Week 2 Chapter 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  The individuals in an experiment are the experimental units. If they are human, we call them subjects participants.  The explanatory variables in an experiment are often called factors.  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.  The factor may be the administration of a drug.  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:  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. FFFFFF FFFFFFFF FFFFF FFFFFFFF FFFFF FFFF

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

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. 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 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.

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.