Survival Epi2 Spring2023

Survival Analysis
PUBH6687
Week 5
Objective of Survival Analysis
• To compare the cumulative incidence of an
event (or the proportion surviving event-free)
in exposed and unexposed (characteristic
present or absent) while adjusting for time to
event (follow-up time).
• Basis for the analysis
– Number of EVENTS
– TIME of occurrence
Need to precisely define:
• “EVENT” (failure): • “TIME”
– Death – Time from recruitment
– Disease (diagnosis, start into the study
of symptoms, relapse) – Time from employment
– Remission of symptoms – Time from diagnosis
– Quit smoking (prognostic studies)
– Menopause – Time from infection
– Calendar time
Note: the ”event” isn’t – Age
always a bad thing!
For most methods, it is a
one-time event.
Survival Analysis
• Objective 1: to estimate cumulative incidence or
survival function
– Methods: Life table (Actuarial), Kaplan-Meier
Example: What proportion of people diagnosed with disease
are expected to be alive in 5 years?
• Objective 2: to compare survival in different groups
– Methods: Log-rank test, proportional hazards (Cox)
regression
Example: Are younger people (18-45 yr) expected to survive
longer after diagnosis of this disease than older people
(>45 yr) diagnosed with this disease?
Why survival analysis is “tricky”
• Different follow-up for study participants
– Because of staggered (late) entries
– Because of losses to follow-up
• Incomplete follow-up and censored observations
• Censored data: incomplete information on time
to event, because event was not observed
– Did not occur in study time period
– Person lost to follow up before it occurred
– Person died before it occurred (if not studying
mortality)
Example
• Follow up of 10 patients for 2 years
– 6 Deaths
– 3 left before 2 full years of follow-up
• Censored:
– 1 survived for 2 full years
• Question: What is the Cumulative Incidence
(or the Cumulative Survival) up to 2 years?
Crude Survival: 4 / 10 = 40%
Figure 2.1: Hypothetical cohort of 10
persons followed for up to 24 months
from January 2015 through December
2016. D, death; arrow, censored
observation; ( ), duration of follow-up
in months
(all assumed to be exact whole
numbers).
Death D
Censored observation
(lost to follow-up,
withdrawal)
Number of months of
follow-up (#)
Change time scale to “follow-up” time:
Figure 2.2: Same cohort as in Figure 1,
with person-time represented according
to time since the beginning of the study.
D, death; arrow, censored observation;
( ), duration of follow-up in months (all
assumed to be exact whole numbers).
Actuarial Life Table
• Cumulative probability during a given interval
• Calculation in classic life table
– Assume that censored observations over the
period contribute one-half the persons at risk in
the denominator (censored observations occur
uniformly throughout the follow-up interval).
Actuarial Life Table
• Assumption of censored observations
occurring uniformly across study is a problem
– If the follow-up is long, the risks should not be
assumed to be constant
– Non-constant risks can occur with shorter follow-
up
• Solution: consider how long each person did
contribute
Note: we’re not going to calculate with this method due to the limitations. It’s good to
know it exists and why the next method is usually a better choice.
Solution: Kaplan-Meier Approach
• Calculate the
cumulative probability
of event (and survival)
based on conditional
probabilities at each
event time.
• Step 1: Sort the
survival times from
shortest to longest
Figure 2.3: Same cohort as in Figures 1 and 2, with
individuals sorted according to follow-up time from
shortest to
longest. D, death; arrow, censored observation; ( ),
duration of follow-up in months (all assumed to be
exact whole numbers). As examples, the vertical
arrows mark the individuals who were at risk for the
calculations of the conditional probabilities of death
at three of the event times: 1 month, 3 months, and
17 months (see text).
Kaplan-Meier Approach
• Step 2: For each time of occurrence of an
event, compute the conditional probability (q)
qt = # of events / # of people at risk
Participant # Start of study Time 1 • At start of time 1, all 10 were at risk
1 alive died
• At end of time 1, 9 were still alive
2 alive alive • Risk of death during time 1
3 alive alive = # of events / # at risk
4 alive alive = 1 / 10
5 alive alive = 0.1
6 to 10 alive alive
Cumulative survival
• Step 3: For each time of occurrence of an
event, compute the cumulative survival
(survival function), multiplying conditional
probabilities of survival.
Cumulative survival
= (conditional survival1) x (conditional survival2) x ….
Step 3
• Cumulative survival:
Prob of event = Cumulative prob survival =
# of event / # of individuals Prob of survival = Prob of survival * previous
at risk 1 – prob of event prob of survival
Number of
Time individuals Number of Conditional probability Conditional Cumulative probability
(months) at risk events of the event probability of survival of survival
1 10 1 = 1/10 0.10
3 8 1
9 7 1
13 5 1
17 3 1
20 2 1
Based on Table 2-3 from the textbook (p. 59)

Step 3
Number of
1 10 1 = 1/10 0.10 = 1 - 1/10 0.90
3 8 1
9 7 1
13 5 1
17 3 1
20 2 1
Step 3
Number of
1 10 1 = 1/10 0.10 = 1 - 1/10 0.90 0.90 0.90
3 8 1
9 7 1
13 5 1
17 3 1
20 2 1
Step 3
Number of
1 10 1 = 1/10 0.10 = 1 - 1/10 0.90 0.90 0.90
3 8 1 = 1/8 0.13
9 7 1
13 5 1
17 3 1
20 2 1
Based on Table 2-3 from Szklo & Nieto, 2019 (p. 59)
Step 3
Number of
1 10 1 = 1/10 0.10 = 1 - 1/10 0.90 0.90 0.90
3 8 1 = 1/8 0.13 = 1 - 1/8 0.88
9 7 1
13 5 1
17 3 1
20 2 1
Step 3
Number of
1 10 1 = 1/10 0.10 = 1 - 1/10 0.90 0.90 0.90
= 0.90 *
3 8 1 = 1/8 0.13 = 1 - 1/8 0.88 0.88 0.79
9 7 1
13 5 1
17 3 1
20 2 1
Step 3
Prob of event =
# of event / # of individuals Prob of survival =
at risk 1 – prob of event
Number of
1 10 1 = 1/10 0.10 = 1 - 1/10 0.90 0.90 0.90
= 0.90 *
3 8 1 = 1/8 0.13 = 1 - 1/8 0.88 0.88 0.79
= 0.79 *
9 7 1 = 1/7 0.14 = 1 - 1/7 0.86 0.86 0.68
= 0.68 *
13 5 1 = 1/5 0.20 = 1 - 1/5 0.80 0.80 0.54
= 0.54 *
17 3 1 = 1/3 0.33 = 1 - 1/3 0.67 0.67 0.36
= 0.36 *
20 2 1 = 1/2 0.50 = 1 - 1/2 0.50 0.50 0.18
Cumulative prob survival =

Prob of survival * previous
prob of survival
Plotting the survival function:
Figure 2.4: Kaplan–Meier curve corresponding to the data in Table 3, column 6.

Assumptions in Survival Analysis
• Representative sample
– Not biased
– Represents the sample you want to generalize to
• Independent subjects
– Outcome of one participant not related to outcome of
another participant
• Consistent eligibility criteria and definitions
– Start and end points clearly and consistently defined
Assumptions in Survival Analysis
• In actuarial life tables only
– Risk is constant within each interval.
• If individuals are recruited over a long period of time
– No secular trends. i.e., no changes over time that impact
survival and are not related to the exposure
• Censoring is independent of survival
– Uninformative censoring: those censored at time t have the
same prognosis as those remaining.
– Types of censoring:
• Lost to follow-up (e.g., migration, refusal)
• Death (from another cause)
• Administrative withdrawal (study finished)
Censoring Assumption
• If censored observations tend to have worse
prognosis than those remaining in the study:
Observed survival > True survival
• If censored observations tend to have better
prognosis than those remaining in the study:
Observed survival < True survival
Survival analysis might be useful for which of
the following situations?
A. Were women in Group A more likely to become pregnant

than women in Group B?
B. Did the interpregnancy interval (time between pregnancies)
differ between Group A and Group B?
C. Were women in Group A have more pregnancies than
women in Group B?
D. None of the above.
PollEv.com/maggieholland656 or
Text MaggieHolland656 to 37607 once to join
In Kaplan-Meier analysis, a person who
drops out early (before occurrence of event)
A. Is removed from all analysis

B. Is included in the analysis, contributing their time in the
study as pre-event ("healthy") time
C. Is included in the analysis, contributing half of their time
in the study as pre-event ("healthy") time
D. Is treated as if they had the event at the end of the
study period
E. Is treated as if they had the event when they dropped
out
PollEv.com/maggieholland656 or
Text MaggieHolland656 to 37607 once to join
Comparing groups
• Did Group A have a longer time to event than
Group B?
– Did the new treatment extend time to disease
progression?
– Do people who are overweight have a shorter
survival time after a stroke?
Comparing groups:
Additional Assumptions
• Treatment groups are defined before data
collection began
• Groups are defined clearly and consistently
• Proportional hazards
– For some models
– More later in the semester

Survival Epi2 Spring2023

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Survival Analysis

Based on Table 2-3 from the textbook (p. 59)

Cumulative prob survival =

Figure 2.4: Kaplan–Meier curve corresponding to the data in Table 3, column 6.

A. Were women in Group A more likely to become pregnant

A. Is removed from all analysis

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