Explaining the Phases of Clinical Trials:
A clinical trial can be defined as the prospective biomedical or the behavioral research study that is being conducted on human subjects. A clinical trial will be designed for answering specific questions about the interventions thereby generating safety as well as efficacy data. The clinical trials that are involving new drugs can be classified into different phases. (1) What are the different phases of clinical trials? This article will give you a clear picture about the phases of clinical trials.
Phases of Clinical Trials:
The clinical trials that are involving new drugs can be classified into four phases I to IV as known by most of us. However, before entering into Phase I, there are two other stages which are also important during the drug development process.
Before starting the clinical trials on a drug, the pharmaceutical companies would conduct pre-clinical studies which involve:
- In vitro experiments
- In vivo experiments
As such, these studies would use wide range of doses of the study drug in order to obtain the following preliminary data:
These data would assist the companies in deciding whether the particular drug candidate possesses the scientific merit for developing as 'Investigational New Drug (IND)'.
This phase of the clinical trial can also be called by the term, 'first-in human' clinical trial. The study design of these clinical trials would be exploratory in nature. These trials would also be called as 'Micro-dosing' studies. One among the most distinctive features of this clinical trial includes the administration of single sub-therapeutic doses of the investigational drug to a small group of human subjects. The target number of subjects for the phase 0 study would range from 10 to 15. The primary objective of a phase 0 study will be collect preliminary data on pharmacokinetics of the study drug. And, these studies are specifically designed in order to speed up the development process of the promising drugs. Moreover, these studies would enable go or no-go decisions on the development of particular drug. (2)
These are the initial safety trials that are conducted on an investigational drug and are the first stage of testing in humans. In a phase 1 clinical trial, small number of healthy volunteers will be recruited. More usually, this number would range from 20 to 100 subjects. In this phase of study, an attempt will be made to establish the dose range that is tolerated by the healthy volunteers. It is to be noted that about 70% of the investigational drugs would pass this phase. The phase 1 study will assess the following data:
Phase 1a (Single Ascending Dose):
In these studies, the small group of human subjects will be administered with a single dose of the drug when at the same time they are monitored and tested to confirm the drug's safety.
Phase 1b (Multiple Ascending Dose):
This phase of study would investigate the pharmacokinetics as well as the pharmacodynamics of multiple doses of the investigational drug. Thus, this phase would look at safety and tolerability.
This is relatively a short trial that is designed for investigating any difference that is caused by eating over the absorption of the particular drug by the human body. The food effect studies will usually be a crossover study. (2), (3), (4)
The phase 2 clinical studies are those which are designed for testing the efficacy of a drug. This phase would involve up to several hundred patients (100 to 300). Usually, this second phase would last from several months to up to 2 years and most of them will be designed as randomized trials where one group would receive the investigational drug and the other group would receive the standard of control or placebo. It is to be noted that about 1/3rd of the investigational drugs would successfully complete phase 2 studies.
This particular phase is specifically designed for determining the dosing requirements. The objectives of this phase would focus on:
- Dose response
- Type of patient
- Frequency of dosing
These studies are specifically designed for studying the efficacy of the study drug. These trials are sometimes called as 'pivotal studies' which are the rigorous demonstration of the medicine's efficacy. (2), (3), (4)
The phase 3 clinical trials are the large scale testing, which would involve several hundred to several thousand patients (300 to 3000). These will be designed as randomized and blinded testing and would last for several years. The primary objective of this phase will be aimed at being the definitive assessments of how effective the drug is when compared to the gold standard treatment. It could be noted that 70 to 90% of the study drugs that are entering the phase 3 studies would successfully complete this phase. And, once the phase 3 is complete, the pharmaceutical company could request the FDA approval in order to market the drug.
These are the trials that are conducted after efficacy of the study drug has been demonstrated but before the regulatory submission of New Drug Application.
These clinical trials are conducted after the regulatory submission of New Drug Application but before the approval and launch of the study drug.
This phase of the clinical trial is also called as 'post-marketing surveillance'. These trials would involve the safety surveillance as well as the ongoing technical support of the drug after it receives the permission to be sold. The pharmaceutical companies would have the objectives such as:
- To compare the drug with other standard drugs in the market
- To monitor the long term effectiveness of the drug as well as the impact on the patient's quality of life
- To determine the cost effectiveness of the drug therapy in relation with other traditional as well as new therapies (2), (3), (4)
I hope you have understood the various phases of the clinical trial clearly now!