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I ssue 5

Volume 2

Year 2015

URL http://goo.gl/QDSB5B

#Kidney
KONNECTI ON
Editor: Tejas Desai | Chief: Tushar Vachharajani | Free subscription by @ https: / / goo.gl/ PTVJuo

NOW THAT I UNDERSTAND

SURVIVAL ANALYSES
by Sivakumar Sridharan (@sayitmyway)

Gloria Gaynor "I will Survive" Released 10/23/1978 by Polydor Records

In our continuing efforts to educate

you about the stats used in the
medical literature, this month?s
feature article will be about
survival analyses. If you?ve read
any recent medical literature, and
?survived? through the statistical
portion of the paper, you may have
ended your reading more confused
than when you started! Don?t
worry? we?re here to break down
complicated statistical tests into
understandable concepts. So let?s
get started.
A survival analysis refers to a
wide array of statistical methods to
analyze data related to timing of a
pre-specified event. The
pre-specified event could be any
measurable event depending on the
study protocol e.g. death,

hospitalization, symptomatic
improvement, etc. Survival
analyses have two characteristics
? 1) time to event and 2)
censoring. We?ll talk about each
in further detail soon.
In a survival analysis, study
participants are followed until a
specified period of time or until
the occurrence of the specified
event, whichever is earlier. The
time from study entry (or
randomization) to the occurrence
of the outcome event is called
the ?time to event?or ?survival
time?. However, some
participants may not experience
the outcome event until the end
of follow-up period. These
patients provide what is termed
censored observations. This is

because the information

available for these participants is
incomplete.
Let?s use a hypothetical
example to illustrate these
points. Suppose the participants
of a study are followed up for 12
months after a particular
treatment and that the
pre-specified event is recurrence
of the disease. The time to event
(i.e., when the disease relapses)
for six patients in the study are
as follows:

Patient 1: 10

Patient 4: 12*

Patient 2: 12*

Patient 5: 7

Patient 3: 3

Patient 6: 5*

Patients 1, 3, and 5 had disease

relapses @ 10, 3 & 7 months
respectively during the follow-up
period. Patients 2 and 4 were
disease-free at the end of the study
period (12 months & no disease
relapse). The last patient, #6, was
lost to follow-up after 5 months
(remember, the patients in this
hypothetical study were supposed
to be followed for 12 months). In
those 5 months, patient 6 did not
have disease relapse. For patients
2, 4, & 6, information about their
disease relapse is not available. It
does not mean that they did not
have disease relapse ? it just did
not happen in the specified time
period. These three patients will be
censored at the specified time
points when we cease to collect
information about them. Whenever
you come across survival analysis
data, it is important to examine
that the specified follow-up period
is sufficiently long for the outcome
event to happen and that the
censoring is applied only for
appropriate events.
The survival analysis will be
of assumptions compared to linear
models. An example of Cox model
is given below.

The model shows the hazard ratio

of death for three predictor
variable (age, male gender, and
BMI) in a 24-month follow-up
study. As noted, hazard ratios for

reported as either survival & /or

hazard. Reporting the data as
survival provides the probability
of surviving (or being event-free)
up to the specified time.
Reporting the data as hazard
gives the potential that the event
will occur assuming the
participant has survived until the
specified time. Survival is
expressed using Kaplan ? Meier
curves & the hazard by Cox
proportional hazards regression
models.

vertical line in the graph is a censored

observation. Survival curves provide
information on survival time in a clear

In 1958, Kaplan & Meier

introduced a methodology to
estimate the probability of
surviving event-free as a function
of time. This method is now
widely used & is called
Kaplan-Meier curves; an example
of which is shown to the right.

and easily comprehensible manner.

Kaplan-Meier curves can be used to
show survival curves for the entire
study cohort or the difference in
survival amongst various
sub-groups. The survival differences
between the groups can be tested
using tests such as log-rank test.

In a Kaplan-Meier curve, time is

plotted along the X-axis and
proportion of patients surviving
along the Y-axis. The graph
shows the difference in survival
time between 2 groups of
patients. Each drop in the graph
is an event occurrence and each

The Cox proportional hazards

regression model is a useful method
to explore the ?hazard? of the
predictor variables in relation to the
specified event. The model, although
somewhat similar to parametric
regression models, has a different set

age and BMI are statistically

significant (because their 95%
confidence intervals do not cross
1.00). A hazard ratio of more
than 1 signifies increased risk and
a ratio of less than 1 implies
reduced risk. In the model shown,
for every 1-year increase in age,
there is 3.2% increase in the risk
of death. Similarly, for each
1-unit (kg/m2) increase in BMI,
there is 6.3% reduction in risk of

death.
As you can see, survival analyses are
an essential part of biomedical
statistics. You?ve probably come
across them in the medical literature;
hopefully you have a better handle on
how to interpret the results. It is
important to familiarize oneself with
the basic concepts of this analysis to
interpret and critically analyze the
published literature.