clinical-trial

name	clinical-trial
description	Designs and analyzes clinical trials including sample size calculation, randomization schemes, endpoint selection, CONSORT reporting, and interim analysis planning; trigger when users ask about RCTs, Phase I-IV trials, or clinical study design.

When to Trigger

Activate this skill when the user mentions:

• Clinical trial design, RCT, randomized controlled trial
• Sample size calculation, power analysis for trials
• CONSORT, STROBE, SPIRIT guidelines
• Phase I, II, III, IV trials
• Primary/secondary endpoints, composite endpoints
• Interim analysis, adaptive trial design, futility
• Blinding, randomization, allocation concealment
• Intention-to-treat (ITT), per-protocol analysis

Step-by-Step Methodology

1. Define the research question - Specify PICO (Population, Intervention, Comparator, Outcome). Determine if superiority, non-inferiority, or equivalence design is appropriate.
2. Select trial phase and design - Choose phase (I: safety/dose, II: efficacy signal, III: confirmatory, IV: post-market). Consider parallel, crossover, factorial, or adaptive designs.
3. Primary endpoint selection - Define primary outcome (must be clinically meaningful). Specify measurement timing and minimal clinically important difference (MCID).
4. Sample size calculation - Specify alpha (typically 0.05, two-sided), power (typically 80-90%), expected effect size, and dropout rate. Use appropriate formula for the endpoint type (continuous, binary, time-to-event).
5. Randomization and blinding - Recommend randomization method (simple, block, stratified, minimization). Specify blinding level (open-label, single, double, triple).
6. Statistical analysis plan - Pre-specify primary analysis method (t-test, chi-square, log-rank, mixed models). Define interim analysis schedule with alpha-spending function (O'Brien-Fleming, Lan-DeMets).
7. Reporting - Follow CONSORT for RCTs, STROBE for observational, SPIRIT for protocols. Include flow diagram, enrollment numbers, and all pre-specified analyses.

Key Databases and Tools

• ClinicalTrials.gov - Trial registration and results
• Cochrane Library - Systematic reviews of trials
• FDA / EMA guidance documents - Regulatory requirements
• nQuery / PASS / G*Power - Sample size software
• CONSORT / SPIRIT checklists - Reporting standards

Output Format

• Sample size as a table: assumptions, formula, per-arm and total N.
• Trial design as a structured summary: phase, design type, arms, blinding, duration.
• CONSORT flow diagram description with all participant numbers.
• Statistical analysis plan with pre-specified primary and secondary analyses.

Quality Checklist

• PICO clearly defined
• Primary endpoint is clinically meaningful and measurable
• Sample size assumptions explicitly stated with references
• Dropout rate factored into sample size
• Randomization and blinding method specified
• Multiple comparison adjustment for secondary endpoints
• Interim analysis boundaries pre-specified if applicable
• ITT and per-protocol populations defined
• Regulatory guideline alignment noted (FDA/EMA/ICH)