Phases of Clinical Research: A Detailed Overview
Clinical trials are studies involving human volunteers to research ways to prevent, detect, and treat various medical conditions. The goal is to identify safer, more effective methods of treating illnesses using new drugs or new combinations of existing drugs.
A clinical trial investigating a drug or therapy is typically divided into four phases: Phase I, Phase II, Phase III, and Phase IV. Each phase has a different purpose in testing the treatment’s safety and efficacy. This article explores how the clinical research phases protect study volunteers from harm and ensure new drugs and therapies are developed effectively.
The Importance of Clinical Research in Medical Advancements
Researchers use clinical trials to test a drug’s or other medical treatment’s safety and efficacy. Most modern medicines were developed from clinical trials, and clinical trials remain essential for drug development.
Without clinical studies, our global understanding of medicine would likely stagnate, and novel treatments would cease to emerge. Currently incurable diseases would remain so, without any improvements made to existing drugs and therapies.
Therefore, clinical research is a fundamental aspect of medical advancement. It is the best way for scientists to fully observe and analyze how drugs interact with the human body, and their efficacy as treatments for disease. Clinical trials also allow researchers to further their understanding of specific diseases, which may help identify new potential angles for treatment.
The Phases of Clinical Trials
Clinical trials studying drugs or treatments take place in four main phases. Each phase includes specific elements to ensure participant safety, experiment accuracy, and reliable results.
Phase I: Safety Evaluation
The objective of a Phase I clinical trial is to assess a potential new treatment’s safety, side effects, and dose. Some Phase I trials are also first-in-human (FIH) studies, meaning the treatment has not previously been tested in people.
The aim of a Phase I trial is to determine:
- Whether the treatment is safe to give to humans
- Potential treatment side effects
- In drug trials: how much of the drug is safe to give, and what happens to the drug within the body
Phase I clinical research is usually performed on a small number of healthy participants. These trials typically begin with the administration of a very low dose of the investigational treatment. If the treatment does not produce unacceptable side effects, researchers may increase the dosage.
During the study, researchers observe and record any side effects related to the investigational treatment, along with their severity and dose-dependence. Researchers also look for indications of the treatment positively affecting the target illness.
Phase II: Efficacy and Side Effects
Once an experimental treatment is determined successful in Phase I, it can enter the second phase of clinical testing. The goal of Phase II is to further investigate the safety and effectiveness of the experimental treatment. These studies typically involve a larger group of participants than Phase I (usually 100 – 300 patients), all of whom have the condition the study therapy aims to treat.
Phase II trials usually determines:
- Whether the treatment is safe to give to humans
- Which doses of the treatment are safe to give to humans
- What side effects are associated with the treatment (and how to manage them)
- Whether or not the treatment is effective
- The safety and effectiveness of the new treatment compared to existing treatments
Participants in Phase II clinical trials are usually given the highest “safe” dose of the treatment identified in Phase I. They are then monitored for side effects and signs of effective treatment.
In some Phase II trials, participants are divided into two or more groups. One group may receive the standard treatment for their condition, while others receive the treatment under study. Sometimes, different groups are given different doses of the same therapies.
Comparing the treatment outcomes of these different groups allows researchers to assess the effectiveness of new vs. existing therapies. It also furthers their understanding of the experimental treatment’s dose-dependent outcomes (i.e., the effect on illnesses and side effects each dose may produce).
Phase III: Confirming Safety and Effectiveness
The purpose of a Phase III trial is to find out if the treatment under study is more effective than currently available therapies.
Phase III trials are performed on a larger population sample than Phase I or Phase II, usually involving anywhere from 300 – 3,000 participants. These patients are often divided into random groups to receive different doses and combinations of treatments. This allows researchers to investigate:
- How effective the treatment is compared to standard treatments
- How effective the treatment is at different doses
- The type, frequency, and severity of side effects associated with new vs. existing treatments
- How the treatment affects a patient’s quality of life compared to standard treatments
Drugs performing well in Phase III trials are often put forward for government regulatory approval. Approval confirms the experimental drug or therapy meets the government’s standards for safety and efficacy, and can be used to treat patients outside of clinical trials.
Phase IV: Post-market Surveillance
Phase IV clinical trials, also known as post-marketing or therapeutic use studies, are performed on already tested and approved drugs.
These studies are used to investigate rare but serious side effects the new drug or therapy causes. This is important because side effects affecting very few people (for example, 1 in 1000 people) may not always emerge during a Phase III trial. However, such effects can appear more frequently once a treatment is approved for use among the general population. It is crucial for researchers to engage in ongoing study of the drug so they can identify and manage any serious side effects in participants.
During a Phase IV trial, researchers will observe:
- The frequency and severity of rare side effects in the general population
- The safety of the treatment for those who experience rare side effects
- The long-term risks and benefits associated with the treatment
- The efficacy of the treatment across a larger population sample size
- The risks and benefits of the treatment at different doses
- The risks and benefits of the treatment in combination with other treatments
The Role of Clinical Research in Improving Quality of Life
Clinical research has been a cornerstone of medicine for millennia, with the earliest clinical trial recorded around 500 BCE. The knowledge generated by clinical trials has vastly improved humankind’s quality of life through the development of disease management and prevention strategies.
Disease management strategies are treatment plans aiming to manage the symptoms of chronic illnesses. They often involve a combination of therapeutic drugs and lifestyle changes. Clinical research contributes to the development of disease management plans by providing a platform for testing and developing new therapies. Successful therapies can significantly improve quality of life among patients with incurable conditions by reducing symptoms and even improving life expectancy.
Clinical trial data is also important for disease prevention. For example, current prevention research includes the development of vaccines against diseases caused by Zika and Ebola viruses. Other preventative strategies can help doctors to detect diseases before they become life threatening.
Clinical trials are essential to developing new and better drugs and therapies. Clinical trial findings allow doctors and scientists to explore new avenues for disease treatment, management, and prevention.
Clinical research has paved the way for modern medicine, allowing people to live longer, more comfortable lives than at any other point in history. Medical research continues to develop new, more effective treatments for prevalent and serious illnesses like cancer, Parkinson’s disease, and immunological disorders. In the future, clinical trials could produce novel preventative strategies (like vaccines) against disease, as well as early-detection procedures and possible cures for currently untreatable illnesses.