Week 2Chapter 8. Designing Experiments

Objectives (PSLS Chapter 8)

Designing experiments

Experimental terminology

Comparative, randomized experiments

Completely randomized designs

Block designs (A/B awards)

Matched pairs designs (A/B awards)

Ethics and experimentation

Terminology

Comparative, randomized experimentsExperiments compare the response to a given treatment to:

another treatment

the absence of treatment (often called a control)

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:

Fertilizer had been applied to a field one year and not in another to compare

the yield of grain produced in the two years.

Fertilizer was applied to one field and not to a nearby field in the same year.

Solution: Randomized comparative experiments.

He selected many fields and randomly assigned

the fields to receive fertilizer or not. Grain yield was

then compared for the two conditions.

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F F F F F

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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”

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.

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.

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.

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: Bias and blinding

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?

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?

Carcinogenicity studies administer high doses of a

potential carcinogen to lab rats. Results don’t always

apply to humans (saccharin was delisted in 2000).

In a completely randomized experimental design, individuals are

randomly assigned to groups, then the groups are randomly assigned

to treatments.

Completely randomized designs

Block 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.

Matched pairs designs

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.

What experimental design?

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

Biology deals with life. Experimentations have an impact on live

subjects and ecosystems. What rights do human subjects, animals,

ecosystems have?

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?

Personal standards vary, and extreme

experimentations have occurred.

Committees have been established

to review all research proposals.

Subjects must give “informed” consent.