Study Designs

Question 1

What are the types of study designs? And how are they different?

Answer 1

Interventional- places subjects in forced group allocation and randomizes groups and can prove causation.

Observational- observing the patient and giving no interventions. Applies no exposure or group allocation

Question 2

What are the phases of an interventional study? And describe them?

Answer 2

Pre-clinical- prior to human investigation-bench and animal research.

Phase 1- small N, healthy volunteers, short duration, checking for safety, and pharmacokinetics.

Phase 2- larger N, medium duration, commonly use patients with disease of interest, safety a concern.

Phase 3- right before FDA approval- efficacy of drug is primary focus- superiority, equivalency, and non-inferiority.

Phase 4- post-marketing- checking for long-term effects in a large population of diseased patients. Expanded patient diversity.

Question 3

What are the advantages of interventional study?

Answer 3

They prove causation.

Question 4

What are the disadvantages of interventional studies.

Answer 4

Money
Cost/complexity
Ethical reasons
Generalizability-external validity

Question 5

What are the interventional study types?

Answer 5

Explanatory- not flexible-no dose changes an less realistic to actual treatment.

Pragmatic- more realistic to patient treatment- doesn’t use placebo- allows co morbidities

Question 6

What are the two types of study designs? And what are their sub groups?

Answer 6

Simple- randomized once and only tests one hypothesis.
Factorial- randomized more than once and tests 2 or more hypotheses.

The subgroups are parallel and cross over

Question 7

What phase must happen before groups switch and a cross-over takes place?

Answer 7

Wash-out

Question 8

What is the lead-in

Answer 8

The practice phase that can include a wash out. Can account for placebo effect and Hawthorne effect.

Question 9

What’s an advantage of crossover?

Answer 9

Allows for a lower sample population

Question 10

What are the disadvantages of crossover?

Answer 10

Only good for long term, not curable diseases.
Takes longer
Treatment by period
Smaller N but only if variance within groups is smaller than between groups
Complexity

Question 11

What are the types of outcomes/end points?

Answer 11

Primary, secondary, tertiary etc and composite.

Question 12

What are patient oriented outcomes vs surrogate markers?

Answer 12

Patient ortiented outcomes are life changing such as death stroke MI.

Surrogate markers are usually risk factors like blood pressure and cholesterol.

Question 13

What the difference between non random and random sample selection?

Answer 13

Non-random doesn’t give everyone an equal choice of being allocated into any group.
Random- everyone has an equal chance at being allocated into any group.

Question 14

What is the purpose of randomization?

Answer 14

To make the groups equal

Question 15

Which table gives group characteristics and what value determine if the groups are equal?

Answer 15

Table 1 and the p value

Question 16

What are the three types of randomization?

Answer 16

Simple- equal chance for being in any group.
Blocked- forced equality
Stratified- same level of smokers in each group.

Question 17

What are the different ways of masking?

Answer 17

Single-blind: only subjects are masked
Double blind- both researcher and subjects are masked.
Open-label: neither subject nor researcher is blinded. Only good for objective readings like BP readings.

Question 18

What are dummy therapy and double dummy studies?

Answer 18

dummy therapy- placebo used

Double dummy- more than one placebo used.

Question 19

What are the placebo affect and the Hawthorne affect?

Answer 19

Placebo- feeling better because of attention (psychological)

Hawthorne- reporting positive results to please investigators.

Question 20

What is post-hoc sub group analysis?

Answer 20

Fishing for data, must be prospectively planned.

Question 21

What are ways to manage drop outs?

Answer 21

Keep them via
intent to treat: either use their last assessment or their baseline
* conservative-saves randomization-preserves baseline-maintains statistical power.

Ignore them via:
Per protocol - they must complete a certain percentage of the study to be considered.
Compliance must be predetermined.
* overestimates and reduces generalizability.

Question 22

What is as treated?

Answer 22

Ignores group assignments, allows patients to switch groups.

Question 23

What are ways to test for compliance? And improve compliance?

Answer 23

Drug levels
Pill counters
Bottle counter tops

~

Frequent communication
Treatment alarms
Dosage containers and medication blister packs

Question 24

What are case control studies?

Answer 24

OBSERVATIONAL studies that know if an individual is diseased or not but tries to determine exposure.

Question 25

Are case control studies retrospective or prospective?

Answer 25

Retrospective

Question 26

What are the strengths of case control studies?

Answer 26

• Good for assessing multiple exposures of one outcome.
• Good when diseases are rare
• calculating OR
• less expensive
• useful when ethical issues are a roadblock
• useful for dynamic populations
• useful when disease has a long incubation period.

Question 27

When selecting cases what is so important?

Answer 27

That they are diagnosed correctly! You want to avoid misclassification.

Question 28

Which is more difficult and why, selection of cases or controls?

Answer 28

Selection of controls because they must match up to the cases as accurately as possible.
It’s also the major determination on if the study is valid (internal validly)

Question 29

Controls are randomly selected. How is this different from randomization?

Answer 29

Randomly selected means a number of people are randomly picked from a population.

Randomization is systematically ensuring that 2 groups are equal.

Question 30

Where do the controls come from?

Answer 30

Institutions/organizations
Friends/spouses
Outbreak sources

Question 31

Is is possible to be a case and a control in the same study?

Answer 31

Yes,
In an outbreak with multiple exposures
In change of risk (seasonal)

Question 32

What is a Case-crossover design?

Answer 32

A case control study that addresses the issue of temporality.

Subjects are their own controls during times when they’re not at risk.

Question 33

What is a Nested Case Control study?

Answer 33

A case control study that is conducted after or from a cohort study.

Question 34

Where do the samples Coke from I’m a nestled case control study?

Answer 34

Survivor sample- non-diseased people who never got sick.
Base sampling- non-diseased at the start of the study period.
Risk set-

Question 35

What are selection and recall bias?

Answer 35

Selection- bias when selecting subjects

Recall- subjects not recalling information accurately

Question 36

What are the 2 types of matching?

Answer 36

Individual and group