Experimental designs

What is Thalidomide and its effects

originally prescribes as a extremely safe drug for sleeplessness, that was then discovered could be prescribed off-label for morning sickness. Was later found to cause phocomelia

What year was thalidomide created? Where

1953 by Grunenthal Group in Germany

When was thalidomide first licensed in the UK

1958

When was thalidomide ADRs discovered? By whom?

1961 - Dr. William McBride

When completing a clinical trial, what type of participants are involved in phase 1

“20-100 healthy volunteers or people with the disease/condition”

• very homogenous group

When completing a clinical trial, what type of participants are involved in phase 2

“up to several hundred people with the disease”

• start to see some deviation from “healthy”

When completing a clinical trial, what type of participants are involved in phase 3

“300 to 3,000 volunteers who have the disease or condition”

When completing a clinical trial, what type of participants are involved in phase 4

“several thousand volunteers who have the disease/condition”

• this is who is representative of the population

When completing a clinical trial, what is the typical length of study for phase 1

several months

When completing a clinical trial, what is the typical length of study for phase 2

several months to 2 years

When completing a clinical trial, what is the typical length of study for phase 3

1-4 years

When completing a clinical trial, what is the typical length of study for phase 4

> 4 years

When completing a clinical trial, what is the purpose of the study for phase 1

safety and dosage

When completing a clinical trial, what is the purpose of the study for phase 2

efficacy and side effects

When completing a clinical trial, what is the purpose of the study for phase 3

efficacy and monitoring for ADRs

When completing a clinical trial, what is the purpose of the study for phase 4

safety and efficacy

Approximately what percentage of drugs move on to phase 2

70%

Approximately what percentage of drugs move on to phase 3

33%

Approximately what percentage of drugs move on to phase 4

25-30%

Define Effficacy

benefit of an intervention as compared to a control/standard program

• does it work?

define effectiveness

benefit of an intervention in the “real world”

• how well does it work?

What are 2 things we will need to be able to identify in a study

randomization schemes and number of independent variables

What are 2 types of randomization schemes

completely randomized/between subjects

repeated measured/within subjects

What are 2 types on are named after the number of IVs

single factor/one-way design

multifactor design

What type of data do we analyze with unpaired t-tests

2 groups, interval/ratio data

What type of data do we analyze with analysis of variance

3+ groups, interval/ratio data

What type of data do we analyze with Mann-Whitney U-test

2 groups, ordinal data

What type of data do we analyze with Kruskal-Wallis analysis of varance

3+ groups, ordinal data

Define treatment arms

independent groups of subjects

What is the scientific standard for determining cause and effect

pretest and posttest control group design

What does a pretest and posttest control group design flow chart look like

What is the IV?

RCT to study the effects of exercise program for improving venous hemodynamics in patients with chronic venous insufficiency

31 subjects randomly assigned to 2 groups

•Experimental group received physical therapy with specific exercises for calf strengthening and joint mobility

•Control group=Nothing

•BOTH groups received compression stockings

Dynamic strength, calf pump function and quality of life were assessed at baseline and after 6 months

exercise

How many levels to the IV?

RCT to study the effects of exercise program for improving venous hemodynamics in patients with chronic venous insufficiency

31 subjects randomly assigned to 2 groups

•Experimental group received physical therapy with specific exercises for calf strengthening and joint mobility

•Control group=Nothing

•BOTH groups received compression stockings

Dynamic strength, calf pump function and quality of life were assessed at baseline and after 6 months

2 (exercise and no exercise)

How many DVs?

RCT to study the effects of exercise program for improving venous hemodynamics in patients with chronic venous insufficiency

31 subjects randomly assigned to 2 groups

•Experimental group received physical therapy with specific exercises for calf strengthening and joint mobility

•Control group=Nothing

•BOTH groups received compression stockings

Dynamic strength, calf pump function and quality of life were assessed at baseline and after 6 months

3 (strength, pump function, QoL)

What does a multigroup pretest and posttest design flow chart look like

Is it possible to just compare the posttest

Yes, typically used for practical purposes (FIM scores/ length of stay), or when the pretest can bias the posttest (attitude/behaviors)

What is a factorial design for independent groups

incorporated 2 or more IV, with independent groups of subjects randomly assigned to various combinations of levels of the 2 variables

How are factorial designs usually diagrammed

matrix notation

What are the IVs?

Location	Exercise Intensity
		Moderate	Vigorous
	Home	Home-Mod	Home-Vig
	Community Center	CC-Mod	CC-Vig

Exercise and location (each have 2 levels)

What is the main effect?

Location	Exercise Intensity
		Moderate	Vigorous
	Home	Home-Mod	Home-Vig
	Community Center	CC-Mod	CC-Vig

is there a difference between exercising at home or CC?

is there a difference in mod vs vig exercise?

What is the interaction effect?

Location	Exercise Intensity
		Moderate	Vigorous
	Home	Home-Mod	Home-Vig
	Community Center	CC-Mod	CC-Vig

Is there a relationship between exercise intensity and location

When is a randomized block design used

when an attribute variable (blocking variable) is crossed with an active independent variable

What is the most commonly used blocking variable

gender

What is the key when using blocking variables

the blocks should have some impact on your outcome/DV

What does a randomized block design flow chart look like

What is a repeated measured/within subject design

each subjects acts as his/her own control

What is the advantage of repeated measured/within subject design

controls for individual differences

Disadvantages of repeated measured/within subject design

practice/learning effect/ carry over effect

What is a learning effect

When a subject is exposed to a test over and over again, they will learn how to take the test better

What is a carry over effect

When a subject is exposed to multiple treatments, one treatment effect carries over up to the next

Is a repeated measured/within subject design truly an experiment

not exactly, but if multiple treatments are randomized, then yes

How can we combat learning and carry over effect in a repeated measured/within subject design

providing sufficient time for recovery

What is a sequential trials design

a version of RCT that allows for data to be collected and analyzed in “real-time”

• basically a large experiment consisting of many “little experiments”

When does a terminal decision occur with a sequential trials design

when one boundary is crossed

What is the problem with sequential trials design

ties get thrown out, and there tends to be a lot of them. This causes you to essentially get nowhere

How are sequential trials design kept track of