Find Cohort Gap

Phase 0: Cohort Intake

Collect cohort metadata. Use the template at ${CLAUDE_SKILL_DIR}/references/cohort_profile_template.md.

Required information:

1. Cohort name and setting (institution, country, population type)
2. Sample size (N at baseline, N with follow-up)
3. Time span (enrollment period, follow-up duration, measurement intervals)
4. Variable categories (demographics, labs, imaging, questionnaires, medications, procedures)
5. Endpoints available (mortality, cancer incidence, cardiovascular events, hospitalization)
6. Special strengths (serial measurements, linkage to national registries, unique population)
7. Known limitations (healthy volunteer bias, attrition, missing data patterns)
8. Existing publications from this cohort (if known — to avoid duplication)

If the user provides a data dictionary file (Excel/CSV), read it to extract variable categories and construct the variable cluster map automatically.

Gate: Present the cohort profile summary. Confirm before proceeding.

Phase 1: PI/CA Profiling

Profile the intended PI or corresponding author to find topic-expertise alignment.

1. Search PubMed for the PI's recent publications (last 5 years).
   • Use /search-lit E-utilities: bash "$EUTILS" search "AuthorLastName AuthorFirstInitial[Author]" 30
   • Extract top keyword clusters from titles/abstracts.
2. Identify specialty signals:
   • Academic society positions (president, board member, editor)
   • Subspecialty focus areas
   • Preferred journal tiers
3. Build a PI keyword map: 5-10 keyword clusters ranked by publication frequency.

If no PI is specified, skip this phase and use variable clusters alone in Phase 2.

Output: PI profile card (name, affiliation, top keywords, society roles, preferred journals).

Phase 2: Intersection Matrix

Cross cohort variable clusters with PI expertise to generate candidate topics.

Method

Create a matrix: rows = DB variable clusters, columns = PI keyword clusters. Score each cell 0-3:

• 3: PI has published in this exact intersection (direct match)
• 2: PI's subspecialty covers this area (strong relevance)
• 1: Tangential connection (possible but needs framing)
• 0: No connection

Candidate Generation

1. Extract all cells scoring 2-3 as primary candidates.
2. For cells scoring 1, apply the A-B substitution test: "Has someone published [this analysis] with [a different exposure/outcome] in a similar cohort?" If yes, substituting the PI's specialty variable creates a viable candidate.
3. Generate 20-40 candidate topic statements in PICO format:
   • P: Population from the cohort
   • E: Exposure/predictor variable(s)
   • C: Comparison group
   • O: Outcome (preferably hard endpoint)

Discipline Alignment Filter

Before advancing candidates to saturation scanning, apply a discipline filter:

• Who is the intended first author? Identify their department/specialty.
• Does the primary exposure variable belong to that discipline? The first author's specialty must align with the study's core variable. For example:
  • Radiology first author → imaging variable must be the primary exposure
  • Cardiology first author → cardiac biomarker or ECG finding as exposure
  • Neurology first author → neurological variable or brain imaging as exposure
• Kill candidates where the primary exposure is outside the first author's discipline. A strong PI match alone is insufficient if the first author cannot claim ownership of the core variable.

This filter prevents generating topics where the first author's contribution is not defensible at the variable level.

Gate: Present the intersection matrix and top 20 candidates (post-discipline filter). User selects 8-12 for saturation scanning.

Phase 3: Literature Saturation Scan

For each selected candidate, determine how saturated the literature is.

Search Strategy

For each candidate:

1. Build a PubMed query: (exposure terms) AND (outcome terms) AND (cohort OR longitudinal OR prospective)
2. Execute search via /search-lit E-utilities.
3. Count total results and classify:

Critical Filter

For each candidate in Green/Yellow, ask: "Has anyone published this with serial/repeated measurements?" If no — automatic upgrade by one grade.

"So What" Test

For each candidate, articulate 2-3 potential clinical implications of the findings. If you cannot state why a clinician or policymaker would care about the result, the topic fails regardless of gap score.

Output: Saturation table with grade, paper count, longitudinal gap status, and "So What" statement for each candidate.

Gate: Present saturation results. User selects 3-5 finalists for deep scoring.

Phase 4: 6-Pattern Scoring + Comparison Table

Apply the 6-Pattern framework to each finalist. Score each pattern 0 or 1.

6 Patterns (Universal)

Read the detailed rubric at ${CLAUDE_SKILL_DIR}/references/pattern_scoring_rubric.md.

Comparison Table Construction

For each finalist, build a table comparing the top 3-5 existing papers against THIS STUDY:

| Feature | Author1 (Year) | Author2 (Year) | Author3 (Year) | THIS STUDY |
|---------|----------------|----------------|----------------|------------|
| Design | Cross-sectional | Cohort (5yr) | Cross-sectional | Cohort (20yr) |
| N | 3,200 | 8,500 | 12,000 | ~200,000 |
| Serial data | No | No | No | Yes (avg 5 visits) |
| Hard endpoint | Surrogate | Surrogate | All-cause mortality | CVD + all-cause mortality |
| Population | Referral | General | Screening | Health checkup (no referral bias) |
| Ethnicity | Western | Western | Asian (Japan) | Asian (Korea) |
| Subgroup analysis | No | Age only | No | Age + sex + comorbidity |

Score Interpretation

Gate: Present scoring results and comparison tables. User approves final ranking.

Phase 5: Feasibility Gate

For each scored finalist, verify practical feasibility.

Checks

1. Sample size adequacy:

   • Cox regression: minimum 10 events per predictor variable (EPV rule)
   • Logistic regression: same EPV rule
   • For large cohorts (N>100K): warn about p-value inflation — statistically significant results are nearly guaranteed, so focus on effect size thresholds (e.g., HR >1.2 or <0.8 for clinical relevance)
   • Consider negative control strategy (EPCV) for very large samples

2. Missing data:

   • Key exposure variable: <20% missing acceptable
   • Key outcome: <5% missing
   • If serial data: assess attrition pattern (MCAR/MAR/MNAR)

3. Follow-up adequacy:

   • Outcome must have plausible latency within available follow-up
   • Cancer outcomes: minimum 5 years
   • CVD events: minimum 3 years
   • Mortality: minimum 5 years

4. Operational definition:

   • Can the exposure be defined from available variables?
   • For claims data: ICD codes alone = 40-60% accuracy. Require combination strategy (diagnosis + prescription + visit frequency + special codes)
   • Cross-check expected prevalence against known epidemiological data

5. IRB/ethics:

   • Is the data already IRB-approved for this type of analysis?
   • Any additional approvals needed for data linkage?

6. Disease Novelty Bonus (informational, not Go/No-Go):

   • Idiopathic etiology or debated mechanism → higher journal interest
   • Established mechanism → needs stronger methodological novelty

Decision

• Go: All checks pass.
• Conditional Go: Minor issues solvable (e.g., missing data manageable with imputation).
• No-Go: Fatal flaw (insufficient events, no valid endpoint, key variable unavailable).

Output: Feasibility report for each finalist with Go/Conditional/No-Go status.

Phase 6: Output — Ranked Proposals + One-Pagers

Generate the final deliverables.

Ranked Summary Table

| Rank | Topic (PICO) | Saturation | 6-Pattern Score | Feasibility | Target Journal | Timeline |
|------|--------------|------------|-----------------|-------------|----------------|----------|
| 1 | ... | Green (0 longitudinal) | 5/6 | Go | JACC | 6 months |
| 2 | ... | Green (1 longitudinal) | 4/6 | Go | Eur Heart J | 6 months |
| 3 | ... | Blue (0 papers) | 3/6 | Conditional | Radiology | 8 months |

One-Pager for Each Finalist

Use the template at ${CLAUDE_SKILL_DIR}/references/onepager_template.md.

Each one-pager includes:

1. Title: Working title for the study
2. Background: 3-4 sentences establishing the gap (with "Zero Papers" claim if applicable)
3. Comparison Table: THIS STUDY vs existing papers
4. Objective: Primary research question in PICO format
5. Methods Summary: Study design, key variables, statistical approach
6. PI Role: Why this PI is the right corresponding author
7. Target Journal: With rationale (PI alignment, scope match, gap fit)
8. Timeline: Realistic estimate (data preparation → analysis → drafting → submission)
9. 6-Pattern Score Card: Visual breakdown of each pattern

Save one-pagers as markdown files: {output_dir}/gap_proposal_{rank}_{short_topic}.md

Skill Integration

What This Skill Does NOT Do

• Does not perform the actual statistical analysis (use /analyze-stats)
• Does not write the full manuscript (use /write-paper)
• Does not validate study design (use /design-study)
• Does not generate references (use /search-lit)
• Does not make publication-ready figures (use /make-figures)

Anti-Hallucination

• Never fabricate references. All citations must be verified via /search-lit with confirmed DOI or PMID. Mark unverified references as [UNVERIFIED - NEEDS MANUAL CHECK].
• Never invent clinical definitions, diagnostic criteria, or guideline recommendations. If uncertain, flag with [VERIFY] and ask the user.
• Never fabricate numerical results — compliance percentages, scores, effect sizes, or sample sizes must come from actual data or analysis output.
• If a reporting guideline item, journal policy, or clinical standard is uncertain, state the uncertainty rather than guessing.