Why Participate in Clinical Trials?
People participating in clinical trials have access to experimental medications or devices before they become available to the general public. If you participate, you may receive careful medical attention including examinations and tests at no cost. In most cases, you may be reimbursed for your time and expenses, such as travel.
And some people like the idea that they are contributing to medical science.
But participation is not without risks. Depending upon the phase of clinical trial more risks are known. There are three primary phases of clinical trials in humans that the drug or device must be tested in prior to regulatory approval. The risks and possible side effects specific to the clinical trial are listed in the informed consent form and discussed by the research team before you enter the trial.
Who performs clinical trials?
A common misnomer out in the public is the belief that the FDA performs the clinical studies for pharmaceutical companies. This simply is not true. Pharmaceutical companies contract with independent physician or research organizations to perform the clinical studies. It is the responsibility of the pharmaceutical companies to utilize qualified physicians and researchers to perform their clinical studies. It is the responsibility of the physicians and researchers to comply with the study protocols and laws that govern clinical trials. It is the Food and Drug Administration's responsibility to enforce the laws that govern clinical trials.
Phase I Clinical Trials
Phase I clinical trials are the first stage of testing in human subjects. Normally, a small (10-100) group of healthy participants will take part in the study. The majority of phase I studies do not allow participants to be taking any medications or vitamin supplements since they may pose added risk the participant. Phase I clinical trials are designed to assess four specific scientific areas which include, safety, tolerability, measurement of the amount of drug in the blood stream, and the bodies response to the investigational product. These trials are usually conducted in an inpatient clinic, where the subject can be observed by a full-time medical research team. The subjects who receive the drug is usually observed until the drug has completely been metabolized by the body.
Phase I trials also normally include dose-ranging, also called dose escalation, studies so that the appropriate dose for therapeutic use can be found. The tested range of doses will usually be a small fraction of the dose that causes harm in animal testing. Phase I trials most often include healthy volunteers. However, there are some circumstances when real patients are used, such as patients who have end-stage disease and have exhausted already FDA approved treatment options. This exception to the rule most often occurs in oncology (cancer) and HIV drug trials. Participants are usually compensated a fee for their time spent volunteering for the study. Compensation ranges from a small amount of money for a short period of participation, to a larger amount of up to approx $4,000 depending on length of participation.
There are different kinds of Phase I trials:
SAD
Single Ascending Dose studies are those in which small groups of patients are given a single dose of the drug while they are observed and tested for a set period of time. If they do not exhibit any adverse side effects, and the drug level that is found in the blood stream is roughly in line with predicted safe values, the dose is increased, and a new group of study participants is then given a higher dose. This is continued until pre-calculated drug blood safety levels are reached, or undesirable side effects start showing up (at which point the drug is said to have reached the Maximum tolerated dose (MTD).
MAD
Multiple Ascending Dose studies are conducted to better understand the pharmacokinetics & pharmacodynamics of multiple doses of the drug. In these studies, a group of patients receives multiple low doses of the investigational drug and samples of blood, and/or other fluids are collected at specific time points throughout the study period and analyzed to understand how the drug is processed within the body. The doses are subsequently escalated for further groups, up to a predetermined level or until undesirable adverse effects are observed.
Food effect
Food effect clinical trials are short studies designed to investigate any differences in absorption of the drug by the body, caused by eating before the drug is given. These studies are usually run as a crossover study, with volunteers being given two identical doses of the drug on different occasions; one while fasting, and one after having eaten.
Phase II Clinical Trials
Once the initial safety of the study drug has been identified in the Phase I trials, Phase II trials are commenced on larger groups of 50-300 subjects and are designed to assess how well the drug works in patients that have the conditions that ultimately the drug is intended for. Similar to the Phase I studies continued safety assessments and drug blood levels are monitored in a larger group of study participants in order to observe the metabolizm of the drug in a larger and more evenly distributed demographic.
Phase II studies are sometimes divided into Phase IIa and Phase IIa. Phase IIa is specifically designed to assess dosing requirements, in other words how much drug should be given to achieve the therapeutic range at the lowest dose possible. Whereas phase IIb studies are specifically designed to study efficacy, in other words how well the drug works at the prescribed doses as outlined in the predetermined protocol.
Some trials combine Phase I and Phase II, and test both efficacy and toxicity.
Phase III Clinical Trials
Phase III studies are randomized controlled multi-center clinical trials utilizing large patient groups that include 300-3,000 or more, depending upon the medical condition studied, and up to 300 clinical trial sites. The primary goal(s) of these types of studies are aimed at proving how effective or ineffective the drug is, in comparison with current 'gold standard' treatment and placebo controls. Because of the sheer size of the clinical study and long duration, Phase III trials are the most expensive, time-consuming and difficult trials to design and run, especially in therapies for chronic medical conditions.
It is common practice that certain Phase III trials will continue while the regulatory submission is pending review at the FDA (food and drug administration). This allows patients to continue to receive possibly lifesaving drugs until the drug can be obtained by purchase. Other reasons for performing trials at this stage include attempts by the sponsor at "label expansion" (to show the drug works for additional types of patients/diseases beyond the original use for which the drug was approved for marketing), to obtain additional safety data, or to support marketing claims for the drug. Studies in this phase are by some companies categorised as "Phase IIIb studies".
While not required in all cases, it is typically expected that there be at least two successful Phase III trials, demonstrating a drug's safety and efficacy, in order to obtain approval from the appropriate regulatory agencies.
Once a drug has proved satisfactory after Phase III trials, the trial results are usually combined into a large document containing a comprehensive description of the methods and results of human and animal studies, manufacturing procedures, formulation details, and shelf life. The FDA or appropriate regulatory agency will make the decision as to approve or disprove the drug to be marketed.
Phase IV Clinical Trials
Phase IV trial is also known as Post Marketing Surveillance Trial. Phase IV trials involve the safety surveillance and on going technical support of a drug after it receives permission to be sold. Phase IV studies may be required by regulatory authorities or may be undertaken by the sponsoring company for competitive reasons or other reasons. The FDA may even require a pharmaceutical company to conduct further testing on a drug even though they have approved the product to be sold and marketed.
|
|
|
