medsci-skills 4.1.0

package/skills/meta-analysis/references/phase10_recovery.md

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+# Phase 10 Reference — Self-Audit Recovery (v{N} → v{N+1} Sprint)
+
+Load this reference when any Phase 10 trigger fires during `/meta-analysis`. The SKILL.md
+body carries only the trigger table and summary pointer; all procedural detail lives here.
+
+## Goal
+
+When an audit — internal, or triggered by an incoming co-author comment — 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)
+
+- Extraction CSV disagrees with the primary source for a cell that materially feeds a
+  pooled estimate, subgroup estimate, or a reported proportion.
+- A study that was excluded (or included) by the pre-specified criteria is found to
+  violate those criteria on re-read.
+- A hand-typed numerical literal in the analysis script traces to a wrong value (see the
+  Phase 6b precedent failure pattern).
+- The PROSPERO (or equivalent) protocol and the delivered analysis disagree on a
+  pre-specified outcome, subgroup, or eligibility rule.
+- A dual-reviewer consensus record shows a study was supposed to be excluded, but the
+  locked dataset still contains it (or vice versa).
+
+## 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.
+
+## 10.1 Audit Log
+
+Create `qc/audit_vN_to_vNplus1.md`. For each flagged item, record:
+- Affected study (first author, year).
+- Cell or claim (e.g., TP/FP/FN/TN, k, pooled estimate, CI, subgroup count).
+- Source of the error (extraction, application of criteria, script literal, protocol
+  mismatch, reviewer-consensus mismatch).
+- Proposed resolution (exclude study, re-extract cell, correct script literal, amend
+  protocol, reinstate study).
+
+## 10.2 CSV Re-Verification
+
+For every flagged cell, re-verify against the primary source (paper Table/Figure, page
+number). Any revision-introduced value must carry the `[VERIFY-CSV]` tag until the
+Phase 6b audit clears it.
+
+## 10.3 Re-Run the Analysis Script
+
+Re-execute the full synthesis pipeline with a fixed random seed. Save complete output to
+`analysis/vNplus1_run.log`. Do not re-use partial v{N} output even for subsections that
+"should be unchanged" — prove it with a fresh run.
+
+## 10.4 Manuscript Auto-Sync
+
+Every number the manuscript reports — k, pooled estimate, 95% CI, τ², I², subgroup
+counts, sensitivity-analysis rows, GRADE levels — must be pulled from the fresh output.
+Grep the manuscript for old v{N} numerical values to confirm no residue survives.
+
+## 10.5 Supplementary Regeneration
+
+Re-emit (do not patch):
+- Extraction consensus log.
+- RoB tables.
+- GRADE / Summary of Findings table.
+- PRISMA flow diagram (counts shift when studies are excluded/reinstated).
+
+## 10.6 Figure Regeneration
+
+Regenerate forest plots, funnel plots, subgroup plots, and the PRISMA flow via
+`/make-figures`. Re-embed at the original manuscript positions. Confirm figure captions
+match the new values (captions often contain pooled estimates).
+
+## 10.7 Change Summary
+
+Produce `v{N+1}_change_summary.md` with an explicit delta table:
+
+| Item | v{N} | v{N+1} | Reason |
+|------|------|--------|--------|
+| k | | | |
+| Primary pooled estimate (95% CI) | | | |
+| Heterogeneity (I², τ²) | | | |
+| Studies added | | | |
+| Studies removed | | | |
+| Subgroup re-stratification | | | |
+
+This file is the external audit trail. It must be circulated with the v{N+1} manuscript.
+
+## 10.8 PROSPERO (or Equivalent) Amendment
+
+If eligibility, analysis population, or outcome definitions changed, file an amendment
+to the registered protocol in parallel with the re-build:
+- Keep revision notes within the registry's word limit (often 250 words).
+- Frame the amendment as application correction, not criteria change:
+  > "The pre-specified inclusion criteria are unchanged. The amended application excludes
+  > {N} study(ies) whose characteristics were confirmed on independent re-review to fall
+  > outside the pre-specified criteria."
+- Submit the amendment before — or simultaneously with — re-circulation, so co-authors
+  see an amendment already in flight rather than only a draft change.
+
+## 10.9 Re-Circulation Framing
+
+Use the Phase 9 thread. State the situation plainly in the first paragraph:
+
+> "On re-review of v{N}, we identified {N} study(ies) whose data did not meet the
+> pre-specified inclusion criteria. These were excluded and the analysis regenerated.
+> The manuscript body, supplementary, and all figures have been re-rendered. A change
+> summary is attached."
+
+Tonal anchors worth preserving:
+- "On re-review" — signals internal audit, not external pressure.
+- "Pre-specified criteria" — the protocol itself is unchanged; application is corrected.
+- "Change summary" — an external audit trail is available for scrutiny.
+
+## 10.10 Anti-Patterns (do not)
+
+- Hide the error and submit v{N} as-is. This converts a recoverable finding into a
+  retraction-class incident if the reviewer catches it.
+- Reframe the fix as a "minor revision" with no audit trail. Senior reviewers read audit
+  trails; absence of one signals concealment.
+- Disclose only in the cover letter while leaving Methods silent. Methods and the cover
+  letter must agree.
+
+## 10.11 When the Trigger Fires Post-Submission
+
+If the audit trigger is detected after the journal submission but before an editorial
+decision, notify the editorial office immediately and submit a corrected manuscript
+alongside the disclosure. Do not wait for the reviewer to surface it; editors prefer
+author-initiated correction.
+
+## 10.12 Post-Recovery Loop
+
+After v{N+1} is circulated, Phase 9 restarts. If a further audit trigger emerges during
+the new review window, a second recovery sprint (v{N+1} → v{N+2}) is acceptable — but
+each recovery costs co-author goodwill, so the incoming audit in Phase 6b should be
+tightened each cycle rather than relying on Phase 10 as a routine catch.

package/skills/meta-analysis/references/phase4_km_composite.md

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+# Phase 4 Reference — KM Reconstruction & Composite Exposure Disaggregation
+
+Load this reference when `/meta-analysis` Phase 4 data extraction encounters either
+of two special cases: (a) studies that report outcomes only as Kaplan-Meier curves
+without raw event counts, or (b) studies whose intervention is a composite of
+multiple techniques. The main Phase 4 body of SKILL.md lists the standard
+extraction-form fields and the cross-verification checklist; this reference holds
+the procedural detail for these two scenarios.
+
+---
+
+## 4b. KM Curve Reconstruction (when raw events not reported)
+
+When studies report outcomes only as Kaplan-Meier curves without raw event counts:
+
+1. **Digitise the KM curve**: Use WebPlotDigitizer
+   (https://automeris.io/WebPlotDigitizer/)
+   - Calibrate X/Y axes carefully — verify output range matches the original axis labels.
+   - If coordinates come out in 0–1 range, multiply X by the actual time range
+     (e.g., ×30 for months).
+   - Clip negative Y values to 0 (digitisation artifact).
+   - Export as CSV: `time, cumulative_event_rate` (or survival).
+
+2. **Extract number-at-risk**: Record from the table below the KM plot at each time point.
+
+3. **Reconstruct IPD**: Use the R `IPDfromKM` package (Guyot et al. 2012 method):
+   ```r
+   library(IPDfromKM)
+   dat <- read.csv("digitised_curve.csv")
+   preproc <- preprocess(dat, trisk, nrisk, totalpts, maxy = 1)
+   ipd <- getIPD(preproc, armID = 1)  # armID starts at 1, NOT 0
+   ```
+   - ⚠️ `preprocess()` does NOT accept a `mateflag` parameter (common error).
+   - ⚠️ `armID` starts at 1 (not 0).
+
+4. **Verify**: Generate a reconstructed KM plot and visually compare to the
+   original figure.
+
+5. **Report in Methods**: Cite Guyot et al. 2012 (doi:10.1186/1471-2288-12-9) and
+   state which studies required reconstruction.
+
+**Alternative — Text-based extraction**: When no subgroup-specific KM curve exists
+but the text reports "0% LTP at 12 months" or similar, extract directly from text.
+Document the page number and exact quote.
+
+---
+
+## Composite Exposure Disaggregation
+
+When a study's intervention is a composite of multiple techniques:
+
+1. **Subgroup-specific KM curve** → use KM reconstruction (section 4b above).
+2. **Component-specific Table/multivariate** → extract per-component data from Tables.
+3. **Text-based subgroup report** → extract from narrative (e.g., "APE arm: 0% LTP").
+4. **None available** → include as composite; flag in sensitivity analysis for exclusion.
+
+Always pre-specify a sensitivity analysis excluding composite-exposure studies.
+Document the extraction strategy in the data extraction form Notes column.

package/skills/meta-analysis/references/phase6_statistical_synthesis.md

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+# Phase 6 Reference — Statistical Synthesis
+
+Load this reference when `/meta-analysis` Phase 6 begins executing the pooled
+analysis. It contains the R code templates for DTA and intervention meta-analysis,
+the dual-approach (comparative + single-arm pooled proportion) decision table, and
+the practical cautions (method.tau, HK CI, zero-cell correction, publication-bias
+test power).
+
+**Always use R** (packages: `meta`, `metafor`, `mada`). Companion templates:
+`${CLAUDE_SKILL_DIR}/references/r_templates.md`.
+
+---
+
+## DTA Meta-Analysis
+
+```r
+library(mada)      # bivariate model, forest/SROC plots
+library(meta)      # general meta-analysis utilities
+library(metafor)   # advanced models
+
+# Bivariate model (recommended for DTA)
+fit <- reitsma(data, formula = cbind(tsens, tfpr) ~ 1)
+summary(fit)
+
+# SROC curve with confidence and prediction regions
+plot(fit, sroclwd = 2, main = "SROC Curve")
+
+# Forest plot (paired: sensitivity + specificity)
+forest(fit, type = "sens")
+forest(fit, type = "spec")
+```
+
+### Key outputs for DTA
+- Pooled sensitivity (95% CI)
+- Pooled specificity (95% CI)
+- Pooled positive LR, negative LR
+- Pooled DOR
+- SROC curve with AUC, confidence region, prediction region
+- Heterogeneity: I-squared for sensitivity and specificity separately
+- Threshold effect: Spearman correlation between sensitivity and FPR
+
+---
+
+## Intervention Meta-Analysis
+
+```r
+library(meta)
+library(metafor)
+
+res <- metagen(TE, seTE, data = dat, studlab = study,
+               method.tau = "REML", sm = "OR")
+forest(res)
+funnel(res)
+
+summary(res)  # I-squared, tau-squared, Q test
+metabias(res, method.bias = "Egger")
+metainf(res, pooled = "random")  # leave-one-out
+```
+
+---
+
+## Dual Approach: Comparative + Single-Arm Pooled Proportion
+
+When both comparative and single-arm studies are available, use dual analysis
+(precedent: Lin 2025 PMID:41419890, Su 2026 PMID:41653198). The assignment of
+PRIMARY vs SECONDARY depends on the research question and available evidence:
+
+| Scenario | Primary | Secondary | Rationale |
+|----------|---------|-----------|-----------|
+| Enough comparative studies (k≥8) | Comparative OR/RR | Pooled proportion | Direct comparison answers efficacy |
+| Limited comparative (k<6), many single-arm | Pooled proportion | Comparative OR/RR | Insufficient power for comparative; pooled proportion provides descriptive evidence |
+| Mixed (moderate k, each) | Discuss with co-authors | — | PI/methodologist decision |
+
+The choice should be pre-specified in the PROSPERO protocol and remain consistent
+throughout the manuscript.
+
+```r
+# Comparative MA (binary outcomes)
+res_comp <- metabin(ei, ni, ec, nc, data = dat,
+                     studlab = study, sm = "OR",
+                     method = "Inverse", method.tau = "DL",
+                     common = FALSE, random = TRUE,
+                     method.random.ci = "HK", incr = 0.5)
+
+# Single-arm pooled proportion
+res_prop <- metaprop(event, n, data = dat_single,
+                      studlab = study, sm = "PLOGIT",
+                      method.tau = "DL", method.ci = "CP")
+```
+
+### Key points
+- Comparative answers "is adjunct effective?"; single-arm answers "what outcomes to expect?"
+- Single-arm uses `metaprop()` with logit transformation + Clopper-Pearson CI
+- GRADE certainty lower for single-arm — state explicitly
+- Report both in Results: label PRIMARY/SECONDARY per pre-specified assignment
+- **Selection bias warning**: Single-arm case series may introduce selection bias
+  (experienced centres, favourable patients). When pooling with comparative arms,
+  report both pooled estimates separately and discuss any numerically lower event
+  rate in single-arm studies as a potential selection effect.
+
+---
+
+## Practical R Notes
+
+- Use `method = "Inverse"`, not `"MH"`, to avoid a method.tau conflict.
+- Use `method.tau = "DL"` (DerSimonian-Laird) — REML may not converge with sparse data.
+- Use `method.random.ci = "HK"` (Hartung-Knapp) instead of the deprecated `hakn = TRUE`.
+- Use `common = FALSE, random = TRUE` instead of deprecated `comb.fixed/comb.random`.
+- For zero cells, apply `incr = 0.5` continuity correction.
+- Egger's test is underpowered for k < 10 — note this in results.
+
+---
+
+## Subgroup / Meta-Regression
+
+- Subgroup analysis for pre-specified covariates
+- Meta-regression for continuous moderators
+- Report interaction test p-value, not just within-subgroup p-values
+
+---
+
+## Publication Bias
+
+- DTA: Deeks' funnel plot asymmetry test (standard funnel plots are inappropriate for DTA).
+- Intervention: Funnel plot + Egger's or Peters' test.
+- Note: tests are underpowered for <10 studies.
+
+---
+
+## Sensitivity Analysis
+
+- Leave-one-out analysis (`metainf()`)
+- Excluding high RoB studies
+- Excluding overlapping populations (same institution + enrollment period)
+- Including/excluding borderline studies (sensitivity to inclusion criteria)
+- Alternative model specifications
+
+---
+
+## Error Handling
+
+- If an R script fails, capture the error message, diagnose the likely cause
+  (missing package, data format mismatch, convergence failure), and present a fix.
+  Do not silently re-run.
+- When reporting R output, separate statistical results (pooled estimates,
+  heterogeneity metrics, I-squared) from interpretation. Present numbers first in
+  a "Statistical Results" block, then interpretation guidance in a separate
+  "Interpretation Notes" block.

package/skills/meta-analysis/references/phase9_circulation.md

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+# Phase 9 Reference — Co-author Circulation
+
+Load this reference when Phase 9 is entered (after Phase 8 is complete and Phase 6b
+source-fidelity audit has cleared). The SKILL.md body carries only the goal + summary
+pointer; all procedural detail lives here.
+
+## Goal
+
+Standardized pre-submission circulation of the manuscript to co-authors and senior
+methodologists / reviewers, 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.
+
+## 9.1 Thread Continuity
+
+- If a prior version (v1, v2, ...) of this manuscript was already circulated to the same
+  author team, reply to the same email thread. Preserve `In-Reply-To` and `References`
+  headers so the thread tracks v1 → v2 → v3 in one place.
+- Open a new thread only for the first circulation, or when the author team / target
+  journal has fundamentally changed.
+
+## 9.2 Attachment Scope
+
+**Include:**
+- Manuscript body with figures embedded inline (single DOCX/PDF).
+- Change summary — for v≥2, a delta table vs. the prior circulated version.
+
+**Exclude (circulate separately later):**
+- Graphical abstract — after the body is locked.
+- Cover letter — after the target journal is confirmed.
+- COI forms — after journal format is known.
+- Supplementary appendices — share via a drive link, not attached.
+
+Rationale: bundling all submission artifacts before the body is locked forces co-authors
+to review multiple moving targets at once and telegraphs premature commitment to a
+specific journal (especially when the GA carries journal-specific branding).
+
+## 9.3 Attachment Method
+
+| Total attachment size | Method |
+|---|---|
+| < 5 MB | Direct email attachment |
+| 5 – 25 MB | Direct attachment (within the common 25 MB mailbox limit), but verify at the draft-API level — some clients fail well below the stated message limit |
+| > 25 MB or grey-list formats | Shared drive link only |
+
+A manuscript DOCX with inline figures is typically 0.5 – 1 MB — direct attach is safe.
+
+## 9.4 Recipient Structure
+
+- **TO**: Corresponding author + one senior methodologist reviewer (e.g., a protocol
+  assessor or statistician external to the writing team).
+- **CC**: All remaining co-authors. Include every alternate email address a co-author has
+  used on the thread to avoid dropping them.
+
+Ask the corresponding author explicitly for:
+- target journal preference,
+- 2 – 3 reviewer candidates,
+- any framing adjustments to carry into the cover letter.
+
+## 9.5 Journal-Undetermined Framing
+
+If the target journal is not yet confirmed, state this explicitly:
+
+> "The manuscript is currently formatted to [placeholder journal]'s guidelines. Please
+> suggest an appropriate target journal and we will re-format accordingly."
+
+Do not include the graphical abstract in this round if it carries journal-specific
+branding that would require rework on re-targeting.
+
+## 9.6 Deadline
+
+- Set `(send date + 7 days)` = 5 business days + 1 weekend.
+- Record the deadline in a task tracker with expected responses per recipient.
+- Informal follow-up is acceptable after 4 – 5 days of silence. A formal second message
+  before the 7-day window closes is not appropriate unless an external submission deadline
+  forces it.
+
+## 9.7 Response Tracking
+
+For each recipient, log: date of response, issues raised, and whether the issues trigger
+Phase 10 (Self-Audit Recovery) or are minor in-place revisions.

package/skills/meta-analysis/references/post_submission_release_ops.md

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+# Post-Submission Release Operations
+
+**When**: between the end of Phase 9 (circulation) and journal submission. Separate from Phase 10 (recovery).
+
+**Why it's hard**: during circulation (v7~v18 coexisting), the numbers keep shifting. Mint the DOI too early and a content mismatch forces a re-issue; too late and you are scrambling on submission day.
+
+## Checklist
+
+### Gate 1 — When to issue the release
+
+- [ ] Internal circulation closed: every reviewer (internal PI, external peer) has signed off.
+- [ ] `[VERIFY-CSV]` / `TODO` / `FIXME` / `(to be regenerated)` tags fully removed from manuscript / supplement / figures / code (`rg -n` → 0 hits).
+- [ ] k (number of included studies) matches across the `4_Analysis/*.csv` row count, the manuscript prose, the PRISMA flow, and every figure caption.
+- [ ] Author order / ICMJE COI finalized (just before reflecting it in the Zenodo author metadata).
+
+### Gate 2 — GitHub repo
+
+- [ ] Journal-target bundle regenerates successfully via `_build.sh`.
+- [ ] Repo includes the raw analysis code, extraction_consensus_log.md, PROSPERO amendments tracker, and methodology.
+- [ ] README has a DOI placeholder (replaced after the Zenodo DOI is issued).
+- [ ] `.gitignore` confirmed to exclude raw PDFs / copyrighted material.
+- [ ] LICENSE stated (CC-BY 4.0 or the journal-required license).
+
+### Gate 3 — Zenodo DOI
+
+- [ ] Zenodo record metadata: author order, affiliation, ORCID, keywords, related identifiers (PROSPERO registration number).
+- [ ] Add the GitHub repo release tag URL to `related_identifiers` as `isSupplementTo`.
+- [ ] The submission package (.tar.gz) is uploaded to Zenodo — the journal submission bundle, not the circulation package (vN).
+- [ ] After the DOI is issued, reflect it in the "data availability" section of the manuscript / cover letter / submission portal.
+
+### Gate 4 — Handling re-targeting after rejection
+
+- [ ] Resubmission of identical content to another journal: **do NOT mint a new Zenodo version** (the DOI attaches to the content). Use `_build.sh --journal {new}` to create only a new SUBMISSION folder.
+- [ ] Resubmission after revision: content changed → mint a new Zenodo version. The concept DOI is preserved.
+- [ ] On author changes: redistribute the ICMJE COI + mint a new Zenodo version.
+
+## Common failures
+
+- **F1**: Zenodo DOI minted while `k` (included study count) is still oscillating between versions → content-DOI mismatch forces re-issue. **Blocked by**: Gate 1.
+- **F2**: Journal-specific folders edited by hand without a `_build.sh` → the journal copies drift from master. **Blocked by**: see `submission_package_drift.md`.
+- **F3**: `TODO` / `FIXME` tag left in an R analysis script surfaces only after the repo is pushed to GitHub. **Blocked by**: Gate 1 `rg` scope including code.

package/skills/meta-analysis/references/r_templates.md

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+# R Code Templates for Meta-Analysis
+
+## Required Packages
+
+```r
+# DTA meta-analysis
+library(mada)      # bivariate model, forest/SROC plots
+library(meta)      # general meta-analysis utilities
+library(metafor)   # advanced models
+
+# Intervention meta-analysis
+library(meta)
+library(metafor)
+```
+
+## DTA Meta-Analysis
+
+### Bivariate Model (Recommended)
+
+```r
+# Bivariate model (Reitsma et al.)
+fit <- reitsma(data, formula = cbind(tsens, tfpr) ~ 1)
+summary(fit)
+
+# SROC curve with confidence and prediction regions
+plot(fit, sroclwd = 2, main = "SROC Curve")
+
+# Forest plot (paired: sensitivity + specificity)
+forest(fit, type = "sens")
+forest(fit, type = "spec")
+```
+
+### Key Outputs for DTA
+
+- Pooled sensitivity (95% CI)
+- Pooled specificity (95% CI)
+- Pooled positive LR, negative LR
+- Pooled DOR
+- SROC curve with AUC, confidence region, prediction region
+- Heterogeneity: I-squared for sensitivity and specificity separately
+- Threshold effect: Spearman correlation between sensitivity and FPR
+
+### Publication Bias (DTA)
+
+- Use Deeks' funnel plot asymmetry test (standard funnel plots are inappropriate for DTA)
+
+## Intervention Meta-Analysis
+
+### Random-Effects Model
+
+```r
+# Random-effects model
+res <- metagen(TE, seTE, data = dat, studlab = study,
+               method.tau = "REML", sm = "OR")
+forest(res)
+funnel(res)
+
+# Heterogeneity
+summary(res)  # I-squared, tau-squared, Q test
+
+# Publication bias
+metabias(res, method.bias = "Egger")
+
+# Sensitivity analysis: leave-one-out
+metainf(res, pooled = "random")
+```
+
+### Publication Bias (Intervention)
+
+- Funnel plot + Egger's or Peters' test
+- Note: Tests underpowered for <10 studies
+
+## Subgroup / Meta-Regression
+
+- Subgroup analysis for pre-specified covariates
+- Meta-regression for continuous moderators
+- Report interaction test p-value, not just within-subgroup p-values
+
+## KM Curve Reconstruction (Guyot et al. 2012)
+
+```r
+library(IPDfromKM)
+
+# Read digitised KM curve (time, cumulative event rate)
+dat <- read.csv("digitised_curve.csv")
+
+# Number-at-risk from figure
+trisk <- c(0, 6, 12, 18, 24, 30)  # time points
+nrisk <- c(51, 41, 30, 15, 7, 4)  # at-risk counts
+totalpts <- 51
+
+# Reconstruct IPD
+preproc <- preprocess(dat, trisk, nrisk, totalpts, maxy = 1)
+ipd <- getIPD(preproc, armID = 1)  # armID = 1 (NOT 0)
+
+# Count events for meta-analysis input
+events <- sum(ipd$status == 1)
+total <- nrow(ipd)
+cat(sprintf("Events: %d / %d\n", events, total))
+```
+
+Key pitfalls:
+- `preprocess()` does NOT accept a `mateflag` parameter
+- `armID` starts at 1, not 0
+- Verify reconstructed KM visually against original figure
+
+## Pooled Proportion (Single-arm or combined)
+
+```r
+res_prop <- metaprop(event, n, data = dat,
+                      studlab = study,
+                      sm = "PLOGIT",          # logit transformation
+                      method.tau = "ML",       # maximum likelihood
+                      method.ci = "CP",        # Clopper-Pearson for individual studies
+                      common = FALSE,
+                      random = TRUE)
+
+# Forest plot
+forest(res_prop, xlim = c(0, 1),
+       leftcols = c("studlab", "event", "n"),
+       leftlabs = c("Study", "Events", "Total"))
+
+# Egger's test (k >= 10)
+metabias(res_prop, method.bias = "Egger")
+```
+
+## Sensitivity Analysis
+
+- Leave-one-out analysis
+- Excluding high RoB studies
+- Excluding outliers (identified via influence diagnostics)
+- Alternative model specifications

package/skills/meta-analysis/references/review_orchestration.md

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+# Peer Review Orchestration (3-tier)
+
+**Extends**: the existing `phase9_circulation.md` (circulation email template). This document covers the full internal → external → journal three-round orchestration.
+
+## 3-tier structure
+
+| Tier | Reviewer | Output | Blocking point |
+|---|---|---|---|
+| 1. Internal | Clinical PI (second dual rater) + methodology lead | dual-rating consensus, QUADAS-2 domain table | PI availability |
+| 2. External | Adversarial GPT review + independent peer (optional) | critique memo, defensive-tone audit | — |
+| 3. Journal | Editorial + peer reviewers | reject/revise/accept, Response matrix | — |
+
+## Core rules
+
+### RO-1. Dual-rating work ships as a trio: "figure + per-study table + supplementary", together
+- **Problem pattern**: A QUADAS-2 traffic-light figure ships without an accompanying per-study domain table → PRISMA-DTA Item 19 remains PARTIAL. The supplementary table must be planned alongside the figure, not added one revision later.
+- **Rule**: Plan dual-rating outputs such as QUADAS-2 / RoB2 / GRADE as a three-part set at the design stage. A figure alone does not complete PRISMA-DTA Item 19.
+
+### RO-2. Secure the "second-reviewer lead time" before sending the circulation package
+- **Problem pattern**: Manuscript circulated after only first-reviewer screening → the second-reviewer dual rating then blocks the entire revision cycle for weeks, leaving PRISMA Item 9 PARTIAL.
+- **Rule**: Confirm the clinical PI's second-rating availability window before writing the circulation email. Put blocking items as a bullet at the very top of the email body. Add a "PI availability window" field to the circulation template.
+
+### RO-3. External review specializes in "defensive tone / bias-inflation / upper-bound framing"
+- **Problem pattern**: External adversarial review surfaces over-defensive Methods prose (multi-paragraph justifications for pre-specified protocol deviations) and flags that a homogeneity statistic (e.g., Sp I²=0%) is driven by universalized bias rather than true between-study agreement.
+- **Rule**: Include in the external adversarial-review prompt: (a) a defensive-tone audit (check that protocol-deviation explanations in Methods are ≤3 sentences), (b) a bias-driven homogeneity interpretation check, and (c) an upper-bound/lower-bound framing check. Offload detailed rationale to the Supplement.
+
+### RO-4. The Response matrix tracks reviewer reply + manuscript edit + supplement together
+- **Problem pattern**: During revision, a numeric value (e.g., a subgroup p-value) changes between versions with no before/after diff recorded in the Response matrix → the reviewer's re-review cannot verify the update.
+- **Rule**: For each comment row in the Response matrix, record (a) the reviewer's original text, (b) a response summary, (c) the manuscript edit locator (section/line), and (d) whether a number changed, tagged `[VERIFY-CSV]`. Remove all tags on submission day.
+
+### RO-5. Consolidate protocol deviations into a single PROSPERO amendment
+- **Problem pattern**: Analysis-framework deviation, subgroup deviation, and search-amendment notes split across three manuscript sections and three separate tracker files → the PROSPERO amendment loses provenance.
+- **Rule**: One file at the project root, `protocol_deviations_tracker.md`. Bundle them under one ID when submitting the PROSPERO amendment. Use a single citation in the manuscript too.
+
+## Templates
+
+- Circulation email: see the existing `phase9_circulation.md`. Per RO-2 of this document, propose adding a "PI availability window" field.
+- Internal peer review memo: `internal_peer_review_MA{n}_v{N}_{date}.md`
+- External GPT review memo: `external_review_gpt_MA{n}_{date}.md`
+- Response matrix: the existing `/revise` skill template. Per RO-4, add a `[VERIFY-CSV]` field.