
It is the responsibility of the U.S. Food and Drug Ad-
ministration (FDA), through its Center for Drug Evalua-
tion and Research (CDER), to ensure that drugs are safe
and effective. But CDER does not do the actual testing
of new drugs itself. It is the responsibility of the com-
pany seeking to market a new drug to test it and submit
evidence that it is safe and effective. CDER statisticians
and scientists then review the evidence submitted.
Companies seeking approval of a new drug conduct
extensive statistical studies to support their application.
The testing process in the pharmaceutical industry
usually consists of three stages: (1) preclinical testing,
(2)testingforlong-termusageandsafety, and (3) clinical
efficacytesting.Ateachsuccessivestage, the chance that
adrug willpassthe rigoroustestsdecreases; however,the
cost of further testing increases dramatically. Industry
surveys indicate that on average the research and devel-
opmentfor one newdrug costs $250million and takes 12
years. Hence, it is important to eliminate unsuccessful
newdrugsintheearlystagesofthetestingprocess,aswell
as to identify promising ones for further testing.
Statistics plays a major role in pharmaceutical re-
search, where government regulations are stringent and
rigorously enforced. In preclinical testing, a two- or
three-population statistical study typically is used to de-
termine whether a new drug should continue to be stud-
ied in the long-term usage and safety program. The
populations may consist of the new drug, a control, and a
standard drug. The preclinical testing process begins
when a new drug is sent to the pharmacology group for
evaluation of efficacy—the capacity of the drug to pro-
duce the desired effects. As part of the process, a statisti-
cian is asked to design an experiment that can be used to
test the new drug. The design must specify the sample
size and the statistical methods of analysis. In a two-
population study, one sample is used to obtain data on the
efficacy of the new drug (population 1) and a second sam-
ple is used to obtain data on the efficacy of a standard
drug (population 2). Depending on the intended use, the
new and standard drugs are tested in such disciplines as
Extensive statistical studies are conducted before a
new drug is approved.
STATISTICS
in PRACTICE
U.S. FOOD AND DRUG ADMINISTRATION
WASHINGTON, D.C.
neurology, cardiology, and immunology. In most studies,
the statistical method involves hypothesis testing for the
difference between the means of the new drug population
and the standard drug population. If a new drug lacks ef-
ficacy or produces undesirable effects in comparison with
the standard drug, the new drug is rejected and withdrawn
from further testing. Only new drugs that show promis-
ing comparisons with the standard drugs are forwarded to
the long-term usage and safety testing program.
Further data collection and multipopulation studies
are conducted in the long-term usage and safety testing
program and in the clinical testing programs. The FDA
requires that statistical methods be defined prior to such
testing to avoid data-related biases. In addition, to avoid
human biases, some of the clinical trials are double or
triple blind. That is, neither the subject nor the investi-
gator knows what drug is administered to whom. If the
new drug meets all requirements in relation to the stan-
dard drug, a new drug application (NDA) is filed with the
FDA. The application is rigorously scrutinized by statis-
ticians and scientists at the agency.
In this chapter you will learn how to construct inter-
val estimates and make hypothesis tests about means and
proportions with two populations. Techniques will be
presented for analyzing independent random samples as
well as matched samples.
Statistics in Practice 393
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