Lecture 8

Question 1

Dictionary of epidemiology:

Answer 1

the process of making a study group and a
comparison group comparable with respect to extraneous factors

Question 2

Making groups as similar as possible is to account for

Answer 2

confounding

Question 3

Like randomization in experimental studies (wait!)
➢ Only difference:

Answer 3

exposure (intervention) status; making exposure groups similar in other
factors after randomization

Question 4

Matching cases to controls
Only difference:

Answer 4

outcome status; making outcome groups similar in other factors

Question 5

Matching in Case-control Studies

Answer 5

After selection of matching factor, for each case a control with the same characteristics will be selected

Question 6

Types of Matching

Answer 6

Individual matching
Frequency matching

Question 7

Individual matching

Answer 7

Performed participant by participant

Question 8

Frequency matchingProviding similar distributions of confounders in groups

Answer 8

Providing similar distributions of confounders in groups

Question 9

Matching in Cohort Studies

Answer 9

➢Exposed matched to unexposed (an effort to mimic randomization)
➢Less common, much less!
➢Expensive
➢Sometimes unpractical
➢May require control (competing risks, loss to F/U)

Question 10

Matching in Case-control Studies

Answer 10

After selection of matching factor, for each case a control
with the same characteristics will be selected
➢Analysis
➢Unit is not a person but a pair
➢Paired analysis
➢Statistical models are well developed

Question 11

Matched Example

Answer 11

We measure the ‘exposure’ status within the pairs
OR: ratio of discordant pairs (only cases exposed/only controls
exposed)

Question 12

James Lind (1716-1794)

Answer 12

➢Scottish naval surgeon
➢Conducted experiment with 12 scurvy victims
➢Each pair received different treatment
➢Pair receiving oranges and lemon recover
➢The 1st recorded randomized clinical trial

Question 13

Edward Jenner (1749-1823)

Answer 13

Experimental but neither randomized nor a control group

Question 14

Experimental Studies Emulate Controlled Laboratory
Experiments

Answer 14

➢In lab experiments, investigator regulates all important aspects of
experimental conditions: genetically similar animals, same physical
environment, same diet, same schedule, same route of administration of test
chemical. Only difference is the dissimilar test chemical.
➢Experimental studies among free-living humans never achieve same degree
of control, but many aspects of human experimental research emulate
principles of lab and/or animal research.
➢Ethical issues are rampant
➢History

Question 15

Ethical Issues are Rampant examples

Answer 15

Nazi human experimentation
Tuskegee Syphilis study
➢The “Monster Study”: children
> were randomized to positive speech therapy and
belittling to induce stuttering!

Question 16

The Process

Answer 16

1. Research Questions for Experimental Studies
2. Types of Experimental Studies
3. Study Population
4. Consent, Enrollment, Exposure Assignment
5. Minimizing Bias
6. Analysis

Question 17

Research Questions for Experimental
vs. Observational Studies

Answer 17

• Experimental Studies:
  Investigator intervenes
  >Research question involves
  prevention or treatment.
  >Feasible and ethical.
  >Small population level effect
  expected.
• Observational Studies:
  Investigator watches
  >Research question involves
  prevention, treatment, or causal
  factor.
  >Experimental study not feasible
  or ethical.
  >Moderate/large population level
  effect expected.

Question 18

Types of Experimental Studies:
Purpose of Trial

Answer 18

Prevention Trial
Agent given to healthy or high-risk individuals to prevent disease occurrence
➢Does removing lead contaminated soil prevent lead poisoning in high-risk urban children?
➢Does the drug tamoxifen lower the incidence of breast cancer in high-risk women?
Therapeutic (Clinical) Trial
Agent given to diseased individuals to treat or cure disease
➢Does the drug Herceptin lower the risk of recurrence and improve survival among
women diagnosed with breast cancer?

Question 19

Types of Experimental Studies:
Unit of Allocation

Answer 19

Individual Trial:
Community (cluster) Trial:

Question 20

Community (cluster) Trial:

Answer 20

➢Treatment allocated to entire community
➢Study impact of drinking water fluoridation on frequency of dental caries in one
community (e.g., Newburgh, NY) versus no fluoridation in a similar community (Kingston, NY)

Question 21

Individual Trial:

Answer 21

➢Treatment allocated to individuals
➢Study effectiveness of treatment with two drugs versus three drugs among adults
infected with HIV

Question 22

Study Population
Considerations

Answer 22

➢Choice of population depends on purpose of trial
➢Specific inclusion/exclusion criteria (eligibility criteria) based on
scientific, safety, and practical considerations
➢ People in population of interest, at risk for outcome, among whom intervention could be effective
➢ People with a high likelihood of compliance with treatment, likely to be followed for total study period
➢ May need to exclude certain people, such as those with conditions for which drug under study is
contraindicated

Question 23

Generalizability

Answer 23

The extent to which the results from a study can be generalized (or extended) to people who did not participate in the study.

Question 24

Reference population:

Answer 24

group to whom results are applicable/generalizable
➢ All humans
➢ All men, all women
➢ Urban children at risk of lead poisoning

Question 25

Recruitment of study population is important because

Answer 25

it directly impacts to
whom the results generalize once the study is over.
➢If there are many inclusion/exclusion criteria, study loses generalizability.
➢ Reference population: group to whom results are applicable/generalizable
➢ All humans
➢ All men, all women
➢ Urban children at risk of lead poisoning

Question 26

Consent Process, Enrollment, Exposure Assignment

Answer 26

➢All eligible individuals must give informed consent before enrolling in a trial.
➢Informed consent includes clear explanation of research goals and methods,
risks and benefits of participating, assurance of confidentiality, right to
withdraw, etc.
➢Once consented and enrolled, treatment assignment occurs.
➢Random assignment vs. non-random assignment

Question 27

Key Concept: Randomization

Answer 27

Each study participant has the same probability of receiving treatment

Question 28

How randomization is achieved:

Answer 28

➢Toss a coin: heads = A, tails = B
➢Computer-generated randomization
➢Other assignment schemes have potential problems.
➢Subject self-selects
➢Day of week, order of visit, etc.
➢Note: Randomization prevents biased group assignment.

Question 29

Allocating Participants into Experimental and
Control Groups

Answer 29

Randomization means that the assignment of participants into
Experimental and Control groups is random
This should create similarity between groups for potential
confounding variables (e.g., age)

Question 30

Sometimes simple randomization doesn’t work especially when

Answer 30

Chance differences between groups due to sampling error are more likely to occur when the study sample
is small (<100 per group). In this case, stratified randomization should be considered.

Question 31

Randomization Balances

Answer 31

Confounders

Question 32

Randomization creates two groups that are

Answer 32

the same except one group has the treatment and one group
does not.

Question 33

What does “same” mean?

Answer 33

➢ At baseline, treatment and comparison group characteristics are balanced: For example, exposed and unexposed
groups have same % males, % <18 years, % persons with hypertension, etc.
➢ With randomization, this occurs for both known and unknown confounders.
This only works when:
➢ Study is large enough
➢ Treatment assignment is not influenced by investigator

Question 34

How do respondent and observer (information) biases happen in observation studies?

Question 35

Minimizing Information Bias:

Answer 35

Blinding (Masking)
Placebos
Compliance

Question 36

Blinding or Masking =

Answer 36

Method of ensuring that participants and/or study investigators have
no knowledge of whether a study participant has been assigned to the treatment or
comparison group

Question 37

Single-blind:

Answer 37

study participant does not know whether they are receiving treatment or no treatment

Question 38

Double-blind:

Answer 38

neither the (1) study participant nor the (2) study investigator administering the treatment
knows who is receiving treatment or no treatment.

Question 39

Triple-blind:

Answer 39

neither the (1) study participant nor the (2) study investigator administering the treatment
nor the (3) study investigator monitoring the effects of the treatment knows who is receiving treatment or
no treatment

Question 40

Blinding is not always possible because:

Answer 40

certain interventions such as surgery and psychotherapy, exercise
regimens, diet, with serious side effects.

Question 41

Why use a placebo?

Answer 41

➢ Makes exposed and unexposed groups’ experiences as comparable as possible (this
goal harkens back to lab experiments)
➢ One method of blinding

Question 42

Placebos cannot always be used because:

Answer 42

➢ Interventions such as surgery, exercise, diet, etc.
➢ Placebos are not always ethical; often use current standard of care instead of
placebo

Question 43

“Placebo Effect” =

Answer 43

Participants assigned to placebo group improve because they are
told that they will. This stems from the power of suggestion.

Question 44

Compliance =

Answer 44

Following the study protocol exactly as required throughout the course of the trial

Question 45

Goals of compliance

Answer 45

Goal # 1: Have groups be as alike as possible on other important characteristics (randomization)
➢ Goal # 2: Have groups be as different as possible on exposure (intervention)
➢ No contamination
➢ For example, in Physicians’ Health Study: Compliance involved taking pill every day
➢ Deviations from protocol can occur for many reasons: side effects, illness, level of interest, and
length of follow-up
➢ Worst: contamination. “Inadvertent application of the experimental procedure to the control group”
or vise versa

Question 46

Importance of Compliance

Answer 46

➢Noncompliance tends to make treatment and comparison groups more alike.
➢This reduces ability to detect a difference (in the outcome due to exposure) between
groups.
➢ Remember: we are comparing the difference between treatment and comparison
groups. If they become more similar, we will not observe a difference, even if one
exists.
➢ Thus, we do many things to ensure good compliance.