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Week 2
Chapter 8. Designing Experiments
Objectives (PSLS Chapter 8)
Designing experiments
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Experimental terminology
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Comparative, randomized experiments
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Completely randomized designs
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Block designs (A/B awards)
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Matched pairs designs (A/B awards)
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Ethics and experimentation
Terminology
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The individuals in an experiment are the experimental units. If they
are human, we call them subjects participants.
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The explanatory variables in an experiment are often called factors.
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A treatment is any specific experimental condition applied to the
experimental unit (e.g. participants). If an experiment has several
factors, a treatment is a combination of specific levels of each factor.
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The factor may be the administration of a drug.
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One group of people may be placed on a diet/exercise program for 6
months (treatment), and their blood pressure (response variable) would
be compared with that of people who did not diet or exercise.
Comparative, randomized experiments
Experiments compare the response to a given treatment to:
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another treatment
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the absence of treatment (often called a control)
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a placebo (a fake treatment)
Experiments randomize the assignment of subjects to treatments.
Experiments use replication: several or many individuals are studied.
Inventing experimental design
Fisher was sent to a UK agricultural station to evaluate the effect
of fertilizers. He found decades worth of bad data:
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Fertilizer had been applied to a field one year and not in another to compare
the yield of grain produced in the two years.
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Fertilizer was applied to one field and not to a nearby field in the same year.
Solution: Randomized comparative experiments.
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He selected many fields and randomly assigned
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the fields to receive fertilizer or not. Grain yield was
then compared for the two conditions.
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Importance of design
Gastric freezing was once a recommended treatment for peptic
ulcers. Patients would swallow a balloon through which a refrigerated
liquid was pumped for an hour to cool the stomach. The treatment was shown to
be safe and significantly reduce ulcer pain and it was widely used for years
(2500 gastric freeze machines sold and 15,000 patients chilled).
A randomized comparative experiment was later performed to compare the
effect of gastric freezing with that of a placebo:
- 28 of the 82 patients subjected to gastric freezing improved,
- 30 of the 78 patients in the control group improved.
Gastric freezing was then abandoned…
About the “placebo effect”
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The placebo effect is not entirely understood. It is an improvement in
health or perceived condition due, not to any active treatment, but only to
the patient’s belief that he or she is being cared for or helped.
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It can ease the symptoms of a variety of ills, from asthma to pain to high
blood pressure and even to heart attacks. It can have therapeutic results
on up to 35% of patients.
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An opposite, or “negative placebo effect,” has been observed when
patients believe their health will get worse.
Perhaps the most famous placebo is the kiss, blow, hug,
band aid—whatever your technique—that parents
use (quite effectively) for minor injuries in kids.
Design issue: Bias and blinding
Response & Measurement Bias is a particularly challenging
problem when dealing with human subjects because (1) of the
placebo effect, and (2) of human bias, conscious or unconscious, on
the experimenter side.
A double-blind experiment is one in which neither the subjects nor
the experimenter(s) know which individuals received which treatment
until the experiment is completed.
However, subjects must be informed that they will get one of a
number of treatments, and must consent to that condition
(it would be unethical otherwise).
Design issue: Lack of realism
Random sampling is meant to gain
information about the larger
population from which we sample.
population
sample
Is the treatment appropriate for the response you want to study?
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Is studying the effects of eating red meat on cholesterol values in a group of
middle-aged men a realistic way to study factors affecting heart disease
problem in humans?
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Carcinogenicity studies administer high doses of a
potential carcinogen to lab rats. Results don’t always
apply to humans (saccharin was delisted in 2000).
Completely randomized designs
In a completely randomized experimental design, individuals are
randomly assigned to groups, then the groups are randomly assigned
to treatments.
Block designs
In a block design, subjects are divided into groups, or blocks, prior to
the experiment to test hypotheses about differences between the
groups.
The blocking, or stratification, here is by gender.
Matched pairs designs
 Choose pairs of subjects that are closely matched (like
twins, 2 siblings, or 2 pups of the same litter). Within each pair,
randomly assign who will receive which treatment.
 Or give both treatments to a single person over time, in random
order. In this case the “matched pair” is just the same person at
different points in time. This is called a cross-over design.
Generics are brand-name drugs manufactured by a different
company but with identical active ingredients and properties.
Individuals are given either Brand X or its generic version one day so that drug
absorption can be measured. One week later, each individual receives the other
drug to measure drug absorption. A difference in absorption extent between
Brand X and its generic is then calculated for each individual.
What experimental design?
Is there a significant difference in resting pulse rates for men and
for women? A random sample of 28 men and 24 women had their
pulse rate measured at rest in the lab.
Many dairy cows now receive injections of BST, a hormone
intended to spur greater milk production. The milk production
of 60 dairy cows was recorded before and after they received
a first injection of BST.
In a study of sickle cell anemia, 150 patients were given the
drug hydroxyurea, and 150 were given a placebo (dummy pill).
The researchers counted the episodes of pain in each subject
at the end of the study.
Ethics and experimentation
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Biology deals with life. Experimentations have an impact on live
subjects and ecosystems. What rights do human subjects, animals,
ecosystems have?
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There is a difference between what can physically be done and what
can be done ethically. When is it ok/not ok to include a placebo
group? When should an experiment be interrupted?
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Personal standards vary, and extreme
experimentations have occurred.
Committees have been established
to review all research proposals.
Subjects must give “informed” consent.