Precision in estimates of treatment effects

Question 1

Compare the 3 study designs of a trial

Answer 1

Question 2

Do you think it is important to pre-specify primary and subsidiary outcomes?

Answer 2

Yes
- Failure to do so decreases the validity of the trial and avoids the impression that the researchers are “fishing” for a positive result.- Studies that fail to do so are also less influential when evidence is assessed to determine clinical guidelines

Question 3

Issues with studying the whole population:

Answer 3

•Very difficult to do!
•Possible if routine sources of health data are 
available... still limited
•Not necessary
•Things change over time
•Need updated information

Question 4

Why do we use samples?

Answer 4

We use samplesto provide estimatesof population parameters

Question 5

Sampling Bias

Answer 5

Sample is selected in such a way that the individuals chosen are not representative of
the whole study population

Example:- estimating SBP in middle aged adults in England, but only those that are in
employment will underestimate true answer

Question 6

How do we avoid bias?

Answer 6

Take random sample if possible of the population of interest

Question 7

Difference between accuracy and precision

Answer 7

Accuracy is to do with getting
the right answer – avoiding bias

Precision is to do with inherent
error associated with any
estimate

Question 8

Define Reference Range

Answer 8

A measure of the spread of the continuous numerical data only

Question 9

What is confidence interval

Answer 9

confidence interval is a measure of statistical uncertainty
or “precision”

Confidence intervals are
used to quantify the
precision (or uncertainty)
around estimates

A measure of the precision of a sample estimate

Question 10

How would you interpret confidence interval

Answer 10

• Reference range: In population of similar 45y old men, mean SBP is ~133mmHg, expect 95% of men to have SBP values between ~104-162mmHg;
• Confidence interval: 95% sure that average SBP in similar population of men would be from 132-133mmHg

Question 11

Formula for reference range

Formula for confidence interval

Answer 11

Formula: Mean +/- 2 Standard Deviations

Formula: Mean +/- 2 Standard Errors

Question 12

When is the confidence interval statistically significant?

Answer 12

It is statistically significant when it doesn’t include a null value (0)

Question 13

Risk ratio

Answer 13

Risk ratio (RR) = risk of outcome in drug ÷ risk of outcome in placebo (control)

Question 14

Calculate relative risk

Answer 14

Value of no effect = “1”
Unitless ratio (units cancel out)

Question 15

Risk ratio = 0.79 for simvastatin vs placebo

How would you interpret this?

Answer 15

Risk of vascular event 21% lower for simvastatin vs placebo

Tip! You can derive this interpretation by subtracting 1 from the relative risk

0. 79 minus 1 = -0.21 => 21% decrease
1. 79 minus 1 = +0.79 => 79% increase

Question 16

The 95%CI for the relative risk for any vascular event was 0.72 to 0.81 between simvastatin & placebo group

What can you conclude here? There is …

Answer 16

Strong evidence to suggest that simvastatin reduces overall risk

We are 95% confident that the interval contains the “true” treatment effect

• Since the 95% CI for the relative risk does not contain 1 (which would represent no reduction in risk) and both ends of the interval are <1 suggesting a reduction

Question 17

Absolute Risk Difference = -5.4% for simvastatin vs placebo

How would you interpret this?

Answer 17

The difference in the overall risk of a vascular event in the simvastatin group is 5.4 percent lower compared to placebo

In a group of 1,000 people, 54 fewer people with have a vascular event if they all switch from placebo to Simvastatin

1 less person will have a vascular event for approximately every 19 people that switch from placebo to simvastatin

Question 18

Mean LDL Difference = -0.9 mmol/L, 95%CI = -1.06 to -0.74 mmol/L

What would you conclude based on these findings? There is …

Answer 18

Evidence to suggest simvastatin decreases LDL

Since both ends of the 95%CI are in the same direction. i.e. a reduction in LDL and zero (no benefit) is not included in the 95%CI, we have evidence to conclude that the results are consistent with an overall benefit of simvastatin in lowering LDL cholesterol levels after 3 years of treatment.

Question 19

Calculate the absolute difference?

Answer 19

Value of no effect (no difference) = “0”

Differences have “UNITS” e.g.