medsci-skills 4.1.0

package/skills/meta-analysis/SKILL.md

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+---
+name: meta-analysis
+description: 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.
+triggers: meta-analysis, systematic review, PROSPERO, forest plot, funnel plot, PRISMA, QUADAS, ROBINS, HSROC, bivariate model, pooled sensitivity, pooled specificity, search strategy, study selection, data extraction form
+tools: Read, Write, Edit, Bash, Grep, Glob
+model: inherit
+---
+
+# 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**: `${CLAUDE_SKILL_DIR}/references/post_submission_release_ops.md` -- Zenodo DOI gating, tag-cleanup gates, reject-retarget versioning
+
+### Built-in Templates (`${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.
+
+---
+
+## 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.
+
+1. **Structure the research question**:
+   - DTA: PIRD (Population, Index test, Reference standard, Diagnosis)
+   - Intervention: PICO (Population, Intervention, Comparator, Outcome)
+
+2. **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
+
+3. **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
+
+4. **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)
+
+5. **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
+
+6. **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.
+
+1. **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)
+
+2. **Combine with Boolean operators**:
+   - Within blocks: OR
+   - Between blocks: AND
+
+3. **Execute search per database** using `/search-lit`:
+   - PubMed: MeSH + free text
+   - Embase: Emtree + free text
+   - Additional databases as specified in protocol
+
+4. **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.
+
+5. **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)
+1. Define exclusion codes from protocol (e.g., E1=Not target population, E2=Not intervention, E3=Ineligible type, E4=Non-human, E5=Duplicate).
+2. For each record, screen title+abstract against eligibility criteria.
+3. Mark each record as INCLUDE / EXCLUDE / MAYBE with reason code.
+4. Output: `round1_{date}.tsv` with color-coded decisions.
+
+#### 3b. Round 2 — Dual Independent Title/Abstract Screening
+1. A second independent reviewer (or AI as a documented second-pass tool with human verification) re-screens all R1 records.
+2. Compute Cohen's kappa at title/abstract stage; report in Methods.
+3. Tag each record's `round2_tag` as INCLUDE / EXCLUDE / MAYBE based on R1+R2 agreement (MAYBE = disagreement OR either reviewer flagged uncertain).
+4. Output: `round2_{date}.tsv` (adds `round2_tag`, `round2_reason` columns).
+
+#### 3c. Round 3 — Adjudication of Disagreements (first reviewer)
+1. Build R3 sheet: all MAYBE records first, followed by INCLUDE records (which receive a brief confirmation pass).
+2. The **first reviewer** independently adjudicates each row, recording `round3_decision` (INCLUDE/EXCLUDE) and `round3_reason` (only when overturning R2).
+3. **Optional AI-assisted pre-screening** to compress R3 effort:
+   - Use `references/ai_pre_screening_template.py` (customize per project).
+   - Pre-screen produces `ai_suggestion` (INCLUDE/EXCLUDE/UNCERTAIN/CONFIRM-INCLUDE) + `ai_reason` columns.
+   - Sort priority: UNCERTAIN → EXCLUDE → INCLUDE → CONFIRM-INCLUDE.
+   - First reviewer must independently confirm or overturn every AI suggestion against the title, abstract, and (when needed) full text. AI suggestions are **not** final decisions.
+   - Methods boilerplate: "Round 3 adjudication was performed by the first reviewer with AI-assisted pre-screening ({model name and version}). The AI was prompted with the prespecified PECOS criteria and produced a suggestion plus brief justification for each record; the first reviewer independently confirmed or overturned every suggestion. AI suggestions were not used as final inclusion decisions."
+4. Output: `round3_{date}.tsv` with finalized `round3_decision`.
+
+#### 3d. Round 4 — Full-text Screening
+1. For records with `round3_decision = INCLUDE`, retrieve full-text PDFs (use `/fulltext-retrieval`).
+2. Apply full-text exclusion criteria (F1=No extractable outcome, F2=No comparative data, F3=Cannot separate target population data, F4=Inadequate sample/follow-up, F5=Full-text unavailable).
+3. Two independent reviewers; compute Cohen's kappa at full-text stage.
+4. Resolve disagreements by consensus or third reviewer.
+5. Flag comparative studies for priority extraction.
+
+#### 3e. PRISMA Flow
+Track numbers at each stage for PRISMA flow diagram (R1 → R2 → R3 → R4 → final included).
+Use `/make-figures` to generate PRISMA flow diagram when numbers are finalized.
+
+#### 3f. Post-Consensus Count Reconciliation Gate (MANDATORY before Phase 5 write-up)
+
+Before handing the screening artifacts to Phase 5 (statistical synthesis) or to `/write-paper` / `/self-review`, run an explicit ID-set reconciliation and record the canonical totals in a single source-of-truth file (typically `2_Screening/screening_consensus.md` §Net Impact or equivalent):
+
+Use the deterministic helper when TSV/CSV artifacts are available:
+
+```bash
+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 should consume `screening_consensus.json` for counts and
+ID sets. The Markdown consensus document remains the human explanation.
+
+1. **Enumerate ID sets from raw artifacts (not from prose summaries):**
+   - A = screening TSV INCLUDE IDs
+   - B = consensus spreadsheet Exclude IDs
+   - C = consensus spreadsheet Include-qualitative IDs (FLAG-resolved additions)
+   - T = Table 1 / bivariate-eligible IDs (2×2-extractable studies)
+
+2. **Compute canonical totals via set algebra:**
+   - k_qualitative = |A \ B| + |C|
+   - k_bivariate = |T|
+   - k_narrative-only = k_qualitative − k_bivariate
+   - k_FT-excluded = |full-text reviewed| − k_qualitative
+
+3. **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 ID set (A ∪ C) \ B \ T.
+
+4. **Prohibit "N → M" transitions without ID receipts.** Any sentence of the form "k rose from 30 to 32 after FLAG consensus" must cite the specific added/removed IDs. A transition claim with no enumerable ID set is a P0 error and blocks the Phase 5 hand-off.
+
+5. **Record in a reconciliation table** inside the screening-consensus document:
+
+   | Quantity | v_prev draft | v_current (ID-verified) | Derivation |
+   |---|---|---|---|
+   | k_full-text | ... | ... | ... |
+   | k_FT-excluded | ... | ... | |TSV EXCLUDE| + |consensus-downgrades| |
+   | k_qualitative | ... | ... | |A \ B| + |C| |
+   | k_bivariate | ... | ... | |T| |
+   | k_narrative-only | ... | ... (explicit IDs listed) | (A ∪ C) \ B \ T |
+
+**Precedent incident (a PRISMA-DTA meta-analysis revision):** a late-revision manuscript shipped with k_qualitative = 32 / k_narrative-only = 10 / k_FT-excluded = 46. ID-set reconciliation (performed only after an adversarial audit at post-Stage 4 QC) revealed true counts 24/2/54. An early-draft prose total ("30 → 32 after FLAG consensus") had been carried forward without ever being reconciled against the screening TSV intersected with the consensus spreadsheet; four downstream artifacts echoed the same wrong total. This gate would have caught the drift at the Phase 5 hand-off.
+
+#### 3f.5 Pool composition lock (MANDATORY at adjudication freeze)
+
+After Phase 3f reconciliation passes, freeze the pool composition into a
+single source-of-truth YAML so every downstream artifact (extraction TSV,
+manuscript prose counts, PRISMA flow caption, supplementary INDEX, cover
+letter free-text) can be checked against it.
+
+Why this lock exists
+^^^^^^^^^^^^^^^^^^^^
+
+Cross-project precedent (anonymized): an LLM reporting-quality SR carried
+five documents that disagreed on INCLUDE (63 vs 64) and EXCLUDE
+(108/109/111). Three EXCLUDE rows existed in the extraction sheet without
+matching INCLUDE. The drift traced to a late round-3 adjudication whose
+result was applied to some artifacts and not others — there was no single
+canonical post-freeze count to reference.
+
+How to lock
+^^^^^^^^^^^
+
+1. Copy the template:
+   ```bash
+   cp "${CLAUDE_SKILL_DIR}/templates/FINAL_POOL_LOCK.yaml.template" \
+       2_Data/FINAL_POOL_LOCK.yaml
+   ```
+2. Fill in counts and UID lists from the reconciliation in Phase 3f.
+3. Compute the SHA-256 integrity hash from the sorted UID list.
+4. Commit the lock to git BEFORE starting Phase 4 extraction.
+
+Downstream gates
+^^^^^^^^^^^^^^^^
+
+- `/meta-analysis` Phase 4 entry: extraction TSV's UID set MUST equal
+  `include_uids` ∪ `mixed_uids` from the lock. See Phase 4 entry gate.
+- `/sync-submission` Phase 5
+  (`scripts/cross_document_n_check.py --pool-lock`): every numeric claim
+  in manuscript / abstract / supplementary that maps to a locked
+  category must match the locked value.
+- Manuscript prose: NEVER re-derive `k included` from 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.**
+  The Abstract/Results aggregate denominators ("a total of 483 patients /
+  531 lesions") are derived from the lock, never hand-carried. Lock them as
+  explicit fields and distinguish **arm-separable** from **both-arm** rows:
+  a study contributing one arm to a comparison must not have its full-cohort
+  patient 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 (the analysis-side
+  mirror of `/self-review` `check_cohort_arithmetic.py` partition checks).
+
+If a late post-freeze decision changes the pool, treat it as a formal
+PROSPERO amendment: file the amendment, re-freeze the lock as a new
+file (`FINAL_POOL_LOCK_v2.yaml`), and propagate to every artifact.
+
+### 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, run the deterministic UID-set check
+to confirm that the round-3 adjudication TSV and `FINAL_POOL_LOCK.yaml`
+(produced in Phase 3f.5) agree on which UIDs are included.
+
+```bash
+python "${CLAUDE_SKILL_DIR}/scripts/check_pool_consistency.py" \
+    --lock 2_Data/FINAL_POOL_LOCK.yaml \
+    --adjudication-tsv 2_Screening/round3_adjudication.tsv \
+    --decision-col round3_decision \
+    --uid-col uid \
+    --include-labels "INCLUDE,INCLUDE_MIXED" \
+    --out qc/pool_consistency.json
+```
+
+Output `qc/pool_consistency.json`:
+
+```json
+{
+  "submission_safe": false,
+  "match": false,
+  "lock_include_n": 42,
+  "tsv_include_n": 43,
+  "in_lock_not_tsv": ["UID_007"],
+  "in_tsv_not_lock": ["UID_055"]
+}
+```
+
+The gate fails closed: any UID disagreement blocks extraction. To
+resolve, either (a) re-freeze the lock with the corrected set of UIDs
+and propagate to downstream artifacts, or (b) correct the adjudication
+TSV if a row was mis-labeled. Do NOT proceed to Phase 4 with a
+mismatch — the resulting extraction matrix will not align with the
+locked pool, and the drift surfaces as a fabrication-grade red flag at
+peer review.
+
+
+> **Failure-mode cross-ref** → `references/data_integrity_checklist.md` DI-1~DI-5 are mandatory during extraction (2x2 arm-swap, KM audit trail, methodology mismatch, PRISMA 5-way drift, single-source k).
+
+**Recommended extraction form**: For SR-MA targeting high-impact radiology / medical AI journals, use `${CLAUDE_SKILL_DIR}/templates/extraction_form_v2.md`. Dual-extractor + source-page-reference + verbatim-quote columns prevent the 2x2 cell-swap and cohort-overlap blind spots surfaced in recent SR-MA peer-review cycles. New required columns: `cohort_source`, `source_page_ref`, `source_verbatim_quote`, `extraction_consensus_status`, `overlap_flag_reviewer1/2`, `sample_n_dta_pool` vs `sample_n_prognostic_pool`.
+
+#### 4.0 AI-drafted starting document gate
+
+Before opening the extraction form: if a senior mentor or collaborator has shared an AI-drafted starting document (Claude / ChatGPT / Gemini draft of the study list, 2x2 cells, or effect estimates) — even when the sender flags it as "for reference only" — apply `~/.claude/rules/ai-drafted-document-policy.md`:
+
+- Save the file with a `_DO_NOT_USE_VERBATIM` (or `_AI_DRAFT_REFERENCE_ONLY`) filename suffix.
+- Treat every per-study N, denominator, event count, OR/CI, and author/year as **hallucination-suspect** until re-verified against the source PDF + own analysis script. AI-drafts collapse multiple denominator definitions (treatment-naïve / full-cohort / per-arm) into one and silently mis-route counts.
+- Record any reconciled discrepancy in `extraction_consensus_log.md` with a verbatim quote of the AI-draft value and the corrected value with PDF page coordinate.
+- Trust hierarchy for this phase: **SSOT (source PDF + own analysis stdout) > mentor's direct text (email / track-changes) > attached AI-draft**. Do not promote an AI-draft from tier 3 to tier 2.
+
+Precedent (an active meta-analysis project): Ishikawa 2017 "treatment support 5/70 vs no support 12/33" in Claude-drafted directive → source PDF was 35/68 (single arm). Verbatim absorption would have produced a denominator-hallucinated meta-analysis.
+
+#### DTA Meta-Analysis:
+Generate a data extraction form with:
+- Study ID (first author, year)
+- Study characteristics (country, design, setting, enrollment period)
+- Population (n, age, sex, disease prevalence)
+- Index test details (technique, threshold, manufacturer, reader experience)
+- Reference standard details
+- 2x2 table (TP, FP, FN, TN)
+- Additional outcomes (AUC per study, if reported)
+- Notes on partial verification, differential verification, uninterpretable results
+
+#### Intervention Meta-Analysis:
+Generate a data extraction form with:
+- Study ID
+- Study characteristics
+- Population
+- Intervention / comparator details
+- Outcome data (means, SDs, event counts, sample sizes)
+- Effect measures (OR, RR, HR, MD, SMD as appropriate)
+
+Output: Excel/CSV template for data entry.
+
+#### 4b. Special cases (KM reconstruction, composite exposure)
+
+When studies report outcomes only as Kaplan-Meier curves (no raw event counts) or
+when the intervention is a composite of multiple techniques, load
+`${CLAUDE_SKILL_DIR}/references/phase4_km_composite.md` for the WebPlotDigitizer
+→ `IPDfromKM` reconstruction procedure (cite Guyot et al. 2012,
+doi:10.1186/1471-2288-12-9) and the 4-path composite-exposure disaggregation
+decision tree. Pre-specify a sensitivity analysis excluding composite-exposure
+studies and document extraction strategy in the form's Notes column.
+
+#### Data Extraction Cross-Verification
+
+When comparing extraction results between independent reviewers (minimum 2), check:
+
+0. **Inter-reviewer agreement**: Calculate and report screening agreement: % agreement or Cohen's kappa at title/abstract and full-text stages. If kappa was not calculated, report the exact number of discrepant records and the resolution method.
+
+1. **Denominator consistency**: Verify sample sizes match between reviewers.
+   Watch for per-patient vs per-lesion/per-tumor unit confusion.
+   **CRITICAL**: The denominator may differ across outcomes within the same study
+   (e.g., LTP assessed only among treatment-naive nodules, but complications assessed
+   among all treated tumors). For each outcome, back-calculate: `event ÷ denominator`
+   must equal the percentage reported in the paper's Tables. If it does not match,
+   investigate the analysis population definition in the Methods section.
+   If denominators differ, return to the original paper's Tables/Flow diagram.
+2. **Arithmetic verification**: Back-calculate proportions from event/total counts and cross-check against original text (e.g., 78/91 = 85.7%).
+3. **Kaplan-Meier estimate distinction**: KM curve estimates differ from raw event counts. Always record the data source (Table vs KM curve vs text) during extraction.
+4. **Discrepancy resolution**: List all discrepancies → verify against original text → reach consensus → if consensus fails, use third reviewer. Log all consensus decisions in `{project}/consensus_log.md`.
+5. **Dataset lock**: After resolving all discrepancies, lock the final dataset. Any subsequent changes require documented justification with date.
+
+#### Phase 4c: Extraction QC & Cohort Overlap Detection
+
+After dual-extractor consensus, run two QC scripts before locking the extraction table for statistical synthesis.
+
+**1. 2x2 Cell Integrity Check** -- `scripts/dta_extraction_qc.py`:
+
+Validates manuscript forest-plot cells (TP / FN / TN / FP) against source-paper-reported sens/spec within a tolerance (default 0.02). Catches sens/spec swap at extraction stage -- a common error pattern where a single-study k=1 subgroup outlier flips conclusions due to cell-assignment swap.
+
+```bash
+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
+```
+
+Any `FLAG_SWAP` or `FLAG_MISMATCH` row requires third-reviewer adjudication before Phase 6 statistical synthesis.
+
+**Flag → form-edit forced transition.** A confirmed flag is not resolved until the extraction form itself is edited. Track each flag through `confirmed → acted`: after the adjudicator confirms a `FLAG_SWAP`/`FLAG_MISMATCH`/unit-of-analysis violation, the extraction CSV row MUST be corrected and the QC re-run to clear it. A flag that is "confirmed" but whose form row is unchanged (the correction lived only in a review note) silently re-enters synthesis. Verify the form's mtime advanced and the re-run QC shows zero open flags before locking.
+
+**2. Cohort Overlap Check** -- `scripts/cohort_overlap_check.py`:
+
+Clusters included studies by (a) shared public ICU/EHR database (MIMIC-IV, eICU, MIMIC-III, KNHIS, UK Biobank, Optum, MarketScan, TriNetX, IBM), (b) same institution + overlapping enrollment period, (c) shared first-author surname + ±2y year proximity. Flags HIGH / MEDIUM overlap confidence.
+
+```bash
+python3 "${CLAUDE_SKILL_DIR}/scripts/cohort_overlap_check.py" \
+  --input 2_Extraction/studies.csv \
+  --enrich \
+  --out 2_Extraction/qc/cohort_overlap.md
+```
+
+HIGH-confidence overlap pairs require Limitations acknowledgment + sensitivity analysis excluding one of the pair.
+
+Cross-links: `/peer-review` Phase 2A P1 (cell integrity) + P2 (cohort overlap).
+
+### Phase 5: Risk of Bias Assessment
+
+**Goal**: Guide structured RoB assessment with the appropriate tool.
+
+Select tool based on meta-analysis type (see table above), then read the corresponding checklist:
+
+| Tool | Checklist File |
+|------|---------------|
+| QUADAS-2 (DTA) | `${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) | `${CLAUDE_SKILL_DIR}/references/checklists/JBI_Case_Series.md` |
+
+For AI/ML prediction models, also apply PROBAST+AI extensions.
+
+**Output**: Summary table + traffic light plot (use `/make-figures`).
+
+### Phase 6: Statistical Synthesis
+
+**Goal**: Execute meta-analysis and generate publication-ready outputs.
+
+> **Failure-mode cross-ref** → `references/data_integrity_checklist.md` DI-6/DI-7/DI-9 are the consistency gate (CSV ↔ script ↔ prose; single-source k; 3-way numeric reconciliation before Stage 4).
+
+**IMPORTANT**: Always use R for meta-analysis (packages: `meta`, `metafor`, `mada`).
+See `${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:**
+
+1. **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:
+     ```r
+     # 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))
+     ```
+
+2. **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.
+
+3. **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.
+
+4. **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.
+
+5. **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.
+
+6. **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:
+1. Risk of bias (from QUADAS-2)
+2. Indirectness (applicability concerns)
+3. Inconsistency (heterogeneity)
+4. Imprecision (wide CIs, small sample)
+5. 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-ref** → `references/submission_package_drift.md` — apply the `_build.sh` pattern + `DO_NOT_EDIT_HERE` gate when staging multi-journal submission folders.
+
+1. **Check reporting compliance**: Use `/check-reporting` with PRISMA-DTA or PRISMA 2020
+2. **Write manuscript**: Use `/write-paper` with meta-analysis type selected
+3. **Figures**: Use `/make-figures` for:
+   - PRISMA flow diagram
+   - Forest plots (paired for DTA)
+   - SROC curve (DTA)
+   - Funnel plot
+   - RoB summary (traffic light plot)
+4. **Tables**:
+   - Characteristics of included studies
+   - 2x2 data per study (DTA)
+   - RoB assessment results
+   - Summary of findings / GRADE table
+
+---
+
+### 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-ref** → `references/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-ref** → `references/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 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 (2026-05)
+
+Synthesized from recent SR-MA peer-review cycles. Drives the Phase 4 extraction form schema, Phase 4c QC scripts, and submission-gate enhancements documented above.
+
+1. **Dual-extractor + source-page-reference + verbatim quote** is mandatory for 2x2 cell integrity. Single-extractor without source-page citation invites sens/spec swap that is invisible to forest-plot-level review.
+
+2. **Cohort overlap detection** must cluster by shared public database + institution + author. Independent-cohort assumption for MA pooling fails when multiple included studies use the same public ICU/EHR cohort with overlapping enrollment windows. Sensitivity analysis excluding overlap is the minimum acknowledgment.
+
+3. **Diagnostic subset N transparency** in mixed DTA + prognostic MAs: report `sample_n_dta_pool` separately from `sample_n_prognostic_pool` with explicit prevalence. Aggregate N in Abstract misleads readers about diagnostic-subset power.
+
+4. **Small-k subgroups are not robust (k < 4)**: a subgroup test driven by a single study (k=1) is descriptive-only, and the same caution extends to k=2–3 — heterogeneity and the trend are not estimable from so few strata. Any subgroup with k < 4 must be labelled descriptive / exploratory rather than entered into a formal subgroup interaction test. Post-hoc subgroups require a PROSPERO amendment with a visible record.
+
+5. **Supplementary 8-file package** is the minimum bar for high-impact journals: PRISMA checklist, PROSPERO PDF, full search strategy, full-text exclusion list with reasons, per-study extraction table, per-study x per-domain RoB, subgroup forests, sensitivity / publication-bias analyses. See `templates/supplementary_8file_checklist.md`.
+
+6. **PROSPERO 14-char ID format** (`^CRD42\d{9}$` = `CRD42` + 4-digit year + 5-digit sequence, e.g. `CRD42024500001`). A 15-character ID is a stray-digit transcription error; pre-2020 IDs may be shorter. Validate with `grep -oE 'CRD42[0-9]+'` + length assert, and request the live registration URL in the cover letter for protocol cross-check.
+
+7. **AI Disclosure presence** for SR-MA submissions to RYAI / Radiology / RSNA / Lancet / JAMA / BMJ / Nature families. Absence triggers MINOR-to-MAJOR finding at peer review.
+
+8. **Sensitivity analyses are recomputed, not copied** (Phase 6b rule 5). Leave-one-out / erosion / alternative-model effect sizes identical to the primary analysis to 2 decimals across ≥4 values means the recomputation did not run. Re-derive from the modified dataset; the inputs (means/SDs/counts) change even when the effect size is close.
+
+9. **Outcome harmonization before pooling.** Studies that report the same-named outcome under different definitions (an imaging-detected event vs a clinically diagnosed one; different thresholds) must not be presented as a single pooled range or pooled estimate. Split by ascertainment method (or pool only the harmonizable subset) and state the definition per stratum — a "6.9–46%" range that silently mixes imaging-detected and clinical events is a heterogeneity artifact, not a finding.
+
+10. **Heterogeneous RoB instruments → no single pooled κ.** When studies are assessed with different risk-of-bias tools (QUADAS-2 for DTA + NOS for cohorts, etc.), do not report one pooled inter-rater κ across the mixed set. Report agreement per instrument, and use an ordinal weighted κ when the domain judgments are ordered (low/some/high). A single κ over a heterogeneous instrument set is uninterpretable.
+
+9. **Prognostic / survival-outcome MAs carry survival-specific concerns** beyond the DTA pitfalls: censoring handling, competing risks (cause-specific vs Fine-Gray), cutoff-derivation optimism, comparator time-horizon alignment, C-index variant transparency (Harrell vs Uno vs IPCW), and calibration beyond discrimination. When pooling prognostic models, pre-specify these in the protocol and report them per study; for the reviewing counterpart see the survival/prognostic 7-probe in `/peer-review`.
+
+---
+
+## 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 |
+| Co-author circulation (Phase 9) | `/gws` + `/handoff` | Thread-reply send, deadline task registration |
+| 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.