Survival concepts
Survival function: S(t) (also called the survivorship function) the survival
function shows the fraction of the original group who survive at various
points in time. The function starts with 100% at time zero and decreases
over time as the events happen to the individuals in the study.
Failure function: F(t) the failure function shows the cumulative fraction
of the original group for whom the event has happened by various points
in time. The function starts at zero percent at time zero and increases
over time as the events occur.
At any point in time, the sum of the survival fraction and the failure
fraction must equal 1.00. That is S(t) + F(t) = 1 at all times t.
Density function: f(t) (also called the probability density function)
the density function gives the fraction of the original group for whom the
event occurs during the time interval at t adjusted for the width of the
time interval. If d = F(t
2) - F(t
1) is the number
of events (deaths) that occur between t
1 and t
2, then
f(t) is d/(t
2 - t
1). If we think of continuous
time, we can think of the time interval between t
1 and t
2
as being infinitesimally small. In this case f(t) is the derivative
of F(t). f(t) = F'(t)
Hazard function: h(t) or lambda(t) the hazard function gives the
fraction of the individuals who survived to time interval t for whom the
event will occur in time interrval t. Thinking of continuous time,
the hazard function is f(t)/S(t)
The graph below illustrates these functions for deaths in an unusual population
where people die randomly but the deaths are distributed evenly over a 100-year
span. The density function, f(t), shows that has just as great a chance
of dying at age 98 as at age 4. The hazard function, h(t), shows that
as the person ages, the chance that the next year will be the person's last
increases until it reaches 100% for someone who reaches the age of 99 years.
(When I say this, I am thinking of time in descrete years. Of course
if we think in terms of descrete months the hazard only reaches 100% when
the person reaches the age of 1199 months--one month short of 1200 months.
In continuous time, the hazard only reaches 100% at age 100.)
S(t) = 1.00 - 0.01t F(t) = 1.00 - S(t) = 0.01t f(t)
= F'(t) = 0.01 h(t) = 0.01/(1.00 - 0.01t) = 1/(100 -
t)
Survival functions with Uniform Density f(t) =
0.01
The exponential density function shown below, results in a constant hazard
function. This is the same pattern as shown by the radioactive decay
of uranium. In this graph, lambda is the constant hazard rate and
is shown to be about 10%. That means that each year, 10% of the
survivors
are expected to fail. The half life is the time until the survival
rate is 50%--which is where S(t) and F(t) cross.
S(t) = e
-(lambda)t F(t) = 1.00 - e
-(lambda)t
f(t) = F'(t) = (lambda) e
-(lambda)t
h(t) = f(t)/S(t) = (lambda)
Survival functions with Exponential Density f(t) = (lambda)
e-(lambda)t
Censoring
One of the key features of survival analysis is the way it handles censored
data. The times to failure are said to be censored if we cannot observe
the starting point (left censored) or the ending point (right censored).
The methods discussed here assume that some of the data have been right
censored, that is that for some individuals or items, the event had not yet
happened before the analysis was performed. Data will be censored if
failure does not occur before the end of the study period, or if for some
reason we are not able to get a final reading on the individual or item.
(Patients may move away and be "lost to follow-up". Test samples
may be destroyed by laboratory accidents.)
Why "hard-numbers" approach is biased.
Physicians often want to see the survival rate for the "hard numbers"
usually after a year or five years. By this they mean the proportion
of people who are known to have died out of all patients whose status is
known after five years. Since survivors can get lost, but dead people
are known to be dead, the "hard-numbers" approach has a bias toward counting
deaths and missing lost survivors. So, the "hard-numbers" estimates
will be biased toward lower survival rates. Unbiased estimates can
only be obtained by dealing with the censored data.
There are three general approaches to survival analysis:
- Product limit (Kaplan-Meier) estimates. Each time an individual
or item fails, the S(t) is re-calculated. The new S(t) is the old S(t-m)
times the fraction of those who were being followed at time t-m who survived
to time t. People who were lost in the meantime are removed from both the
numerator and the demoninator of the fraction. For example, if the old
rate at t = 26 months was 0.60 and at time t = 29 one case out of 18 failed,
then the new survival rate for time t = 29 would be 0.60 x (17/18) = 0.5667.
When data are censored, the survival rate does not change, but its
variance will change. The survival function is plotted as a stair-step
graph with each step ending when a failure occured. JMP IN performs
a product-limit analysis.
- Life table estimates. These are similar to product-limit estimates,
except that instead of recalculating when a failure occurs, life-table estimates
recalculate after even intervals of time, such as a month or a year. There
may have been several failures and several cases lost to follow up during
that interval. The survival function is plotted by connecting each period's
survival rate to the next with a diagonal line segment. This reflects
the fact that we do not know when the failures occured within the period
and that we assume the failures occured at evenly spaced times within the
interval. Before the development of personal computers, life-table methods
were used to calculate survival functions from large data sets. These
days, the speed and convenience of personal computers allows product-limit
analyses of large data sets.
- Parametric. There are several approaches that try to fit a
specific equation to the data by finding the parameters for the equation
that optimize the equation in some way. One popular example is Cox
regression. Cox regression assumes that the hazard function for one
group of cases is always proportional to the hazard function of a different
group.