Gil Harari

Statistical considerations in clinical trials

www.medistat.co.il

Elephants, Diamonds & Biostatistics ???

Analyses Variables

• Primary Efficacy Variables

• Secondary Efficacy Variables

• Safety Variable Adverse Events. Physical examinations. Laboratory measurements . Reasons for discontinuation.

Statistical considerations in biomedical studies

Is risk factor X associated with disease Y?

From the sample, we compute an estimate of the effect of X on Y (e.g., risk ratio if cohort study):

-Is the effect real? Did chance play a role?

Why worry about chance?

Population

Sampling variability… -you only get to pick one sample!

Interpreting the results

PopulationSelection of subjects

Inference

Make inferences from data collected using laws of probability and statistics

-tests of significance (p-value) -confidence intervals

How do we determine if an association is significant?

• Significance is in context of “Statistical” significance

– p-Value – Treatment Effect– Confidence Interval

8

Subjects for Discussion

1. What is a p-Value?

2. Sample Size Calculation

3. Clinical Significance Versus Statistical Significance

Basic Principles of Statistical Analysis

Significance Tests

Difference Between Treatments

Is it by chance?

Apply a significance test

Sample Size Calculations

Sample Size Calculation

Sample Size Calculation

Based on:

1 .Study Design

2 .Treatment Effect (Effect Size) (δ)

3 .Type I error (α), Type II error (β)

4. Power of the study (1-β)

Clinical significance Versus Statistical Significance

CR

TA

%Im

prov

emen

t %Im

prov

emen

t

43%

65%

Clinical Significance Statistical Significance

P=0.17

P=0.03

TBCR

52%

41%

N = 15 N = 60

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