSPERO, search strategy, exclusion list, extraction table, per-study x per-domain RoB, subgroup forests, sensitivity / publication bias). AI Disclosure presence check (cross-link /peer-review Phase 2A P8). Cite-list duplicate check via /verify-refs Gate 5 (duplicate PMID/DOI). |


Error Handling

  • If study type is ambiguous (DTA vs intervention), ask user to clarify before proceeding.
  • If fewer than 4 studies for DTA, warn that bivariate model may not converge.
  • If data extraction is incomplete (missing 2x2 cells), suggest contacting authors or sensitivity analysis with imputed values.
  • If PROSPERO ID is missing, flag as a limitation but continue.
  • Always remind user: this is a methodological support tool; final decisions rest with the research team and ideally include a biostatistician/methodologist.

Anti-Hallucination

  • Never fabricate variable names, dataset column names, or variable codings. If a variable mapping is uncertain, output [VERIFY: variable_name] and ask the user to confirm against the data dictionary.
  • Never fabricate statistical results — no invented p-values, effect sizes, confidence intervals, or sample sizes. All numbers must come from executed code output.
  • Never generate references from memory. Use /search-lit for all citations.
  • If a function, package, or API does not exist or you are unsure, say so explicitly rather than guessing.

How to use it

Copy the folder

Take aperivue/meta-analysis from the repository into ~/.claude/skills for personal use, or into .claude/skills inside a project.

Check the name does not clash

The agent identifies a skill by the name field in its header. Two skills with the same name cannot sit side by side — one of them will be ignored.