Clinical Trial Protocol Skill

Clinical Trial Protocol Skill

⚠️ EXECUTION CONTROL - READ THIS FIRST

CRITICAL: This orchestrator follows a SIMPLE START approach:

1. Display the welcome message FIRST (shown in "Startup: Welcome and Confirmation" section below)
2. Ask user to confirm they're ready to proceed - Wait for confirmation (yes/no)
3. Jump directly into Full Workflow Logic - Automatically run subskills sequentially
4. Do NOT pre-read subskill files - Subskills are loaded on-demand only when their step executes

Why this matters:

• Pre-reading all subskills wastes context and memory
• Subskills should only load when actually needed during execution
• Workflow automatically handles resuming from existing waypoints

Overview

This skill generates clinical trial protocols for medical devices or drugs using a modular, waypoint-based architecture

What This Skill Does

Starting with an intervention idea (device or drug), this orchestrated workflow offers two modes:

🔬 Research Only Mode (Steps 0-1):

1. Initialize Intervention - Collect device or drug information
2. Research Similar Protocols - Find similar trials, FDA guidance, and published protocols

• Deliverable: Comprehensive research summary as formatted .md artifact

📄 Full Protocol Mode (Steps 0-5):

1. Initialize Intervention - Collect device or drug information
2. Research Similar Protocols - Find similar trials, FDA guidance, and published protocols
3. Protocol Foundation - Generate protocol sections 1-6 (foundation, design, population)
4. Protocol Intervention - Generate protocol sections 7-8 (intervention details)
5. Protocol Operations - Generate protocol sections 9-12 (assessments, statistics, operations)
6. Generate Protocol - Create professional file ready for stakeholder review

Architecture

Waypoint-Based Design

All analysis data is stored in waypoints/ directory as JSON/markdown files:

waypoints/
├── intervention_metadata.json           # Intervention info, status, initial context
├── 01_clinical_research_summary.json   # Similar trials, FDA guidance, recommendations
├── 02_protocol_foundation.md            # Protocol sections 1-6 (Step 2)
├── 03_protocol_intervention.md          # Protocol sections 7-8 (Step 3)
├── 04_protocol_operations.md            # Protocol sections 9-12 (Step 4)
├── 02_protocol_draft.md                 # Complete protocol (concatenated in Step 4)
├── 02_protocol_metadata.json            # Protocol metadata
└── 02_sample_size_calculation.json      # Statistical sample size calculation

Rich Initial Context Support: Users can provide substantial documentation, technical specifications, or research data when initializing the intervention (Step 0). This is preserved in intervention_metadata.json under the initial_context field. Later steps reference this context for more informed protocol development.

Modular Subskill Steps

Each step is an independent skill in references/ directory:

references/
├── 00-initialize-intervention.md    # Collect device or drug information
├── 01-research-protocols.md         # Clinical trials research and FDA guidance
├── 02-protocol-foundation.md        # Protocol sections 1-6 (foundation, design, population)
├── 03-protocol-intervention.md      # Protocol sections 7-8 (intervention details)
├── 04-protocol-operations.md        # Protocol sections 9-12 (assessments, statistics, operations)
└── 05-generate-document.md          # NIH Protocol generation

Utility Scripts

scripts/
└── sample_size_calculator.py   # Statistical power analysis (validated)

Prerequisites

1. clinical trials MCP Server (Required)

Installation:

• Install via drag-and-drop .mcpb file into Claude Desktop
• Or configure manually in Claude Desktop settings

Available Tools: search_clinical_trials - Search by:

condition - Disease or condition (e.g., "pancreatic cancer") intervention - Drug, device, or treatment (e.g., "pembrolizumab", "CAR-T") sponsor - Sponsor or collaborator name (e.g., "Pfizer", "NIH") location - City, state, or country (e.g., "California", "Boston") status - "recruiting" (default), "active", "completed", "all" phase - Trial phase: "1", "2", "3", "4", "earlyphase1" maxresults - Default 25, max 100

get_trial_details - Get comprehensive details for a specific trial using its nct_id (e.g., "NCT04267848"). Returns eligibility criteria, outcomes, study design, and contact information.

Verification: Step 1 will automatically test MCP connectivity at startup.

2. FDA Database Access (Built-in)

Purpose: FDA regulatory pathway research via explicit database URLs

Sources:

• Step 1: FDA device/drug databases (510(k), PMA, De Novo, Drugs@FDA, Orange Book, Purple Book)
• All sources use direct FDA database URLs - no generic web searches

3. Clinical Protocol Template

Template Files: Any .md files in the assets/ directory

Purpose: Reference template for protocol structure and content guidance. The system automatically detects available templates and uses them dynamically.

4. Python Dependencies (Required for Step 2)

Installation:

pip install -r requirements.txt

Dependencies:

• scipy >= 1.11.0 (statistical calculations)
• numpy >= 1.24.0 (numerical operations)

Purpose: Accurate statistical sample size calculations for clinical protocols

How to Use

Simply invoke the skill and select your desired mode:

🔬 Research Only Mode:

1. Select "Research Only" from the main menu
2. Provide intervention information
3. Receive comprehensive research summary as formatted .md artifact
4. Option to continue with full protocol generation or exit

📄 Full Protocol Mode:

1. Select "Full Protocol" from the main menu
2. Guide you through all steps sequentially (Steps 0-5)
3. Pause after Step 4 to review the draft protocol
4. Generate the final protocol document when ready

Resume Capability: If interrupted, simply restart the skill and it will automatically resume from your last completed step.

Execution Flow

Startup: Welcome and Mode Selection

When skill is invoked, display the following message:

🧬 CLINICAL TRIAL PROTOCOL

Welcome! This skill generates clinical trial protocols for medical devices or drugs.

[If waypoints/intervention_metadata.json exists:]
✓ Found existing protocol in progress: [Intervention Name]
  Type: [Device/Drug]
  Completed: [List of completed steps]
  Next: [Next step to execute]

📋 SELECT MODE:

1. 🔬 Research Only - Run clinical research analysis (Steps 0-1)
   • Collect intervention information
   • Research similar clinical trials
   • Find FDA guidance and regulatory pathways
   • Generate comprehensive research summary as .md artifact

2. 📄 Full Protocol - Generate complete clinical trial protocol (Steps 0-5)
   • Everything in Research Only, plus:
   • Generate all protocol sections
   • Create professional protocol document

3. ❌ Exit

Please select an option (1, 2, or 3):

🛑 STOP and WAIT for user selection (1, 2, or 3)

• If 1 (Research Only): Set execution_mode = "research_only" and proceed to Research Only Workflow Logic
• If 2 (Full Protocol): Set execution_mode = "full_protocol" and proceed to Full Workflow Logic
• If 3 (Exit): Exit gracefully with "No problem! Restart the skill anytime to continue."

---

Research Only Workflow Logic

This workflow executes only Steps 0 and 1, then generates a formatted research summary artifact.

Step 1: Check for Existing Waypoints

• If waypoints/intervention_metadata.json exists: Load metadata, check if steps 0 and 1 are already complete
• If no metadata exists: Start from Step 0

Step 2: Execute Research Steps (0 and 1)

For each step (0, 1):

1. Check completion status: If step already completed in metadata, skip with "✓ Step [X] already complete"

1. Execute step:

• Display "▶ Executing Step [X]..."
• Read and follow the corresponding subskill file instructions
• Wait for completion
• Display "✓ Step [X] complete"
• Step execution method (ON-DEMAND LOADING): When a step is ready to execute (NOT before), read the subskill markdown file and execute ALL instructions within it
• Step-to-file mapping:
• Step 0: references/00-initialize-intervention.md (collect intervention info)
• Step 1: references/01-research-protocols.md (clinical research and FDA guidance)

1. Handle errors: If step fails, ask user to retry or exit. Save current state for resume capability.

Step 3: Generate Research Summary Artifact

After Step 1 completes successfully:

1. Read waypoint files:

• waypoints/intervention_metadata.json (intervention details)
• waypoints/01_clinical_research_summary.json (research findings)

1. Create formatted markdown summary: Generate a comprehensive, well-formatted research summary as a markdown artifact with the following structure:

# Clinical Research Summary: [Intervention Name]

## Intervention Overview
- **Type:** [Device/Drug]
- **Indication:** [Target condition/disease]
- **Description:** [Brief intervention description]
- **Mechanism of Action:** [How it works]

## Similar Clinical Trials
[List top 5-10 similar trials with NCT ID, title, phase, status, key findings]

## FDA Regulatory Pathway
- **Recommended Pathway:** [510(k), PMA, De Novo, IND, NDA, BLA, etc.]
- **Regulatory Basis:** [Rationale for pathway selection]
- **Key Requirements:** [Major regulatory considerations]

## FDA Guidance Documents
[List relevant FDA guidance documents with links and key excerpts]

## Study Design Recommendations
- **Suggested Study Type:** [RCT, single-arm, etc.]
- **Phase Recommendation:** [Phase 1, 2, 3, etc.]
- **Primary Endpoint Suggestions:** [Based on similar trials]
- **Sample Size Considerations:** [Preliminary thoughts]

## Key Insights and Recommendations
[Synthesized recommendations for protocol development]

## Next Steps
[If user wants to proceed with full protocol development]

---
*Generated by Clinical Trial Protocol Skill*
*Date: [Current date]*

1. Save artifact: Write the formatted summary to waypoints/research_summary.md

1. Display completion message:

✅ RESEARCH COMPLETE

Research Summary Generated: waypoints/research_summary.md

📊 Key Findings:
  • Similar Trials Found: [X trials]
  • Recommended Pathway: [Pathway name]
  • FDA Guidance Documents: [X documents identified]
  • Study Design: [Recommended design]

📄 The research summary has been saved as a formatted markdown artifact.

Would you like to:
1. Continue with full protocol generation (steps 2-5)
2. Exit and review research summary

Option 1 Logic (Continue to Full Protocol):

• Set execution_mode = "full_protocol"
• Continue to Full Workflow Logic starting from Step 2 (since 0 and 1 are complete)

Option 2 Logic (Exit):

• Display: "✓ Research summary saved. Restart the skill anytime to continue with protocol generation."
• Exit orchestrator gracefully

---

Full Workflow Logic

Step 1: Check for Existing Waypoints

• If waypoints/intervention_metadata.json exists: Load metadata, check completed_steps array, resume from next incomplete step
• If no metadata exists: Start from Step 0

Step 2: Execute Steps in Order

For each step (0, 1, 2, 3, 4, 5):

1. Check completion status: If step already completed in metadata, skip with "✓ Step [X] already complete"

1. Execute step: Display "▶ Executing Step [X]...", read and follow the corresponding subskill file instructions, wait for completion, display "✓ Step [X] complete"

• Step execution method (ON-DEMAND LOADING): When a step is ready to execute (NOT before), read the subskill markdown file and execute ALL instructions within it
• IMPORTANT: Do NOT read subskill files in advance. Only read them at the moment of execution.
• Step-to-file mapping:
• Step 0: references/00-initialize-intervention.md (read when Step 0 executes)
• Step 1: references/01-research-protocols.md (read when Step 1 executes)
• Step 2: references/02-protocol-foundation.md (read when Step 2 executes - sections 1-6)
• Step 3: references/03-protocol-intervention.md (read when Step 3 executes - sections 7-8)
• Step 4: references/04-protocol-operations.md (read when Step 4 executes - sections 9-12)
• Step 5: references/05-concatenate-protocol.md (read when Step 5 executes - final concatenation)

1. Handle errors: If step fails, ask user to retry or exit. Save current state for resume capability.

1. Display progress: "Progress: [X/6] steps complete", show estimated remaining time

1. Step 4 Completion Pause: After Step 4 completes, pause and display the Protocol Completion Menu (see below). Wait for user selection before proceeding.

Step 2.5: Protocol Completion Menu

After Step 4 completes successfully, display the EXACT menu below (do not improvise or create alternative options):

✅ PROTOCOL COMPLETE: Protocol Draft Generated

Protocol Details:
  • Study Design: [Design from metadata]
  • Sample Size: [N subjects from metadata]
  • Primary Endpoint: [Endpoint from metadata]
  • Study Duration: [Duration from metadata]

Protocol file: waypoints/02_protocol_draft.md
File size: [Size in KB]

📋 WHAT WOULD YOU LIKE TO DO NEXT?

1. 📄 Review Protocol in Artifact - click on the .md file above

2. 📄 Concatenate Final Protocol (Step 5)

3. ⏸️  Exit and Review Later

Option 1 Logic (Review in Artifact): Pause, let user open the section files, wait for further instruction

Option 2 Logic (Concatenate Protocol):

1. Execute Step 5 by reading and following references/05-concatenate-protocol.md
2. Step 5 will concatenate all section files into final protocol document
3. Continue to Step 3 (Final Summary) after Step 5 completes

Option 3 Logic (Exit):

1. Display: "✓ Protocol sections saved. You can resume with Step 5 anytime to concatenate."
2. Exit orchestrator gracefully

Step 3: Final Summary

Display completion message with:

• Intervention name, type (device/drug), indication
• Protocol details (design, sample size, endpoints, duration)
• All completed steps list
• Final deliverable: Complete protocol markdown file location (waypoints/protocol_complete.md)
• Waypoint files list for reference
• Important disclaimers (FDA Pre-Sub, biostatistician review, IRB approval required)
• Thank you message

Technical Details

Waypoint File Formats

JSON Waypoints (Steps 0, 1):

• Structured data for programmatic access
• Small file sizes (1-15KB)
• Easy to parse and reference

Markdown Waypoints (Steps 2, 3, 4):

• Step 2: 02_protocol_foundation.md (Sections 1-6)
• Step 3: 03_protocol_intervention.md (Sections 7-8)
• Step 4: 04_protocol_operations.md (Sections 9-12)
• Step 4: 02_protocol_draft.md (concatenated complete protocol)
• Human-readable protocol documents
• Can be directly edited by users
• Individual section files preserved for easier regeneration

Data Minimization Strategy

Each step implements aggressive summarization:

• Keep: Top-N results (5-10 max)
• Keep: Key facts and IDs (NCT numbers, endpoint types)
• Keep: Concise rationale (2-3 sentences)
• Discard: Raw MCP query results (not needed after analysis)
• Discard: Full FDA guidance text (only excerpts/citations kept)
• Discard: Lower-ranked search results

Step Independence

Each subskill is designed to:

• Read only from waypoint files (not conversation history)
• Produce complete output in single execution
• Not depend on conversation context from previous steps
• Be runnable standalone

Error Handling

MCP Server Unavailable

• Detected in: Step 1
• Action: Display error with installation instructions
• Allow user to retry after installing MCP server
• No fallback available - MCP server is required for protocol

…

Source & license

This open-source skill is cataloged on AgentStack and links to its original source — we do not rehost the code.

• Author: Shoko-official
• Source: Shoko-official/Claude-Science-System-Prompts
• License: Apache-2.0

Install and usage instructions live in the source repository linked above.