Wednesday, January 18, 2017

Survival analysis-Kaplan-Meier Theory

Property A: For a random variable x, the variance of g(x) can be approximated by
image024
Proof: The proof uses the Delta method, namely from the Taylor series for any constant a, we have
image025x
Thusimage026x
Now, let a = mean of x. Then
image027x
Thusimage028x
since var(y+c) = var(y), var(c) = 0 and var(cy) = c ⋅ var(y) for any y and constant c.
Property 1 (Greenwood): The standard error of S(t) for any time t tk ≤ t < tk+1 is approximately
image014x
Proof: First we note that
image015x
where pj = 1 − dj/nj the probability that a subject survives to just before tj. Taking the natural logs
image016xThusimage017x
We now assume that the number of subjects that survive in the interval [tj, tj+1) has a binomial distribution B(njπj) where pj is an estimate for πj. Since the observed number of subjects that survive in the interval is nj − dj, it follows (based on the variance of a binomial random variable) that
image018x
Thusimage019x
Based on Property A
image020x
Thus
image064x
But using Property A again, we also have
image021x
and soimage022x
which means that
image023x
Taking the square root of both sides of the equation completes the proof.
Property 2: The approximate 1−α confidence interval for S(t) for t tk ≤ t < tk+1, is given by the formula
image032x
where zα/2 = NORMSINV(1−α/2).
Proof: We could use a confidence interval of S(t) ± zα/2 ⋅ s.e., but it has the defect that it can result in values outside the range of S(t), namely 0 to 1. Thus it is better to use a transformation which transforms S(t) to the range (-∞,∞) and then take the inverse transformation. We use the transformation ln(−lnx) to accomplish this. This transformation is defined for x = S(t), except when S(t) = 0 or 1.
By Property A
image063x
From this and the proof of Property 1, it follows that
image033x
image034x
Thus the standard error of  is
image035x
The result now follows by taking the inverse transformations.
Property Bimage015v

Proof: By definition
image013v
Thusimage014v


No comments:

Post a Comment