1.

Abstract

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2.

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3.

Internal External validity

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4. Critical Appraisal

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5. External validity

general population

-->

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--> outcome

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6. Internal validity




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7. Internal validity
study design

experimental study trial common

trial
bias

--> allocation bias

confounding factor bias randomization

allocate
randomization study method baseline
characteristics Results

--> ascertainment bias investigator

bias
double-
blinded
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8. clinical trial equivalence, superiority non-
inferiority?


design

--> equivalence trial A is not too

different from B equivalency
null hypothesis
reject null
hypothesis A B reject
A B
therapeutic trial
equivalency
--> non-inferiority trial A is not much
worse than B much
non-
inferior
non-inferiority margin null hypothesis
margin upper limit 95% CI

margin reject null hypothesis A is not
much worse non-inferior to B one-tailed test
unbounded
equivalence trial superiority
trial

--> superiority trial

A is better than B null hypothesis equivalence trial


equally effective

reject null hypothesis superiority reject
A B (abesence of proof is not
proof of absence)
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9. non-inferiority trial reject
null hypothesis 6
-->

--> poor compliance drop out
intention-to-treat analysis
--> non-reflective outcome? outcome proven benefits
reflect patients' benefit
--> missing data
--> too short follow-up time
--> set non-inferiority margin sample
size
non-inferiority trial margin expected
event rate N set margin N
underpowered
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10. NI margin treatment effect

lower limit

reject Ho preserve at least 50%

treatment effect
FDA
1.3
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11.
Intention-to-treat on treatment
analysis
--> ITT randomized
follow-up
period
--> on treatment follow-up
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12. ITT allocation bias pragmatic
underestimate (true) treatment effect
superiority trial non-inferiority
falsely conclude non-inferiority non-inferiority
trial
on treatment analysis
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13. On treatment Per protocol
explanatory
effect safety analysis formulate
hypothesis future trials
bias disrupt initial
randomization
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14. study design analysis
follow up compliance drop out rate
internal validity
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15.
-->
event rate
expected event rate
sample size
absolute risk (1/AR = NNT) relative
risk reduction (clinical significance)
-->
95% CI HR p
value (statistical significance)
--> subgroup analysis
primary secondary
endpoints
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16. meta-analysis
clinical trials
systematic review

meta-
analysis

-->

HR 95% CI

% weight sample
size total HR
95% CI heterogeneity
test chi-square, p-value I^2
heterogeneity test
 p-value total hazard ratio chi-square
p-value
null hypothesis trials

p chi-square sig reject Ho

herogeneity

p sig heterogeneity
heterogeneity test
p value

heterogeneity test
0.10 cut-off 0.05
I^2 quantitative test heterogeneity

degree heterogeneity
25% (low), 50%(intermediate), 75%(high)

total HR fixed random effect

fixed effect
true effect size

heterogeneity
random effect

total hazard ratio heterogeneity

--> Forest Plot

sample size
HR

95% CI