Health care has been a hot topic in the news lately, and so have the terms clinical trials and research studies. Let's examine what these terms mean.
A clinical trial or research study is essentially an experiment conducted to test how well a new chemical entity (drug), screening procedure or methodology, or other treatment works to treat or identify a disease or other condition. Before a drug makes it to your pharmacy, many steps have to be completed. In most cases, the new chemical entity is created and registered with the FDA, or Food and Drug Administration. The entity is then subjected to extensive laboratory and animal testing. Once the results of these tests conclusively prove that the treatment is potentially valid, the original NDA (New Drug Application) is amended and reviewed, and if approved, clinical trials in humans can commence.
Phases of trials
The approval systems includes many checks and balances along the highway to final approval by the FDA. There is a series of trial designs that must be followed in sequence, and the results of the trials must be filed before the next phase of research can begin. These phases are summarized below:
In most cases, Phase I studies are performed in normal, healthy volunteers, who are compensated for their time. These studies usually last a few weeks to months, and often require that the research participants remain in a research facility overnight or longer. The drug is administered in various conditions (with or without food is a very common scenario) and multiple blood draws are done to determine how the drug behaves in the body, how it is metabolized and excreted, how safe it is, and what the maximum tolerated dose of the drug might be. The exceptions to this rule are drugs which are potentially toxic but are needed to treat serious and life-threatening diseases such as cancer. In this case, Phase I studies require different study designs, and actual patients with the disease under study are treated (see an example of oncology Phase I study designs here).
In Phase II trials, the drug is typically given to patients with the disease that the drug is intended to treat. The number of patients treated are usually small (in the hundreds range), and extensive testing continues with multiple blood draws being performed at different times of administration of the drug, typically before the drug is given, followed by increments of one, followed by fifteen minutes of time, continued through twelve to twenty-four hours post dose. Dose finding is also common in these studies, which are often run in cohorts, or sections. Safety data is analyzed after each dosing group before the next higher dose is allowed to continue. Often, this data is reported to a third party group, called a Data Safety Monitoring Committee, so that potential bias is eliminated, Again potentially toxic but required treatments for oncology indications are treated somewhat differently. An example of a Phase II oncology study design can be found here.
Depending on the indication under study, Phase III trials can range from the upper hundreds, to tens of thousands of patients, from one or multiple countries. At least two Phase III trials must be completed with similar results before the drug can be approved for marketing. These studies can have a variety of study designs, comparing the drug to a placebo (or a sugar pill or saline for injected drugs), or to what is termed standard of care treatments, or the treatment most commonly used at the time of the study. Recent concerns over safety of all drugs have prompted more stringent monitoring of cardiac and liver effects, so most subjects should expect to receive screening and treatment ECGs and more frequent blood draws to check for these often hidden potential side effects. Oncology drugs do have special considerations in this phase as well as noted here. If the studies are successful, the maker of the drug can submit the data to the FDA and request approval to market the product.
Phase IV studies are conducted for many reasons, but are primarily intended to provide additional safety data regarding the monitoring of adverse events once a drug reaches the greater population. These studies are often call Post Marketing Surveillance studies. In some cases, drugs are given conditional approval by the FDA, and the condition often imposed is that a variety of additional studies be performed. These studies reveal how a drug performs in relation to other treatments, provide long term treatment effects, and also can reveal how the drug reacts differently in sub-groups of the population.
There has been increasing concern over how the results of the clinical trials are presented to the medical community, and the public. Last year (2008), new legislation was enacted where clinical trial results must be made publicly available. Results of trials in their various phases of research can be found on a government sponsored website. ClinicalTrials.gov provides patients, family members, and members of the public easy and free access to information on clinical studies for a wide range of diseases and conditions.
In subsequent articles we will review clinical trials terminology, as well as learn how to read an informed consent, and how to research clinical trials being conducted in our metropolitan area.