Clinical trials involve a series of studies that test the safety and effectiveness of drugs and other medical treatments. To ensure research is carried out thoroughly and safely, there are several different stages of clinical trials.
In order to make sure the treatment is safe and effective for use in patients, it must successfully pass through every clinical trial phase.
Each phase is designed to assess the safety and/or the efficacy of the treatment in different ways, testing treatments firstly on a smaller number of healthy volunteer participants, progressing onto larger sample groups, involving patients.
There are typically 3 main stages of clinical trials: phase 1, phase 2 and phase 3. Some trials involve pre-clinical study phases (phase 0), and post-clinical study phases (phase 4).
Different Phases Of Clinical Trials Explained
The three main stages of clinical trials are designed to ensure the treatment undergoes thorough testing before it is made available to patients. By staging the trial across different phases, researchers are able to determine whether it is safe to progress to the next stage of testing and, finally, safe to push to market.
Each stage of clinical development is governed by strict regulations to make sure no treatment progresses through research stages without being approved for safe use.
Early phases test the treatment on smaller numbers of participants, where researchers are able to identify any general adverse reactions or side effects. Later phases test on larger population groups, where researchers can identify any long term or previously unknown side effects.
As well as participant group size, there are several other major differences between each phase.
Some trials involve a pre-clinical study phase, often referred to as phase 0. This phase takes place at the earliest stage of research before the main study begins.
Phase 0 is unlike the main three stages of clinical trials (phases 1 to 3), in that only a small sample of the treatment is tested on a very small number of volunteers – usually around 10 people. The purpose of pre-clinical phases is to ensure that the small dosage of the drug results in no harm to humans before the research continues using larger doses in the main study phases.
Pre-clinical phases are not always used, and are not a requirement for testing new drugs. Circumstances where phase 0 trials may be used could be to test if a treatment can successfully reach tumours during oncology research, or to see how the human body reacts to the drug.
This early phase can help speed up the drug approval process, with additional supporting data to showcase the safety and effectiveness of the treatment.
Phase I: Safety
Phase 1 is the first main stage of the clinical trial process. For treatments that have not undergone a pre-clinical phase, phase 1 research will be the first time the treatment is tested on human volunteers – often referred to as first-in-human (FiH) studies.
Phase 1 trials are carried out in order to test the general safety of the new treatment. During this first phase, researchers will test different dosage levels in human participants to determine how much of the drug or treatment can be administered safely without adverse effects.
Testing is carried out on a small number of volunteers (usually around 20 to 80 people). During this initial phase, volunteers are healthy individuals, rather than patients with the relevant condition. This is to firstly ensure that the new treatment is generally safe for use in the human body and that there are no major safety issues.
In phase 1 clinical trials, researchers may be able to identify some of the potential side effects that may occur when taking the new treatment. Participants are given a low dosage of the test treatment to begin with and are monitored very closely.
If there are very few, or no side effects that occur with the low dosage, researchers then give a higher dosage to the following set of participants. This enables researchers to identify the optimal dosage that has the fewest side effects. With enough data to support the treatment’s general safety, the study can continue through to the next phase of research and test on more volunteers.
Around 70% of test treatments in phase I are approved for the next clinical trial phase.
Phase II: Efficacy
When a drug or treatment is evaluated as safe and approved for testing beyond phase 1, the research can progress through to phase 2.
Phase 2 clinical trials are designed to test whether the treatment actually works, whilst continuing to assess its safety. Since the first phase has approved the general safety of the drug, phase 2 trials involve more volunteers – usually several hundred.
During the second phase, researchers will assess how well the treatment delivers its intended effects. The intended effects might not always be to cure the condition. The intended effect could be to prevent further spread of the condition, or even to provide a better quality of life for the patient by relieving certain symptoms.
To assess how well the treatment works, researchers will determine an exact intended effect and measure how well the drug meets this need.
Unlike phase 1, this part of the research involves volunteer patients who suffer from the condition in order to analyse the treatment’s interactions with the condition. Research in this phase can take place over the course of several months, or in some cases, years.
At this stage, patients can directly benefit from taking part in the trial, as it is possible that the treatment may start to show positive impacts on the test condition. Some doctors may even suggest clinical trial participation as an alternative treatment for patients with certain conditions.
With a larger volunteer group and a longer period of time having passed, phase 2 research helps uncover potential side effects that may not have been present during phase 1 trials. However, the volunteer sample size is still not large enough at this point to determine the overall safety of the medication, and it is not until phase 3 that a more definite evaluation of safety can be established.
Around 33% of treatments are approved to progress beyond the phase 2 stage.
Phase III: Comparison & Side Effects
When the treatment is approved for research beyond phase 2 trials, development continues through to phase 3.
The purpose of this third phase is to evaluate the effectiveness of the new treatment in comparison to the best available current treatments for the same condition. In order to progress beyond phase 3, research must show that the new treatment is at least as effective and safe as current treatments. This helps demonstrate whether the new treatment is useful for a specific population.
Phase 3 trials provide the largest amounts of safety data. Studies in this third phase are longer in duration and involve hundreds, if not thousands, of participants. This means that results are much more likely to display any rarer side effects that did not appear in the earlier phases of research, as well as evaluate effectiveness across a more reliable sample size.
Treatments that demonstrate effectiveness and safety throughout this phase will be eligible for regulatory approval, which if successful, allows the drug to enter the market and become available for doctors to prescribe.
This extensive testing means that only around 25-30% of all the drugs in the clinical development processare approved to finally make it on to the market.
Post Market Safety Monitoring
Phases 1 to 3 are considered the main three stages of clinical trials and involve the largest amounts of research. However, beyond this, researchers continue to monitor the treatment after the drug has gone to market.
This final stage of monitoring is often referred to as phase 4, or the post-market safety monitoring phase. At this point, the test treatment has undergone regulatory approval for use and is available for doctors to prescribe to their patients.
Even after years of clinical trial research and regulatory approval, the safety of the drug is still a main priority for Clinical Research Organisations (CROs). For instance, researchers will monitor whether there are rarer side effects that were not present during the main trial phases, or whether side effects appear after a much longer period of taking the medication.
The Phases Of Clinical Trials: Summary
Clinical trials are phased across three main stages in order to test new treatments thoroughly and identify possible safety issues. In summary, the purpose of these three main phases are:
- Phase 1 is the first stage of research, testing for general safety with a small volunteer group.
- Phase 2 tests how well the treatment works on a larger volunteer group.
- Phase 3 evaluates how effective the treatment is in comparison to current treatments.
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