Clinical Trial Protocol Skill

Step 3: Clinical Protocol Intervention Details

Purpose

This subskill generates the intervention-specific sections (6-7) of a clinical study protocol. It adds detailed intervention administration, dose modifications (if applicable), preparation/handling, randomization/blinding, compliance monitoring, and discontinuation procedures to the protocol foundation.

Prerequisites

Required Files:

• waypoints/intervention_metadata.json (must contain protocol_template field from Step 2)

• waypoints/01_clinical_research_summary.json

• waypoints/02_protocol_foundation.md (sections 1-5 from Step 2)

• waypoints/02_protocol_metadata.json (must show step_2_status: "completed")

What This Subskill Does

1. Verifies Step 2 completion

2. Reads protocol template (from metadata) and shared guidance

3. Synthesizes intervention-specific content for Sections 6-7

4. Creates new file waypoints/03_protocol_intervention.md with Sections 6-7

5. Updates protocol metadata tracking file

Execution Flow

Step 1: Verify Step 2 Completion

Read waypoints/02_protocol_metadata.json and verify:

• step_2_status is "completed"

• waypoints/02_protocol_foundation.md exists (Step 2 output)

If Step 2 not completed:

Error: Step 2 must be completed before Step 3.
Step 2 status: [current status]

Please complete Step 2 first to generate protocol foundation (Sections 1-6).

Exit.

If Step 2 completed: Proceed to Step 2.

Step 2: Read Protocol Template and Shared Guidance

1. Read waypoints/intervention_metadata.json to get the protocol_template and template_source field values

2. Read the protocol template file:

   • The path is stored in protocol_template field (could be assets/[name].md OR a user-provided path)

   • Read the file at that path (focus on Sections 6-7)

   • Note: The template_source field indicates whether this is "directory" or "user_provided" (for logging/debugging only)

3. Read waypoints/02_protocol_foundation.md to understand existing context (especially study design, endpoints, and population from Sections 1-5)

Internalize:

• Template structure for Sections 6-7

• Content depth targets from shared guidance

• Intervention-specific terminology (device vs drug)

• Dose modification table requirements (for complex drugs)

• Quality principles (comprehensive over brief, specific over generic)

Step 3: Synthesize Intervention Details Content

Generate Sections 6-7 following template structure, adapted for this specific intervention and indication.

Use data from:

• Intervention metadata (intervention type, name, classification, regulatory status)

• Step 1 clinical research summary (similar trials, dosing information, safety profiles)

• Existing protocol draft (study design, endpoints, schedule of activities)

Follow guidance from:

• Selected protocol template from Step 2 (structure, regulatory requirements)

Section Generation Instructions

Section 6: STUDY INTERVENTION (1,000 lines)

This section varies based on intervention complexity.

6.1 Study Intervention(s) Administration (300 lines)

For DEVICES (300 lines):

Device Identification and Regulatory Status (30 lines):

• Device name (commercial/investigational)

• Manufacturer name and location

• FDA classification: Class I/II/III with product code

• Regulatory status:

  • If 510(k) cleared: K-number and clearance date

  • If De Novo: DEN-number and classification date

  • If PMA approved: P-number and approval date

  • If investigational: "Investigational device, IDE application [submitted/pending/approved], IDE number [if applicable]"

If 510(k) Pathway (40 lines):

• Predicate device(s): Name, manufacturer

• Predicate 510(k) number (K-number)

• Substantial equivalence rationale:

  • Similar intended use (explain how)

  • Similar technological characteristics (materials, design, energy source)

  • Similar performance data

• Key differences from predicate and justification that differences don't affect safety/effectiveness

Detailed Device Description (100 lines):

• Physical characteristics: Size, weight, dimensions, shape

• Materials: List all materials in contact with tissue/blood

• Components and their functions: Describe each major component

• Principle of operation: How the device works at a technical level

• Mechanism of action: How the device achieves its clinical effect

• Power source (if applicable): Battery type, recharging, expected life

• Software/firmware (if applicable): Version, key functions

Intended Use (20 lines):

• Intended use per proposed labeling

• Specific indications

• Patient population

• Anatomical location

• Clinical setting

Instructions for Use Summary (100 lines):

Patient Selection per IFU (20 lines):

• Indications from IFU

• Contraindications from IFU

• Warnings and precautions

Pre-Procedure Requirements (30 lines):

• Patient preparation (fasting, medications, positioning)

• Equipment setup and testing

• Sterility requirements

• Anesthesia/sedation requirements

Procedure Steps (50 lines):

• Step-by-step implantation/use procedure

• Anatomical landmarks

• Imaging guidance (if applicable)

• Device settings and programming

• Intraoperative testing/verification

• Expected procedure duration

Post-Procedure Care (30 lines):

• Immediate post-procedure monitoring

• Hospital stay duration

• Activity restrictions

• Follow-up schedule for device checks

• Patient instructions

Device Settings/Parameters (20 lines):

• Programmable settings (if applicable)

• Adjustment procedures

• Optimization protocol

Device-Specific Training Requirements (30 lines):

• Investigator training requirements

• Site staff training

• Certification requirements

• Proctoring requirements (if applicable)

For DRUGS/BIOLOGICS (300 lines):

Drug Identification and Regulatory Status (30 lines):

• Drug name: Generic name, trade name (if applicable)

• Manufacturer name and location

• Regulatory status:

  • If FDA approved: List approved indications and approval date

  • If investigational: "Investigational drug, IND number [if known], IND application [submitted/approved]"

Formulation Details (30 lines):

• Dosage form: Tablet, capsule, injection, infusion, etc.

• Strength(s): Available strengths

• Active ingredient(s): Chemical name, quantity per unit

• Excipients: List inactive ingredients

• Appearance: Physical description

• Packaging: How supplied

Mechanism of Action (100 lines):

• Biological target: Receptor, enzyme, pathway, cell type

• Drug-target interaction: How drug binds/interacts with target (agonist, antagonist, inhibitor, etc.)

• Downstream cellular effects: Intracellular signaling, gene expression changes, metabolic effects

• Tissue-level effects: How cellular changes manifest at tissue level

• Clinical effects: How mechanism translates to clinical benefit

• Why mechanism is relevant to disease: Connect to disease pathophysiology (from Section 3.2)

• Supporting evidence: Cite preclinical and clinical data

Pharmacokinetics Summary (40 lines, if known):

• Absorption: Route-specific bioavailability, Tmax (time to peak concentration), Food effects

• Distribution: Volume of distribution (Vd), Protein binding (%), Tissue distribution

• Metabolism: Metabolizing enzymes (CYP450 isoforms), Active metabolites, Drug-drug interaction potential

• Excretion: Elimination half-life (t1/2), Primary route of elimination (renal/hepatic), Renal/hepatic impairment considerations

Pharmacodynamics (30 lines, if known):

• Dose-response relationship

• Time course of effect

• Target engagement biomarkers

• Duration of action

Dosing Details (50 lines):

Dose Specification:

• Dose amount: [X] mg/kg or fixed dose [Y] mg

• Dose calculation: If weight-based, specify calculation method

  • Body surface area (BSA) cap: Maximum BSA for calculation (e.g., "BSA capped at 2.0 m²")

  • Rounding: Specify rounding rules (e.g., "Round to nearest 10 mg")

• Route of administration: IV, PO, SC, IM, etc.

• Frequency: QD (once daily), BID (twice daily), Q3W (every 3 weeks), etc.

• Duration: Number of cycles or total treatment duration

  • Cycle definition: Define cycle length (e.g., "One cycle = 21 days")

  • Number of cycles: Specify planned number or duration criteria

Administration Instructions:

• If IV: Infusion preparation, infusion rate/duration, infusion pump requirements, line flushing

• If PO: Timing relative to meals, instructions for swallowing (with water, do not crush)

• If SC: Injection technique, rotation of injection sites, needle specifications

• Administration schedule: Specify days within cycle (e.g., "Days 1, 8, and 15 of each 21-day cycle")

Pre-medications (if required):

• List all required pre-medications

• For each: Drug name, dose, route, timing relative to study intervention

• Rationale: Why pre-medication needed (prevent infusion reactions, nausea, etc.)

• Examples: Antihistamines, antipyretics, antiemetics, corticosteroids

Supportive Care Medications:

• Medications to manage expected toxicities

• Growth factors (G-CSF, erythropoietin)

• Prophylactic medications (antiviral, antifungal, PCP prophylaxis)

• Criteria for use

6.2 Dose Modifications (IF applicable for drugs - 300 lines)

NOTE: Only generate this subsection if intervention requires dose modifications (complex chemotherapy, immunotherapy, targeted therapy with known toxicities). For simple interventions, devices, or fixed-dose drugs without modifications, state: "No dose modifications are planned for this study. If unacceptable toxicity occurs, study intervention will be discontinued per Section 7."

If dose modifications required:

General Principles (40 lines):

• When to hold intervention: Typically for Grade 3-4 toxicities

• Maximum hold duration: Specify (e.g., "Hold up to 4 weeks for toxicity resolution")

• Dose reduction levels: Can reduce dose up to X levels

• Re-escalation policy: State whether dose can be increased after reduction (typically NO)

• Permanent discontinuation criteria: Conditions requiring permanent stop

1. Generate Dose Level Table (20 lines):

2. Generate Dose Modification Tables by Toxicity Category (200 lines total):

Generate 3-5 tables (one per major toxicity category relevant to the intervention):

Table: Hematologic Toxicity Dose Modifications (60 lines):

Table: Hepatic Toxicity Dose Modifications (40 lines):

Table: Renal Toxicity Dose Modifications (40 lines):

Table: [Intervention-Specific Toxicity] Dose Modifications (60 lines):

For immunotherapy:

• Immune-related pneumonitis

• Immune-related colitis/diarrhea

• Immune-related hepatitis

• Immune-related endocrinopathies (thyroid, pituitary, adrenal)

• Immune-related dermatitis

• Include management algorithms: Corticosteroid dosing (prednisone 1-2 mg/kg/day), taper schedule, resumption criteria

For chemotherapy:

• Peripheral neuropathy (with functional impact grading)

• Ototoxicity

• Cardiotoxicity (with LVEF thresholds)

• Mucositis/stomatitis

For targeted therapy:

• Rash/dermatologic toxicity

• Diarrhea

• Hypertension

• Hand-foot syndrome

• Target-specific toxicities

Example format:

3. General Toxicity Management Guidelines (100 lines):

Criteria to Hold Intervention:

• Any Grade 4 toxicity (except specific exceptions like lab abnormalities without clinical sequelae)

• Grade 3 toxicity that is symptomatic or clinically significant

• Specific organ toxicities at lower grades (specify)

• Inability to manage toxicity with supportive care

Duration of Hold:

• Standard hold: Hold until toxicity resolves to Grade ≤1 or baseline

• Maximum hold duration: Specify (e.g., "Maximum 4 weeks")

• If toxicity does not resolve within maximum hold: Permanently discontinue

Dose Reduction Guidelines:

• Reduce by one dose level for specified toxicities

• Maximum number of dose reductions: Specify (typically 2-3 levels)

• No dose re-escalation once reduced

• If toxicity recurs at lowest dose level: Permanently discontinue

Permanent Discontinuation Criteria:

• Grade 4 toxicity recurrence after dose reduction

• Inability to tolerate lowest dose level

• Specific life-threatening toxicities (list)

• Failure of toxicity to resolve within maximum hold period

• Participant or investigator decision

Supportive Care Management by Toxicity Type:

• Hematologic: G-CSF indications, transfusion thresholds

• Gastrointestinal: Antiemetics, antidiarrheals, nutritional support

• Immune-related (for immunotherapy): Corticosteroid protocols, additional immunosuppression

• Organ-specific: Targeted management strategies

Re-challenge Considerations:

• Criteria for re-challenging after toxicity resolution

• Conditions where re-challenge is contraindicated

6.3 Preparation/Handling/Storage/Accountability (100 lines)

Acquisition (20 lines):

• How intervention is obtained: Sponsor provides, commercial source, pharmacy procurement

• Shipping: Temperature controlled, special handling

• Receipt verification: Pharmacy procedures

Storage Requirements (30 lines):

• Temperature: Specify range (e.g., "Store at 2-8°C", "Room temperature 20-25°C", "Frozen -20°C")

• Light protection: State if light-sensitive ("Store in original carton to protect from light")

• Humidity considerations

• Storage location: Pharmacy, investigational drug storage area

• Expiration dating: Shelf life, beyond-use dating after reconstitution

• Stability: Stability data supporting storage conditions

Preparation Instructions (40 lines):

• Reconstitution (if applicable): Diluent type and volume, mixing instructions, final concentration, stability after reconstitution

• Dilution (if applicable): Final volume, compatible diluents (e.g., 0.9% NaCl, D5W), incompatibilities

• Special handling: Cytotoxic precautions, biohazard handling, personal protective equipment (PPE)

• Preparation area: Biological safety cabinet, sterile compounding area

• Visual inspection: Appearance after preparation, rejection criteria (particulates, discoloration)

• Labeling: Required label elements

Handling Precautions (30 lines):

• Cytotoxic precautions (if applicable): NIOSH guidelines, closed-system transfer devices, double gloves, gown

• Biohazard considerations: Bloodborne pathogens, infectious material handling

• Spill management: Spill kit availability, cleanup procedures, reporting

• Personnel training: Training requirements for handling

Dispensing and Accountability (30 lines):

• Dispensing process: Pharmacy verification, double-check procedures

• Tracking: Drug accountability logs, subject ID assignment

• Documentation: Date dispensed, quantity, lot number, expiration date

• Return of unused product: Procedures for return, reconciliation

• Destruction: Procedures for expired or unused product destruction

• Audit trail: Record-keeping for regulatory inspection

Expiration and Stability (20 lines):

• Expiration dating: Check expiration before dispensing

• Stability after preparation: Use immediately or within X hours

• Temperature excursions: Procedures if storage conditions breached

6.4 Measures to Minimize Bias: Randomization and Blinding (50 lines)

If Randomized:

Randomization Method (20 lines):

• Randomization procedure: Computer-generated randomization schedule, permuted blocks, stratified randomization

• Allocation ratio: 1:1, 2:1, etc.

• Stratification factors (if applicable): List factors (e.g., age <65 vs ≥65, disease stage, site)

• Randomization system: Interactive Web Response System (IWRS), Interactive Voice Response System (IVRS), sealed envelopes (specify method)

• Who performs randomization: Independent statistician, central randomization service, pharmacy

• Timing: When is participant randomized? (after consent and eligibility confirmation, before first dose)

Randomization Code Security (10 lines):

• Code storage: Sealed, stored securely

• Access restrictions: Only authorized unblinded personnel

If Blinded:

Blinding Methods (30 lines):

• Who is blinded: Participants, investigators, outcome assessors, data analysts

• How blinding achieved: Matching placebo (identical appearance), identical packaging, masked labeling

• Labeling: Blinded labels with study ID and randomization number

• Administration: Identical administration procedures for all arms

• Blinding maintenance: Procedures to maintain blinding throughout study

Unblinding Procedures (20 lines):

• Emergency unblinding: When permitted (medical emergency requiring knowledge of treatment), how to unblind (24/7 phone line, break-the-seal envelope), documentation required

• Planned unblinding: When does unblinding occur (after database lock, after primary analysis)

• Impact of unblinding: Participant continues or discontinues after emergency unblinding (specify)

If Open-Label:

Justification (20 lines):

• Why open-label design: Objective endpoint not susceptible to bias, blinding not feasible (e.g., device vs medical therapy), regulatory precedent for indication

• Bias mitigation: Blinded outcome assessment, blinded data analysis

6.5 Study Intervention Compliance (30 lines)

Compliance Monitoring Methods:

• For oral medications: Pill counts (count returned pills), participant diary (daily log), pharmacy dispensing records

• For IV/injectable: Direct observation (administered in clinic), infusion logs

• For devices: Device interrogation (if applicable), device diary, follow-up assessments

• Pharmacy records review

• IWRS tracking

Compliance Calculation (if applicable):

• Formula: (Actual doses taken / Expected doses) × 100%

• For continuous dosing: Compliance = (Days with medication taken / Total days in period) × 100%

Acceptable Compliance Threshold:

• Typically ≥80% compliance expected

• Per-protocol population: Participants with ≥80% compliance

Documentation of Compliance:

• Record compliance at each visit

• Document reasons for non-compliance

• Review compliance with participant at visits

Procedures for Non-Compliance:

• Investigator discusses with participant

• Assess barriers to compliance

• Provide education and support

• If persistent non-compliance: Consider study discontinuation per Section 7

6.6 Concomitant Therapy (50 lines)

Allowed Medications (20 lines):

• Permitted concomitant medications: Standard of care for underlying disease, supportive care, medications for comorbidities

• Required medications: Specify if any medications must be continued (e.g., "Participants must continue standard of care [specific therapy]")

• Rescue medications: Permitted rescue therapies for breakthrough symptoms

• Over-the-counter medications: Generally permitted unless contraindicated

• Vitamins and supplements: Generally permitted (document)

Prohibited Medications (20 lines):

• Specific drugs or drug classes not allowed during study

• Examples:

  • Other investigational agents

  • Chemotherapy (unless specified as combination)

  • Immunosuppressive agents (specify exceptions for immune-related AE management)

  • Strong CYP450 inhibitors/inducers (if drug-drug interactions expected)

  • [List specific drugs relevant to this intervention]

• Washout requirements: If previously taken, specify washout period before enrollment

Required Standard of Care (10 lines):

• Medications that must be continued: Specify standard of care that cannot be withheld for ethical reasons

• Background therapy: If study intervention is added to standard of care

Documentation:

• All concomitant medications documented at each visit: Drug name, dose, route, frequency, indication, start date, stop date

• Medication changes documented in real-time

• Concomitant medications recorded in eCRF

Review and Management:

• Investigator reviews medications at each visit

• Assess for drug-drug interactions

• Assess for prohibited medications

• Document compliance with concomitant therapy restrictions

Section 7: STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL (80 lines)

Generate three subsections:

7.1 Discontinuation of Study Intervention (30 lines)

Participant stops receiving study intervention but continues in study follow-up.

Criteria for Discontinuing Intervention:

• Disease progression: Per protocol-defined criteria (reference Section 9 for assessment)

• Unacceptable toxicity: Toxicity meeting permanent discontinuation criteria (reference Section 7.2 or list specific toxicities)

• Intercurrent illness: Illness or condition preventing safe continuation of intervention

• Investigator decision: Safety concern identified by investigator

• Participant decision: Participant withdraws consent for intervention but agrees to continued follow-up

• Protocol deviation: Major deviation requiring intervention discontinuation

• Pregnancy: Pregnancy detected during study (reference Section 9.3.9)

• Non-compliance: Persistent non-compliance with study intervention (reference Section 7.5)

• Death: Participant dies

• Sponsor decision: Study termination or intervention deemed unsafe

Procedures After Intervention Discontinuation:

• Continue study follow-up: Participants continue scheduled visits per Schedule of Activities (Section 2.3)

• Safety follow-up: Continue AE monitoring for 30 days after last dose (or longer for devices/long-acting agents)

• Efficacy assessments: Continue primary and secondary endpoint assessments per protocol

• Survival follow-up: If survival is an endpoint, continue survival status collection

• End-of-treatment visit: Complete end-of-treatment assessments per SoA

• Document reason: Clearly document reason for intervention discontinuation in eCRF

7.2 Participant Discontinuation/Withdrawal from the Study (30 lines)

Participant withdraws completely from study (no further participation).

Criteria for Study Withdrawal:

• Participant withdraws consent: Participant withdraws consent for all study procedures (no further data collection)

• Lost to follow-up: Unable to contact participant despite documented attempts (see Section 7.3)

• Investigator decision: Safety concern requiring immediate study discontinuation

• Sponsor decision: Entire study terminated

• Death: Participant dies (continue to collect date and cause of death)

Procedures for Withdrawn Participants:

• Document reason for withdrawal: Record specific reason in eCRF

• Perform safety assessments if possible: Encourage participant to complete safety follow-up visit

• Collect data up to withdrawal: All data collected prior to withdrawal will be included in analyses

• No replacement: Withdrawn participants are not replaced unless protocol specifies otherwise

• Intent-to-treat analysis: Withdrawn participants included in ITT population

Withdrawal of Consent:

• Partial withdrawal: Participant may withdraw from intervention but continue follow-up visits

• Complete withdrawal: No further data collection after withdrawal

• Use of previously collected data: Clarify whether previously collected data may be used (per informed consent)

Death:

• Document date and cause: Obtain death certificate or medical records if possible

• Report as SAE: All deaths reported as serious adverse events (Section 9.3.6)

• Continue survival follow-up for other participants

7.3 Lost to Follow-Up (20 lines)

Definition:

• Lost to follow-up (LTFU): Participant who fails to return for scheduled study visits and cannot be contacted despite documented attempts

Differentiation:

• LTFU ≠ Withdrawal: LTFU is passive (cannot contact); withdrawal is active (participant declines)

• Participant is not considered LTFU until all contact attempts exhausted

Contact Attempt Procedures:

• Minimum contact attempts: At least 3 documented attempts via different methods

• Contact methods: Phone calls (multiple times, different times of day), certified mail, email (if permitted by IRB), text message (if permitted), contact of emergency contact person (per consent), query site staff/coordinators, check medical records for recent visits

• Documentation: Document each contact attempt (date, time, method, outcome) in study records

• Timing: Attempts made over at least 2-4 weeks

Reporting:

• Report to sponsor: Notify sponsor of LTFU

• Report to IRB: Per IRB requirements

Analysis:

• ITT population: LTFU participants included in ITT analysis

• Last observation: Use data up to last contact

• Missing data: Handle per statistical analysis plan (Section 10.4.10)

Do Not:

• Do not consider participant withdrawn without documented contact attempts

• Do not replace LTFU participants (unless protocol specifies)

Step 4: Create Intervention Details File

IMPORTANT: This creates a NEW file with only Sections 6-7.

Create waypoints/03_protocol_intervention.md with Sections 6-7 only.

Procedure:

1. Generate Section 6 content

2. Generate Section 7 content

3. Write both sections to new file waypoints/03_protocol_intervention.md

4. Confirm file creation successful

Step 5: Update Protocol Metadata

Update waypoints/02_protocol_metadata.json:

• Set step_3_status to "completed"

• Add sections 7 and 8 to sections_completed array

• Update protocol_status to "intervention_complete"

• Update notes

Example:

{
  "intervention_id": "[from metadata]",
  "intervention_name": "[from metadata]",
  "protocol_version": "1.0 Draft",
  "protocol_date": "[current date]",
  "study_design": "[from Phase 1]",
  "enrollment_target": "[from Phase 1]",
  "primary_endpoint": "[from Section 4]",
  "duration_months": "[from Phase 1 or generated]",
  "regulatory_pathway": "[IDE or IND]",
  "protocol_status": "intervention_complete",
  "step_2_status": "completed",
  "step_3_status": "completed",
  "step_4_status": "pending",
  "sections_completed": [1, 2, 3, 4, 5, 6, 7, 8],
  "sections_pending": [9, 10, 11, 12],
  "notes": [
    "DRAFT for planning purposes",
    "Protocol foundation and intervention details (Sections 1-8) completed",
    "Continue to Step 4 for assessments, statistics, and operations",
    "Requires biostatistician review",
    "Requires IRB approval",
    "Requires FDA feedback",
    "Sponsor TBD items require completion"
  ]
}

Step 6: Display Summary

Display concise summary with:

• Intervention name, protocol version, date

• Step 3 completion status

• Sections completed: 7-8 (Study Intervention, Discontinuation)

• Protocol file updated with size

• DRAFT disclaimer

• Next steps: Review intervention details, continue to Phase 4 for assessments and statistics (Sections 9-12)

Example output:

✅ Step 3: Intervention Details - COMPLETED

Intervention: [Name]
Protocol: Version 1.0 Draft (2025-12-03)

Sections Completed (7-8):
  ✓ Section 7: Study Intervention
    - Administration procedures and dosing
    - Dose modifications [if applicable]
    - Preparation, handling, storage
    - Randomization and blinding
    - Compliance monitoring
    - Concomitant therapy
  ✓ Section 7: Study Intervention Discontinuation and Participant Discontinuation/Withdrawal

Files Updated:
  • waypoints/03_protocol_intervention.md (appended ~[size]KB, now [total lines] lines)
  • waypoints/02_protocol_metadata.json

Protocol Status: Sections 1-8 complete (Foundation + Intervention)

Output Files

Created:

• waypoints/03_protocol_intervention.md (Sections 6-7 only, ~1,200 lines)

Updated:

• waypoints/02_protocol_metadata.json (step 3 marked complete)

NOT updated yet:

• waypoints/intervention_metadata.json (will be updated after Step 4 completes)

• waypoints/02_protocol_draft.md (will be created by Step 4 concatenation)

Error Handling

If Phase 2 not completed:

Error: Step 2 must be completed first.
Current status: step_2_status = [status]

Please complete Step 2 to generate protocol foundation (Sections 1-6) before proceeding to Phase 3.

If protocol foundation file missing:

Error: Protocol foundation file not found.
Expected: waypoints/02_protocol_foundation.md

Please run Step 2 first to create the protocol foundation.

If user declines intervention details:

Intervention details skipped at user request.
Step 3 not completed.
User can return to this phase later if needed.

If Step 3 already completed:

Warning: Phase 3 appears to be already completed.
Metadata shows: step_3_status = "completed"

Would you like to:
  1. Skip Step 3 and continue to Phase 4
  2. Regenerate Step 3 (will overwrite Sections 6-7)
  3. Exit

Quality Checks

Before finalizing, verify:

• [ ] Section 6 generated with all required subsections (6.1-6.6)

• [ ] Intervention-specific content (device vs drug terminology used correctly)

• [ ] Dose modifications section appropriate for intervention type

• [ ] Section 7 includes all three subsections (7.1-7.3)

• [ ] Content appended successfully to existing protocol draft

• [ ] Protocol metadata updated correctly

• [ ] Intervention details length: ~1,200 lines (appropriate for complexity)

• [ ] Total protocol now contains Sections 1-7

Notes

• This subskill generates approximately 1,200 lines of protocol content

• Output stays within token limits by focusing on Sections 6-7 only

• Step 4 will complete the protocol by adding assessments, statistics, and operational content