clinical-trial

## 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)