Clinical Trial Designs

Question 1

List eight advantages of proper clinical trial design

Answer 1

1. Allows investigators to satisfy ethical constraints.
2. Permits efficient use of scarce resources.
3. Isolates the treatment effect of interest from confounders.
4. Controls precision
5. Reduces selection bias and observer bias
6. Minimizes and quantifies random error or uncertainty
7. Simplifies and validates the analysis.
8. Increases the external validity of the trial.

Question 2

Clinical trial design should accomplish the following 6 things.

Answer 2

1. Quantifying reduce errors due to chance
2. Reduce or eliminate bias.
3. yield clinically-relevant estimates of effects and precision.
4. Be simple in design and analysis.
5. Provide a high degree of credibility reproducibility and external validity.
6. Influence future clinical practice.

Question 3

Give two examples of uncontrolled observational study types

Answer 3

A case report and a case series.

Question 4

A case report can only demonstrate that what?

Answer 4

A clinical event of interest is possible.

Question 5

Can a k-series prove efficacy of a treatment? Why or why not?

Answer 5

A case series and case reports are susceptible to large selection biases.

Question 6

Difference between database analysis and case series.

Answer 6

A database analysis may have a control group depending on the data source.

Question 7

Two types of epidemiologic studies

Answer 7

Case control or cohort design, both comparative observational studies.

Question 8

Give an example of an epidemiological study.

Answer 8

a trial that measures the risk of illness or death in an expose population compared to that risk in an identical unexposed population.

Question 9

What’s a case-control study?

Answer 9

A retroactive analysis which identifies cases, subjects with the disease, and controls, subjects without the disease.

Question 10

What bias is inherent to a case-control study and why?

Answer 10

Selection bias. The investigator selects cases and controls retrospectively.

Question 11

What is a prospective cohort study?

Answer 11

Individuals are followed forward in time with subsequent evaluations to determine which individuals develop into cases.

Question 12

Pro and con of prospective cohort design

Answer 12

prospective studies tend to have fewer design problems and less bias than retrospective studies but they are more expensive with respect to time and cost.

Question 13

What type of trial contains all of the key components of a true experimental design?

Answer 13

A replicated and controlled clinical trial.

Question 14

Experimental unit vs. Observational unit

Answer 14

Experimental unit receives the treatment directly. Observational unit has measurements taken on it.

Question 15

Give an example when the experimental unit is different than the observational unit.

Answer 15

Treatment administered to mother rat (experimental unit) observational unit could be pups.

Question 16

Factor definition

Answer 16

Variables that are controlled

Question 17

One-way design vs. Two-way design. Give example of each.

Answer 17

One-way design is only one factor, treatment with a few levels.
Two-way factorial design tests various combinations of two factors. For example temperature and pressure, or various combinations of doses of two chemotherapeutic agents comprising the treatment arms.

Question 18

Parallel vs. Crossover design

Answer 18

In a parallel design patients remain on the same treatment they are randomized to throughout the course of the trial.

Question 19

Randomization removes what bias.

Answer 19

Selection

Question 20

Selection bias occurs when?

Answer 20

A physician decides treatment assignment and systematically selects a certain type of patient for a particular treatment.

Question 21

Blocking and stratification are used to control what?

Answer 21

Variation.

Question 22

Stratification example

Answer 22

Assume younger patients are healthier. Therefore stratify into age groups. For example age 18 to 30, age 31 to 50 etc. Allow limited number of people into each group.

Question 23

Additional benefit of stratification

Answer 23

Interim subgroup analysis.

Question 24

Treatment masking is?

Answer 24

Blinding

Question 25

Blinding ensures what?

Answer 25

Objectivity in person measuring outcome.

Question 26

Example of when blinding is impossible

Answer 26

Surgical procedure.

Question 27

Confounding definition

Answer 27

The effect of other relevant factors on the outcome that may be incorrectly attributed to the difference between study groups.

Question 28

Internal validity refers to

Answer 28

Observed difference in outcome between study groups is real and not due to bias chance or confounding.

Question 29

External validity refers to

Answer 29

How well study results can be generalized to a broader population.

Question 30

What is a large simple trial?

Answer 30

the trial whose purpose it is to attempt to discover small advantages of a treatment that is expected to be used in a large population.

Question 31

What is a pragmatic trial?

Answer 31

Pragmatic trials study treatment in practices outside academic medical centers. This can involve a broad range of clinical practices.

Question 32

Not all trials aim to prove superiority of new treatment. Explain.

Answer 32

Some studies test equivalency and non-inferiority.

Question 33

Explain what a TM trial is.

Answer 33

Treatment mechanism; ie pKs looking at bioavailability, or studying an operative procedure.

Question 34

DF trial looks for what?

Answer 34

DF=dose finding. Looks for MTD.

Question 35

Phase IV study

Answer 35

Expanded safety study. After FDA approval

Question 36

Prevention trial is

Answer 36

Is done in healthy individuals to determine if there’s prevents a disease.

Question 37

Diagnostic or screening trial.

Answer 37

Used to determine if agent can diagnose a disease.