Common Phase I Clinical Trial Designs and Sample Size

Design Type	Primary Objective	Typical Use Scenario	Key Design Features	Typical Sample Size (Total)
3+3 Dose Escalation Design	Safety, MTD	FIH, conventional phase I	Rule-based; 3–6 patients per dose level; dose escalation/de-escalation based on DLTs	15–30
BOIN Design	Safety, MTD	Oncology phase I	Interval-based rule design; no explicit model; operationally similar to 3+3	20–36
CRM / mCRM	Accurate MTD estimation	Oncology, targeted therapies	Bayesian model-based design; continual updating of dose–toxicity relationship	20–36
Dose Expansion Cohort	Further safety, signal exploration	After RP2D / MTD determination	Enrollment at selected dose levels; descriptive analyses only	10–30 per cohort
Phase I/1b (Escalation + Expansion)	Safety + preliminary efficacy	Oncology targeted / immunotherapies	Dose escalation followed by multiple expansion cohorts	30–60+
Healthy Volunteer Phase I (SAD/MAD)	Safety, PK	Non-oncology small molecules	Single- and multiple-ascending dose; sequential dosing	40–80

Common Phase II Clinical Trial Designs and Sample Size

Design Type	Primary Objective	Typical Use Scenario	Key Design Features	Typical Sample Size (Total)
Single-Arm Phase II	Preliminary efficacy	No standard therapy; rare diseases	Single treatment arm; comparison with historical control; formal statistical hypothesis	25–50
Single-Arm Phase II (Simon Two-Stage)	Go / no-go decision	Early efficacy screening	Two-stage design with early stopping for futility	30–40 (average fewer)
Randomized Controlled Phase II	Comparative efficacy	Existing standard of care	Randomized (e.g., 1:1 or 2:1); screening comparison	60–120 (≈30–60 per arm)
Randomized Non-Comparative Phase II	Regimen or dose selection	Multiple doses or combinations	Randomized arms analyzed independently; no formal between-arm comparison	25–50 per arm
Adaptive Phase II	Efficient decision-making	Multiple regimens / biomarkers	Pre-specified interim adaptations; flexible sample size	Variable (often 50–100)
Phase II in Rare Diseases	Signal detection	Limited patient population	Relaxed assumptions on α and power; often single-arm	15–30

Common Phase III Clinical Trial Designs and Sample Size

Design Type	Primary Objective	Typical Use Scenario	Key Design Features	Typical Sample Size (Total)
Randomized Controlled Phase III (Superiority)	Confirm efficacy and safety	Established standard of care	Randomized (typically 1:1); formal hypothesis testing versus standard therapy	300–1,000+
Randomized Controlled Phase III (Non-inferiority)	Demonstrate non-inferiority	Effective standard therapy exists	Pre-specified non-inferiority margin; choice of control critical	500–2,000+
Placebo-Controlled Phase III	Confirm efficacy	No effective standard therapy	Randomized, double-blind, placebo-controlled	200–800
Event-Driven Phase III	Evaluate time-to-event outcomes	PFS / OS as primary endpoint	Sample size driven by required number of events; long-term follow-up	600–2,000+
Adaptive Phase III	Improve efficiency	Multiple doses or populations	Pre-specified interim analyses and adaptations	Variable (often several hundred to >1,000)
Phase III in Rare Diseases / Accelerated Programs	Support registration	Limited patient population	Smaller sample size with strong justification; regulatory flexibility	100–300