medsci-skills 5.12.0 → 5.13.0

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package/metadata/distribution_manifest.json

@@ -1,6 +1,6 @@
 {
   "schema_version": 1,
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package/package.json

@@ -1,6 +1,6 @@
 {
   "name": "medsci-skills",
-  "version": "5.12.0",
+  "version": "5.13.0",
   "description": "MedSci Skills — a medical/scientific research skill suite for AI coding agents (Claude Code, Codex, Cursor, Copilot). The npm package is a terminal-friendly installer shortcut; the canonical distribution remains the GitHub repository and the Claude Code plugin marketplace.",
   "license": "SEE LICENSE IN LICENSE",
   "homepage": "https://github.com/Aperivue/medsci-skills#readme",

package/skills/analyze-stats/SKILL.md

@@ -393,6 +393,7 @@ tbl %>% as_flex_table() %>% flextable::save_as_docx(path = "table.docx")
 
 ### Diagnostic Accuracy
 
+- **Methodology guide**: `references/analysis_guides/diagnostic_accuracy.md` (**load before generating code** — every metric with a CI on a stated analysis unit; the confidence-weighted trap [unweighted-baseline AUC + monotonic-encoding check, produce-side of probe D9]; paired DeLong vs MRMC for reader-generalising claims; per-stratum admissibility [D10]; one-scale-per-comparison [D11])
 - Template: `references/templates/diagnostic_accuracy.py`
 - Always report: sensitivity, specificity, PPV, NPV, accuracy, AUC
 - CIs: Wilson score for proportions, DeLong for AUC
@@ -487,6 +488,7 @@ tbl %>% as_flex_table() %>% flextable::save_as_docx(path = "table.docx")
 
 ### Survival Analysis
 
+- **Methodology guide**: `references/analysis_guides/survival.md` (**load before generating code** — competing risks first [naive 1−KM overestimates → produce the Aalen–Johansen/Fine–Gray CIF; cause-specific vs subdistribution for which question, produce-side of probe S3]; PH check → RMST when violated; reverse-KM follow-up + C-index variant [S6]; estimand provenance [S8])
 - Table type guide: `references/table-standards/table-types/survival_results.md` (Cox results table: events/person-time, reverse-KM median follow-up, univariable + adjusted HR with CI, PH-assumption footnote, EPV/sparse-stratum and RMST-when-PH-violated rules)
 - Kaplan-Meier curves with number-at-risk table
 - Log-rank test for group comparison

package/skills/analyze-stats/references/analysis_guides/diagnostic_accuracy.md

@@ -0,0 +1,184 @@
+# Diagnostic Accuracy & Reader-Study Guide
+
+Estimating how well an index test (or an AI model / reader) separates disease from
+no-disease against a reference standard. The point estimates are easy to compute; the
+ways these analyses fail review are (1) reporting AUC / sensitivity / specificity **without
+CIs or on the wrong analysis unit**, (2) a **confidence-weighted / rating** score whose
+novelty is never tested against the simpler **unweighted** baseline, and (3) comparing two
+AUCs with a **fixed-reader** test when the claim is meant to **generalise to readers**.
+
+---
+
+## When to Use
+
+- **Single index test** vs a reference standard → sensitivity, specificity, PPV, NPV, accuracy
+  (each with a 95% CI), and AUC (with a DeLong or bootstrap CI).
+- **Two tests / models on the same cases** → a **paired** AUC comparison (DeLong `roc.test`,
+  `paired = TRUE`) — never two independent CIs eyeballed for overlap.
+- **Multi-reader multi-case (MRMC)** reader study (AI-vs-reader, modality comparison) → an
+  MRMC method (Obuchowski–Rockette / DBM) that carries **reader + case** variance; see
+  `table-standards/table-types/reader_study.md` and `make-figures` `exemplar_plots/mrmc_roc.md`.
+- NOT for: pooling accuracy across studies (that is a DTA meta-analysis — bivariate / HSROC via
+  `mada`; see the `/meta-analysis` DTA path); not for rater **agreement** (that is
+  `analysis_guides/agreement_reliability.md`).
+
+---
+
+## Every metric with a CI, on a stated analysis unit (the floor)
+
+A bare AUC / sensitivity / specificity is not reportable. Compute the CI, and state the unit
+(**per-patient vs per-lesion** — multiple lesions per patient are clustered, exactly as in
+`agreement_reliability.md`; a per-lesion count inflates *n*).
+
+```python
+import numpy as np, pandas as pd
+from sklearn.metrics import roc_auc_score
+from statsmodels.stats.proportion import proportion_confint
+
+df = pd.read_csv("reader_calls.csv")   # truth (0/1), call (0/1), confidence (1..K), stratum
+
+# sensitivity / specificity / PPV / NPV at the operating point, each with a Wilson CI
+tp = int(((df.truth == 1) & (df.call == 1)).sum()); fn = int(((df.truth == 1) & (df.call == 0)).sum())
+tn = int(((df.truth == 0) & (df.call == 0)).sum()); fp = int(((df.truth == 0) & (df.call == 1)).sum())
+for name, num, den in [("sensitivity", tp, tp+fn), ("specificity", tn, tn+fp),
+                       ("PPV", tp, tp+fp), ("NPV", tn, tn+fn)]:
+    lo, hi = proportion_confint(num, den, method="wilson")
+    print(f"{name} = {num/den:.3f} (95% CI {lo:.3f}-{hi:.3f}), n={den}")
+```
+
+PPV and NPV are **prevalence-dependent** — do not transport them to a population with a
+different base rate; report sensitivity/specificity (prevalence-invariant) plus the study
+prevalence, and recompute predictive values at the target prevalence with Bayes' rule.
+
+---
+
+## The confidence-weighted trap comes first (this, not the AUC, is the issue)
+
+When the novelty is a **confidence-weighted / rating-collapsed** score used as the ROC
+predictor, you must (a) confirm the (call × confidence) encoding is **strictly monotone** — a
+folded encoding silently collides the most-confident-positive with a negative call — and
+(b) report the **unweighted binary-call AUC** beside the weighted one, so the weighting earns
+its place. This is the produce-side of self-review / peer-review probe **D9**.
+
+```python
+K = int(df.confidence.max())
+
+# intended strictly-monotone composite: negative calls rank below positive calls, and within
+# a call higher confidence pushes further from the decision boundary.
+def composite(call, conf, K):
+    return np.where(call == 1, K + conf, K + 1 - conf)   # neg: 1..K, pos: K+1..2K
+
+# (1) MONOTONIC-ENCODING CHECK — every distinct (call, confidence) must map to a distinct,
+#     correctly-ordered score. A collision is the folded-score bug (e.g. real/1 == ai/1).
+combos = df[["call", "confidence"]].drop_duplicates().copy()
+combos["score"] = composite(combos.call.values, combos.confidence.values, K)
+if combos.score.nunique() != len(combos):
+    raise ValueError("ENCODING COLLISION — the confidence weighting is not strictly monotone "
+                     "(folded-score bug); fix the encoding before computing AUC.")
+
+# (2) UNWEIGHTED BASELINE beside the weighted primary
+df["score"] = composite(df.call.values, df.confidence.values, K)
+print(f"AUC (confidence-weighted) = {roc_auc_score(df.truth, df.score):.3f}")
+print(f"AUC (unweighted binary call) = {roc_auc_score(df.truth, df.call):.3f}")
+```
+
+If the weighted AUC materially exceeds the unweighted one, the weighting must be justified;
+if it does not, report the simpler estimator as primary. A weighted score that changed a
+hypothesis's direction versus its unweighted baseline is a **post-lock change to disclose**,
+not a silent primary.
+
+---
+
+## AUC confidence intervals and comparing two AUCs
+
+DeLong is the field-standard analytic AUC CI and paired comparison; `pROC` (R) is canonical.
+
+```r
+library(pROC)
+d  <- read.csv("reader_calls.csv")
+rw <- roc(d$truth, d$score, quiet = TRUE)
+ci.auc(rw)                                   # DeLong 95% CI for the weighted AUC
+ru <- roc(d$truth, d$call,  quiet = TRUE)
+roc.test(rw, ru, method = "delong", paired = TRUE)   # paired, SAME cases (fixed-reader)
+```
+
+A portable Python bootstrap CI (use when a DeLong implementation is unavailable):
+
+```python
+def auc_ci_bootstrap(y, s, n_boot=2000, seed=42):
+    rng = np.random.default_rng(seed); y = np.asarray(y); s = np.asarray(s); n = len(y)
+    boots = [roc_auc_score(y[i], s[i]) for i in (rng.integers(0, n, n) for _ in range(n_boot))
+             if len(np.unique(y[i])) == 2]
+    return tuple(np.percentile(boots, [2.5, 97.5]))
+```
+
+**Fixed-reader vs MRMC.** A paired DeLong test treats the readers/cases as fixed. If the claim
+is that the result **generalises to readers** (a reader sample), a fixed-reader CI understates
+uncertainty — use an MRMC method (Obuchowski–Rockette / DBM) that carries reader + case
+variance, report per-reader and reader-averaged AUC, and state the unit (per-patient vs
+per-lesion) and the superiority/non-inferiority margin. This is probe D9's MRMC lead.
+
+---
+
+## Per-stratum admissibility: produce the table the claim is checked against (D10)
+
+A blanket "no subgroup met AUC ≥ 0.75 with lower bound ≥ 0.70" is falsified by a single tabled
+stratum that meets it. Produce the per-stratum AUC + CI and test each row against the rule
+rather than asserting a global negative.
+
+```python
+rule = lambda auc, lo: (auc >= 0.75) and (lo >= 0.70)
+for name, g in df.groupby("stratum"):
+    if g.truth.nunique() < 2:                       # single-class stratum: not estimable
+        print(f"{name}: not estimable (one class)"); continue
+    auc = roc_auc_score(g.truth, g.score); lo, hi = auc_ci_bootstrap(g.truth, g.score)
+    print(f"{name}: AUC {auc:.3f} (95% CI {lo:.3f}-{hi:.3f}) "
+          f"{'QUALIFIES' if rule(auc, lo) else 'below'}")
+```
+
+With *k* strata some crossings are expected — frame qualifying strata as hypothesis-generating
+(note the multiplicity), but do **not** deny a row the paper's own table satisfies.
+
+---
+
+## One scale per comparison (D11)
+
+Two values sharing a comparison column (or a row-wise "A vs B") must be computed under the
+**same normalisation / definition** — e.g. both volume errors as a standard relative error, not
+one relative and one range-normalised. If they are not identical, recompute on a common scale
+before any superiority/comparability claim, or footnote "not on the same scale".
+
+---
+
+## Reporting
+
+- Sensitivity, specificity, PPV, NPV, accuracy, and AUC each **with a 95% CI**; the operating
+  point and how it was chosen (Youden vs a prespecified clinical threshold — a threshold picked
+  on the same data is optimistic and needs a held-out or cross-validated estimate).
+- The **analysis unit** (per-patient vs per-lesion) and clustering handling; study prevalence.
+- For a weighted-score primary: the **unweighted-baseline AUC** beside it (D9).
+- AUC alone is insufficient for a clinical claim — pair discrimination with **calibration** and a
+  **decision-curve / net-benefit** pass at the relevant threshold (see the incremental-value
+  table type and the `make-figures` decision-curve exemplar).
+
+---
+
+## Common failures (flag at review)
+
+- **AUC / sensitivity / specificity with no CI**, or a per-lesion count reported as if per-patient.
+- **Confidence-weighted AUC with no unweighted baseline** and no monotonic-encoding check (D9) —
+  the weighting may have created the result or hidden a folded-score bug.
+- **Two AUCs compared by CI overlap** instead of a paired DeLong test; a **fixed-reader** CI used
+  for a claim that generalises to readers (needs MRMC).
+- **"No stratum met the rule" contradicted by the per-stratum table** (D10).
+- **Mixed-normalisation head-to-head** in one column (D11).
+- **PPV/NPV transported** across a prevalence change.
+
+---
+
+## Anti-Hallucination
+
+- Never hand-type an AUC, sensitivity/specificity, or CI — compute it from the calls CSV with a
+  seeded script; carry each estimate together with its CI (never a bare AUC).
+- Do not report a weighted-score AUC without the unweighted baseline the code produced.
+- Do not quote a DeLong comparison p-value that a paired test on the same cases did not produce.

package/skills/analyze-stats/references/analysis_guides/survival.md

@@ -0,0 +1,149 @@
+# Survival / Time-to-Event Guide
+
+Estimating time-to-event outcomes and prognostic effects. The estimator is easy to
+call; the ways these analyses fail review are (1) ignoring **competing risks** so a naive
+1−KM **overestimates** the cumulative incidence, (2) reporting a **single time-averaged
+hazard ratio** when the proportional-hazards assumption is violated, and (3) **estimand
+drift** — quoting a subdistribution hazard for an etiologic claim or a cause-specific hazard
+for an absolute-risk claim. This guide produces the right estimand; the operational caveats
+(EPV gate, cluster-robust CIs, interval-censoring) live in the SKILL.md `### Survival
+Analysis` section.
+
+---
+
+## When to Use
+
+- **Single event type, right-censored** → Kaplan–Meier (unadjusted) + Cox proportional-hazards
+  (adjusted HR with 95% CI); the log-rank test for a KM group comparison.
+- **≥2 competing event types** (recurrence + competing death, or cause-specific mortality) →
+  cumulative incidence functions + **cause-specific Cox** or **Fine–Gray** — see below.
+- **Prognostic model discrimination** → a C-index variant matched to the censoring + a
+  time-dependent AUC at a clinical horizon (S6).
+- NOT for: events detected only at scheduled visits → interval-censored methods (SKILL.md);
+  recurrent events per subject → a cluster-robust or frailty model (SKILL.md cluster rule);
+  rater agreement → `analysis_guides/agreement_reliability.md`.
+
+---
+
+## Competing risks come first (this, not the HR, is the issue)
+
+If a subject can experience an event that **precludes** the event of interest (death before
+recurrence), treating the competing event as ordinary censoring is *informative* censoring:
+the naive **1−KM overestimates** the cumulative incidence of the event of interest. Produce the
+**cumulative incidence function (CIF)** with an Aalen–Johansen / Fine–Gray estimator instead.
+This is the produce-side of probe **S3**.
+
+```python
+# lifelines: cumulative incidence for a competing-risks event of interest
+from lifelines import AalenJohansenFitter, KaplanMeierFitter
+import pandas as pd
+df = pd.read_csv("survival.csv")   # time, event_type (0=censored, 1=interest, 2=competing)
+
+ajf = AalenJohansenFitter()
+ajf.fit(df["time"], df["event_type"], event_of_interest=1)
+print(ajf.cumulative_density_.tail(1))          # correct CIF for cause 1
+
+kmf = KaplanMeierFitter()                        # NAIVE (cause 2 censored) — overestimates
+kmf.fit(df["time"], (df["event_type"] == 1).astype(int))
+print("naive 1-KM:", float(1 - kmf.survival_function_.iloc[-1, 0]))
+# the naive value will exceed the Aalen-Johansen CIF whenever the competing event is common.
+```
+
+**Which model for which question (S8 estimand):**
+
+- **Cause-specific hazard** (a Cox model that censors the competing event) answers an
+  **etiologic** question — "does X change the rate of recurrence among those still at risk?"
+- **Fine–Gray subdistribution hazard** (`cmprsk::crr` / `survival::finegray` in R) answers a
+  **prognostic / absolute-risk** question — "does X change the cumulative *incidence*?" Quote an
+  sHR for an incidence claim and a cause-specific HR for an etiologic claim — not the reverse.
+
+```r
+library(survival)                       # Fine-Gray via a weighted Cox on the finegray split
+fg  <- finegray(Surv(time, factor(event_type)) ~ ., data = d, etype = 1)
+crr <- coxph(Surv(fgstart, fgstop, fgstatus) ~ x, weight = fgwt, data = fg)   # subdistribution HR
+```
+
+---
+
+## Proportional hazards, and RMST when it fails
+
+A single Cox HR is a time-average; if PH is violated it averages a changing effect. Test PH,
+and when it fails report a **restricted mean survival time (RMST) difference** at a fixed
+horizon (an estimand that stays interpretable under non-PH) rather than one HR.
+
+```python
+from lifelines import CoxPHFitter
+cph = CoxPHFitter().fit(df, "time", "event")
+cph.check_assumptions(df, p_value_threshold=0.05)   # Schoenfeld; significant -> PH violated
+```
+
+```r
+library(survRM2)
+rmst2(time, status, arm, tau = 3)   # RMST difference at tau=3 years, valid under non-PH
+```
+
+Do not report a single time-averaged HR alongside a significant Schoenfeld test without also
+giving a piecewise/time-stratified HR or an RMST difference (SKILL.md PH-violation rule).
+
+---
+
+## Follow-up and discrimination (S6)
+
+- **Reverse Kaplan–Meier median follow-up** — the honest "how long were people followed"
+  (median event time answers a different question). Compute it by **swapping the event
+  indicator** (censored observations become the "events"); report it per cohort and per
+  outcome, with the censoring date.
+
+```python
+kmf.fit(df["time"], 1 - df["event"])            # swap: censored -> event
+print("reverse-KM median follow-up:", kmf.median_survival_time_)
+```
+
+- **C-index variant** — Harrell's C is biased under heavy or non-random censoring; report
+  **Uno's IPCW C** (`survC1::Est.Cval` / `timeROC`) and a **time-dependent AUC at a clinical
+  horizon** (2-/3-year) beside it, and state which variant and horizon (S6).
+
+---
+
+## Estimand provenance (S8)
+
+State the survival estimand explicitly and hold it consistent across Abstract / Methods /
+Results — event-free survival vs cause-specific cumulative incidence vs all-cause mortality,
+and subject vs population level — with the evaluation horizon fixed in advance. Do not
+re-designate the primary endpoint, model, or horizon after seeing results, and make every
+derived statistic (an E-value, an sHR-vs-cause-specific contrast) trace to the *declared
+primary* estimand. The self-review skill automates the registration ↔ manuscript and E-value
+arithmetic checks (Phase 2.5f); see also `estimand-provenance-lock`.
+
+---
+
+## Reporting
+
+- KM curves **with a number-at-risk table**; median survival with 95% CI (or the reason it is
+  not reached).
+- Cox HR (95% CI) with the **PH check stated**; for competing risks, the CIF and whether the
+  HR is cause-specific or subdistribution.
+- Events and person-time per group; the **reverse-KM median follow-up**; EPV for the model.
+- The estimand and horizon, stated once and consistent everywhere.
+
+---
+
+## Common failures (flag at review)
+
+- **Competing risks ignored** — naive 1−KM (or a cause-specific model presented as absolute
+  risk) overestimates incidence; report a CIF and name cause-specific vs subdistribution (S3/S8).
+- **A single time-averaged HR under a violated PH assumption** — needs a piecewise HR or RMST.
+- **Harrell's C under heavy censoring** with no Uno/IPCW variant and no horizon (S6).
+- **Median *survival* reported as "follow-up"** instead of the reverse-KM follow-up.
+- **Estimand drift** — a primary endpoint/model/horizon re-designated post-hoc, or a derived
+  statistic quoted off a non-primary estimate (S8).
+
+---
+
+## Anti-Hallucination
+
+- Never hand-type an HR, median, CIF, or CI — compute it from the time-to-event CSV with a
+  seeded script, and carry each estimate together with its CI.
+- Do not report a Cox HR without the proportional-hazards check the code actually ran.
+- Under competing risks, do not quote a 1−KM cumulative incidence — report the Aalen–Johansen /
+  Fine–Gray CIF the code produced.

package/skills/peer-review/references/domain-probes/diagnostic_accuracy.md

@@ -47,6 +47,7 @@ A checklist for **diagnostic test accuracy (DTA) primary studies** — an index
 - When a reader study's novelty is a **confidence-weighted** (or rating-collapsed) score used as the ROC/AUC predictor, the **unweighted binary-call AUC** must be reported side-by-side (as a sensitivity analysis). Without it, you cannot tell whether the weighting *created* the result or hid an estimator fragility (e.g. a folded/non-monotonic encoding that collapses `real/5` with `ai/1`).
 - Lead: if the primary predictor is a confidence/rating→single-score collapse and no unweighted binary-call AUC appears, ask for it; also confirm the (call × confidence) encoding is strictly monotonic (no boundary collision) — the folded-score bug understates one hypothesis and can flip another.
 - Severity: MAJOR when the weighted score is the headline and no unweighted baseline is shown; the weighting must "earn its place" against the simpler estimator.
+- Produce the fix: `analyze-stats` `references/analysis_guides/diagnostic_accuracy.md` has the monotonic-encoding check + the unweighted-baseline AUC beside the weighted primary (and the per-stratum admissibility table for D10 and the one-scale-per-comparison rule for D11).
 
 **D10 — "No stratum met threshold X" vs a per-stratum table that does meet X**:
 - When the manuscript states a numeric admissibility/deployability rule (e.g. "AUC ≥ 0.75 **and** lower 95% bound ≥ 0.70") and concludes "**no stratum met** the rule" / "all strata were below", cross-check that claim against the **per-stratum AUC + CI table**. A blanket negative-stratum claim contradicted by a tabled stratum that literally satisfies the rule (e.g. ultrasound 0.789, CI 0.742–0.834) is a self-contradiction a reviewer verifies with arithmetic.

package/skills/peer-review/references/domain-probes/survival_prognostic.md

@@ -28,6 +28,7 @@ A 9-probe checklist for time-to-event outcomes and prognostic model development.
 - Cause-specific hazards or Fine-Gray subdistribution hazards used?
 - Patient developing one event still at risk for the other (informative censoring by death)?
 - If competing-risks structure is ignored and outcomes are treated as independent right-censored events → MAJOR.
+- Produce the fix: `analyze-stats` `references/analysis_guides/survival.md` has the Aalen–Johansen/Fine–Gray cumulative-incidence code (naive 1−KM overestimates) + the cause-specific-vs-subdistribution estimand choice (S8) and the PH→RMST fallback.
 
 **S4 — Cutoff derivation optimism**:
 - Cutoffs derived via maximally selected log-rank statistics, AUC-based Youden's J, or similar data-driven methods?

package/skills/self-review/references/domain-probes/diagnostic_accuracy.md

@@ -47,6 +47,7 @@ A checklist for **diagnostic test accuracy (DTA) primary studies** — an index
 - When a reader study's novelty is a **confidence-weighted** (or rating-collapsed) score used as the ROC/AUC predictor, the **unweighted binary-call AUC** must be reported side-by-side (as a sensitivity analysis). Without it, you cannot tell whether the weighting *created* the result or hid an estimator fragility (e.g. a folded/non-monotonic encoding that collapses `real/5` with `ai/1`).
 - Lead: if the primary predictor is a confidence/rating→single-score collapse and no unweighted binary-call AUC appears, ask for it; also confirm the (call × confidence) encoding is strictly monotonic (no boundary collision) — the folded-score bug understates one hypothesis and can flip another.
 - Severity: MAJOR when the weighted score is the headline and no unweighted baseline is shown; the weighting must "earn its place" against the simpler estimator.
+- Produce the fix: `analyze-stats` `references/analysis_guides/diagnostic_accuracy.md` has the monotonic-encoding check + the unweighted-baseline AUC beside the weighted primary (and the per-stratum admissibility table for D10 and the one-scale-per-comparison rule for D11).
 
 **D10 — "No stratum met threshold X" vs a per-stratum table that does meet X**:
 - When the manuscript states a numeric admissibility/deployability rule (e.g. "AUC ≥ 0.75 **and** lower 95% bound ≥ 0.70") and concludes "**no stratum met** the rule" / "all strata were below", cross-check that claim against the **per-stratum AUC + CI table**. A blanket negative-stratum claim contradicted by a tabled stratum that literally satisfies the rule (e.g. ultrasound 0.789, CI 0.742–0.834) is a self-contradiction a reviewer verifies with arithmetic.

package/skills/self-review/references/domain-probes/survival_prognostic.md

@@ -28,6 +28,7 @@ A 9-probe checklist for time-to-event outcomes and prognostic model development.
 - Cause-specific hazards or Fine-Gray subdistribution hazards used?
 - Patient developing one event still at risk for the other (informative censoring by death)?
 - If competing-risks structure is ignored and outcomes are treated as independent right-censored events → MAJOR.
+- Produce the fix: `analyze-stats` `references/analysis_guides/survival.md` has the Aalen–Johansen/Fine–Gray cumulative-incidence code (naive 1−KM overestimates) + the cause-specific-vs-subdistribution estimand choice (S8) and the PH→RMST fallback.
 
 **S4 — Cutoff derivation optimism**:
 - Cutoffs derived via maximally selected log-rank statistics, AUC-based Youden's J, or similar data-driven methods?