ST 520 Statistical Principles of Clinical Trials - NCSU Statistics ...

CHAPTER 9 ST 520, A. TSIATIS and D. Zhang
9 Survival Analysis in Phase III Clinical Trials
In chronic disease clinical trials; e.g. Cancer, AIDS, Cardiovascular disease, Diabetes, etc., the
primary endpoint is often time to an event, such as time to death, time to relapse of disease, etc.
For such clinical trials the major focus is to compare the distribution of time to event among
competing treatments.
Typically, the clinical trials occur over a finite period of time and consequently the time to event
is not ascertained on all the patients in the study. This results in censored data. In addition,
since patients enter the clinical trial at different calendar times (staggered entry), the length
of follow-up varies by the individual. The combination of censoring and differential follow-up
creates some unusual difficulties in the analysis of such data that do not allow standard statistical
techniques to be used. Because of this, a whole new research area in Statistics has emerged to
study such problems. This is called Survival Analysis or Censored Survival Analysis. A
brief introduction of Survival Analysis will be given in this chapter, but for a more thorough
study of this area I recommend the course in Applied Survival Analysis offered every Spring
semester and for individuals interested in a more rigorous treatment of the subject there is a
course on Advanced Survival Analysis offered every other year.
In survival analysis, the endpoint of interest is time to an event which we denote by the positive
random variable T. Some examples include
• survival time (time from birth to death)
• time from treatment of lung cancer to death among patients with lung cancer
• among patients with an infection that are treated with an antibiotic, the time from treat-
ment until eradication of infection
In order to be unambiguous, the start and end of the event must be clearly identified.
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