DrugEpi 3-2 Experimental Study - Buprenorphine Example Module 3 Introduction Content Area: Analytical Epidemiology Essential Question (Generic): Is there

DrugEpi 3-2 Experimental Study - Buprenorphine Example

Module 3 IntroductionContent Area: Analytical EpidemiologyEssential Question (Generic): Is there an association between the hypothesized cause and the disease?Essential Question (Drug Abuse Specific): Is there an association between the hypothesized cause and drug use?Enduring Epidemiological Understanding: Causal hypotheses can be tested by observing exposures and diseases of people as they go about their daily lives. Information from these observational studies can be used to make and compare rates and identify associations.

Synopsis

In Module 3, students explore how hypotheses are tested epidemiologically. Students begin to uncover and develop the following epidemiological concepts and skills: the meaning of the term “association;” the need for a control group; uses of the 2x2 table in calculating risks and relative risks; experimental study design; the importance of ethics in human research; observational study designs used in epidemiology; and the strengths and limitations of each design.

Lesson 3-1: Associations and the 2x2 TableLesson 3-2: Experimental Study - Buprenorphine ExampleLesson 3-3: An Actual Randomized Controlled TrialLesson 3-4: Observational Studies of Natural Experiments - Sensation-Seeking ExampleLesson 3-5: Fundamentals of Study DesignLesson 3-6: Study Design Exercises


Module 3 - Analytical Epidemiology

Lesson 3-2 Experimental Study

- Buprenorphine Example

Content

• Continued study of the concepts of “association” and hypothesis-testing• Use of the 2x2 table as a way to numerically express risk and relative risk• Example of an experimental study to examine beneficial health-related effects• Understanding of population sampling and inference• Demonstration of the necessity and impact of a control group

Big Ideas• An experimental study of a sample of a population can test a hypothesized

association between an exposure and a beneficial health-related outcome• In order for an experimental study to be meaningful, it has to include controls • The 2x2 table, which includes consideration of a control group, is a tool used

to express the numbers of people with and without the exposure, and with and without the outcome, and clarifies how rates and relative risks are calculated.

This project is supported by a Science Education Drug Abuse Partnership Award, Grant Number 1R24DA016357-01, from the National Institute on Drug Abuse,

National Institutes of Health.


1. How is this disease distributed?

Health-related conditions and behaviors are not distributed uniformly in a population. They have unique distributions that can be described by how they are distributed in terms of person, place, and time.

2. What hypotheses might explain the distribution of disease?

Clues for formulating hypotheses can be found by observing the way a health-related condition or behavior is distributed in a population.

3. Is there an association between the hypothesized cause and the disease?

Causal hypotheses can be tested by observing exposures and diseases of people as they go about their daily lives. Information from these observational studies can be used to make and compare rates and identify associations.

4. Is the association causal?

Causation is only one explanation for an association between an exposure and a disease. Because observational studies are complicated by factors not controlled by the observer, other explanations also must be considered.

5. What should be done when preventable causes of disease are found?

Policy decisions are based on more than the scientific evidence. Because of competing values - social, economic, ethical, environmental, cultural, and political factors may also be considered.

Essential Questions Enduring Understandings

Where are we?


What do we mean when we say that there is an association between two things?

Associated

Tied Related

Linked

Things that are associatedare linked in some way that makes them

turn up together.

Review of the Concept of Association


Suicide Higher in Areas with Guns

Smoking Linked to Youth Eating Disorders

Snacks Key to Kids’ TV- Linked Obesity: China Study

Family Meals Are Good for Mental Health

Lack of High School Diploma Tied to US Death

Rate

Study Links

Spanking to

Aggression

Breakfast Each Day May Keep Colds Away

Study Concludes: Movies Influence

Youth Smoking

Study Links Iron

Deficiency to Math

Scores

Kids Who Watch R-Rated Movies More Likely to Drink, Smoke

Pollution Linked with Birth Defects in US Study

Depressed Teens More Likely to Smoke

Review - Things That Turn Up Together


Review - Module 3 is about Analytical Epidemiology

Analytical epidemiology can test hypotheses

about associations

Epidemiologic studies that are concerned with determinants of disease

and the reasons for relatively high or low

frequencies of disease in specific population

subgroups


Hypothesis about

associations

Generate

Descriptive Epidemiology

Test

Analytical Epidemiology

An unproven idea, based on observation or reasoning, that can be supported or refuted through investigation

An educated guess

Hypotheses in epidemiology are statements that suggest associations between an exposure and an outcome

Review - Epidemiology and Associations


Hypothesis:

Buprenorphine will stop heroin addicts from using heroin.

Testing Hypotheses


Sample 100

Heroin Addicts

10 Weeks

79 Heroin Addicts Tested Positive for Heroin

Trial 1



Handout


Bupe

Tested Positive for Heroin Total

10079 21

Tested Negative for Heroin

Trial 1



When you can measure what you are speaking about, and express it in numbers, you know something about it.

Lord Kelvin

But when you cannot measure it, when you cannot express it in

numbers, your knowledge is of a meager and unsatisfactory kind.


A measure of how often an outcome occurs in a defined population in a defined period of time. It consists of a numerator and a denominator.

RATE

The numerator is the number of people in the population or sample who experienced the outcome and the denominator is the total number of people in the population or sample.

Population / Sample

Outcome

Denominator

Numerator

Review - Express It In Numbers


Rate: A measure of how often an outcome occurs in a defined group of people

in a defined period of time.

Risk: The likelihood of an outcome occurring in a defined group of people in a defined time

period.

Concepts of Rate and Risk


Express It In Numbers

… the rate of positive heroin tests is 79/100 positives per 10-week period

79 tested positive for heroin 100 study

subjects

Numerator

Denominator


Trial 1

Bupe


10079 21


79

100or 79 %

Tested Rate of Using Heroin

Calculating a Rate / Risk in Trial 1


Process of predicting from what is observed in a sample to what is true for the entire population.

Inference


Trial 1

Bupe


10079 21


79

100or 79 %


What Can Trial 1 Tell Us About the Hypothesis?

What does this tell you about the hypothesis?


People who participate in a trial, but do not get the treatment.

People whose results are compared to the group that

was treated.

Control Group


Bupe


10079 21


79

100or 79 %


Including a Control Group

Extend and label the table to include a control group.


Bupe


10079 21


79

100or 79 %


100?

100or ? %No Bupe

Including a Control Group


79

100or 79 %


?

100or ? %

Total

1002179

100

Tested Positive for Heroin


Bupe

No Bupe

Exposure

Outcome / Disease

a b

c d

2x2 Table


A cross-classification of data where categories of one variable are presented in rows and categories of another variable

are presented in columns.

The simplest contingency table is the 2x2 table

Review - Contingency Table


Sample 100

Heroin Addicts

10 Weeks

79 Heroin Addicts Tested Positive for Heroin

Trial 1

Testing Hypotheses - Buprenorphine Trial 1


Total

?

100? %

a b

c d

Bupe




No Bupe

Trial 2

2x2 Table for Trial 2

100

100?

100? %


E

Assigned

E

O

O

O

OHeroin AddictsVolunteer Heroin Addicts

Study Diagram

Time


Trial 2 Study Sample

Assign Volunteers to 2 Groups Trial 2


Trial 2 Results

Total

79

100or 79%

a b

c d

79 21Bupe



100


Trial 2

or79 21 10079

10079%No Bupe


The value obtained by dividing one quantity by another.

Ratio


Comparing Rates - A Risk Ratio for Trial 2

Total

79

100or 79%

a b

c d

79 21Bupe



100


Trial 2

or79 21 10079

10079%

Ratio: The value obtained by dividing one quantity by another

Risk Ratio: The ratio of two risks

1

Risk Ratio

No Bupe


A Formula for Comparing Rates

Total

79

100or 79%

a b

c d

79 21Bupe



100


or79 21 10079

10079%

Risk Ratio: The ratio of two risks.

1

Risk Ratio

Create a formula

a

a + b

c

c + dNo Bupe


Risk Ratio

Total

79

100or 79%

a b

c d

79 21Bupe



100


or79 21 10079

10079%

1

Risk Ratio

Trial 2

Relative Risk: The ratio of the risk of an outcome among the exposed to the risk of the outcome among the unexposed.

Relative Risk

Relative Risk

No Bupe


Trial 2 Inference

Total

79

100or 79%

a b

c d

79 21Bupe



100


or79 21 10079

10079%

Inference: Process of predicting from what is observed in a sample

to what is occurring in the entire population

The inference here is that there is no effect of Buprenorphine

1

Risk Ratio

Trial 2

Relative Risk

No Bupe


Total

?

100? %

a b

c d

Bupe




Trial 3


100

100?

100? %

No Bupe



Buprenorphine Trial 3No Buprenorphine


Trial 3 Results

Total

79

100or 79%

a b

c d

79 21Bupe



100


Trial 3

or38 62 10038

10038%No Bupe


Total

79

100or 79%

a b

c d

79 21Bupe



100


Trial 3

or38 62 10038

10038%

Trial 3 Relative Risk

Relative Risk

2.08


No Bupe


Total

79

100or 79%

a b

c d

79 21Bupe



100


Trial 3

or38 62 10038

10038%


Relative Risk

2.08

The heroin addicts who received Buprenorphine were ____ times as likely to use heroin as those

who did not receive Buprenorphine.2.08

No Bupe


Total

79

100or 79%

a b

c d

79 21Bupe



100


Trial 3

or38 62 10038

10038%

Trial 3 Inference

Relative Risk

2.08


to what is occurring in the entire population.

No Bupe


Total

?

100? %

a b

c d

Bupe




Trial 4


100

100?

100? %

No Bupe



Buprenorphine Trial 4No Buprenorphine


Trial 4 Results

Total

79

100or 79%

a b

c d

79 21Bupe



100


Trial 4

or94 6 10094

10094%No Bupe


Total

79

100or 79%

a b

c d

79 21Bupe



100


Trial 4

or94 6 10094

10094%


Relative Risk

.84


No Bupe


The heroin addicts who received Buprenorphine were ____ times as likely to use heroin as those

who did not receive Buprenorphine.

Total

79

100or 79%

a b

c d

79 21Bupe



100


Trial 4

or94 6 10094

10094%


Relative Risk

0.84

0.84

No Bupe


Total

79

100or 79%

a b

c d

79 21Bupe



100


Trial 4

or94 6 10094

10094%

Relative Risk

0.84

Trial 4 Inference


to what is not observed in a population.

No Bupe


Total

79

100or 79%

a b

c d

79 21Bupe



100


Trial 1

Review of the Four Hypothetical Trials

What do the results of tell us about the hypothesis that Buprenorphine will stop heroin addicts from using heroin?

Nothing


10079 219079

100

or 79%

Nothing

Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Trial 1 Trial 2

Trial 3 Trial 4


Bupe

No Bupe

Bupe

No Bupe

Bupe

Total

Tested Positive

for Heroin

Rate of Using

Heroin


Relative Risk

No Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Relative Risk

Total

Tested Positive

for Heroin

Rate of Using

Heroin


Relative Risk

10079 219079

100

or 79%

10079 219079

100

or 79%

10079 219079

100

or 79%


10079 219079

100

or 79%

Nothing

Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Trial 1 Trial 2

Trial 3 Trial 4


Bupe

No Bupe

Bupe

No Bupe

Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Relative Risk

No Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Relative Risk

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Relative Risk

10079 219079

100

or 79%

10079 219079

100

or 79%

10079 219079

100

or 79%

10079 219079

100

or 79%

There is no association between Bupe and heroin use.

1


10079 219079

100

or 79%

Nothing

Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Trial 1 Trial 2

Trial 3 Trial 4


Bupe

No Bupe

Bupe

No Bupe

Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Relative Risk

No Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Relative Risk

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Relative Risk

10079 219079

100

or 79%

10079 219079

100

or 79%

10079 219079

100

or 79%

10079 219079

100

or 79%

10038 629038

100

or 38%


Bupe is associated with an increase in heroin use.

1

2.08


10079 219079

100

or 79%

Nothing

Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Trial 1 Trial 2

Trial 3 Trial 4


Bupe

No Bupe

Bupe

No Bupe

Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Relative Risk

No Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Relative Risk

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Relative Risk

10079 219079

100

or 79%

10079 219079

100

or 79%

10079 219079

100

or 79%

10079 219079

100

or 79%

10038 629038

100

or 38% 10094 69094

100

or 94%


Bupe is associated with a decrease in heroin use.

1

.842.08


10079 219079

100

or 79%

Nothing

Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Trial 1 Trial 2

Trial 3 Trial 4


Bupe

No Bupe

Bupe

No Bupe

Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Relative Risk

No Bupe

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Relative Risk

Total

Tested Positive

for Heroin

Rate

of Using

Heroin


Relative Risk

10079 219079

100

or 79%

10079 219079

100

or 79%

10079 219079

100

or 79%

10079 219079

100

or 79%

10038 629038

100

or 38% 10094 69094

100

or 94%


Bupe is associated with a decrease in heroin use.Bupe is associated with an increase in heroin use.

1

.842.08

Nothing

Compared to what?


Big Ideas in this Lesson (3-2)

• An experimental study of a sample of a population can test a hypothesized association between an exposure and a beneficial health-related outcome

• In order for an experimental study to be meaningful, it has to include controls

• The 2x2 table, which includes consideration of a control group, is a tool used to express the numbers of people with and without the exposure, and with and without the outcome, and clarifies how rates and relative risks are calculated.

• .

This project is supported by a Science Education Drug Abuse Partnership Award, Grant Number 1R24DA016357-01, from the National Institute on Drug Abuse,

National Institutes of Health.

Re-Cap


6.

Where are we?Next Lesson

Buprenorphine

Buprenorphine & Naloxone

Placebo

An Actual Randomized Controlled Study

Documents

DrugEpi 3-2 Experimental Study - Buprenorphine Example Module 3 Introduction Content Area: Analytical Epidemiology Essential Question (Generic): Is there