Randomized Controlled Trials

Question 1

Who was the first person thought to conduct an RCT?

Answer 1

Sir Austin Bradford Hill

Question 2

What is an RCT?

Answer 2

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

Question 3

How are subjects assigned to groups in RCTs?

Answer 3

randomized
-subjects assigned to study groups randomly
-equal probability of being assigned to either group (intervention or control)

Question 4

True or false: RCTs can only contain two groups

Answer 4

false
can be >2 groups

Question 5

What are the three types of RCT designs?

Answer 5

parallel:
-intervention and control group and then follow both over time and compare results
cluster:
-clusters of individuals are randomized instead of individuals
-often used in studying patient care
cross over:
-two groups, follow them and then swap the groups (control becomes intervention, vice versa)
-uses a washout period
-compares self to self

Question 6

What are the advantages and disadvantages of cross-over RCTs?

Answer 6

advantages:
-less people needed
-minimizes confounding
disadvantages:
-complex
-sometimes a longer washout period

Question 7

True or false: you can conduct an RCT before designing the trial

Answer 7

false
must design before it begins

Question 8

Why do you need to make sure a study is designed before it begins?

Answer 8

to limit bias

Question 9

What should be considered when choosing a population for an RCT?

Answer 9

start with a defined population
-who we want to study
-where do we get them from
specific inclusion and exclusion criteria
-much more strict in RCT
-can limit generalizability
sample size (n)
-how many subjects do we need?
-optimal number is determined statistically

Question 10

What is the study power?

Answer 10

ability to show a difference between groups if a difference really exists
-n too low=underpowered
-n too high=unnecessary exposure, more resources

Question 11

When should sample size for an RCT be determined?

Answer 11

before the study starts

Question 12

Give examples of interventions that are specific and well done.

Answer 12

drug: dose, regimen, delivery method, follow-ups, length of therapy, etc
procedure: whats involved, timing, follow-up, length of intervention

Question 13

What are some examples of what we can compare our intervention to?

Answer 13

nothing (placebo/usual care)
different dose
a different drug/procedure
standard treatment

Question 14

What is the key takeaway regarding the treatment of the intervention and control groups?

Answer 14

they should be treated the same, the only difference is the intervention

Question 15

Differentiate between an objective endpoint and a subjective endpoint.

Answer 15

objective: measurable (ex: BP, LDL)
subjective: subjects interpretation (ex: back pain)

Question 16

Differentiate between hard endpoints and surrogate endpoints.

Answer 16

hard:
-major and non-disputable
-well defined, no subjectivity
surrogate:
-proxy or estimate
-can shorten duration of study

Question 17

Differentiate between primary endpoint and secondary endpoint.

Answer 17

primary endpoint:
-main result that is measured at the end of the study to see the effect of the intervention
secondary endpoint:
-additional results of interest but not the main focus
-caution when interpreting as study wasnt designed around them
-never make a decision based on a secondary endpoint

Question 18

What is a composite endpoint?

Answer 18

a primary endpoint that contains several events

Question 19

What are the benefits and disadvantages of composite endpoints?

Answer 19

benefits:
-less subjects needed
disadvantages:
-hard to determine the true effect of the intervention on each of the event types

Question 20

What are the results of doing randomization correctly?

Answer 20

ensures groups are similar in all aspects
-similar in things we can measure (age, sex, etc)
-similar in things we cant measure (genetics)

Question 21

What is an important aspect of randomization?

Answer 21

should not be able to tell which group will be assigned next

Question 22

What are the three methods of randomization?

Answer 22

complete
block
stratified

Question 23

What is complete randomization?

Answer 23

no limitations-complete randomization
wont necessarily get equal numbers in each group

Question 24

What is block randomization?

Answer 24

used to force balance in the number of subjects in each group
ex: block of 6=for every 6 subjects randomized,3 in intervention and 3 in control

Question 25

What is stratified randomization?

Answer 25

used to achieve similarities in certain baseline characteristics
usually randomization is centralized and offsite (allocation concealment)

Question 26

Differentiate between ITT and per protocol.

Answer 26

ITT: analyzing the data for ALL patients and according to the group they were originally randomized to
-preserves the value of randomization
per protocol: analyzing data from subjects who completed the study or followed protocol exactly

Question 27

What is blinding?

Answer 27

unaware of what study group a subject is in

Question 28

What can occur if group assignment is known?

Answer 28

subjects may report outcomes or AE differently or behave differently
investigators may report outcomes differently or treat subjects differently
researches may collect data, classify outcomes, and interpret responses differently

Question 29

True or false: the more subjective an outcome is, the less critical blinding is

Answer 29

false
the more OBJECTIVE the outcome is, the less critical blinding is

Question 30

What is the placebo effect?

Answer 30

perceived or actual effect from an ineffectual or inactive treatment
-conscious belief about drug/treatment
-subconscious association between being treated and recovery
-can be positive or negative
-sugar pill, saline, sham procedure