Although most people are aware of the fact that approval by the FDA can clear a medication or treatment course for public use, individuals are not always aware of what this truly means. Clinical trials are conducted under strict guidelines in order to both gauge the safety of a substance and support the efficacy of that pharmaceutical for a specific use. For this reason, stating that a drug is just FDA approved does not always mean that it has been found applicable for the use that is being promoted. This is also why certain drugs which are approved may also not be fully covered by insurance if the treatment course is not in accordance with trial results.
Clinical trials are actually conducted through the drug manufacturer or distributor, although they may utilize third party researchers when required. Before the drug trial begins, the principle investigator in charge of the research must submit the appropriate paper work for registration to the FDA. Once a confirmation is given that the clinical trial is considered applicable and all appropriate paperwork has been completed by the annual deadline, then researchers may proceed with the actual study.
What is an Appropriate Clinical Trial?
In order to receive the go ahead for testing, principle investigators must verify both the protocols of the study and the process. This includes verifying that:
- Treatment of participants is ethical and consensual
- Drug toxicity is within acceptable levels for testing
- The trial will offer new and applicable information
This also means that while a number of new pharmaceuticals may be tested for market, researchers can also test new applications for existing drugs in order to receive approval for that type of treatment.
Phases of Trials
Clinical trials need to be conducted in three phases in order for a drug to receive full approval by the FDA. This is not only to ensure that the medication is safe for human use, but that it actually works in the manner that is purported. Prior to clinical trial phases, the medication must undergo pre-testing on animals in order to determine any immediate toxicity or possible adverse effects. After this has happened, the application for trial is submitted and upon confirmation, researchers are allowed to proceed.
Manufacturers will often conduct a number of trade studies before this stage, and although the results may be promising, they are not considered conclusive until the FDA clinical trials. However, this type of research is often used as supporting documentation when applications for clinical trial approval are submitted.
Phase I trials refer to the initial round of testing that is performed on healthy subjects. This is done in order to determine the baseline effects of the drug, without symptom complications that may be specifically related to the progression of an illness. Results that will be evaluated through a Phase I trial include:
- Possible toxicity to humans
- List and severity of side effects
- Dosage impacts on regular physical function
- Speed at which the drug is metabolized
This information can act as guidance through future trials, but also begins to ensure that the medication is safe enough to be considered for disease treatment.
Phase I trials need to be conducted before any other trial phases can be considered. This is true even if the drug has been previously tested as safe, but was not show effective to a specific treatment. Reestablishing the baselines is necessary in order for future data to be analyzed. These trials are also conducted on a relatively small sample size of the population, and randomization of subjects is generally required.
Phase II trials will proceed to further test the safety and possible long term effects of the medication, but the major focus of this round of study is to determine effectiveness of treatment. A slightly larger population sample is selected, although this round of research requires that all participants must experience some stage of the disease in question. This sample is randomized and further divided into groups, so that investigators can evaluate how well the new drug performs as compared to both existing therapies and a placebo.
Phase II trials do continue to monitor side effects as well, and all of this data is submitted to the FDA for evaluation as well. At this point, even incremental differences in the treatment performance can be considered as a positive sign. As long as safety is still shown for subjects taking the new medication and beneficial responses are shown in terms of disease remediation, then the possibility to move on the Phase III is considered.
Before actually starting a Phase III trial, the researchers and the FDA will need to decide on how large of a sample will be used for part of the study. Once an agreement has been reached, investigators can begin a larger scale application of the drug.
Phase III trials are conducted similarly to Phase II trials, although the sample population is closer to 3,000 participants. Along with continued testing of safety and effectiveness, this phase of the clinical trials will also consider the following information:
- Dosage amounts
- Effectiveness in combination with other medications
- Possible interactions with foods and other drugs
- Difference of effects on different populations
- Impact of drug as it relates to other population demographics, such as age or gender
Although many of the aspects of Phase III are the same as Phase II, the information that is gathered is far more extensive, and also gives more data on concerns such as long term risks and side effects.
After the Phase Trials
Once the three phases of the clinical trials are complete, and the drug has still shown relative safety and effectiveness, then the FDA can pass approval for marketing. Although the drug has been given the go ahead to be dispensed to the public, manufacturers will still need to conduct post-market research. This is to further monitor long term effects and safety, and is especially important if the drug can qualify for new drug application (NDA) status.