inclusion-criteria-gen

# Inclusion Criteria Generator

Generate and optimize clinical trial subject inclusion/exclusion criteria to balance scientific rigor with recruitment feasibility.

## Use Cases

- **Protocol Design**: Create initial eligibility criteria for new clinical trials
- **Criteria Optimization**: Refine existing criteria to improve enrollment without compromising safety/efficacy
- **Competitive Analysis**: Analyze eligibility patterns across similar trials
- **Recruitment Strategy**: Identify and mitigate barriers to enrollment
- **Feasibility Assessment**: Evaluate if proposed criteria are realistic for target population

## Usage

### CLI Usage

```bash
# Generate criteria from study design
python scripts/main.py generate \
  --indication "Type 2 Diabetes" \
  --phase "Phase 2" \
  --population "adults" \
  --duration "24 weeks" \
  --output criteria.json

# Optimize existing criteria
python scripts/main.py optimize \
  --input current_criteria.json \
  --enrollment-target 200 \
  --current-enrollment 120 \
  --output optimized_criteria.json

# Analyze criteria complexity
python scripts/main.py analyze \
  --input criteria.json \
  --output analysis_report.json

# Compare with competitor trials
python scripts/main.py benchmark \
  --input criteria.json \
  --condition "Type 2 Diabetes" \
  --output benchmark_report.json
```

### Python API

```python
from scripts.main import CriteriaGenerator, CriteriaOptimizer

# Generate new criteria
generator = CriteriaGenerator()
criteria = generator.generate(
    indication="Type 2 Diabetes",
    phase="Phase 2",
    population="adults",
    study_duration="24 weeks",
    endpoints=["HbA1c reduction", "weight change"]
)

# Optimize existing criteria
optimizer = CriteriaOptimizer()
optimized = optimizer.optimize(
    criteria=existing_criteria,
    enrollment_target=200,
    current_enrollment=120,
    retention_rate=0.85
)

# Analyze criteria complexity
analysis = optimizer.analyze_complexity(criteria)
```

## Input Format

### Study Design Parameters

```json
{
  "indication": "Type 2 Diabetes Mellitus",
  "phase": "Phase 2",
  "population": "adults",
  "age_range": {"min": 18, "max": 75},
  "study_duration": "24 weeks",
  "treatment_type": "oral",
  "primary_endpoints": ["HbA1c change from baseline"],
  "safety_considerations": ["cardiovascular risk"],
  "concomitant_meds_allowed": ["metformin"]
}
```

### Existing Criteria Format

```json
{
  "inclusion_criteria": [
    {
      "id": "I1",
      "criterion": "Age 18-75 years",
      "rationale": "Adult population per regulatory guidance",
      "category": "demographics"
    }
  ],
  "exclusion_criteria": [
    {
      "id": "E1",
      "criterion": "HbA1c < 7.0% or > 11.0%",
      "rationale": "Ensure measurable treatment effect",
      "category": "disease_severity"
    }
  ]
}
```

## Output Format

### Generated/Optimized Criteria

```json
{
  "inclusion_criteria": [
    {
      "id": "I1",
      "criterion": "Age 18-75 years, inclusive",
      "category": "demographics",
      "rationale": "Adult population; upper limit for safety",
      "priority": "required",
      "impact": "low"
    }
  ],
  "exclusion_criteria": [
    {
      "id": "E1",
      "criterion": "HbA1c < 7.5% or > 10.5% at screening",
      "category": "disease_severity",
      "rationale": "Optimal range for detecting treatment effect",
      "priority": "required",
      "impact": "medium",
      "flexibility": "widen by 0.5% if enrollment slow"
    }
  ],
  "optimization_notes": [
    "Widened HbA1c range from 7.0-11.0% to 7.5-10.5% based on feasibility data"
  ],
  "recruitment_metrics": {
    "estimated_screen_success_rate": 0.35,
    "estimated_enrollment_rate": 0.65,
    "key_barriers": ["HbA1c upper limit", "concomitant medication restrictions"]
  }
}
```

## Criteria Categories

| Category | Description | Examples |
|----------|-------------|----------|
| demographics | Age, sex, race, ethnicity | Age 18-75, women of childbearing potential |
| disease_severity | Disease stage, severity markers | HbA1c range, tumor stage, NYHA class |
| medical_history | Prior conditions, comorbidities | No cardiovascular events within 6 months |
| concomitant_meds | Allowed/prohibited medications | Stable metformin dose allowed |
| laboratory | Lab value requirements | eGFR > 30 mL/min, normal liver function |
| lifestyle | Diet, exercise, habits | Non-smoker, willing to maintain diet |
| compliance | Ability to participate | Able to provide informed consent |
| safety | Risk minimization criteria | No history of severe hypoglycemia |

## Optimization Strategies

### Common Modifications

| Issue | Strategy | Example |
|-------|----------|---------|
| Narrow age range | Widen limits | 18-70 → 18-75 years |
| Restrictive lab values | Adjust thresholds | eGFR > 60 → eGFR > 30 mL/min |
| Comorbidity exclusions | Add time limits | Exclude "current" vs "history of" |
| Medication washouts | Shorten periods | 4 weeks → 2 weeks |
| Geographic barriers | Add telemedicine | Include remote visits option |

### Retention Considerations

- Minimize visit frequency when possible
- Allow window periods for visit timing
- Provide transportation assistance language
- Consider patient-reported outcome burden

## Technical Details

- **Difficulty**: Medium
- **Standards**: ICH E6(R2) GCP, CDISC Protocol Representation Model
- **Data Sources**: ClinicalTrials.gov eligibility patterns, literature feasibility data
- **Dependencies**: None (pure Python)

## References

- `references/criteria_templates.json` - Templates by therapeutic area
- `references/optimization_guidelines.md` - Best practices for criteria optimization
- `references/common_pitfalls.md` - Frequent eligibility design mistakes
- `references/regulatory_guidance.md` - FDA/EMA guidance on eligibility criteria
- `references/feasibility_data.json` - Screen failure rates by criterion type

## Risk Assessment

| Risk Indicator | Assessment | Level |
|----------------|------------|-------|
| Code Execution | Python scripts with tools | High |
| Network Access | External API calls | High |
| File System Access | Read/write data | Medium |
| Instruction Tampering | Standard prompt guidelines | Low |
| Data Exposure | Data handled securely | Medium |

## Security Checklist

- [ ] No hardcoded credentials or API keys
- [ ] No unauthorized file system access (../)
- [ ] Output does not expose sensitive information
- [ ] Prompt injection protections in place
- [ ] API requests use HTTPS only
- [ ] Input validated against allowed patterns
- [ ] API timeout and retry mechanisms implemented
- [ ] Output directory restricted to workspace
- [ ] Script execution in sandboxed environment
- [ ] Error messages sanitized (no internal paths exposed)
- [ ] Dependencies audited
- [ ] No exposure of internal service architecture
## Prerequisites

```bash
# Python dependencies
pip install -r requirements.txt
```

## Evaluation Criteria

### Success Metrics
- [ ] Successfully executes main functionality
- [ ] Output meets quality standards
- [ ] Handles edge cases gracefully
- [ ] Performance is acceptable

### Test Cases
1. **Basic Functionality**: Standard input → Expected output
2. **Edge Case**: Invalid input → Graceful error handling
3. **Performance**: Large dataset → Acceptable processing time

## Lifecycle Status

- **Current Stage**: Draft
- **Next Review Date**: 2026-03-06
- **Known Issues**: None
- **Planned Improvements**: 
  - Performance optimization
  - Additional feature support

## Parameters

| Parameter | Type | Default | Description |
|-----------|------|---------|-------------|
| `--indication` | str | Required | Therapeutic indication |
| `--phase` | str | Required |  |
| `--population` | str | "adults" | Target population |
| `--duration` | str | "" | Study duration |
| `--output` | str | Required | Output file path |
| `--age-min` | int | 18 | Minimum age |
| `--age-max` | int | 75 | Maximum age |
| `--input` | str | Required | Input criteria JSON file |
| `--enrollment-target` | int | Required | Target enrollment |
| `--current-enrollment` | int | Required | Current enrollment |
| `--output` | str | Required | Output file path |
| `--input` | str | Required | Input criteria JSON file |
| `--output` | str | Required | Output file path |
| `--input` | str | Required | Input criteria JSON file |
| `--condition` | str | Required | Medical condition |
| `--output` | str | Required | Output file path |