Biomedical Engineering Reference
In-Depth Information
when a larger group of volunteers and patients receive the treatment. This second
phase of testing can last from several months to 2 years. Some Phase II trials are
designed as case series, demonstrating a drug's safety and effi cacy in participants.
Other Phase II trials are designed as randomized clinical trials, where half of partici-
pants are randomly selected to receive the tested treatment while the other half of
participants receive a placebo or a standard treatment. This design can provide the
most compelling evidence on how the treatment under study affects human health.
Often these randomized clinical trials are “double-blinded” in the sense that neither
participants nor researchers know who received what treatments. This “blinding”
has the advantage of preventing biases, which may be caused by researchers being
tempted to give specifi c treatments to specifi c participants or by participants who
may choose to quit the treatment process had they known they were getting the
placebo. About one-third of study treatments pass both Phase I and Phase II trials.
Like most Phase II trials, Phase III trials are also randomized clinical trials,
although these trials typically include far more participating patients (ranging from
several hundred to several thousand) and can last several years. This large-scaled
testing provides the pharmaceutical company and regulatory agencies with a more
defi nitive assessment of how effective the tested drug is, in comparison with the so-
called gold standard treatment, i.e., the standard or the best known treatment in the
marketplace. In these trials, half of the participants in the study are chosen at ran-
dom to receive the tested drug treatment and the others receive the “gold standard”
treatment. Other reasons for performing Phase III trials include attempts by the
pharmaceutical company to expand the label,
4
that is, to show the drug works for
additional types of patients or diseases beyond the original use for which the drug
was approved for marketing, to obtain additional safety data, or to support market-
ing claims for the drug. While not required in all NDA cases, it is typically expected
that the pharmaceutical company proves the safety and effectiveness of the drug
through at least two successful Phase III trials, in order to obtain approval from the
regulatory agencies, such as the FDA in the United States and the EMA (European
Medicines Agency) in the European Union.
After a new drug obtains approval from the regulatory agencies, pharmaceutical
companies may also conduct Phase IV clinical trials, also known as post-marketing
surveillance trials. Pharmaceutical companies have several objectives at this stage:
(1) to provide a safety surveillance, which is designed to detect any rare or long-
term side effects of the treatment over a much larger patient population and a much
longer timer period than was possible during the Phase I, II, and III trials, after a
drug receives permission to be sold; (2) to compare the drug with other drugs
already in the market; (3) to monitor the long-term effect of the drug on a patient's
quality of life; and (4) to determine the relative cost-effectiveness of the drug treat-
ment. Harmful side effects discovered by Phase IV studies may result in the drug
being taken off from the market or restricted to certain use. The aforementioned
Vioxx case is one such example.
4
Studies for this purpose are sometimes categorized as “Phase IIIB” studies.
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