Topic 6: Sample Size

Question 1

What three things do we need enough participants for

Answer 1

To be generalisable, to estimate the treatment effect precisely, to have a good chance of reliably detecting a treatment effect, or to conclude no treatment effect if the results don’t show it.

Question 2

What things aside from validity do we need to consider in terms of sample size

Answer 2

Ethics - exposing to risk. Economics - may be an upper limit to sample size due to cost.

Question 3

What are the three main kinds of endpoint

Answer 3

Continuous, binary, time to event

Question 4

When comparing proportions, what kind of regression is used

Answer 4

Logistic regression (binomial)

Question 5

When comparing rates, what kind of regression is used

Answer 5

poisson regression

Question 6

When comparing means between treatment groups, what kind of regression is used

Answer 6

Linear

Question 7

What are the 6 key considerations in determining sample size (Think sample size formula)

Answer 7

Nature of primary outcome, method of analysis, what results are anticipated in control, treatment difference to be detected, variability of the response, degree of certainty needed to detect a treatment difference.

Question 8

How do we know the standard deviation of endpoint and the results anticipated in the control group?

Answer 8

Prior data from similar trials

Question 9

What is a type 1 error

Answer 9

False positive

Question 10

What is a type 2 error

Answer 10

False negative

Question 11

What does increasing the sample size do the type 1 and 2 error rates

Answer 11

Reduces them

Question 12

When do you declare statistical significance

Answer 12

When the test statistic lies beyond the threshold (critical value) determined by the type 1 error rate (the significance level).

Question 13

How does the sample size formula change when changing what is being compared in the analysis

Answer 13

The form of the standard error is different

Question 14

Do you need a smaller or larger sample size to detect a smaller treatment difference

Answer 14

Larger

Question 15

If we reduce the power needed, what does this do to the sample size

Answer 15

Reduces sample size needed

Question 16

When the standard deviation of the outcome is larger, what does this do to required sample size

Answer 16

Larger sample size needed.

Question 17

What does an imprecise estimate of the true effect say about the conifidence intervals

Answer 17

Wide confidence intervals around the estimate

Question 18

Give three ways to increase sample size

Answer 18

Increase accrual rate, relax scientific requirements, run a small pilot study.

Question 19

How can you increase the accrual rate

Answer 19

Multi-centre trials, relax eligibility

Question 20

How do pilot studies help when considering sample size

Answer 20

Give more accurate estimates of the various parameters we need in our sample size calculation.

Question 21

Give 3 things that may affect sample size, and therefore that sample size can be inflated to account for

Answer 21

Incomplete outcome data/missing data, patients moving between arms, unequal allocation.

Question 22

Why might we get incomplete outcome data

Answer 22

Loss to follow up, death before outcome can be measured, withdraw consent, becomes ineligible, randomised in error, technical problems collecting outcome.

Question 23

Why do we need to inflate sample size for patients moving arms

Answer 23

Because when this happens generally the groups in the trial will become more similar and the treatment effect will get smaller and smaller.

Question 24

What is the design effect

Answer 24

How much we need to inflate the sample size when using a more complex design compared to an individually randomised trial

Question 25

What is used to calculate the design effect in a trial with clustered data

Answer 25

ICC and cluster size.

Question 26

As the clusters increase in size, what does this to do the required sample size

Answer 26

The bigger the cluster, the more we need to inflate the sample size by.

Question 27

Does required sample size change for a non-inferiority trial

Answer 27

Yes

Question 28

Does required sample size change for an equivalence trial

Answer 28

Yes