PharPoint’s Pharma 101: An article series to teach you all about how drugs make it to market. This week: Phase I Clinical Trials.
You might not always think about it when you are buying prescription at your pharmacy, but all drugs and treatments being sold on today’s market have undergone rigorous testing and various trials to make it to your doorstep. In our previous post, Pharma 101: What is a Clinical Trial? we provided an overview of the clinical trial process, covering the clinical trial basics, from who is involved in a trial to why clinical trials are so important. For lesson 2 of PharPoint’s Pharma 101 Series we’ll explore the steps and elements that occur in Phase I the clinical trial process.
Many people have heard of clinical trials and know about the FDA, but what would your response be if someone asked you “What takes place in Phase I of the clinical process? What are researchers attempting to achieve at this early stage of development?”
C. Movement through the body
D. Biochemical and physiological effects
E. All of the above
If you chose “E” then you would be correct. The purpose of a Phase I clinical trial is to assess the pharmacovigilance (PV), tolerability, pharmacokinetics, and pharmacodynamics of a drug or treatment, with the ultimate goal of learning how to administer the right drug at the right dose to the right patient at the right time.
- Pharmacovigilance, also known as drug safety, is the pharmacological science relating to the collection, detection, assessment, monitoring, and prevention of adverse effects with pharmaceutical products.
- The degree to which overt adverse effects of a drug can be tolerated in the body.
- The movement of the drug into, through, and out of the body. The study of pharmacokinetics evaluates the time course of a drug’s absorption, distribution, metabolism, and excretion.
- The study of the biochemical and physiological effects of drugs on the body and the mechanisms of drug action and the relationship between drug concentration and effect.
General information about Phase I clinical trials
Now that we know what researchers are testing a drug or treatment for, the question becomes how are researchers accomplishing this? The answer, by collecting data on the dosage, timing, treatment safety and side effects from human subjects.
By Phase I of the clinical process, researchers have already proven that a drug or treatment is safe for animals, so people who join Phase I trials are the first human subjects to test a new therapy or combination of therapies. Usually, Phase I trials last from several months up to a year with 20 – 100 participants. Researchers recruit such a small number of participants to minimize the risks of experimental therapy. Healthy volunteers are typically included in Phase I, though there are some instances where subjects with serious diseases are enrolled into a trial. Examples of this would be those subjects with terminal cancer or HIV where the experimental treatment is one of the last viable options they have. Participants are closely monitored throughout the duration of the trial and must often agree to routine visits or checkups.
How is the therapy administered?
The quick answer? Slowly. Doctors incrementally increase the dose of the drug being studied to trial participants. Their goal is to determine the dose that is most appropriate without causing severe side effects. It is assumed at the onset of a Phase I clinical trial that an increased dose of a drug is associated with increased efficacy, or the ability to produce a desired or intended result. For this reason, Phase I trials are known as dose-escalation trials that are designed to determine the maximum tolerable dosage (MTD) associated with an acceptable level of dose-limiting toxicity (DLT).
In addition, doctors must also determine the best way to administer a drug. This could be either orally or intravenously depending on the therapy. It’s also worth noting that placebos are never used in Phase I clinical trials.
Are there different kinds of Phase I clinical trials?
Yes, there are 3 kinds of Phase I clinical trials that study different components of a drug’s effect on the human body.
- In these trials, small groups of participants are given one dose of the drug and are observed and tested for a period of time to confirm whether or not the drug is safe. If the participants react well to the drug, a new group of participants are given a higher dose. This process is continued until intolerable side effects begin or pharmacokinetic safety levels are reached.
- These trials investigate the pharmacokinetics and pharmacodynamics of multiple doses of the drug, looking specifically at safety and tolerability. Low doses of the drug are administered, and fluid samples are taken from the participants at different points throughout the trial to learn how the drug is processed in the body.
- These are short trials designed to investigate differences in absorption of the drug in the body which is caused by eating before the drug is taken.
What happens next?
A Phase I clinical trial is complete once a dose or a range of doses is determined that is safe and effective in trial participants. While about 70% of experimental drugs move on to Phase II trials, the work isn’t over yet. The drug or treatment must pass through 3 more phases of development before it is approved for market use and less than 12% of medicines that make it into Phase I clinical trials will go on to be approved by the FDA.
One of the foremost limitations to conducting clinical research is finding suitable trial participants. Volunteers for clinical trials are always needed and participating is one of the best ways to help advance scientific research to aid in healthcare development.
Interested in learning about what happens after a drug successfully passes through Phase I? Stay tuned for our next chapter of PharPoint’s Pharma 101 Series as we discuss the ins and outs of Phase II trials.