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NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

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Page 1: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

NASSER DAVARZANI

DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS

22 OCTOBER 2012

Introduction to Survival Analysis

Page 2: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Contents Introduction to Survival Analysis

Censored DataTerminologies and NotationsKaplan-Meier Method Modeling in Survival DataParametric Regression

ModelsCox Proportional Regression

Model

2

April 19, 2023Survival Analysis (N. Davarzani)

Page 3: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Contents Introduction to Survival Analysis

Censored DataTerminologies and NotationsKaplan-Meier Method Modeling in Survival DataParametric Regression

ModelsCox Proportional Regression

Model

3

April 19, 2023Survival Analysis (N. Davarzani)

Page 4: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

What is survival analysis?

Outcome variable: Time until an event occurs

Time: years, months, weeks, or days

Start follow-up Event

Event: death, disease, relapse, recovery

TimeTime

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April 19, 2023Survival Analysis (N. Davarzani)

Page 5: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Time ≡ survival time

It gives the time that an individual has survived over some follow up period

Event ≡ failureThe event of interest usually is death, disease or any other negative individual experience.Maybe failure is a positive event

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April 19, 2023Survival Analysis (N. Davarzani)

Page 6: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Examples

1) Leukemia patients/time in remission (weeks) Event: Going out of remission Outcome: Time in weeks until a person goes out of remission

2) Disease-free cohort/time until heart disease (years) Event: Developing heart disease Outcome: time in years until a person develops heart disease.

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Page 7: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Examples

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3) Elderly (60+) population/time until death (years) Event: Death Outcome: Time in years until death

4) Parolees (recidivism study)/time until get rearrested

Event: Getting rearrested Outcome: Time in weeks until rearrest

Page 8: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Contents Introduction to Survival Analysis

Censored DataTerminologies and NotationsKaplan-Meier Method Modeling in Survival DataParametric Regression

ModelsCox Proportional Regression

Model

8

?April 19, 2023Survival Analysis (N. Davarzani)

Page 9: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Censored data

We don’t know the survival time exactly.

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Page 10: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Why censoring may occur?

1) A person does not experience the event before the study ends.

2) A person is lost to follow-up during the study period.

3) A person withdraws from the study because of death (if death is not the event of interest)

or some other reason.

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April 19, 2023Survival Analysis (N. Davarzani)

Page 11: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Examples

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Page 12: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Table of Survival Time

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Page 13: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Right Censored Data

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Page 14: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Contents

Introduction to Survival Analysis

Censored DataTerminologies and NotationsKaplan-Meier Method Modeling in Survival DataParametric Regression

ModelsCox Proportional Regression

Model

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April 19, 2023Survival Analysis (N. Davarzani)

Page 15: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Terminology and Notation

T = Survival time (T ≥ 0)t = Specific value for TSurvives > 5 years?T > t = 5

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Survival Function16

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Survival Curve

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Page 18: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Hazard function

The hazard function gives the instantaneous potential per unit time for the event to occur, given that the individual has survived up to time t

Hazard function focuses on failing

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Page 19: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Different type of hazard functions

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Page 20: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Relationship of S(t) and h(t)

If you know one, you can determine the other

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Page 22: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Appropriate Distributions

Some popular distributions for estimating survival curves are:

WeibullExponentiallog-normallog-logistic

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2: To compare survivor and/or hazard functions.

1: To estimate and interpret survivor and/or hazard functions from survival data.

3: To assess the relationship of explanatory variables to survival time.

Page 24: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

How to Draw the Survival Curves?

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Page 25: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Contents

Introduction to Survival Analysis

Censored DataTerminologies and NotationsKaplan-Meier Method Modeling in Survival DataParametric Regression

ModelsCox Proportional Regression

Model

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April 19, 2023Survival Analysis (N. Davarzani)

Page 26: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Kaplan – Meier Method

The Kaplan – Meier (KM) estimator is the most widely used for estimating survival function

product-limit estimatornonparametric maximum likelihood

estimator.When there are no censored data, the KM

estimator is simple estimator

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Page 27: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Practical Example

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Page 28: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

How to estimate Survival Curve?

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Suppose there are k distinct event times

At each time there are individuals who are said to be at risk of an event.At risk, means they have not experienced an event nor have they been censored prior to time .

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Lifetime Table

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Page 30: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

KM Estimator

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The KM estimator is defined as

Where number of failures at time jm

Page 31: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Lifetime Table

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Are KM curves statistically equavalent?

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Page 33: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

H: Survival functions of all groups are the same

Log-Rank testWald testScore testLR testWilcoxon testPeto testTaron-Ware test

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Page 34: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Weakness of KM method

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Teatment V.S Placebo

Continuous variablesEffect of several variables

0

1

TreatmentRx

Placebo

Page 35: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Contents

Introduction to Survival Analysis

Censored DataTerminologies and NotationsKaplan-Meier Method Modeling in Survival DataParametric Regression

ModelsCox Proportional Regression

Model

35

April 19, 2023Survival Analysis (N. Davarzani)

Page 36: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Modeling Survival Data with Regression

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Page 37: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Parametric Regression Models

are the regression coeffcients of interest.

is a scale parameter

is the random disturbance term

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Page 38: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

The Cox Proportional Hazard Model38

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Page 39: NASSER DAVARZANI DEPARTMENT OF KNOWLEDGE ENGINEERING MAASTRICHT UNIVERSITY, 6200 MAASTRICHT, THE NETHERLANDS 22 OCTOBER 2012 Introduction to Survival Analysis

Semi parametric Model

is unspecified

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Proportional Hazard40

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bb

h1

h2

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