Phase Four Clinical Trial: What's It All About?

Often we hear a lot about the first three clinical trial phases. These include the first treatment trials on people (phase I), testing for efficacy and side effects (phase II), and evaluating the effectiveness of new treatment against current options (phase III).

Phase four examines already FDA-approved treatments according to long-term safety. Keep reading to learn what this stage is all about.

What is a clinical trial?

A clinical trial is a well-controlled research process that involves human volunteers as participants. Clinical trials test new drugs. All new treatments must go through clinical trials before they are approved. A trial may also test medical devices or already regulatory approved drugs, looking at their long-term impact. 

Where does phase IV fit in the clinical trial process?

The clinical trial process begins after laboratory or pre-clinical trials. Laboratory studies have two phases.

1. Cell studies: These are the preliminary tests done on a new drug or drug combination. Researchers test the drug on a group of animal or human cells and note its effects. For instance, in the case of cancer treatment, the researcher may use human or animal cancer cells.

2. Animal studies: After the cell studies are completed, researchers move on to the second part of pre-clinical trials, where they test the new drug on live animals. This phase reports the safety of drugs, drug combinations, or medical devices as observed on a living animal.

Laboratory studies give tons of useful information, but it doesn’t stop there. Animals and humans have important physiological and metabolic differences. How you absorb and eliminate drugs from your body is very different from rats and mice (which are the most commonly used animals in preclinical trials). This is why clinical trials become necessary.

When pre-clinical trials are done, and the results look promising, the next phase requires FDA approval.

After laboratory studies, the researchers need to apply for IND2 (investigational new drug) approval from the FDA to begin human trials. The IND form has the following information:

1. Who makes the drug? What's in it? Is it stable? Where and how is it made?

2. Whether the drug is safe to test on humans.

3. Study protocols, which are details about the study which assess the risks involved.

4. Evaluation of the clinical team and their qualifications to run the clinical trials.

The research sponsors must sign a form, which states that they must get informed consent from all clinical trials participants. They must also allow the IRB (Institutional Review Board) to review the clinical study and ensure that all rules governing clinical trials get followed.

Once the researchers receive IND approval from the FDA, the clinical trials can start.

Clinical trials come in five phases, four of which are compulsory. Each stage provides necessary information for future phases.

Phase 0

The first phase of clinical trials determines whether or not a drug works and how it works. Then, treatment will be given to a small group of healthy people at low doses.

The point of this phase is to save time and money and speed up the approval process by showing that the drug does what it's supposed to and that it’s safe for human consumption. This phase is not always mandatory.

Phase I

The primary clinical trial stage, phase I, tests the treatment’s safety. In addition, it addresses whether or not there are any immediate side effects, and if so, their severity.

This phase also studies the highest treatment dose that may be given without causing side effects and the best way to administer the new treatment.

Phase II

This stage shows whether or not the treatment works. The main point is to see whether participants benefit from the treatment according to its claimed purpose.

Phase III

During this stage, the effectiveness of the new drug gets compared to already existing treatments.

A key feature of phase III clinical trials is randomized and double-blind studies. Participants are picked at random, and neither doctors nor patients know who received the trial drug.

At this point, the researchers may submit the drug for NDA (new drug application) approval from the FDA, which reviews all the findings from the trials and other relevant sources.

Based on this information, the FDA may approve the drug for use in patients with that particular disease.

Phase IV

In phase IV, the drug and its effects are monitored over a long time to assess its full effects. Thousands or even millions of participants are watched for rare side effects and studied to determine whether the drug delivers on its intended purpose.

Generally, how many clinical trials make it to phase IV?

Approximately 25-30% of drugs make it to phase IV clinical trials.¹ This low percentage correlates to challenges like unnecessary risk exposure in the primary drug testing phases, underqualified researchers, insufficient information when seeking participant consent, evidence of coercion, and lack of enough information about the drug's risks.

The lowdown

Clinical trials are an important process of drug research. They help us know which drugs, drug combinations, and medical devices are safe to use and how effective they are compared to already existing treatment options.

If you want to join a trial, you don't have to start from the beginning in phase one. A phase four clinical trial can be the safest way to volunteer for clinical research, as the treatment has already been given to a large number of people.

Search for your condition here to see which clinical trials you may be eligible for.