@bgicli/bgicli 2.1.1 → 2.2.0

package/data/skills/clinical-decision-support/SKILL.md

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+---
+name: clinical-decision-support
+description: "Generate professional clinical decision support (CDS) documents for pharmaceutical and clinical research settings, including patient cohort analyses (biomarker-stratified with outcomes) and treatment recommendation reports (evidence-based guidelines with decision algorithms). Supports GRADE evidence grading, statistical analysis (hazard ratios, survival curves, waterfall plots), biomarker integration, and regulatory compliance. Outputs publication-ready LaTeX/PDF format optimized for drug development, clinical research, and evidence synthesis."
+allowed-tools: [Read, Write, Edit, Bash]
+---
+
+# Clinical Decision Support Documents
+
+## Description
+
+Generate professional clinical decision support (CDS) documents for pharmaceutical companies, clinical researchers, and medical decision-makers. This skill specializes in analytical, evidence-based documents that inform treatment strategies and drug development:
+
+1. **Patient Cohort Analysis** - Biomarker-stratified group analyses with statistical outcome comparisons
+2. **Treatment Recommendation Reports** - Evidence-based clinical guidelines with GRADE grading and decision algorithms
+
+All documents are generated as publication-ready LaTeX/PDF files optimized for pharmaceutical research, regulatory submissions, and clinical guideline development.
+
+**Note:** For individual patient treatment plans at the bedside, use the `treatment-plans` skill instead. This skill focuses on group-level analyses and evidence synthesis for pharmaceutical/research settings.
+
+## Capabilities
+
+### Document Types
+
+**Patient Cohort Analysis**
+- Biomarker-based patient stratification (molecular subtypes, gene expression, IHC)
+- Molecular subtype classification (e.g., GBM mesenchymal-immune-active vs proneural, breast cancer subtypes)
+- Outcome metrics with statistical analysis (OS, PFS, ORR, DOR, DCR)
+- Statistical comparisons between subgroups (hazard ratios, p-values, 95% CI)
+- Survival analysis with Kaplan-Meier curves and log-rank tests
+- Efficacy tables and waterfall plots
+- Comparative effectiveness analyses
+- Pharmaceutical cohort reporting (trial subgroups, real-world evidence)
+
+**Treatment Recommendation Reports**
+- Evidence-based treatment guidelines for specific disease states
+- Strength of recommendation grading (GRADE system: 1A, 1B, 2A, 2B, 2C)
+- Quality of evidence assessment (high, moderate, low, very low)
+- Treatment algorithm flowcharts with TikZ diagrams
+- Line-of-therapy sequencing based on biomarkers
+- Decision pathways with clinical and molecular criteria
+- Pharmaceutical strategy documents
+- Clinical guideline development for medical societies
+
+### Clinical Features
+
+- **Biomarker Integration**: Genomic alterations (mutations, CNV, fusions), gene expression signatures, IHC markers, PD-L1 scoring
+- **Statistical Analysis**: Hazard ratios, p-values, confidence intervals, survival curves, Cox regression, log-rank tests
+- **Evidence Grading**: GRADE system (1A/1B/2A/2B/2C), Oxford CEBM levels, quality of evidence assessment
+- **Clinical Terminology**: SNOMED-CT, LOINC, proper medical nomenclature, trial nomenclature
+- **Regulatory Compliance**: HIPAA de-identification, confidentiality headers, ICH-GCP alignment
+- **Professional Formatting**: Compact 0.5in margins, color-coded recommendations, publication-ready, suitable for regulatory submissions
+
+## Pharmaceutical and Research Use Cases
+
+This skill is specifically designed for pharmaceutical and clinical research applications:
+
+**Drug Development**
+- **Phase 2/3 Trial Analyses**: Biomarker-stratified efficacy and safety analyses
+- **Subgroup Analyses**: Forest plots showing treatment effects across patient subgroups
+- **Companion Diagnostic Development**: Linking biomarkers to drug response
+- **Regulatory Submissions**: IND/NDA documentation with evidence summaries
+
+**Medical Affairs**
+- **KOL Education Materials**: Evidence-based treatment algorithms for thought leaders
+- **Medical Strategy Documents**: Competitive landscape and positioning strategies
+- **Advisory Board Materials**: Cohort analyses and treatment recommendation frameworks
+- **Publication Planning**: Manuscript-ready analyses for peer-reviewed journals
+
+**Clinical Guidelines**
+- **Guideline Development**: Evidence synthesis with GRADE methodology for specialty societies
+- **Consensus Recommendations**: Multi-stakeholder treatment algorithm development
+- **Practice Standards**: Biomarker-based treatment selection criteria
+- **Quality Measures**: Evidence-based performance metrics
+
+**Real-World Evidence**
+- **RWE Cohort Studies**: Retrospective analyses of patient cohorts from EMR data
+- **Comparative Effectiveness**: Head-to-head treatment comparisons in real-world settings
+- **Outcomes Research**: Long-term survival and safety in clinical practice
+- **Health Economics**: Cost-effectiveness analyses by biomarker subgroup
+
+## When to Use
+
+Use this skill when you need to:
+
+- **Analyze patient cohorts** stratified by biomarkers, molecular subtypes, or clinical characteristics
+- **Generate treatment recommendation reports** with evidence grading for clinical guidelines or pharmaceutical strategies
+- **Compare outcomes** between patient subgroups with statistical analysis (survival, response rates, hazard ratios)
+- **Produce pharmaceutical research documents** for drug development, clinical trials, or regulatory submissions
+- **Develop clinical practice guidelines** with GRADE evidence grading and decision algorithms
+- **Document biomarker-guided therapy selection** at the population level (not individual patients)
+- **Synthesize evidence** from multiple trials or real-world data sources
+- **Create clinical decision algorithms** with flowcharts for treatment sequencing
+
+**Do NOT use this skill for:**
+- Individual patient treatment plans (use `treatment-plans` skill)
+- Bedside clinical care documentation (use `treatment-plans` skill)
+- Simple patient-specific treatment protocols (use `treatment-plans` skill)
+
+## Visual Enhancement with Scientific Schematics
+
+**⚠️ MANDATORY: Every clinical decision support document MUST include at least 1-2 AI-generated figures using the scientific-schematics skill.**
+
+This is not optional. Clinical decision documents require clear visual algorithms. Before finalizing any document:
+1. Generate at minimum ONE schematic or diagram (e.g., clinical decision algorithm, treatment pathway, or biomarker stratification tree)
+2. For cohort analyses: include patient flow diagram
+3. For treatment recommendations: include decision flowchart
+
+**How to generate figures:**
+- Use the **scientific-schematics** skill to generate AI-powered publication-quality diagrams
+- Simply describe your desired diagram in natural language
+- Nano Banana Pro will automatically generate, review, and refine the schematic
+
+**How to generate schematics:**
+```bash
+python scripts/generate_schematic.py "your diagram description" -o figures/output.png
+```
+
+The AI will automatically:
+- Create publication-quality images with proper formatting
+- Review and refine through multiple iterations
+- Ensure accessibility (colorblind-friendly, high contrast)
+- Save outputs in the figures/ directory
+
+**When to add schematics:**
+- Clinical decision algorithm flowcharts
+- Treatment pathway diagrams
+- Biomarker stratification trees
+- Patient cohort flow diagrams (CONSORT-style)
+- Survival curve visualizations
+- Molecular mechanism diagrams
+- Any complex concept that benefits from visualization
+
+For detailed guidance on creating schematics, refer to the scientific-schematics skill documentation.
+
+---
+
+## Document Structure
+
+**CRITICAL REQUIREMENT: All clinical decision support documents MUST begin with a complete executive summary on page 1 that spans the entire first page before any table of contents or detailed sections.**
+
+### Page 1 Executive Summary Structure
+
+The first page of every CDS document should contain ONLY the executive summary with the following components:
+
+**Required Elements (all on page 1):**
+1. **Document Title and Type**
+   - Main title (e.g., "Biomarker-Stratified Cohort Analysis" or "Evidence-Based Treatment Recommendations")
+   - Subtitle with disease state and focus
+   
+2. **Report Information Box** (using colored tcolorbox)
+   - Document type and purpose
+   - Date of analysis/report
+   - Disease state and patient population
+   - Author/institution (if applicable)
+   - Analysis framework or methodology
+   
+3. **Key Findings Boxes** (3-5 colored boxes using tcolorbox)
+   - **Primary Results** (blue box): Main efficacy/outcome findings
+   - **Biomarker Insights** (green box): Key molecular subtype findings
+   - **Clinical Implications** (yellow/orange box): Actionable treatment implications
+   - **Statistical Summary** (gray box): Hazard ratios, p-values, key statistics
+   - **Safety Highlights** (red box, if applicable): Critical adverse events or warnings
+
+**Visual Requirements:**
+- Use `\thispagestyle{empty}` to remove page numbers from page 1
+- All content must fit on page 1 (before `\newpage`)
+- Use colored tcolorbox environments with different colors for visual hierarchy
+- Boxes should be scannable and highlight most critical information
+- Use bullet points, not narrative paragraphs
+- End page 1 with `\newpage` before table of contents or detailed sections
+
+**Example First Page LaTeX Structure:**
+```latex
+\maketitle
+\thispagestyle{empty}
+
+% Report Information Box
+\begin{tcolorbox}[colback=blue!5!white, colframe=blue!75!black, title=Report Information]
+\textbf{Document Type:} Patient Cohort Analysis\\
+\textbf{Disease State:} HER2-Positive Metastatic Breast Cancer\\
+\textbf{Analysis Date:} \today\\
+\textbf{Population:} 60 patients, biomarker-stratified by HR status
+\end{tcolorbox}
+
+\vspace{0.3cm}
+
+% Key Finding #1: Primary Results
+\begin{tcolorbox}[colback=blue!5!white, colframe=blue!75!black, title=Primary Efficacy Results]
+\begin{itemize}
+    \item Overall ORR: 72\% (95\% CI: 59-83\%)
+    \item Median PFS: 18.5 months (95\% CI: 14.2-22.8)
+    \item Median OS: 35.2 months (95\% CI: 28.1-NR)
+\end{itemize}
+\end{tcolorbox}
+
+\vspace{0.3cm}
+
+% Key Finding #2: Biomarker Insights
+\begin{tcolorbox}[colback=green!5!white, colframe=green!75!black, title=Biomarker Stratification Findings]
+\begin{itemize}
+    \item HR+/HER2+: ORR 68\%, median PFS 16.2 months
+    \item HR-/HER2+: ORR 78\%, median PFS 22.1 months
+    \item HR status significantly associated with outcomes (p=0.041)
+\end{itemize}
+\end{tcolorbox}
+
+\vspace{0.3cm}
+
+% Key Finding #3: Clinical Implications
+\begin{tcolorbox}[colback=orange!5!white, colframe=orange!75!black, title=Clinical Recommendations]
+\begin{itemize}
+    \item Strong efficacy observed regardless of HR status (Grade 1A)
+    \item HR-/HER2+ patients showed numerically superior outcomes
+    \item Treatment recommended for all HER2+ MBC patients
+\end{itemize}
+\end{tcolorbox}
+
+\newpage
+\tableofcontents  % TOC on page 2
+\newpage  % Detailed content starts page 3
+```
+
+### Patient Cohort Analysis (Detailed Sections - Page 3+)
+- **Cohort Characteristics**: Demographics, baseline features, patient selection criteria
+- **Biomarker Stratification**: Molecular subtypes, genomic alterations, IHC profiles
+- **Treatment Exposure**: Therapies received, dosing, treatment duration by subgroup
+- **Outcome Analysis**: Response rates (ORR, DCR), survival data (OS, PFS), DOR
+- **Statistical Methods**: Kaplan-Meier survival curves, hazard ratios, log-rank tests, Cox regression
+- **Subgroup Comparisons**: Biomarker-stratified efficacy, forest plots, statistical significance
+- **Safety Profile**: Adverse events by subgroup, dose modifications, discontinuations
+- **Clinical Recommendations**: Treatment implications based on biomarker profiles
+- **Figures**: Waterfall plots, swimmer plots, survival curves, forest plots
+- **Tables**: Demographics table, biomarker frequency, outcomes by subgroup
+
+### Treatment Recommendation Reports (Detailed Sections - Page 3+)
+
+**Page 1 Executive Summary for Treatment Recommendations should include:**
+1. **Report Information Box**: Disease state, guideline version/date, target population
+2. **Key Recommendations Box** (green): Top 3-5 GRADE-graded recommendations by line of therapy
+3. **Biomarker Decision Criteria Box** (blue): Key molecular markers influencing treatment selection
+4. **Evidence Summary Box** (gray): Major trials supporting recommendations (e.g., KEYNOTE-189, FLAURA)
+5. **Critical Monitoring Box** (orange/red): Essential safety monitoring requirements
+
+**Detailed Sections (Page 3+):**
+- **Clinical Context**: Disease state, epidemiology, current treatment landscape
+- **Target Population**: Patient characteristics, biomarker criteria, staging
+- **Evidence Review**: Systematic literature synthesis, guideline summary, trial data
+- **Treatment Options**: Available therapies with mechanism of action
+- **Evidence Grading**: GRADE assessment for each recommendation (1A, 1B, 2A, 2B, 2C)
+- **Recommendations by Line**: First-line, second-line, subsequent therapies
+- **Biomarker-Guided Selection**: Decision criteria based on molecular profiles
+- **Treatment Algorithms**: TikZ flowcharts showing decision pathways
+- **Monitoring Protocol**: Safety assessments, efficacy monitoring, dose modifications
+- **Special Populations**: Elderly, renal/hepatic impairment, comorbidities
+- **References**: Full bibliography with trial names and citations
+
+## Output Format
+
+**MANDATORY FIRST PAGE REQUIREMENT:**
+- **Page 1**: Full-page executive summary with 3-5 colored tcolorbox elements
+- **Page 2**: Table of contents (optional)
+- **Page 3+**: Detailed sections with methods, results, figures, tables
+
+**Document Specifications:**
+- **Primary**: LaTeX/PDF with 0.5in margins for compact, data-dense presentation
+- **Length**: Typically 5-15 pages (1 page executive summary + 4-14 pages detailed content)
+- **Style**: Publication-ready, pharmaceutical-grade, suitable for regulatory submissions
+- **First Page**: Always a complete executive summary spanning entire page 1 (see Document Structure section)
+
+**Visual Elements:**
+- **Colors**: 
+  - Page 1 boxes: blue=data/information, green=biomarkers/recommendations, yellow/orange=clinical implications, red=warnings
+  - Recommendation boxes (green=strong recommendation, yellow=conditional, blue=research needed)
+  - Biomarker stratification (color-coded molecular subtypes)
+  - Statistical significance (color-coded p-values, hazard ratios)
+- **Tables**: 
+  - Demographics with baseline characteristics
+  - Biomarker frequency by subgroup
+  - Outcomes table (ORR, PFS, OS, DOR by molecular subtype)
+  - Adverse events by cohort
+  - Evidence summary tables with GRADE ratings
+- **Figures**: 
+  - Kaplan-Meier survival curves with log-rank p-values and number at risk tables
+  - Waterfall plots showing best response by patient
+  - Forest plots for subgroup analyses with confidence intervals
+  - TikZ decision algorithm flowcharts
+  - Swimmer plots for individual patient timelines
+- **Statistics**: Hazard ratios with 95% CI, p-values, median survival times, landmark survival rates
+- **Compliance**: De-identification per HIPAA Safe Harbor, confidentiality notices for proprietary data
+
+## Integration
+
+This skill integrates with:
+- **scientific-writing**: Citation management, statistical reporting, evidence synthesis
+- **clinical-reports**: Medical terminology, HIPAA compliance, regulatory documentation
+- **scientific-schematics**: TikZ flowcharts for decision algorithms and treatment pathways
+- **treatment-plans**: Individual patient applications of cohort-derived insights (bidirectional)
+
+## Key Differentiators from Treatment-Plans Skill
+
+**Clinical Decision Support (this skill):**
+- **Audience**: Pharmaceutical companies, clinical researchers, guideline committees, medical affairs
+- **Scope**: Population-level analyses, evidence synthesis, guideline development
+- **Focus**: Biomarker stratification, statistical comparisons, evidence grading
+- **Output**: Multi-page analytical documents (5-15 pages typical) with extensive figures and tables
+- **Use Cases**: Drug development, regulatory submissions, clinical practice guidelines, medical strategy
+- **Example**: "Analyze 60 HER2+ breast cancer patients by hormone receptor status with survival outcomes"
+
+**Treatment-Plans Skill:**
+- **Audience**: Clinicians, patients, care teams
+- **Scope**: Individual patient care planning
+- **Focus**: SMART goals, patient-specific interventions, monitoring plans
+- **Output**: Concise 1-4 page actionable care plans
+- **Use Cases**: Bedside clinical care, EMR documentation, patient-centered planning
+- **Example**: "Create treatment plan for a 55-year-old patient with newly diagnosed type 2 diabetes"
+
+**When to use each:**
+- Use **clinical-decision-support** for: cohort analyses, biomarker stratification studies, treatment guideline development, pharmaceutical strategy documents
+- Use **treatment-plans** for: individual patient care plans, treatment protocols for specific patients, bedside clinical documentation
+
+## Example Usage
+
+### Patient Cohort Analysis
+
+**Example 1: NSCLC Biomarker Stratification**
+```
+> Analyze a cohort of 45 NSCLC patients stratified by PD-L1 expression (<1%, 1-49%, ≥50%) 
+> receiving pembrolizumab. Include outcomes: ORR, median PFS, median OS with hazard ratios 
+> comparing PD-L1 ≥50% vs <50%. Generate Kaplan-Meier curves and waterfall plot.
+```
+
+**Example 2: GBM Molecular Subtype Analysis**
+```
+> Generate cohort analysis for 30 GBM patients classified into Cluster 1 (Mesenchymal-Immune-Active) 
+> and Cluster 2 (Proneural) molecular subtypes. Compare outcomes including median OS, 6-month PFS rate, 
+> and response to TMZ+bevacizumab. Include biomarker profile table and statistical comparison.
+```
+
+**Example 3: Breast Cancer HER2 Cohort**
+```
+> Analyze 60 HER2-positive metastatic breast cancer patients treated with trastuzumab-deruxtecan, 
+> stratified by prior trastuzumab exposure (yes/no). Include ORR, DOR, median PFS with forest plot 
+> showing subgroup analyses by hormone receptor status, brain metastases, and number of prior lines.
+```
+
+### Treatment Recommendation Report
+
+**Example 1: HER2+ Metastatic Breast Cancer Guidelines**
+```
+> Create evidence-based treatment recommendations for HER2-positive metastatic breast cancer including 
+> biomarker-guided therapy selection. Use GRADE system to grade recommendations for first-line 
+> (trastuzumab+pertuzumab+taxane), second-line (trastuzumab-deruxtecan), and third-line options. 
+> Include decision algorithm flowchart based on brain metastases, hormone receptor status, and prior therapies.
+```
+
+**Example 2: Advanced NSCLC Treatment Algorithm**
+```
+> Generate treatment recommendation report for advanced NSCLC based on PD-L1 expression, EGFR mutation, 
+> ALK rearrangement, and performance status. Include GRADE-graded recommendations for each molecular subtype, 
+> TikZ flowchart for biomarker-directed therapy selection, and evidence tables from KEYNOTE-189, FLAURA, 
+> and CheckMate-227 trials.
+```
+
+**Example 3: Multiple Myeloma Line-of-Therapy Sequencing**
+```
+> Create treatment algorithm for newly diagnosed multiple myeloma through relapsed/refractory setting. 
+> Include GRADE recommendations for transplant-eligible vs ineligible, high-risk cytogenetics considerations, 
+> and sequencing of daratumumab, carfilzomib, and CAR-T therapy. Provide flowchart showing decision points 
+> at each line of therapy.
+```
+
+## Key Features
+
+### Biomarker Classification
+- Genomic: Mutations, CNV, gene fusions
+- Expression: RNA-seq, IHC scores
+- Molecular subtypes: Disease-specific classifications
+- Clinical actionability: Therapy selection guidance
+
+### Outcome Metrics
+- Survival: OS (overall survival), PFS (progression-free survival)
+- Response: ORR (objective response rate), DOR (duration of response), DCR (disease control rate)
+- Quality: ECOG performance status, symptom burden
+- Safety: Adverse events, dose modifications
+
+### Statistical Methods
+- Survival analysis: Kaplan-Meier curves, log-rank tests
+- Group comparisons: t-tests, chi-square, Fisher's exact
+- Effect sizes: Hazard ratios, odds ratios with 95% CI
+- Significance: p-values, multiple testing corrections
+
+### Evidence Grading
+
+**GRADE System**
+- **1A**: Strong recommendation, high-quality evidence
+- **1B**: Strong recommendation, moderate-quality evidence  
+- **2A**: Weak recommendation, high-quality evidence
+- **2B**: Weak recommendation, moderate-quality evidence
+- **2C**: Weak recommendation, low-quality evidence
+
+**Recommendation Strength**
+- **Strong**: Benefits clearly outweigh risks
+- **Conditional**: Trade-offs exist, patient values important
+- **Research**: Insufficient evidence, clinical trials needed
+
+## Best Practices
+
+### For Cohort Analyses
+
+1. **Patient Selection Transparency**: Clearly document inclusion/exclusion criteria, patient flow, and reasons for exclusions
+2. **Biomarker Clarity**: Specify assay methods, platforms (e.g., FoundationOne, Caris), cut-points, and validation status
+3. **Statistical Rigor**: 
+   - Report hazard ratios with 95% confidence intervals, not just p-values
+   - Include median follow-up time for survival analyses
+   - Specify statistical tests used (log-rank, Cox regression, Fisher's exact)
+   - Account for multiple comparisons when appropriate
+4. **Outcome Definitions**: Use standard criteria:
+   - Response: RECIST 1.1, iRECIST for immunotherapy
+   - Adverse events: CTCAE version 5.0
+   - Performance status: ECOG or Karnofsky
+5. **Survival Data Presentation**:
+   - Median OS/PFS with 95% CI
+   - Landmark survival rates (6-month, 12-month, 24-month)
+   - Number at risk tables below Kaplan-Meier curves
+   - Censoring clearly indicated
+6. **Subgroup Analyses**: Pre-specify subgroups; clearly label exploratory vs pre-planned analyses
+7. **Data Completeness**: Report missing data and how it was handled
+
+### For Treatment Recommendation Reports
+
+1. **Evidence Grading Transparency**: 
+   - Use GRADE system consistently (1A, 1B, 2A, 2B, 2C)
+   - Document rationale for each grade
+   - Clearly state quality of evidence (high, moderate, low, very low)
+2. **Comprehensive Evidence Review**: 
+   - Include phase 3 randomized trials as primary evidence
+   - Supplement with phase 2 data for emerging therapies
+   - Note real-world evidence and meta-analyses
+   - Cite trial names (e.g., KEYNOTE-189, CheckMate-227)
+3. **Biomarker-Guided Recommendations**:
+   - Link specific biomarkers to therapy recommendations
+   - Specify testing methods and validated assays
+   - Include FDA/EMA approval status for companion diagnostics
+4. **Clinical Actionability**: Every recommendation should have clear implementation guidance
+5. **Decision Algorithm Clarity**: TikZ flowcharts should be unambiguous with clear yes/no decision points
+6. **Special Populations**: Address elderly, renal/hepatic impairment, pregnancy, drug interactions
+7. **Monitoring Guidance**: Specify safety labs, imaging, and frequency
+8. **Update Frequency**: Date recommendations and plan for periodic updates
+
+### General Best Practices
+
+1. **First Page Executive Summary (MANDATORY)**: 
+   - ALWAYS create a complete executive summary on page 1 that spans the entire first page
+   - Use 3-5 colored tcolorbox elements to highlight key findings
+   - No table of contents or detailed sections on page 1
+   - Use `\thispagestyle{empty}` and end with `\newpage`
+   - This is the single most important page - it should be scannable in 60 seconds
+2. **De-identification**: Remove all 18 HIPAA identifiers before document generation (Safe Harbor method)
+3. **Regulatory Compliance**: Include confidentiality notices for proprietary pharmaceutical data
+4. **Publication-Ready Formatting**: Use 0.5in margins, professional fonts, color-coded sections
+5. **Reproducibility**: Document all statistical methods to enable replication
+6. **Conflict of Interest**: Disclose pharmaceutical funding or relationships when applicable
+7. **Visual Hierarchy**: Use colored boxes consistently (blue=data, green=biomarkers, yellow/orange=recommendations, red=warnings)
+
+## References
+
+See the `references/` directory for detailed guidance on:
+- Patient cohort analysis and stratification methods
+- Treatment recommendation development
+- Clinical decision algorithms
+- Biomarker classification and interpretation
+- Outcome analysis and statistical methods
+- Evidence synthesis and grading systems
+
+## Templates
+
+See the `assets/` directory for LaTeX templates:
+- `cohort_analysis_template.tex` - Biomarker-stratified patient cohort analysis with statistical comparisons
+- `treatment_recommendation_template.tex` - Evidence-based clinical practice guidelines with GRADE grading
+- `clinical_pathway_template.tex` - TikZ decision algorithm flowcharts for treatment sequencing
+- `biomarker_report_template.tex` - Molecular subtype classification and genomic profile reports
+- `evidence_synthesis_template.tex` - Systematic evidence review and meta-analysis summaries
+
+**Template Features:**
+- 0.5in margins for compact presentation
+- Color-coded recommendation boxes
+- Professional tables for demographics, biomarkers, outcomes
+- Built-in support for Kaplan-Meier curves, waterfall plots, forest plots
+- GRADE evidence grading tables
+- Confidentiality headers for pharmaceutical documents
+
+## Scripts
+
+See the `scripts/` directory for analysis and visualization tools:
+- `generate_survival_analysis.py` - Kaplan-Meier curve generation with log-rank tests, hazard ratios, 95% CI
+- `create_waterfall_plot.py` - Best response visualization for cohort analyses
+- `create_forest_plot.py` - Subgroup analysis visualization with confidence intervals
+- `create_cohort_tables.py` - Demographics, biomarker frequency, and outcomes tables
+- `build_decision_tree.py` - TikZ flowchart generation for treatment algorithms
+- `biomarker_classifier.py` - Patient stratification algorithms by molecular subtype
+- `calculate_statistics.py` - Hazard ratios, Cox regression, log-rank tests, Fisher's exact
+- `validate_cds_document.py` - Quality and compliance checks (HIPAA, statistical reporting standards)
+- `grade_evidence.py` - Automated GRADE assessment helper for treatment recommendations
+