How Clinical Trials Work

A guide to understanding the clinical trial process, phases, and what to expect as a participant.

What Is a Clinical Trial?

Clinical trials are research studies that test whether new medical approaches work in humans. These studies may also test whether new treatments are safe. Clinical trials are the primary method researchers use to determine whether a new medical treatment is effective and safe enough for widespread use.

Every drug, medical device, or treatment approach currently in use was once studied in clinical trials. The trials are typically funded by pharmaceutical companies, government agencies like the NIH, or medical research institutions.

Trial phases at a glance

The four-phase structure is regulatory shorthand for a longer continuum of questions that must be answered before a new therapy reaches widespread use. The table below summarizes the participant count, primary question, and typical duration at each phase.

The Four Phases of Clinical Trials

Phase 1: Safety Testing

Phase 1 trials are the first stage of testing in humans. They typically involve 20–80 healthy volunteers or people with the condition being studied. The primary goal is to determine the safety of the treatment and identify any side effects.

• Goal: Evaluate safety, dosage, and side effects
• Participants: 20–80 volunteers
• Duration: Several months
• Success rate: Approximately 67% advance to Phase 2

Phase 2: Efficacy & Side Effects

Phase 2 trials test whether the treatment works and continue to evaluate its safety. These trials involve more participants, typically 100 to 300 people who have the disease or condition being studied.

• Goal: Evaluate whether the treatment works; continue safety evaluation
• Participants: 100–300 people with the condition
• Duration: Several months to 2 years
• Success rate: Approximately 31% advance to Phase 3

Phase 3: Confirmation

Phase 3 trials compare the new treatment to existing standard treatments and confirm effectiveness in larger, more diverse populations. Most Phase 3 trials are randomized controlled trials (RCTs) - the gold standard for clinical evidence.

• Goal: Confirm effectiveness, compare to existing treatments, monitor side effects
• Participants: 1,000–3,000+ people
• Duration: 1–4 years
• Success rate: Approximately 58% of Phase 3 trials succeed; about 1 in 7 drugs entering Phase 1 ultimately reach FDA approval

Phase 4: Post-Market Surveillance

Phase 4 trials occur after a treatment has been approved by the FDA and is available to the public. These studies collect additional information about risks, benefits, and optimal use in the general population.

• Goal: Monitor long-term effectiveness and safety in the general population
• Participants: Thousands of people
• Duration: Ongoing

Why most candidates never reach Phase 3

Industry analyses consistently show that only a minority of drug candidates that enter Phase 1 testing eventually reach FDA approval. Most attrition occurs at Phase 2, the point at which the therapy must demonstrate not just safety but actual benefit on the disease endpoint. Phase 3 failures are rarer but more expensive, since the trial population is larger and the comparator is already an approved standard-of-care.

Adaptive and platform trial designs

Modern trial methodology increasingly uses adaptive designs that allow the protocol to evolve based on accumulating data, modifying randomization ratios to favor better-performing arms, dropping ineffective arms early, or expanding promising arms with additional participants. Platform trials test multiple therapies against a shared control under a common protocol, accelerating the pace of evidence generation in fields like oncology where many candidate therapies compete for the same patient population.

Trial Design: Randomization and Blinding

Most clinical trials use randomization, participants are randomly assigned to either the treatment group or the control group. This prevents selection bias and ensures the groups are comparable.

Many trials also use blinding:

• Single-blind: Participants don't know which treatment they're receiving
• Double-blind: Neither participants nor researchers know (the gold standard)
• Placebo-controlled: Some participants receive an inactive treatment (placebo) for comparison

Every drug on the pharmacy shelf made the same four-phase journey. The trials that didn't are the reason we know the drugs that did are safe and effective.

Informed Consent

Before joining a clinical trial, you'll go through an informed consent process. This involves reviewing and signing a document that explains the study's purpose, how it works, what's expected of you, and the potential risks and benefits. You can withdraw from a trial at any time.

Finding a Trial

Use PlainTrial's Recruiting Trials finder to search by condition and US state. You can also browse trials by condition or explore what specific sponsors are testing. Always verify current trial information directly at ClinicalTrials.gov before making any decisions.