Clinical trials are studies involving human volunteers to research ways to answer specific health questions or medical conditions. They look at new ways to prevent, detect, or treat disease. Treatments might be new drugs or new combinations of drugs, new surgical procedures or devices, or new ways to use existing treatments. Well-conducted clinical trials provide the fastest and safest way to find medical treatments that work in people and ways to improve health. The main objective is to identify safer, more effective methods of treating diseases using new drugs or new combinations of existing drugs. Clinical trials may also look at other aspects of care, such as improving the quality of life for people with chronic diseases.
This article explores how the clinical trial phases ensure investigational medicinal products, new drugs, biologic products and/or methods/therapies are developed effectively.
The Research Phases: 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
Phase I clinical trials are usually performed on a small number of participants. Phase I studies are done to find the highest dose of the new treatment that can be given safely without causing severe side effects. 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. These studies also help to decide on the best way to give the new treatment.
The objective of Phase I clinical trials is:
- To determine best and safe dose
- To evaluate safety
- To identify side effects
- In drug trials: how much of the drug is safe to give, and what happens to the drug within the body and what the body does with the drug
During such study, researchers observe, record, and monitor any side effects related to an investigational treatment, along with their severity and dose-dependence. Researchers also look for indications of the treatment positively affecting the target disease.
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 experimental treatment. These studies typically involve a larger group of participants than Phase I, all of whom have the condition the study therapy aims to treat.
Phase II trials usually determine:
- Whether the treatment is safe
- Which doses of the treatment are safe
- What side effects are associated with the treatment and how to manage the side effects
- 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 diseases and side effects each dose may produce).
Phase III: Confirming Safety and Effectiveness
Phase III trials are performed on a larger population sample than Phase I or Phase II. These patients are often divided into random groups to receive different doses and combinations of treatments. 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 usually investigate:
- To monitor effectiveness of the treatment
- To monitor side effects
- To compare the type, frequency, and severity of side effects associated with new and existing treatments
- How effective the treatment is compared to standard treatments
- How the treatment affects a patient’s quality of life compared to standard treatments
Phase III studies provide most of the safety data. In previous studies, it is possible that less common side effects might have gone undetected. Because these studies are larger and longer in duration, the results are more likely to show long-term or rare side effects
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 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 observe:
- The safety of the treatment for those who experience rare side effects
- The efficacy of the treatment across a larger population sample size
- The long-term risks and benefits associated with the treatment
- The risks and benefits of the treatment at different doses
- The frequency and severity of rare side effects in the general population
- The risks and benefits of the treatment in combination with other treatments
Keywords: Research Compliance, Research Operations, Clinical Development, Clinical Operations.
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