Introducing Clinical Trials: Phase 1-4 explained

This blog article provides information about various clinical trial phases for patients and caregivers who are discovering treatment options that may be available in clinical trials, the second article in our ‘Introducing Clinical Trials’ blog series, the first of which discussed ‘Safety information to consider’. And the third blog is ‘How to find clinical trials for cancer’.

Clinical trials are initiated once a drug or other type of treatment has been evaluated in a preclinical study. Preclinical studies are laboratory studies that use cultured cells and animals, providing useful information about a potential treatment.

As explained in our previous blog post, a clinical trial is a research study that people volunteer to take part in, that must be approved by a regulatory body, such as the FDA. Many important questions can only be answered with clinical trials, such as the following:

• Is the treatment safe in humans?
• Does a new treatment work inside the human body?
• Does a new treatment work better than current treatments?
• What side effects does the new treatment cause?

Answering these questions helps regulatory authorities decide whether a new treatment is safe and effective for use and should be approved. In addition to treatments or drugs, clinical trials may also test new ways of diagnosing disease or to see if certain lifestyle changes can prevent disease.

Clinical trial phases

New treatments, such as medicines, progress through a number of phases of a clinical trial before becoming approved treatments. These are Phase 1 (I), Phase 2 (II), Phase 3 (III) and Phase 4 (IV). Phase 0 trials are only used in some cases. Clinical trials are sometimes combined as Phase 1/2 and Phase 2/3. The phases of clinical trials differ in terms of how many participants are included and the type of research questions being answered. The stepwise progression of clinical research through phases is designed to keep participants as safe as possible.

Phase 0 clinical trials

Phase 0 trials take place before Phase 1. Phase 0 trials are a less widely used type of study used on a very small number of people to help researchers determine if the drugs perform as expected inside the human body. This can potentially speed up the clinical research process. For example, a Phase 0 trial may find out if a cancer drug reaches cancer cells or where the drug goes in the body. A very low dose of a drug is used in Phase 0 on a very small number of people to check that it is not harmful. Phase 0 studies may not help the person enrolled but will benefit other people in the future.

Phase 1 clinical trials

Phase 1 trials are focused on safety and finding the best dosage of a treatment. This helps doctors learn the best way to administer the medication, how often it should be given, which dose is best, and what side effects may occur. Phase 1 trials usually include a small group of patients divided into cohorts and, the study usually lasts for less than a year. Doctors want to monitor how the drug behaves inside the body and to do this, they collect blood or urine samples to measure drug levels at certain time points.

The first cohort receives the lowest dose of a drug and if they do not have severe side effects, the next cohort will receive the drug at a higher dose. Doctors will test increasing doses of the drug until they determine the dose most likely to work without severe side effects. Patients in Phase 1 trials are monitored to see if they are responding to the treatment, but Phase 2 will collect more data about how well the drug works on the disease.

A treatment progresses from Phase 1 to Phase 2 once it is determined that it is safe. If one or more serious adverse events occurred in the Phase 1 trial, the local government regulator might not allow the treatment to enter Phase 2. Serious adverse events include toxic, undesirable, or unwanted effects that cause danger to health or death. According to the FDA, about 70% of drugs move on to Phase 2.

Phase 2 clinical trials

Phase 2 trials check how well the treatment works on the disease and study any side effects. Phase 2 trials usually include up to 100 patients and last from a few months, to two years. Data collected in Phase 2 will help researchers design Phase 3. Treatments move to Phase 3 if they are shown to work in Phase 2. Researchers use different techniques to determine whether the treatment works. For cancer treatments, researchers may look for whether a tumor shrinks, whether patients live longer or whether an improvement in quality of life is shown. The FDA states that approximately 33% of drugs move from Phase 2 to Phase 3.

Phase 3 clinical trials

Phase 3 trials test how well the treatment works compared to the placebo or the standard treatment, which is the treatment widely used for the condition. Doctors also learn whether the new treatment has more or fewer side effects than the current standard treatment. In some cases, a treatment under investigation in Phase 3 will be compared to a placebo. Phase 3 trials enroll hundreds to thousands of participants from across a country or multiple countries and usually last for one to three years.

Patients in Phase 3 clinical trials are divided into groups. The control group receives the standard treatment (or placebo if used). The study group (treatment group) receives the new treatment being tested. There may be more than one study group involving different drug combinations. If a placebo is used as the control, this will not contain the medication, but it will look the same and be given in the same way as the new treatment being tested. For cancer clinical trials, a placebo is rarely given alone. A new cancer treatment will be given alongside the standard cancer treatment for the study group and the control group will receive standard treatment and placebo.

The participants in Phase 3 trials are usually randomly assigned to groups by a computer to help avoid bias. It is better for patients and doctors not to know which treatment they are receiving as this can affect their behavior and impact study results. A double-blind study is when both the doctors and patients do not know which group patients are assigned to. The results of Phase 3 clinical trials are reviewed by regulatory authorities, such as the FDA, to ensure the treatment is safe and effective and, also to decide if the treatment should be approved and available to all patients.

Phase 4 clinical trials

Phase 4 trials investigate the long-term benefits and side effects of a treatment that has already been approved. Researchers may use Phase 4 clinical trials to study taking medication at different doses or times or to study how it works in children or older adults.

Who can join a clinical trial?

People with certain diseases or health problems may be eligible for clinical trials. The researchers who design the trials set rules about who can enter. Eligibility may depend on age or the presence of other medical conditions. You may need to answer questions or have a medical exam to see if you are eligible. Some clinical trials enroll healthy people who do not have a disease or condition. Certain clinical trials enroll people who have family members with certain diseases or conditions.

The potential benefits of enrolling in a clinical trial

If you have a disease and do enroll in a clinical trial, you may potentially benefit from the chance to receive a new treatment earlier than the general public. People who enroll in clinical trials can also benefit from having their disease followed closely by doctors who are experts in that area of medicine. Clinical trials are a way for a person living with a certain disease to help contribute to research and widen understanding about that disease. As a healthy volunteer, enrolling in a clinical trial is a way to help others, learn about medical research, and learn more about your health.

The potential risks and downsides of enrolling in a clinical trial

Since the treatment is still under investigation, a person enrolled in a clinical trial may experience unexpected side effects. A drug that has made it to clinical trials is not guaranteed to work. Drugs can behave differently in humans than they did in animal tests and cell cultures. Clinical trials may end up showing that the new treatment works less well than the standard treatment normally used.

Phase 1 clinical trials carry the most potential risk, but they can be the right choice for patients who have exhausted all other treatment options. In Phase 3 trials, when two treatments are compared, it is important to be aware that you don’t get to choose whether you get the new treatment or the standard treatment (or placebo if it is used).

Deciding if a clinical trial is right for you

Enrolling in a clinical trial is a personal decision. You will have to weigh up the risks and benefits to your health and consider how it may impact your life in other ways. You do not pay to be in a clinical trial, but you or your insurance may be billed for treatments, tests, or other healthcare that you need during the trial. There may be other considerations such as travel or childcare costs if you enroll. You should discuss all the questions you have with your treating physician before deciding to enroll in a clinical trial.

We hope this blog helped explain the various clinical trial phases. Look out for our next and last blog in the series which takes a closer look at cancer-specific clinical trials and how to find them.

To learn more about possible clinical trials and get help finding clinical trials, schedule a call with a myTomorrows Patient Navigator. Find out more here

The information in this blog is not intended as a substitute for a medical consultation. Always consult a doctor before receiving a diagnosis or treatment.

The myTomorrows team
Anthony Fokkerweg 61-2
1059CP Amsterdam
The Netherlands