methods 04 [Schreibgeschützt] - Christian-Albrechts ...· Objectives of Epidemiology-determine the

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  • Bis vivit qui bene vivit

    Epidemiology

  • What is Epidemiology?

    Epidemiology is the study of how a disease is distributed in a population and of the factors that influence or determine this

    distribution.

    http://www.usuhs.mil/2005/Epid_Notes_1.htm

    Epidemiology, literally translated from Greek, means "the study of [a] people".http://www.aea.asn.au/home_whatisepidemiology.htm

  • Objectives of Epidemiology

    - determine the extent of disease in a population- study the natural history and prognosis of a

    disease - characterise the aetiology of a disease- identify risk factors or protective factors

    - evaluate preventive and therapeutic measures - provide the foundation for developing public

    policy and regulatory decisions

  • Historical Examples

    - smallpox survivors were immune to the disease- variolation, the administration of material from infected people, was common (dangerous) practice

    - cowpox (mild form of smallpox) was found inmilkmaids, who never contracted smallpox

    - pus from cowpox-infected patient was used toperform the first successful smallpox vaccination

    Edward Jenner(1749-1823)

    - miasmatic theory of cholera: cloud of disease close to earth, with lower altitudes more susceptible than higher ones

    - house to house survey of where cholera deaths obtained their water

    - proof of contagious nature and transmission pathwaysJohn Snow

    (1813-1858)

  • Morbidity MeasuresPrevalence ()

    Point Prevalence

    proportion of affected individuals present in a population at a specific time pointmathematically: probability t that an individual randomly drawn at a specific time point is affected

    Period Prevalence

    proportion of affected individuals present in a population during a specific time periodmathematically: probability d that a randomly drawn individual is, or has been, affected during a specific time period

  • period prevalence point prevalence

    time

    30 years

    Period and Point Prevalence

    43.07

    3t ==57.0

    7

    4d ==

  • Confidence Interval

    The number X of diseased individuals in a sample of size n follows a Bin(n,) distribution.

    n

    )1(t:KI 1n,2/1

    yields a confidence interval for the estimate of .

    57.035

    20d ==

    17.057.035

    43.057.004.257.0 =95%KI:

    Example: 20 diseased among 35 probands

  • Morbidity MeasuresIncidence Proportion (), "Risk"

    A: number of new cases in a population at risk that occur during a specified time period

    N: number of individuals at risk during a specified time period

    mathematically: probability (or risk) that an unaffected, randomly chosen individual gets affected during the time period of interest

    N

    A=

  • time

    T: 30 years

    Incidence Proportion

    333.09

    3 ==

  • Morbidity MeasuresIncidence Rate (), "Risk"

    N: number of individuals at risk during time periodA: number of new cases arising during time periodTi: time units spent under risk by the i

    th individual

    mathematically: (time) rate at which unaffected, randomly chosen individuals get affected

    ==

    N

    1i iT

    A

  • time

    T: 30 years

    321

    309

    224

    1730

    027

    Incidence Rate

    incidents per person-year018.0163

    3 ==

  • Prevalence and IncidenceD: disease duration

    expected prevalence pool inflow

    expected prevalence pool outflow

    t)1( t)D(E

    1

    1-

    )D(E1

    prevalence pool

  • Prevalence and Incidence

    Through causing longer disease duration, improved medical care may increase the disease burden

    to society in the form of an increased prevalence.

    In a stable, closed population(i.e. without migration into, or out of, the population)

    )D(E1

    =

    t)D(E

    1t)1( =

    so that

  • Typhus

    Pediculus humanus Rickettsia prowazekii

    In the German population, the incidence rate of typhus is 210-6 per year. The average disease duration is approximately one month.

    76 1067.112

    1102)D(E

    1 ===

    In the German population, approximately 81.51061.6710-7=14 cases of typhus are to be expected at any point in time.

  • - ambiguous or incorrect diagnoses, latency- identification of highly selected cases from

    hospital admissions (severity, policy)- bad recording of cases (incomplete, missing)- variable diagnostic standards (temporal,

    regional)- ambiguous definition of population base

    (medical, ethnic, social)- temporal changes of disease patterns (spatial,

    phenotypical)

    Prevalence and IncidenceProblems

  • Effect Measures

    Let a population be stratified into two strata (e.g. "exposed", "not exposed") with corresponding

    incidence rates or proportions ("risks") e and n during the observational period.

    Relative Risk ()

    is called the 'relative risk' under exposure.

    >1: "risk factor",

  • time

    exp

    ose

    dnot

    exp

    ose

    d

    30 years

    Relative Risk ()

    50.22.0

    5.0

    10/2

    10/5 ===

  • Experimental (Interventional)

    Types of Epidemiological Studies

    Clinical Trials

    - evaluation of therapeutic measures (e.g. drugs)

    Field Trials

    - performed on single diseased individuals in a clinical setting

    - evaluation of preventive measures (e.g. vaccination)- performed on single non-diseased individuals in the field

    Community Interventions

    - evaluation of preventive measures (e.g. water treatment)- performed on groups of non-diseased individuals

    Assignment of Exposure by Investigator

  • time

    exp

    ose

    dnot

    exp

    ose

    d

    Archetypal Experimental Study

  • Types of Epidemiological Studies

    Cohort Studies

    Case-Control Studies

    - performed prospectively on non-diseased individuals of known exposure status, disease incidences are recorded

    Cross-Sectional (Prevalence) Studies

    - performed retrospectively on individuals of known diseasestatus, exposure status is recorded

    - performed retrospectively on the whole population or on a representative sample, disease and exposure is recorded

    Non-Experimental (Observational)

    Assignment of Exposure by Nature

  • time

    Archetypal Observational Study

  • To identify the common factors or characteristics that contribute to cardiovascular disease (CVD) by following its development over a long period of time in a large group of participants who had not yet developed overt symptoms of CVD or suffered a heart attack or stroke.

    In 1948, 5209 men and women between the ages of 30 and 62 were recruited from Framingham, Massachusetts (representing 2/3 of the adult population). In 1971, another sample of 5135 men and women was established, comprising the offspring of the original cohort and their spouses.

    Objective

    Design

    The Framingham Study

  • Careful monitoring of the Framingham Study population has led to the identification of the major CVD risk factors- high blood pressure- high blood cholesterol- smoking- obesity- diabetes- physical inactivity and critical information upon related factors such as age, gender, and psychosocial issues.

    The Framingham study has produced approximately 3500 articles in leading medical journals.

    The Framingham Study

    Results

  • Risk and Odds

    "The risk of catching a viral flue this winter is 0.20."one affected among five at risk

    "The odds of catching a viral flue this winter is 0.25."one affected for every four non-affected

    Risk1

    RiskOdds

    =

  • Horse Race Betting

    "Old Mule"

    payoffodds

    1:5 1:10 1:50 1:200

    5-110-150-1

    200-1

    fair poor poor poorgood fair poor poorgood good fair poorgood good good fair

  • Effect Measures

    If risks e and n are "sufficiently small" for the chosen time unit, i.e. of the order a few percent, then

    Odds Ratio (OR)

    )1/(

    )1/(OR

    nn

    ee

    =

    =

    =

    n

    e

    nn

    ee

    )1/(

    )1/(OR

  • time

    exp

    ose

    dnot

    exp

    ose

    d

    Odds Ratio (OR)

    time unit: 10 years

    00.210/1

    10/2 ==25.2

    9/18/2

    OR ==

    10 years

  • Odds Ratio (OR)

    time

    exp

    ose

    dnot

    exp

    ose

    d

    time unit: 30 years

    00.48/2

    5/5OR == 50.2

    10/2

    10/5 ==

    30 years

  • Which Effect Measure ?

    exposed

    affectednot

    affected

    a b

    not exposed c d

    total a+c b+d

    total

    a+b

    c+d

    n

    Cohort Studies (Relative Risk)

    ==

    ++

    )dc/(c

    )ba/(a

    n

    e

    e

    e

    N

    A

    ba

    a + n

    n

    N

    A

    dc

    c +

    and

  • Which Effect Measure ?Case-Control Studies (Odds Ratio)

    exposed

    affectednot

    affected

    a b

    not exposed c d

    total a+c b+d

    total

    a+b

    c+d

    n

    n

    e

    A

    A

    c

    a nn

    ee

    AN

    AN

    d

    b

    and

    OR)1/(

    )1/(...

    )AN/()AN(

    A/A

    d/b

    c/a

    nn

    ee

    nnee

    ne ===

  • Effect MeasuresConfidence Intervals

    )dc/(c

    )ba/(a

    ++=

    d/b

    c/aOR =

    dc

    1

    c

    1

    ba

    1

    a

    1 )ln( +

    ++

    = d

    1

    c

    1

    b

    1

    a

    1 )ORln( +++=

    conf