Clinical Trials

Question 1

what is selection bias?

Answer 1

a distortion in a measure of association because the sample selection does not accurately reflect the target population

Question 2

what is performance bias?

Answer 2

Performance bias occurs when the studiers are aware of the participant’s treatment and intentionally or unintentionally influences their responses to treatment.

Question 3

what is detection bias?

Answer 3

Detection bias is any differences between groups changing the way the outcome is determined. For example, larger men have larger prostates and therefore may be easier misdiagnosed for prostate cancer via biopsy due to a physical difference

Question 4

what is attrition bias?

Answer 4

Systematic differences between study groups in the number and way participants are lost from a study

Question 5

what is reporting bias?

Answer 5

occurs when researchers do not report all of their data, which could lead to drawing false conclusions from the study outcome

Question 6

how do we mitigate selection bias?

Answer 6

We use RANDOMIZATION to place the study groups… a computerized random number generator is preferred to truly have random allocation of subjects

Question 7

how do we mitigate performance/detection bias?

Answer 7

We use BLINDING to keep subjects, investigators, and staff unaware of treatment allocation AFTER randomization. We use blinding of treatments to mitigate, such as making sure the two “drugs” are similar, both in appearance and maybe even known side effects

Question 8

how do we mitigate attrition bias?

Answer 8

we use INTENTION TO TREAT PROTOCOL where all subjects in initial randomization are included in final analysis regardless if they receive treatment

Question 9

how do we mitigate reporting bias?

Answer 9

Use studies that are performed using INDUSTRY SPONSORED RESEARCH

Question 10

what are 3 methods of randomization to ensure allocation concealment?

Answer 10

simple randomization
block randomization
stratified randomization

Question 11

what is simple randomization?

Answer 11

50/50 chance for each subject

Question 12

what is block randomzation?

Answer 12

subjects randomized in “blocks” to make sure groups are equivalent sizes

Question 13

what is stratified randomization?

Answer 13

Separate by a common factor (men separate from women)

Question 14

what is allocation concealment and the benefits from doing so?

Answer 14

A successful implementation of a random allocation sequence…
Pros:shields all people involved from knowing upcoming treatment/control assignments

Question 15

what is the difference b/w allocation concealment and blinding?

Answer 15

allocation concealment is randomization before the trial begins, blinding is a method to mask treatment after allocation occurs.

Question 16

define a per-protocol analysis. when is it a preferred method?

Answer 16

collects data from only patients who adhere to the protocol and is preferred fr equivalence/non-inferiority trials

Question 17

define an intention-to-treat analysis

Answer 17

collects data from all patients in initial randomization to help preserve the randomization

Question 18

what is the purpose of a survival analysis?

Answer 18

It shows an estimate of median survival times over the duration of the study

Question 19

what is a cox proportional hazards model?

Answer 19

creates survival curves with hazard functions that are proportional over time, and the relationship between each variable is linear

Question 20

what is the purpose of a p-value? what value is considered statistically significant?

Answer 20

determine if we can reject the null hypothesis.
p-value should be 0.05 or lower

Question 21

How can we use confidence intervals to show non-inferiority?

Answer 21

look at image 1

Question 22

define relative risk

Answer 22

The risk of an event occurring in one group compared to the other group. A RR less than 1 means the outcome is decreased by the exposure

Question 23

calculate relative risk

Answer 23

look at image 2

Question 24

define relative risk reduction

Answer 24

how much risk is reduced relative to the risk reduction. shows how much the treatment reduces the risk of an outcome

Question 25

calculate relative risk reduction

Answer 25

RRR=(1-RR)100= % RRR
example:RRR= (1-0.46)100 = 54%
meaning the treatment reduced the risk of the adverse outcome by 54%

Question 26

define number needed to treat

Answer 26

Number needed to treat is based on the amount of patients within the specified period of time to prevent one adverse outcome

Question 27

calculate number needed to treat

Answer 27

look at image 4
NNT= 1/risk difference

Question 28

what is internal validity?

Answer 28

examines if the study design, conduct, and analysis answer the research question without bias. This encompasses all of our analyzing for potential bias

Question 29

what is external validity? (what is PICOS)

Answer 29

examines if the study findings are applicable towards patients outside the trial study. For external validity we use “PICOS”, or Patients (exclusion criteria, characteristics), Intervention (differences b/w trial procedures and real world practice), Comparison (are placebo vs. active appropriate), Outcomes (does event matter?), and Setting

Question 30

what does it mean if a study has subgroup analyses?

Answer 30

researchers create separate data based on differing characteristics from the overall number of participants in the study. For example, the researchers wanted to specifically see how African-Americans responded to the treatment and thus made additional data on that population group.

Question 31

what are surrogate outcomes?

Answer 31

Surrogate outcomes depict data that is used to demonstrate the greater efficacy of the treatment drug by showing data on non-primary outcomes. For example, providing data on how the drug lowered A1C or blood pressure when the primary outcome was if the drug reduced mortality. They are a way to beef up the drug

Question 32

what are composite outcomes?

Answer 32

Composite outcomes are when multiple outcomes are combined into one composite outcome to improve the power/efficiency of trials. For example, the researchers give one data point (major adverse cv events) for how the drug prevented nonfatal stroke, MI, and CV death. These are all separate outcomes, but combined can show a greater efficacy of how the drug prevented major CV events

Question 33

define absolute risk reduction/difference

Answer 33

The proportion of patients who are spared the adverse outcome as a result of having received the experimental treatment rather than the control

Question 34

calculate absolute risk reduction/difference

Answer 34

placebo risk: 0.76%
treatment risk: 0.35%
RD= 0.76% - 0.35% = 0.41%
the absolute risk of event is reduced by 0.41% compared to placebo