drug lit - bio stats 2

Question 1

If everything else remains constant, what will happen as the sample size increases?

A
The power of the study increases

B
The study’s alpha increases

C
The difference in the primary endpoint between the two groups increases

D
The standard deviation increases

Answer 1

A
The power of the study increases

the more subjects, the greater the probability that if there is aj significant difference then we will detect it

SD will get smaller because we have more people and so we will be more sure of the results we get

Question 1

“We calculated a sample size (n = 200) sufficient to detect a 20% difference between the two groups’ cure rates with 80% power and α=0.05.” The study enrolled 189 patients and detected an 18% difference between the two groups’ cure rates. Which one of the following is true?

A
If p < 0.05, the results ARE statistically significant

B
If p < 0.05, the results are NOT statistically significant because the study was underpowered

Answer 1

A
If p < 0.05, the results ARE statistically significant

power relates to type II error, which is a false negative

Question 2

What does the hazard ratio below tell you?

A
Patients treated with clopidogrel experienced 840% more primary endpoints at 12 months versus ticagrelor

B
Patients treated with ticagrelor experienced 84% of the primary endpoints as patients treated with clopidogrel at 12 months

Answer 2

B
Patients treated with ticagrelor experienced 84% of the primary endpoints as patients treated with clopidogrel at 12 months

HR is similar to RR which is how frequently the dichotomous endpoint

for every 1 person in Clopidogrel, 84 Ticagrelor had it…

Question 3

What does the odds ratio below tell you?

A
Being prescribed a bisphosphonate DECREASED the odds of developing esophageal cancer

B
Being prescribed a bisphosphonate INCREASED the odds of developing esophageal cancer

Answer 3

B
Being prescribed a bisphosphonate INCREASED the odds of developing esophageal cancer

because the OR is greater than 1

developing esophageal cancer is a dichotomous endpoint

Question 4

What is the absolute risk reduction?

Answer 4

ARR = % of patients in the control group - % of patients in the experimental group who experienced the outcome

clopidogrel is the control and the ticagrelor is the experiment/intervention so
11.7 - 9.8 = 1.9% ARR

Question 5

What is the number-needed-to-treat?

Answer 5

NNT = 100/% ARR
ARR = 11.4 - 9.3 = 2.1
100/2.1 = 47.61
but the round up to the nearest whole person so 48

make sure that you read the question and know what is the control and the experiment :)

Question 6

What is the number-needed-to-harm?

Answer 6

looking at major bleeding
this result is a significant difference due to the p-value of 0.001
NNH: 3.7 - 2.7 = 1
100/1% = 100

Question 7

What is the relative risk reduction?

A
0.16%

B
0.84%

C
16%

D
84%

Answer 7

RR = % experimental group / % control group
9.8 / 11.7 = 0.83

RRR: the absolute difference between RR and 1, then convert decimal to %
1 - 0.83 = 0.16 = 16%

C
16%

Question 8

What is the relative risk increase for major bleeding with clopidogrel versus placebo?

A
138%

B
13%

C
38%

D
67%

Answer 8

1.38 - 1 = 0.38 or 38%

RR = 1.38
3.7 - 2.7 =1

Question 9

Based on the HR and 95% confidence interval shown for the result below, was the difference between the two groups statistically significant?

A
Yes

B
No

Answer 9

A
Yes

because the interval does not cross 1

Question 10

Patients who are current smokers are significantly more likely to have a myocardial infarction.

A
True

B
False

Answer 10

A
True
because the OR interval does not cross 1

Question 11

Patients who are former smokers are significantly more likely to have a myocardial infarction.

A
True

B
False

Answer 11

B
False
because the OR crosses 1

Question 12

Patients taking empagliflozin had significantly better renal function compared to placebo

A
True

B
False

Answer 12

true because it does not cross zero

Question 13

objective

Answer 13

for calculating and interpreting the absolute risk reduction, absolute risk increase, number, number-needed-to-treat, and number and number-needed-to-harm

Question 14

absolute risk reduction (ARR)

Answer 14

the proportion of subjects in the control group with an outcome subtracted by the proportion of subjects in the intervention group with an outcome

the % of patients who are spared an outcome as a result of receiving a treatment

only for dichotomous endpoints

ARR = % control group - % experimental group

Question 15

number need to treat (NNT)

Answer 15

the # of patients who need to receive the intervention instead of the control to avoid 1 additional negative outcome (or achieve 1 additional positive outcome

put into the context of the duration of the study (ex: median duration of treatment)

NNT = 100/% ARR

always round up for NNT

Question 16

absolute risk increase (ARI)

Answer 16

the % of patients who experience an outcome as a result of reducing the treatment instead of the control

the same as ARR, except ARI is calculated when the intervention increased the probability of an outcome in the treatment vs the control group

usually refers to negative outcomes but can be applied to a positive outcome that intervention increases the probability of, like a cure for an infection
- adverse effects
- negative outcomes

ARI = % intervention group - % control group

Question 17

number needed to harm (NNH)

Answer 17

also referred as number needed to treat to harm

exactly the same as NNT except calculated when the intervention increased the chance of a harmful outcome in the treatment vs the control group
- adverse effects
- negative outcomes

NNH = 100/ARI

always round down for NNH

Question 18

Important caveats

Answer 18

only calculate NNT/NNH for dichotomous endpoints with statistically significant results

ARR/ARI will always be a positive number because it refers to the absolute difference between 2 study groups

round UP for NNT

round DOWN for NNH

ARR = % control group / % intervention group

ARI = % intervention group - % control group

NNT = 100/% ARR

NNH = 100/ARI

Question 19

Relative risk (risk ratio)

Answer 19

a comparison of the probability of an event/outcome happening in the treatment group vs the control group

RR = 1 means the probability of the event happening in the treatment group is the same as the probability of the event happening in the control group

RR < 1 means the probability of the event happening in the treatment group is less than the probability of the event happening in the control group

RR > 1 means the probability of the event happening in the treatment group is more than the probability of the event happening in the control group

RR = % treatment group / % control group

OR = (A/B) / (C/D)

RR = (A/A + B) / (C/C + D)

Question 20

relative risk calculation and interpretation

Answer 20

RR = % intervention group / % control group

Question 21

odds ratio

Answer 21

a measure of association between exposure and an outcome
- the odds that an outcome will occur in the presence of exposure, compared to the odds that the outcome will occur

OR is similar to RR byt RR is calculated using probability and OR is calculated using the ratio of odds

OR = means the exposure did not affect the odds of the outcome e

OR < 1 means the exposure is associated with lower odds of the outcome

OR > 1 means the exposure is associated with a higher odds of the outcome

Question 22

calculating the odds ratio

Answer 22

disease (case). no disease (control)
exposed A B
unexposed C D

OR = odds that a case was exposed/odds that a control was exposed

OR = (A/D) / (B/C)

Question 23

hazard ratios

Answer 23

a comparison of the probability of events in a treatment group vs the probability of events in a control group

used for survival analysis - measures if patients in the treatment group are progressing faster or slower than patients in the control group an outcome
- death/other adverse outcome (ex: stroke, heart attack)
- positive outcome like cancer-free survival or clinical cure

HR = 1 means no difference between the treatment vs control group
HR < 1 means the treatment group was less likely to have the outcome vs the control group
HR > 1 means the treatment group was more likely to have the outcome vs the control group

Question 24

relatiev risk reduction (RRR)

Answer 24

the % of risk that is removed as a result of the treatment compared to the control

calculated by subtracting the RR from 1 and converting the decimal to %
- when RR is greater than 1 (ex: the intervention increased the risk of an outcome versus the control the RRR is the absolute difference between the RR and 1 (and it is reported as the relative risk increase)

Question 25

the disadvantage of RRR

Answer 25

it doesn’t tell the magnitude of absolute risk

Question 26

the solution

Answer 26

absolute risk reduction
- more clinically relevant than relative risk reduction
- allows you to calculate the number needed to treat and the number needed to harm

both relative risk reduction and absolute risk reduction are important components of reporting clinical study results

Question 27

a reminder about P-values

Answer 27

will tell you “Yes or no, are results statistically significant”

need to take into account reasons for the increased risk of type I and type II errors when interpreting

multiple ways to calculate

Question 28

95% confidence interval

Answer 28

imagine you want to find out if the true chance of getting heads on any single coin toss = 0.5 (50%)

toss the coin 2 times
- get 1 heads, 1 tails

toss a coin 100 times
- get 50 heads, 50 tails

Question 29

confidence intervals

Answer 29

given a study result, the confidence interval gives an estimate of the range of values that the true difference between 2 study groups lies between

tells you “Yes or no, are the results statistically significant”
- also tells you “How sure of this study result am I”

the smaller the study sample, the wider the confidence interval

the larger the study sample, the more narrow the confidence interval (more likely that the observed difference is close to the true difference)

Question 30

95% confidence intervals

Answer 30

given a study result, the 95% confidence interval shows the range of plausible values that the true difference lies between
- 95% of the time, the true results lie in the range
- if the study were repeated 100 times, the result would be within that range 95 times
- based on 1 study sample, provides an estimate of the true result in the larger population

Question 31

using confidence intervals to determine statistical significance

Answer 31

dichotomous (yes/no) endpoints
- if the 95% CI crosses 1, it is NOT statistically significant
- if the 95% CI does NOT cross 1, it is significant significant

Question 32

using confidence intervals to determine statistical significance

Answer 32

calculate the relative risk reduction/relative risk increase for a 95% confidence interval and decide for yourself if the relative risks are still clinically significant

for statistically significant results, are the results still clinically significant at the lowest end of the 95% confidence interval
- if no, then the results might not be clinically meaningful

for nonsignificant results, are the results clinically significant at the highest end of the 95% confidence interval
- if yes, maybe a new study with better power should be conducted

Question 33

formulas to know

range

power

relative risk

hazard ratio

odds ratio (OR) and the 2X2 table

Relative risk reduction

absolute risk reduction

absolute risk increase

NNT

NNH

Answer 33

relative risk = % intervention / % control same as hazard ratio (?)

OR = AD/BC - use the 2X2 table :)

RRR = 1 - RR

RRI = 1 - RR

ARR = % of patients in the control group - % of patients in the experimental group who experienced the outcome
so ARR = % control - % intervention

ARI (absolute risk increase) = % of patients in the control group - % of patients in the experimental group who experienced the outcome, except when the intervention increased the probability of an outcome
so ARI = % control - % intervention

NNT = 100/ARR - round up

NNH = 100/ARI - roun down