Phase 0 Clinical Trials: What They Are and Why They Exist

When people read about clinical trials, they usually hear about Phase I, Phase II, or Phase III studies. Those are the stages where a new drug is tested for safety, then to see if it works, and then in large numbers of patients before it can be approved. For a small number of drugs, there is an even earlier kind of study. It is called a Phase 0 clinical trial.

A Phase 0 clinical trial is a very small, very short study that tests a new drug in people at doses much lower than would ever be used for treatment. Its goal is not to treat anyone. The goal is to answer a specific research question about how the drug behaves in the human body, so that researchers can decide whether to continue developing it. Phase 0 trials usually involve only 10 to 15 participants and were created under a pathway the U.S. Food and Drug Administration (FDA) set up in 2006 for very early studies.

What a Phase 0 Clinical Trial Is

A Phase 0 study is the first time a new drug is given to people in many cases, but at a dose that is far too small to produce the effect the drug is eventually designed to have. If a normal medicine dose might be compared to a teaspoon, a Phase 0 dose might be compared to a few drops from an eyedropper. The exposure is also very brief, often a single dose or a short course over just a few days.

Because the dose is so small, a Phase 0 trial is not designed to treat the participant's condition. Researchers explain this clearly and upfront to anyone considering the study. Participants are contributing to the early research that helps decide which drug candidates move forward. They are not receiving a new therapy.

Phase 0 trials are one of several kinds of clinical trial, and the earliest of them. Learning how clinical trials work in general makes it easier to see where a Phase 0 study fits in and what makes it different from others.

Why Researchers Run Phase 0 Trials

A new drug has to go through many stages of testing before it can become a treatment. Those stages are expensive, and more than nine out of ten drug candidates never make it to approval. Researchers want to find out as early as possible whether a new drug is worth continuing to develop, which is the problem Phase 0 is designed to help with.

In a Phase 0 study, researchers ask specific questions about what the drug does inside the body at very small doses. They might ask whether the drug reaches the right part of a cell, whether the body absorbs it the way they hoped, or whether it behaves similarly to how it did in earlier animal testing. The answers help researchers decide whether to keep developing the drug or stop and redirect resources somewhere else.

Phase 0 trials can also be used to compare several candidate drugs that are being developed for the same purpose. Giving tiny doses of each one to a small number of people can show which candidate looks most promising, helping researchers pick the best one to move into a Phase I trial. Even when a Phase 0 study does not directly help any individual participant, the information gathered from it feeds into the long process by which new treatments advance into medicine.

How Phase 0 Fits Among the Phases

Most clinical trials follow a familiar sequence:

• Phase I: the first careful test in people, usually a few dozen participants, focused on safety and finding the right dose.
• Phase II: a study with a larger group, usually a few hundred participants, to see if the drug actually works for its intended purpose.
• Phase III: a large study, often with thousands of participants, comparing the new drug to existing treatments before it can be approved.
• Phase IV: long-term studies after the drug is approved, watching how it performs in wider everyday use.

Phase 0 comes before all of these. It is a much smaller and shorter study than a Phase I trial, and it uses much lower doses. Importantly, a Phase 0 study does not replace Phase I. If a drug's Phase 0 results are encouraging, the drug still has to go through a Phase I trial for safety and dosing, and then through the later phases, before it could ever become an approved treatment.

Not every new drug has a Phase 0 trial. Most drugs move directly from laboratory and animal testing into a Phase I study. Phase 0 is used only when researchers have a specific early question they want to answer before committing to a full Phase I program.

Who Joins a Phase 0 Trial

Most Phase 0 trials to date have been done in cancer drug development. In these studies, participants are often patients whose cancer has not responded to standard treatments and who are exploring research options. Some Phase 0 trials use healthy volunteers rather than patients, particularly when the study is focused on how the body absorbs and processes a new drug.

Whether patient or healthy volunteer, everyone who joins a clinical trial as a volunteer goes through the same basic protections: a written informed consent process, a safety review by an independent committee, and the right to ask questions and withdraw at any time.

The independent committee is called an Institutional Review Board, usually shortened to IRB. Before a Phase 0 study can open, the IRB reviews the plan to make sure the risks to participants are reasonable compared to the knowledge expected to come out of the study. The IRB also reviews how participants will be informed, how their samples will be handled, and how their rights will be protected throughout the study. This is the same kind of oversight that applies to any clinical trial.

What to Know If You're Considering One

A Phase 0 clinical trial asks for a particular kind of contribution, and it helps to understand what that contribution involves before deciding whether to take part.

Tissue samples are often required. For Phase 0 cancer studies, this usually means a biopsy, which is a procedure in which a small sample of tumor tissue is taken for analysis. Biopsies carry real risks, and the study team explains those risks during the consent process. If you cannot or do not want to undergo the procedure, a Phase 0 trial may not be the right study for you.

The time commitment is usually short because Phase 0 studies are brief, but there are still clinic visits, tests, and follow-up. The research team will walk you through everything the study requires so that you can weigh the time and effort against your own schedule and health needs.

One protection built into well-designed Phase 0 studies is that participation is meant not to block your access to other trials. The waiting time between trials, called a washout period, is typically kept short on both sides of a Phase 0 study so that participants can still join other research that might offer a treatment benefit afterward. If you are considering a Phase 0 trial while also researching other studies, ask the research team directly how participation could affect your future options.

As with any clinical trial you are considering, it helps to walk in with a list of questions to ask before joining the study. Good questions cover why this particular study is being run, what the possible risks are, what the time commitment looks like, whether there are any costs to you, and what happens after the study ends.

Next Steps

Phase 0 trials are rare and specialized, and they are most commonly found in cancer research, so most people researching clinical trials will not encounter one. But if you do come across a study described as Phase 0, knowing what that label means helps you ask the right questions and decide whether to take part.

If you are thinking about joining a clinical trial of any phase, the first step is finding studies that might be a match for your condition. DecenTrialz helps with that part. You share some basic information about yourself and your health, get matched with trials that could fit, and talk to a nurse who walks you through what each study involves before you decide whether to sign up. The research team running the study makes the final decision on who can take part, but DecenTrialz makes it easier to find and enroll in a clinical trial that may be right for you.

It also helps to talk with your own doctor, especially if you are receiving active treatment for a condition, before deciding to take part in any research study. You can learn more about DecenTrialz at decentrialz.com.