Randomized Controlled Trials

Question 1

What is the goal of a Randomized Controlled Trial (RCT)?

Answer 1

Test whether an intervention works by comparing it to a control condition

Question 2

What quality of RCTs make them the gold standard for drug studies?

Answer 2

Randomization as it reduces the effects of confounding

Question 3

How are patients separated into groups in parallel randomization?

Answer 3

The study sample is divided into two groups and different intervention/control are applied

Question 4

How are patients divided into groups in a cluster randomized RCT design?

Answer 4

Instead of individuals randomly separated between control/intervention groups, entire clusters of individuals are randomized

Ex. All patients at Pharmacy A receive intervention, while all patients at Pharmacy B receive placebo

Question 5

How are patients separated into groups when using cross-over randomization?

Answer 5

Study sample is randomly divided into groups and outcomes are evaluated. A period of time without interventions passes, and the groups switch intervention/control and a second set of outcomes are evaluated

Now researchers have data on intervention vs. Control in the same patient, the patient serves as their own control which reduces confounding in the study

Question 6

Why should a study be well-designed before it begins?

Answer 6

To limit bias in the study and outcomes. Pre-defined process reduces the ability to change the results to fulfill a preferred outcome. Also hold the researcher accountable for the integrity of the study

Question 7

What is power in regards to sample size in a research study?

Answer 7

This value is the minimum sample size that allows the study to reliably detect differences between groups

Question 8

What are the consequences of a study that is overpowered in terms of sample size?

Answer 8

There could be ethical concerns with unnecessary exposure to intervention

Cost considerations with a larger sample size

Question 9

What is the benefit of increasing sample size in a research study?

Answer 9

It can reduce chance in the findings of a given study

Question 10

What is the intervention compared against in RCTs?

Answer 10

1. Placebo/usual care
2. A different dose
3. A different drug/procedure
4. Standard treatment (most common control in drug studies)

Question 11

What are hard endpoints in a study?

Answer 11

These are the final events that the study is hoping to prevent

Ex. Death, stroke, MI

Question 12

What are the two types of research outcomes?

Answer 12

1. Objective (measurable): blood pressure, lipid levels
2. Subjective (patient interpretation): back pain

Question 13

What are surrogate endpoints in research studies?

Answer 13

These are outcomes that our study hopes to see change. Surrogate endpoints are correlated with hard endpoints

Ex. Blood pressure (surrogate endpoint) —> Stroke (hard endpoint)

Question 14

What are the limitations of surrogate endpoints?

Answer 14

The extent to which surrogate endpoints and hard endpoints are correlated is not always known

Question 15

What is the primary endpoint?

Answer 15

This is the main result measured at the end of the study to see the effect of the intervention

Question 16

What are secondary endpoints?

Answer 16

These are additional results of interest, but not the main focus of the study

These results can serve as the basis for future studies where they are the primary endpoints

Question 17

What are composite endpoints?

Answer 17

This is a primary endpoint that contains several events

Ex. MACE (Major Adverse Cardiovascular Events) looks at MI, stroke and death together instead of death (hard endpoint) alone

Question 18

What threat to internal validity does randomization reduce?

Answer 18

Confounding is reduced

Question 19

What are the qualities of well randomized groups?

Answer 19

1. Similar in things we can measure (ex. Age, sex, BP)
2. Similar in things that are unknown (ex. Genetics)

Question 20

What are the three methods of randomization?

Answer 20

1. Complete
2. Block
3. Stratified

Question 21

What are some qualities of complete randomization?

Answer 21

1. There are no limitations to randomization
2. won’t necessarily get equal numbers in each group (ex. Sample A: 52, Sample B: 48)

Question 22

What are some characteristics of block randomization?

Answer 22

Used to force balance in the number of subjects in each group

Ex. Block of 6 (6 subjects randomized (3 into invention, and 3 into control), followed by block of 10 (5 into intervention, and 5 into control), continue once all participants have been randomized

Question 23

What are some characteristics of stratified randomization?

Answer 23

Used to achieve similarities in certain baseline characteristics between all groups

Ex. Everyone under 65 is randomized, then everyone over 65 is randomized. This ensures both groups have the same age composition

Question 24

What is IIT in RCT study outcome analysis?

Answer 24

IIT (intention to treat)

When a study follows IIT, they analyze the data for all patients (even those that dropped out, died, etc.) and according to the group they were originally randomized to

IIT preserves the value of randomization and reasons for why patients left study

Question 25

What is blinding in a study?

Answer 25

This is when parties to a study are unaware of what study group a subject has been randomized into

Question 26

What are the consequences of known group assignment?

Answer 26

1. Subjects may report outcomes or adverse effects differently or behave differently
2. Physicians/investigators may report outcomes or events differently or treat subjects differently
3. Researchers may collect data, classify outcomes or events and interpret subject response differently

If any of the above occur, it affects the internal validity of the study (bias)

Question 27

What is an unblinded (open-label) study?

Answer 27

Participants, researchers, and study evaluators all know what group subjects have been placed into

Question 28

What is a single blinded study?

Answer 28

Study evaluators do not know group assignment, while researchers and participants know what group they fall under

Question 29

What is a double blind study?

Answer 29

This is the minimum standard

Either researcher of study evaluator do not know group assignement, but subjects do not know their group assignment

Question 30

What is a triple blinded study?

Answer 30

Neither study evaluators, researchers, and participants do not know group assignment

Used by drug studies hoping for drug approval (very rigorous blinding method)

Question 31

What is placebo effect?

Answer 31

This is the perceived or actual effect from an ineffectual or inactive treatment