1. Sample Size Planning of Clinical Trials, Introduction
Dr. Gu Ming Gao
Department of Statistics, CUHK
For PgD / MSc Programme in Epidemiology & Biostatistics, CUHK
11/20/2018

2. Clinical trials are important in
Evidence-based medicine
Compare different treatments, quality of care or medicine, study into Chinese medicine
Development, improvement of clinical practice guidelines
Finding new factors and relationships which effect our health, drug development
For PgD / MSc Programme in Epidemiology & Biostatistics, CUHK
11/20/2018

3. Two types of clinical trials
Trials involve immediate responses
Trials involve time-to-event responses
The statistical procedures for handling those two types of data are very different
Survival analysis
Cox regression model
For PgD / MSc Programme in Epidemiology & Biostatistics, CUHK
11/20/2018

4. Trials with immediate responses, comparing two samples
Control vs. treatment
Assumptions on the distribution
Statistic: T-test statistic
Type-I error and power
Formula for sample size calculations under normal distribution assumptions
For PgD / MSc Programme in Epidemiology & Biostatistics, CUHK
11/20/2018

5. Trials with time-to-event responses, comparing two samples
Normal assumption on the distribution of the life-time is always violated
We usually only have vague ideas about the underlying distribution functions
No exact simple size calculation formula
Uses of Monte-Carlo simulations
For PgD / MSc Programme in Epidemiology & Biostatistics, CUHK
11/20/2018

6. Censoring Censoring caused by patient withdraw
Censoring by other illness, competing risks
Censoring by design of the trial
Censoring caused by pre-scheduled date of termination of the trial
For PgD / MSc Programme in Epidemiology & Biostatistics, CUHK
11/20/2018

7. Noncompliance Noncompliance is also called crossovers Drop-in rates
Drop-out rates
For PgD / MSc Programme in Epidemiology & Biostatistics, CUHK
11/20/2018

8. Log-rank statistics
An intuitive view of Log-rank statistics: boys computing with girls
General payment functions, Wilcoxon statistic
Rank statistics are more robust than the t-test, less assumptions on the distribution functions
The Log-rank statistics are very powerful
For PgD / MSc Programme in Epidemiology & Biostatistics, CUHK
11/20/2018

9. Sequential monitoring of clinical trials
Trials are monitored for safety reasons
Group sequential trials, planning and design
Complications caused: what is my type-I error and what is my power?
For PgD / MSc Programme in Epidemiology & Biostatistics, CUHK
11/20/2018

10. Different stopping rules in clinical trials
Pocock boundary
O’Brein-Fleming boundary
Haybittle boundary
Use function approach by Lan & DeMetes
Complications caused different stopping rules
For PgD / MSc Programme in Epidemiology & Biostatistics, CUHK
11/20/2018

11. The DSSP program
Use DSSP program to find the power of the test for a given sample size
Use the DSSP program for sample size.
The program is window based and easy to use
Intro to the program will be given next week
Available at
For PgD / MSc Programme in Epidemiology & Biostatistics, CUHK
11/20/2018