Before a new drug, surgical procedure, or therapy becomes available to the
public, it must go through a rigorous testing process and be evaluated by the US
Food and Drug Administration (FDA). This testing process consists of a series of
clinical trials that are designed to test the safety and usefulness of the new
drug compared to the current standard treatment.
The clinical trials that make headlines are usually what are called phase III
trials. These are large-scale tests with hundreds or thousands of patients. They
are the culmination of earlier phase I and phase II trials that include many
fewer people and still earlier preclinical experiments with animals. They are
also the final tests in humans before the FDA is asked to authorize sale of new
Why Are Large-Scale Trials
Clinical trials are designed to test whether a drug is safe for humans, and
whether the drug is effective in treating human diseases or conditions. Although
the drug has generally gone through extensive animal testing before the trial
begins, animal trials cannot always predict how new medicines will affect
humans. Even the most painstaking tests with animals give only approximate
indications of how people will respond to drugs. At some point, after thorough
study in animals (and when the FDA is convinced human experimentation will
probably be safe), tests with humans become necessary.
Not only is it necessary to test new drugs in humans, but they need to be
tested in a large number of humans in order for the results of the trial to be
clear. The reason so many volunteers are required is that people are highly
variable in how they respond to drugs. It is not unusual, for example, for a
drug be somewhat effective in only 30 percent of those who take it. For medical
researchers to prove such a slight benefit requires testing the drug in as many
as several thousand patients.
This extensive testing is part of what drives up the cost of new drugs – the
average development time is over 10 years and costs from 500 to 700 million
What Goes on Prior to a Large-Scale
Phase III Trial?
An enormous amount of testing has gone on by the time a drug is ready for
phase III. In general, a new drug or treatment goes through preclinical testing
in animals, then small phase I and phase II trials in humans before being ready
for large-scale testing.
When a drug is discovered that seems to have medical potential, a drug
company will test it exhaustively in animals, looking for signs it may be
poisonous, cause cancer, or cause birth defects. Animal studies will also be
used to estimate the initial drug doses to be tested in humans.
When animal experiments are finished, the company asks the FDA for permission
to begin clinical trials. The FDA only grants approval once they are satisfied
that the animal experiments are sound and that clinical trials are likely to be
The first test of the drug in humans is known as phase I. It is designed to
find out if the drug is safe rather than whether the drug is effective. Phase I
is also used to learn what drug doses to use in later trials, how the drug is
broken down in the body and excreted, and study short-term side effects.
A phase I trial rarely has more than 100 participants. Often healthy people
are enrolled in phase I trials rather than patients on the assumption that if
the drug has unexpected side effects, healthy people have the best chance of
escaping permanent harm. But on other occasions, as with a drug treating a
serious disease like cancer, phase I subjects may be patients who have failed