tooluniverse-clinical-trial-design - Claude MCP Skill

# Clinical Trial Design Feasibility Assessment

Systematically assess clinical trial feasibility by analyzing 6 research dimensions. Produces comprehensive feasibility reports with quantitative enrollment projections, endpoint recommendations, and regulatory pathway analysis.

**IMPORTANT**: Always use English terms in tool calls (drug names, disease names, biomarker names), even if the user writes in another language. Only try original-language terms as a fallback if English returns no results. Respond in the user's language.

## Core Principles

### 1. Report-First Approach (MANDATORY)
**DO NOT** show tool outputs to user. Instead:
1. Create `[INDICATION]_trial_feasibility_report.md` FIRST
2. Initialize with all section headers
3. Progressively update as data arrives
4. Present only the final report

### 2. Evidence Grading System

| Grade | Symbol | Criteria | Examples |
|-------|--------|----------|----------|
| **A** | 3-star | Regulatory acceptance, multiple precedents | FDA-approved endpoint in same indication |
| **B** | 2-star | Clinical validation, single precedent | Phase 3 trial in related indication |
| **C** | 1-star | Preclinical or exploratory | Phase 1 use, biomarker validation ongoing |
| **D** | 0-star | Proposed, no validation | Novel endpoint, no precedent |

### 3. Feasibility Score (0-100)
Weighted composite score:
- **Patient Availability** (30%): Population size x biomarker prevalence x geography
- **Endpoint Precedent** (25%): Historical use, regulatory acceptance
- **Regulatory Clarity** (20%): Pathway defined, precedents exist
- **Comparator Feasibility** (15%): Standard of care availability
- **Safety Monitoring** (10%): Known risks, monitoring established

**Interpretation**: >=75 HIGH (proceed), 50-74 MODERATE (additional validation), <50 LOW (de-risking required)

---

## When to Use This Skill

Apply when users:
- Plan early-phase trials (Phase 1/2 emphasis)
- Need enrollment feasibility assessment
- Design biomarker-selected trials
- Evaluate endpoint strategies
- Assess regulatory pathways
- Compare trial design options
- Need safety monitoring plans

**Trigger phrases**: "clinical trial design", "trial feasibility", "enrollment projections", "endpoint selection", "trial planning", "Phase 1/2 design", "basket trial", "biomarker trial"

---

## Core Strategy: 6 Research Paths

Execute 6 parallel research dimensions. See `STUDY_DESIGN_PROCEDURES.md` for detailed steps per path.

```
Trial Design Query
|
+-- PATH 1: Patient Population Sizing
|   Disease prevalence, biomarker prevalence, geographic distribution,
|   eligibility criteria impact, enrollment projections
|
+-- PATH 2: Biomarker Prevalence & Testing
|   Mutation frequency, testing availability, turnaround time,
|   cost/reimbursement, alternative biomarkers
|
+-- PATH 3: Comparator Selection
|   Standard of care, approved comparators, historical controls,
|   placebo appropriateness, combination therapy
|
+-- PATH 4: Endpoint Selection
|   Primary endpoint precedents, FDA acceptance history,
|   measurement feasibility, surrogate vs clinical endpoints
|
+-- PATH 5: Safety Endpoints & Monitoring
|   Mechanism-based toxicity, class effects, organ-specific monitoring,
|   DLT history, safety monitoring plan
|
+-- PATH 6: Regulatory Pathway
    Regulatory precedents (505(b)(1), 505(b)(2)), breakthrough therapy,
    orphan drug, fast track, FDA guidance
```

---

## Report Structure (14 Sections)

Create `[INDICATION]_trial_feasibility_report.md` with all 14 sections. See `REPORT_TEMPLATE.md` for full templates with fillable fields.

1. **Executive Summary** - Feasibility score, key findings, go/no-go recommendation
2. **Disease Background** - Prevalence, incidence, SOC, unmet need
3. **Patient Population Analysis** - Base population, biomarker selection, eligibility funnel, enrollment projections
4. **Biomarker Strategy** - Primary biomarker, alternatives, testing logistics
5. **Endpoint Selection & Justification** - Primary/secondary/exploratory endpoints, statistical considerations
6. **Comparator Analysis** - SOC, trial design options (single-arm vs randomized vs non-inferiority), drug sourcing
7. **Safety Endpoints & Monitoring Plan** - DLT definition, mechanism-based toxicities, organ monitoring, SMC
8. **Study Design Recommendations** - Phase, design type, schema, eligibility, treatment plan, assessment schedule
9. **Enrollment & Site Strategy** - Site selection, enrollment projections, recruitment strategies
10. **Regulatory Pathway** - FDA pathway, precedents, pre-IND meeting, IND timeline
11. **Budget & Resource Considerations** - Cost drivers, timeline, FTE requirements
12. **Risk Assessment** - Feasibility risks, scientific risks, mitigation strategies
13. **Success Criteria & Go/No-Go Decision** - Phase 1/2 criteria, interim analysis, feasibility scorecard
14. **Recommendations & Next Steps** - Final recommendation, critical path to IND, alternative designs

---

## Tool Reference by Research Path

### PATH 1: Patient Population Sizing
- `OpenTargets_get_disease_id_description_by_name` - Disease lookup
- `OpenTargets_get_diseases_phenotypes` - Prevalence data
- `ClinVar_search_variants` - Biomarker mutation frequency
- `gnomAD_search_gene_variants` - Population allele frequencies
- `PubMed_search_articles` - Epidemiology literature
- `search_clinical_trials` - Enrollment feasibility from past trials

### PATH 2: Biomarker Prevalence & Testing
- `ClinVar_get_variant_details` - Variant pathogenicity
- `COSMIC_search_mutations` - Cancer-specific mutation frequencies
- `gnomAD_get_variant_details` - Population genetics
- `PubMed_search_articles` - CDx test performance, guidelines

### PATH 3: Comparator Selection
- `drugbank_get_drug_basic_info_by_drug_name_or_id` - Drug info
- `drugbank_get_indications_by_drug_name_or_drugbank_id` - Approved indications
- `drugbank_get_pharmacology_by_drug_name_or_drugbank_id` - Mechanism
- `FDA_OrangeBook_search_drugs` - Generic availability
- `FDA_get_drug_approval_history` - Approval details
- `search_clinical_trials` - Historical control data

### PATH 4: Endpoint Selection
- `search_clinical_trials` - Precedent trials, endpoints used
- `PubMed_search_articles` - FDA acceptance history, endpoint validation
- `FDA_get_drug_approval_history` - Approved endpoints by indication

### PATH 5: Safety Endpoints & Monitoring
- `drugbank_get_pharmacology_by_drug_name_or_drugbank_id` - Mechanism toxicity
- `FDA_get_warnings_and_cautions_by_drug_name` - FDA black box warnings
- `FAERS_search_reports_by_drug_and_reaction` - Real-world adverse events
- `FAERS_count_reactions_by_drug_event` - AE frequency
- `FAERS_count_death_related_by_drug` - Serious outcomes
- `PubMed_search_articles` - DLT definitions, monitoring strategies

### PATH 6: Regulatory Pathway
- `FDA_get_drug_approval_history` - Precedent approvals
- `PubMed_search_articles` - Breakthrough designations, FDA guidance
- `search_clinical_trials` - Regulatory precedents (accelerated approval)

---

## Quick Start Example

```python
from tooluniverse import ToolUniverse

tu = ToolUniverse(use_cache=True)
tu.load_tools()

# Example: EGFR+ NSCLC trial feasibility
# Step 1: Disease prevalence
disease_info = tu.tools.OpenTargets_get_disease_id_description_by_name(
    diseaseName="non-small cell lung cancer"
)
prevalence = tu.tools.OpenTargets_get_diseases_phenotypes(
    efoId=disease_info['data']['id']
)

# Step 2: Biomarker prevalence
variants = tu.tools.ClinVar_search_variants(gene="EGFR", significance="pathogenic")

# Step 3: Precedent trials
trials = tu.tools.search_clinical_trials(
    condition="EGFR positive non-small cell lung cancer",
    status="completed", phase="2"
)

# Step 4: Standard of care comparator
soc = tu.tools.FDA_OrangeBook_search_drugs(ingredient="osimertinib")

# Compile into feasibility report...
```

See `WORKFLOW_DETAILS.md` for the complete 6-path Python workflow and use case examples.

---

## Integration with Other Skills

- **tooluniverse-drug-research**: Investigate mechanism, preclinical data
- **tooluniverse-disease-research**: Deep dive on disease biology
- **tooluniverse-target-research**: Validate drug target, essentiality
- **tooluniverse-pharmacovigilance**: Post-market safety for comparator drugs
- **tooluniverse-precision-oncology**: Biomarker biology, resistance mechanisms

---

## Reference Files

| File | Content |
|------|---------|
| `REPORT_TEMPLATE.md` | Full 14-section report template with fillable fields |
| `STUDY_DESIGN_PROCEDURES.md` | Detailed steps for each of the 6 research paths |
| `WORKFLOW_DETAILS.md` | Complete Python example workflow and 5 use case summaries |
| `BEST_PRACTICES.md` | Best practices, common pitfalls, output format requirements |
| `EXAMPLES.md` | Additional examples |
| `QUICK_START.md` | Quick start guide |

---

## Version Information

- **Version**: 1.0.0
- **Last Updated**: February 2026
- **Compatible with**: ToolUniverse 0.5+
- **Focus**: Phase 1/2 early clinical development