Clinical trials are often grouped into phases I through IV. This structure helps organize goals like learning how a drug behaves and whether it works. However, many studies do not fit neatly into one box.
Behavioral programs, diet and exercise plans, devices, and surgeries often span multiple goals at once. Even drug trials may blend steps, moving from one phase to the next without a sharp boundary.
Early vs. late phase studies
To keep things simple, many teams think in terms of “early” and “late” phase work.
- Early phase: Focuses on how an intervention behaves in people, what doses may be safe, and early signs it could help.
- Late phase: Confirms whether it works in real patients, compares it with standard care, and tracks safety in larger, more diverse groups.
The classic phases (I–IV) for drug trials
Phase I: First-in-human pharmacology
These studies examine how the body handles a drug and how the drug affects the body. They may be done in healthy volunteers or, for some conditions (for example, cancer), in patients.
- Typical size: about 20–80 participants.
- Key aims: tolerance, metabolism, drug–drug interactions, pharmacokinetics (PK), and pharmacodynamics (PD).
- Design may be uncontrolled or dose-escalation to find a safe range.
Phase II: Therapeutic exploration
These trials look for early signals of benefit at different doses and refine how outcomes are measured. Biomarkers are often used when clinical outcomes take longer to observe.
- Typical size: roughly 100–300 participants.
- Key aims: dose selection, early efficacy signals, and continued safety.
- May include randomized arms or adaptive designs.
Phase III: Therapeutic confirmation
Phase III tests whether the intervention provides meaningful clinical benefit compared with standard care or placebo and characterizes the safety profile in larger groups.
- Typical size: hundreds to several thousand participants.
- Key aims: confirm effectiveness, quantify common adverse effects, and support regulatory review.
- Usually randomized, often multicenter, with predefined clinical endpoints.
Phase IV: Therapeutic use after approval
These studies take place after a drug is approved. They examine how it performs in broader or special populations and look for uncommon side effects.
- Typical size: thousands or more, using registries, pragmatic trials, or observational studies.
- Key aims: long-term safety, rare adverse events, and use in subgroups (for example, older adults or those with kidney disease).
Phases can overlap and blend
In practice, goals often overlap across phases. A Phase I study can include early signals of benefit. A Phase II study may include pharmacology sub-studies. Phase III trials sometimes expand safety learning that continues into Phase IV.
- Example: A dose-finding study may start as Phase I (tolerance) and extend into Phase II (efficacy signals) without a pause.
- Example: A Phase II biomarker study may roll into a Phase III outcomes trial if interim results are promising.
Beyond drugs: surgery, devices, and behavior change
Non-drug interventions do not always map cleanly onto I–IV. A surgical technique may first be tested for feasibility, then refined, and later compared with standard care in larger studies. Behavior-change programs may pilot engagement and adherence before testing clinical outcomes.
- Early work may focus on feasibility, adherence, and learning curves.
- Later work may compare outcomes, quality of life, and safety across settings.
Key takeaways for using phases wisely
International guidelines commonly describe trial phases to organize goals, but real projects may cross boundaries. It is often helpful to think in terms of early (learning) and late (confirming) stages, knowing that questions about pharmacology, dose, benefit, and safety can appear in more than one phase. Early studies—even if small or uncontrolled—may provide essential information that makes later trials safer, faster, and more informative.