pational mortality studies andclinical trials. The cohort study design focuses on
a particular exposure rather than a particular disease as in case–control studies.
There have been several major cohort studies with significant contribution to
our understanding of important public health issues, but this form of study
design is not very popular because cohort studies are time and cost consuming.
In this chapter we focus on study designs. However, since in biomedical
research, the sample survey is not a common form of study, and prospective
studies of past events and cohort studies are not often conducted, we put more
emphasis on the designs of clinical trials which are important because they are
experiments on human beings, and of case–control studies, which are the most
popular of all study designs.
12.2 CLASSIFICATION OF CLINICAL TRIALS
Clinical studies form a class of all scientific approaches to evaluating medical
disease prevention, diagnostic techniques, and treatments. Among this class,
trials, often calledclinical trials, form a subset of those clinical studies that
evaluate investigational drugs.
Trials, especially cancer trials, are classified into phases:
Phase I trials focus on safety of a new investigational medicine. These are
the first human trials after successful animal trials.
Phase II trials are small trials to evaluate e‰cacy and focus more on a
safety profile.
Phase III trials are well-controlled trials, the most rigorous demonstration
of a drug’s e‰cacy prior to federal regulatory approval.
Phase IV trials are often conducted after a medicine is marketed to pro-
vide additional details about the medicine’s e‰cacy and a more complete
safety profile.Phase I trials apply to patients from standard treatment failure who are at
high risk of death in the short term. As for the new medicine or drug to be
tested, there is no e‰cacy at low doses; at high doses, there will be unavoidable
toxicity, which may be severe and may even be fatal. Little is known about the
dose range; animal studies may not be helpful enough. The goal in a phase I
trial is to identify a maximum tolerated dose (MTD), a dose that has reason-
able e‰cacy (i.e., is toxic enough, say, to kill cancer cells) but with tolerable
toxicity (i.e., not toxic enough to kill the patient).
Phase II trials, the next step, are often the simplest: The drug, at the optimal
dose (MTD) found in a phase I trial, is given to a small group of patients who
meet predetermined inclusion criteria. The most common form are single-arm
studies where investigators are seeking to establish the antitumor activity of a
drug usually measured by a response rate. A patient responds when his or her
cancer condition improves (e.g., the tumor disappears or shrinks substantially).
CLASSIFICATION OF CLINICAL TRIALS 447