In previous years, pharmacology and clinical trials were topics which mainly interested medical professionals, rather than the public. However, as a result of the COVID-19 pandemic, there has been a growing interest in clinical trials, alongside the development of the vaccine. As a global community, we have been able to see the development, testing, and production of life-saving vaccines, almost in real time.
The quick turnaround on the Coronavirus vaccine was in part due to decades of research into similar viruses, and how to treat them. But the speed of the process sparked a great deal of interest in how vaccines and similar treatments are tested and developed.
Our experts at Simbec-Orion were keen to provide some insights into critical Phase 2 and Phase 3 clinical trials, as well as the process of taking a drug from its initial research, to the market.
Read on to discover more about the phases of clinical trials, and the key differences between them. Why not read more about how new drugs are developed and tested?
Types of Clinical Trials: An Overview
Pre-clinical Trials
Once a drug has been developed, it’s vital that any potential risks are evaluated on non-human subjects first. These are known as preclinical trials.
Preclinical trials can be conducted in a variety of ways, including digital simulation, where we apply what we already know about similar drugs and their effects on the body to make predictions about the new drug.
The drug may also be tested on small samples of human tissue, such as skin cells or stem cells, to gather data on its effects without posing a risk to an actual person. If these tests are successful, researchers will begin testing the drug on animals to determine its effects on living, organic beings.
If all preclinical trials are a success and the drug poses no obvious risks, researchers will move on to human clinical trials. Clinical trials are performed in phases, with the goal of determining whether a drug is safe to use on humans, and whether it is effective enough to be made available on the pharmaceutical market.
Human clinical trials normally consist of four stages. Researchers test the drug on different groups of people to make determinations about the appropriate dosage, the efficacy of the drug (how well it treats symptoms), and most importantly, flagging any potential side effects that users may experience.
Even commonly available over-the-counter medicine can cause side effects, such as dizziness or headaches, but this doesn’t mean that they are unsafe. Clinical trials allow researchers to be made aware of these side effects early, and make them clear to anybody who plans to administer or use the drug. This allows medical practitioners and consumers to make informed decisions about whether they wish to prescribe, or take, certain drugs.
What are Phase 1 clinical trials?
Phase 1 clinical trials involve testing a new drug on a small group of healthy participants – people with few or no underlying medical conditions, who are in good health and are reasonably fit. The groups may vary in size, but typically consist of between 20 and 100 participants who will test the new drug or vaccine.
The main goals of a Phase 1 trial are to determine the correct dosage of a drug, and most importantly, whether it causes any unexpected side effects or reactions in healthy participants.
Researchers may experiment with different dosages of the active compound or drug, as well as different ways of administering it (for instance, as a pill or an injection). They will also supervise participants closely over the course of the trial to see how and if the drug affects them.
Using healthy participants at this stage allows researchers to determine the effects of the drug on the average person’s body. It also means that any changes seen in participants have a better chance of being attributed to the drug, rather than being due to other factors like poor health or unrelated medical conditions.
What are Phase 2 clinical trials?
If the Phase 1 trial is considered a success, the drug will then progress to Phase 2 clinical trials. Phase 2 trials typically involve larger groups of participants, who have the condition that the drug or vaccine is intended to treat. Rather than sample sizes of under 100, Phase 2 clinical trials will typically involve hundreds of participants.
Whereas Phase 1 is used to determine the effects of the drug on healthy participants, Phase 2 trials focus more on the efficacy of the drug, or how effectively it can treat the condition in humans that are affected by it. In Phase 2, researchers will watch carefully for signs of improvement, as well as any unexpected side effects, as they did in Phase 1.
Researchers will also take note of how different dosages affect participants, in order to maximise the benefits of the drug, while minimising any potential risks. This is a crucial stage of any drug development process, as it is when researchers are able to see whether their hypotheses about certain compounds being effective in the treatment of a specific medical condition can be substantiated.
What are Phase 3 clinical trials?
If the results of the Phase 2 clinical trials of the drug are considered successful, researchers will progress to Phase 3. Phase 3 clinical trials are similar to Phase 2, but happen on a much larger scale.
Phase 3 trials are still conducted on a group of participants who have the condition the drug is intended to treat, but may involve a thousand or more participants, rather than hundreds. The size of the study will normally be reflective of how many members of the population the condition impacts. Conditions which are more common tend to have more funding, and a better chance of finding large numbers of participants.
Another key feature of Phase 3 trials is that the results and data collected on the drug’s efficacy will be compared to the other treatments currently available on the market. If the drug is shown to be effective, safe, and at least as beneficial to patients as other available treatments, it is likely that it will be approved for mass development and distribution.
Phase 3 clinical trials may also involve a test group and a control group, wherein half of the participants are administered with the drug, whilst the other half receive a placebo – a vaccine or pill that has no active medical compounds.
This is to ensure that the benefits felt by participants, when they are self-reporting, are based on the actual effects of the drug. In some cases, when participants are aware that they are receiving treatment, they may perceive certain effects or improvement of their symptoms whereas in reality, there are none. This is commonly known as the ‘placebo effect’.
If the Phase 3 clinical trials are a success, the drug, vaccine, or treatment will often be approved for distribution and in the following months or years, will hopefully be released to the public.
Interested in learning more about phase 3? Read our blog on ‘why drugs fail in phase 2 clinical trials‘.
What are Phase 4 clinical trials?
Phase 4 clinical trials take place after the drug has been released to the market. The purpose of Stage 4 clinical trials is to monitor and evaluate the long-term effects of the drug, and whether there are any side effects that were not apparent in the Phase 2 and Phase 3 clinical trials.
Although the drug has already been through rigorous testing and deemed safe for the public, it’s important to monitor the ongoing effects it has on different age groups, body types, and more. These trials help us to examine the longer-term benefits of the drug, and how it can be used to treat patients after months and years, rather than just in the initial few months of treatment.
Phase 4 clinical trials are also useful for seeing the effect these drugs can have on people with multiple medical conditions, who may need to take more than one prescription drug at a time.
Learn more about the phases of clinical trials in our guide: what are the three main stages of clinical trials?
What’s the difference between Phase 2 and Phase 3 clinical Trials?
The key differences between Phase 2 and Phase 3 clinical trials are:
- Sample size: Phase 2 clinical trials normally use between 100 and 500 people, whereas Phase 3 clinical trials will include between 500 and 3000 participants, on average.
- Length of study: Phase 2 clinical trials last on average about 2 years, whereas Phase 3 clinical trials are often much longer – from 2.5 years upwards.
- Goal of the trial: The main goal of Phase 2 trials is to make determinations about appropriate dosages and the effects of the drug on those affected by the condition being treated. Phase 3 clinical trials have the same goal, but researchers will also compare the data with other comparable treatments available on the market to determine the overall efficacy of the drug.
Can Phase 2 and Phase 3 clinical trials be done at the same time?
There have been instances in some clinical trials where phases 2 and 3 have been performed simultaneously, and the results and data aggregated. In medical journals, you may see phrases like “Phase2/3” or “Phase II/III” used to denote this.
Phase 2/3 trials are an adaptive trial design, which can benefit both researchers and participants by reducing the overall length of the study, and reducing the number of individual participants needed. This trial design is accepted by the medical community, although some researchers and experts favour the traditional style wherein Phase 2 and Phase 3 trials are separated.
The benefits of conducting Phase 2 and Phase 3 clinical trials separately is that findings from Phase 2 can be examined, and then used to improve both the planning and execution of the Phase 3 trials. However, both clinical trial models are valid within the medical community, and each has its own benefits which may make it more suitable for the type of trial being conducted.
We hope that this article has helped you to have a better understanding of the differences between Phase 2 and Phase 3 clinical trials. As a world-leading CRO, we appreciate the opportunity to share insights into the world of clinical pharmacology and development.
If you’d like more resources relating to clinical trials, the study of disease, and much more, we have a wide range of resources available. From clinical white papers to free webinars, we’re proud to be able to offer articles from our outstanding clinical pharmacologists and researchers at Simbec-Orion.
To discover more about our clinical development and laboratory services, feel free to visit our website. And if you would like to learn about Simbec-Orion’s efforts to help tackle the Coronavirus outbreak, feel free to read our company update about how to maintain an agile and collaborative approach during the COVID-19 Pandemic.