Clinical Trial Phases Explained: Phase 1 to Phase 4

In plain English

A clinical trial is a carefully planned study in people. It tests whether a new medicine, device or procedure works, and what side effects it has ^[1].

New medicines are usually tested in steps called phases. Each step involves more people than the one before ^[1]:

Phase 1: a small group, to check safety and how the body handles the medicine.
Phase 2: a larger group, to see if it works as intended.
Phase 3: a much larger group, often compared with an existing treatment or a placebo (a dummy treatment with no active ingredient).
Phase 4: after approval, to keep watching for problems in everyday use.

Most candidate medicines do not make it through all the phases ^[3]. Lab and animal studies come first, but they cannot show how a medicine behaves in people ^[1].

An ethics committee must approve every trial before it starts ^[2].

The short version

Phases 1–3 come before approval; phase 4 comes after ^{[1, 3]}.
Each phase answers different questions ^[4].
Many drugs drop out between phases ^[3].

Key facts

Phase	Main question	Typical number of participants	Typical length (FDA)
Phase 0 (exploratory)	Early look at how the body responds to a very small amount given once or briefly	Very small ^[1]	Not specified
Phase 1	Safety, tolerability and how the body handles the drug	20–80 ^[1]; FDA gives 20–100 ^[3]	Several months ^[3]
Phase 2	Does it work as intended? Further safety	Up to several hundred ^{[1, 3]}	Several months to 2 years ^[3]
Phase 3	Confirm efficacy, compare with standard care or placebo, monitor adverse effects	Several hundred to several thousand; FDA gives 300–3,000 ^{[1, 3]}	1–4 years ^[3]
Phase 4	Effectiveness and adverse effects in wider, longer use after approval	Several thousand ^[3]	Ongoing

What is a clinical trial?

Clinical trials let researchers test new interventions, such as medicines, devices, tests or procedures, in people ^[1]. Computer simulation and animal testing can only go so far. Trials in people are needed to find out whether a medicine developed using animal models, tissue samples or cells is effective and what its risks are ^[1].

Well-run trials rest on rigorous methodology and oversight governed by ethical principles ^[12]. Every trial follows a written study plan. The plan sets out who can take part, the methods and procedures, the interventions and how they are delivered, how long the study runs, and what information is collected ^[2]. Many trials include a control group that receives standard care, another intervention or a placebo, so that any difference can be measured against a comparison ^[2].

Trials are not a single step. Internationally harmonised guidance from the ICH explains that clinical development builds on knowledge from nonclinical (laboratory and animal) studies and from earlier clinical studies, and that the findings of each study should inform the design of the next ^[4]. For the stages before and after trials, see How Peptide Medicines Are Developed.

Phase 0: exploratory studies

Some programmes begin with an exploratory study, sometimes called a phase 0 trial or pilot study. These come before phase 1 and look at how the body responds to an experimental drug. They involve very few people and a very small amount of the drug, given once or for a short time ^[1].

Phase 1: first in humans

Phase 1 trials test a new intervention in people for the first time ^[1]. ICH E8(R1) calls these human pharmacology studies and states that the protection of participants should always be the first priority, especially in first-in-human studies ^[4].

Phase 1 studies typically involve 20–80 people ^{[1, 3]}. They are often run in healthy volunteers, but they can be run in patients who have the condition, depending on the drug and the aims of the programme ^{[3, 4]}. The FDA notes, for example, that phase 1 studies of drugs intended for cancer are run in patients with that cancer ^[3].

Phase 1 aims to identify side effects and tolerability at increasing amounts, and to describe how the body absorbs, distributes, metabolises and excretes the drug (pharmacokinetics) ^{[1, 3, 4]}. The FDA estimates that about 70% of drugs move on to the next phase ^[3].

Phase 2: does it work as intended?

Phase 2 trials involve a larger group, up to several hundred people who have the condition being studied ^{[1, 3]}. ICH E8(R1) describes them as exploratory studies. They examine efficacy in the intended patient population, refine the target population, build a more robust safety profile, and test endpoints (the outcomes to be measured) for later studies ^[4].

Phase 2 studies are usually not large enough to show whether a drug is clinically effective overall. Their findings are used to design phase 3 studies ^[3]. The FDA estimates that about 33% of drugs move from phase 2 to phase 3 ^[3].

Phase 3: confirming the evidence

Phase 3 trials involve large groups, from several hundred to several thousand people ^[1]. They compare the intervention with standard care, another experimental intervention or a placebo, and they monitor adverse effects ^[1]. ICH E8(R1) calls them confirmatory studies, designed to confirm earlier evidence and often intended to provide the basis for marketing approval ^[4].

Because phase 3 studies are larger and longer, they are more likely to detect less common or long-term side effects, and they provide most of the safety data ^[3]. These are sometimes called “pivotal” studies ^[3]. The FDA estimates that about 25–30% of drugs move on from phase 3 ^[3].

Phase 4: after approval

Phase 4 studies happen after an intervention is approved and in use. They monitor effectiveness in the general population and collect information on adverse effects over longer periods. They may also investigate use in a different condition or in combination with other therapies ^[1].

Post-approval monitoring matters because complete safety information cannot be known at the time of approval; the picture develops over a product’s time on the market ^[10].

Phases are a description, not a rulebook

ICH E8(R1) states that the four-phase model is a description and not a requirement, and that phases may overlap or be combined ^[4]. Some programmes run combined phase 1/2 or phase 2/3 studies. Success rates also vary. A large analysis of trial data for more than 21,000 compounds found that estimates differ by disease area and other trial features. For example, oncology had a 3.4% success rate in that sample ^[8].

Why phases matter when reading peptide research

When a news story or website mentions that a peptide “is in clinical trials”, the phase says a lot about the strength of the evidence:

A phase 1 trial tests tolerability in a small group. It is not designed to show efficacy.
A phase 2 finding is exploratory and often not confirmed later.
Phase 3 (confirmatory) studies are the ones typically intended to support approval ^[4].
Being in a trial is not the same as being approved. Even a medicine with provisional approval in Australia is supplied for a limited period while final trials are completed ^[9].

For a broader framework, see How to Read Peptide Research.

What this means in Australia

Trials using unapproved goods. In Australia, clinical trials that use unapproved therapeutic goods run under one of two TGA schemes: the Clinical Trial Notification (CTN) scheme or the Clinical Trial Approval (CTA) scheme. These schemes allow unapproved goods to be imported or supplied solely for experimental purposes in humans. They are not a way to access unapproved goods for an individual patient ^[5].

Ethics approval is always required. All clinical trials need approval from a human research ethics committee (HREC) before they start ^[5]. Trials must follow the therapeutic goods legislation, the Declaration of Helsinki principles, the NHMRC National Statement on Ethical Conduct in Human Research and the relevant Good Clinical Practice guideline ^{[5, 7]}.

Finding trials. The government’s Australian Clinical Trials website explains how trials work for participants ^{[1, 2]}. Internationally, the WHO International Clinical Trials Registry Platform (ICTRP) provides a search portal across registries, and states that registering all interventional trials is a scientific, ethical and moral responsibility ^[6].

“Research use only” products are not trial products. In April 2026 the TGA stated that a “research use only” disclaimer does not make supply lawful, and does not change regulatory status, permit importation, or remove advertising or supply obligations ^[11]. See Are Peptides Legal in Australia?.

This is general information, not legal advice. Laws change; check the current Poisons Standard and TGA guidance.

Frequently asked questions

What are the four phases of clinical trials?

Phase 1 tests a new intervention in a small group for safety; phase 2 explores efficacy in up to several hundred people; phase 3 confirms efficacy and safety in hundreds to thousands; phase 4 monitors use after approval ^{[1, 3]}.

What is a phase 0 trial?

An exploratory study before phase 1 that gives a very small amount of a drug once or briefly to a very small number of people, to see how the body responds ^[1].

How many drugs make it through clinical trials?

The FDA estimates about 70% move from phase 1 to 2, about 33% from phase 2 to 3, and 25–30% move on from phase 3. Rates vary by disease area ^{[3, 8]}.

Do all medicines go through every phase in order?

Not always. ICH guidance says the phase concept is a description, not a requirement, and phases can overlap or be combined ^[4].

Who approves clinical trials in Australia?

A human research ethics committee must approve every trial. Trials of unapproved goods also run under the TGA’s CTN or CTA scheme ^[5].

References

Australian Government. Australian Clinical Trials. What is a clinical trial? australianclinicaltrials.gov.au. Accessed 11 October 2026.
Australian Government. Australian Clinical Trials. How clinical trials work. australianclinicaltrials.gov.au. Accessed 11 October 2026.
US Food and Drug Administration. The drug development process. Step 3: Clinical research. fda.gov. Accessed 11 October 2026.
International Council for Harmonisation. ICH E8(R1): General considerations for clinical studies. 2021. database.ich.org. Accessed 11 October 2026.
Therapeutic Goods Administration. Australian clinical trial handbook. tga.gov.au. Accessed 11 October 2026.
World Health Organization. International Clinical Trials Registry Platform (ICTRP). who.int. Accessed 11 October 2026.
National Health and Medical Research Council. National Statement on Ethical Conduct in Human Research (2025). nhmrc.gov.au. Accessed 11 October 2026.
Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics. 2019;20(2):273–286. doi:10.1093/biostatistics/kxx069. PMID: 29394327
Therapeutic Goods Administration. Fast track approval pathways. tga.gov.au. Accessed 11 October 2026.
US Food and Drug Administration. The drug development process. Step 5: FDA post-market drug safety monitoring. fda.gov. Accessed 11 October 2026.
Therapeutic Goods Administration. Understanding your responsibilities when importing, compounding and supplying unapproved peptide products. Safety advisory, 13 April 2026. tga.gov.au. Accessed 11 October 2026.
Umscheid CA, Margolis DJ, Grossman CE. Key concepts of clinical trials: a narrative review. Postgrad Med. 2011;123(5):194–204. doi:10.3810/pgm.2011.09.2475. PMID: 21904102

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