Clinical Trial Phases: What Each Phase Proves and Whom It Enrolls

The FDA puts a Phase 1 trial at 20 to 100 people and a Phase 3 trial at 300 to 3,000 [1], so one drug asks a recruitment team for very different people at each step. Sources disagree on whether there are four phases or five. The count is four regulatory phases plus an optional Phase 0, and each phase reads best as a recruitment job: who must be found, how many, and across how many sites. Refero does not run recruitment campaigns. We vet and match the clinical research marketing agencies that do, so what follows is written for the buyer, from what those vendors need and see.

How Many Clinical Trial Phases Are There?

There are four clinical trial phases, Phase 1 through Phase 4, and an optional Phase 0 that explains why some sources count five. ICH E8(R1), the international guideline the FDA has adopted, describes clinical development as four temporal phases [2]. Phase 0 is the informal name for what the FDA calls an exploratory IND study: a trial run early in Phase 1 with very limited human exposure and no therapeutic or diagnostic intent, such as a microdose study [3]. IND stands for investigational new drug, the application that opens human testing. A source that counts Phase 0 therefore lists five stages, a source that follows the regulator lists four, and "Phase 5" belongs to neither count.

Each phase answers one question before the next can start.

Participant, length and progression figures are the FDA's approximate ranges.

Read down the second column and the phases become a chain of decisions, each a gate the drug must clear before the next group is recruited. Because only about a third of drugs move on from Phase 2 [1], most drugs that start Phase 2 never reach Phase 3, so early-phase recruitment is bought for a program whose future is unknown.

Clinical Trial Phases at a Glance

The figures a buyer needs sit around the phases as much as inside them: a filing wait, a review clock, a design that merges phases, a per-patient cost and a candidate pool that narrows sharply at enrollment.

• An IND takes effect 30 days after the FDA receives it unless the FDA places a clinical hold [4]
• The FDA's goal is to act on a priority-review application within 6 months, against 10 months under standard review [5]
• Combined Phase 2/3 was the most frequent adaptation, at 57%, in a review of 142 adaptive design trials [6]
• Average cost per enrolled patient is $81,338 in Phase 1 and $35,190 in Phase 4, in 2018 dollars, in one government-funded model [7]
• An early-phase academic trial enrolled 61 of the 1,024 candidates it reviewed [8]

Phase 1 and Phase 2 Clinical Trials: Safety, Dose and First Proof

Phase 1 is the first time a drug is given to people, and Phase 2 is the first test of whether it works in patients with the condition. Before Phase 1, the drug goes through preclinical laboratory and animal studies. The sponsor then files an IND, which takes effect 30 days after the FDA receives it unless the FDA places a clinical hold [4], so that window is the first fixed date a Phase 1 recruitment plan can work backward from.

Phase 1 tests safety and dosage in a small group of healthy volunteers or people with the disease [1]. Phase 2 tests efficacy and side effects in people with the condition [1]. In oncology, the FDA describes first-in-human trials that move from dose escalation to expansion cohorts that estimate antitumor activity, each cohort assessing different aspects of the drug [9]. One early oncology protocol can therefore need several cohorts, each with its own population. The 1a, 1b, 2a, 2b, 3a and 3b labels are informal industry shorthand that no regulator defines, so ask what a protocol means by each. This is not legal advice; confirm filing rules with regulatory counsel and the IRB of record.

Phase 3 and Phase 4: Confirmation, Approval and Real-World Follow-Up

Phase 3 gathers efficacy and safety evidence in a large patient group, and Phase 4 keeps following both once the drug is on the market [1]. A positive Phase 3 result lets the sponsor file a new drug application (NDA) for a drug or a biologics license application (BLA) for a biologic. The FDA then aims to act within 6 months under priority review or 10 months under standard review [5]. Phase 4 begins only after approval, so a postmarketing recruitment plan cannot start until the FDA has acted on that application. Phase 4 follows several thousand people on the marketed drug [1], so adverse effects too rare to appear earlier are more likely to show up in a group that size. This is not legal advice; confirm filing and post-approval rules with regulatory counsel and the IRB of record.

Why Clinical Research Phases Overlap Instead of Running in Line

Clinical trial phases overlap or combine because they describe what a study is for, and ICH E8(R1) states that "the phase concept is a description and not a requirement" [2]. Development follows a logical order, but the phases may overlap or be combined, so a program's calendar looks less tidy than the table. Combined Phase 2/3 designs were the most frequent adaptation, at 57%, in a review of 142 published adaptive design trials, so the figure shows they are common among published adaptive trials but says nothing about trials overall [6]. The FDA accepts a design that selects a dose and confirms efficacy in one trial when the adaptation rule is set in advance [10], and oncology first-in-human trials may run cohorts at the same time [9]. A Phase 1/2 or Phase 2/3 protocol therefore needs one recruitment plan for every population it enrolls, so ask for each part's enrollment target before a vendor scopes the campaign.

What Each Clinical Trial Phase Asks of Recruitment

Each phase sets how many people a study needs and what kind, yet the same phase can be easy or hard to fill. An academic Phase 1/2 trial in patients with B-cell deficiencies reviewed 1,024 candidates; 105 reached a screening visit and 61 enrolled, or 5.9% of candidates [8]. Candidates fell out over immunoglobulin levels, existing antibodies, autoimmune conditions and active cancer treatment [8], so narrow eligibility set the difficulty. Later phases swap narrow eligibility for large multi-site targets, and the enrollment timeline benchmarks show how long enrollment takes at that scale.

Plan for more sites and diagnosed patients once Phase 2 begins

Use this when a sponsor plans its first patient study after a Phase 1 unit trial. Participants shift from healthy volunteers or patients to people who have the condition [1], and the numbers rise, so the recruitment job becomes finding diagnosed patients across more sites, each screening more candidates than it enrolls [8]. Recruitment vendors typically ask for the phase and eligibility criteria before quoting, because together they set how much screening a campaign must cover. Once sites multiply, decentralized elements can change enrollment speed and dropout, and the guide on how decentralized models change enrollment sets out the evidence.

Budget recruitment by therapeutic area before phase

Use this when drafting a recruitment budget from a per-patient figure. One government-funded cost model averages $81,338 per enrolled patient in Phase 1 and $35,190 in Phase 4, in 2018 dollars [7]. In that model, Phase 1 alone runs from $19,399 for anti-infective trials to $349,363 for hematology [7], so therapeutic area moves the budget far more than the gap between phases does. Tufts CSDD's median centralized outreach cost per patient ran from $143 in vaccine studies to $11,392 in immunology [11], though that covers sponsor-initiated outreach and not total recruiting cost. Hold any quote against recruitment cost per patient figures for the same therapeutic area.

Separate pre-screening from screening in the recruitment plan

Use this when writing the screening plan, since a response form may collect eligibility answers before anyone has consented. NIH's IRB office says pre-screening happens before consent, uses minimal and necessary information and must not include research procedures, while screening happens after consent and includes the procedures needed to determine eligibility [12]. Ask the vendor which step each part of its funnel belongs to, and confirm the pre-screening questions with the IRB of record.

If you would rather not run that evaluation alone, Refero screens healthcare marketing and patient recruitment agencies against five published criteria and introduces up to three that fit your brief. It is free for buyers, and there is no obligation to hire anyone we introduce. Tell us what you need.

Frequently Asked Questions

Are all clinical trial phases double blind?

No. Blinding is a design choice, not a feature of a phase. ICH E8(R1) describes open-label, single-blind and double-blind studies, lists randomized, controlled trials among its examples of exploratory and confirmatory studies, and lists observational studies and registries among postapproval examples [2].

What are Phase 5 clinical trials?

Phase 5 is not a regulatory phase. ICH E8(R1) describes four phases of clinical development [2], and the FDA places exploratory IND studies, informally called Phase 0, early in Phase 1 [3].

What is the difference between Phase 2 and Phase 3 clinical trials?

Phase 2 asks whether the drug works in patients, in up to several hundred people [1]. Phase 3 confirms efficacy and monitors adverse reactions in a much larger group and supplies the main evidence for an approval filing [1].

Did COVID-19 vaccines go through every clinical trial phase?

Yes, in a combined protocol. The FDA's briefing document for the Pfizer-BioNTech emergency use authorization describes one Phase 1/2/3 study, and the request included efficacy data from a Phase 3 portion of about 44,000 participants [13]. The phases were combined and the efficacy readout was not skipped.

How long does each clinical trial phase take?

The FDA gives several months for Phase 1, several months to 2 years for Phase 2 and 1 to 4 years for Phase 3, and no length for Phase 4 [1]. Phases may overlap or be combined [2], so a program's calendar does not simply add these ranges together.

Sources

• U.S. Food and Drug Administration. Step 3: Clinical Research. The Drug Development Process (for patients), last updated 2018. Link
• International Council for Harmonisation. E8(R1) General Considerations for Clinical Studies: Guidance for Industry. U.S. Food and Drug Administration, 2022. Link
• U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for Industry, Investigators, and Reviewers: Exploratory IND Studies, 2006. Link
• U.S. Food and Drug Administration. 21 CFR 312.40, General requirements for use of an investigational new drug in a clinical investigation. Code of Federal Regulations. Link
• U.S. Food and Drug Administration. Priority Review. Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review, last updated 2018. Link
• Bothwell LE, Avorn J, Khan NF, Kesselheim AS. Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov. BMJ Open, 2018. Link
• Sertkaya A, Berger C. Drug Development: Final Report. Eastern Research Group for the U.S. Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evaluation, 2024. Link
• Marconato M, Jäger S, Tegeler CM, et al. The challenge of patient recruitment into early phase clinical trials: Is time-effective academic translational research feasible? Lessons from a phase I/II trial in patients with B-cell deficiencies. Frontiers in Medicine, 2026. Link
• U.S. Food and Drug Administration. Expansion Cohorts: Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics: Guidance for Industry, 2022. Link
• U.S. Food and Drug Administration. Adaptive Design Clinical Trials for Drugs and Biologics: Guidance for Industry, 2019. Link
• Kim JY, Lamberti MJ, Do H. Measuring Centralized Patient Outreach Recruitment Strategies and their Costs in Clinical Trials. Therapeutic Innovation & Regulatory Science, 2026. Link
• National Institutes of Health, Office of IRB Operations. Screening for Research Studies. Link
• U.S. Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee Meeting, December 10, 2020: FDA Briefing Document, Pfizer-BioNTech COVID-19 Vaccine. Link