Basic Ideas and Terminology
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Transcript of Basic Ideas and Terminology
Basic Ideas and Basic Ideas and TerminologyTerminology
Ettore BeghiEttore Beghi
Institute for Institute for Pharmacological Research Pharmacological Research Mario Negri, Milano, ItalyMario Negri, Milano, Italy
EPIDEMIOLOGYEPIDEMIOLOGY
Discipline which studies the frequency and the
determinants of a given disease in a well-
defined population
PRINCIPAL AIMS OF PRINCIPAL AIMS OF EPIDEMIOLOGYEPIDEMIOLOGY
• Calculation of the distribution of a Calculation of the distribution of a disease in a given population disease in a given population
• Definition of risk factors and Definition of risk factors and etiological factorsetiological factors
• Development of strategies for Development of strategies for disease prevention disease prevention
• Planning of health assistancePlanning of health assistance
RELEVANT ISSUES IN RELEVANT ISSUES IN EPIDEMIOLOGICAL EPIDEMIOLOGICAL
STUDIESSTUDIES
• Representativeness of the study population
• Sources of cases• Diagnosis (disease definition)• Criteria for the assessment of
causality• Criteria for the assessment of disease
course and impact of treatments
CLASSIFICATION OF CLASSIFICATION OF EPIDEMIOLOGICAL EPIDEMIOLOGICAL
STUDIESSTUDIES• DESCRIPTIVE DESCRIPTIVE
(Population Survey)(Population Survey)
• In populationsIn populations• Frequency of diseaseFrequency of disease• Distribution of Distribution of
diseasedisease - - timetime - - placeplace - person- person
• ANALYTIC ANALYTIC (Case-control & (Case-control & Cohort Studies)Cohort Studies)
• In individualsIn individuals• Test casual Test casual
hypotheseshypotheses• Uncontrolled Uncontrolled
assignmentassignment
SAMPLING AND BIASSAMPLING AND BIAS
TargetTargetpopulationpopulation
IntendedIntendedsamplesample
ActualActualsamplesample
MeasurementsMeasurementsHypothesisHypothesis
testingtesting
Sampling Sampling biasesbiases
BIASBIAS
“Any systematic error in the design, Any systematic error in the design, conduct, or analysis of a study that conduct, or analysis of a study that results in a mistaken estimate of an results in a mistaken estimate of an exposure’s effect on the risk of exposure’s effect on the risk of disease”disease”Schlesselman, 1982Schlesselman, 1982
DIAGRAM OF THE DIAGRAM OF THE IDENTIFICATION OF A DISEASE IDENTIFICATION OF A DISEASE IN THE GENERAL POPULATIONIN THE GENERAL POPULATION
Kurtzke, 1978Kurtzke, 1978
SOURCES OF NEUROLOGICAL SOURCES OF NEUROLOGICAL DISEASES IN DISEASES IN
EPIDEMIOLOGICAL STUDIES EPIDEMIOLOGICAL STUDIES • Hospital records• Ambulatory records• Electrophysiological (EMG) records• General practitioners’ files• Disability records• Lay associations• Tertiary centers• Death certificates• Diagnosis related groups (DRGs)• Disease registries
MEASURES OF DISEASE MEASURES OF DISEASE FREQUENCYFREQUENCY
• INCIDENCEINCIDENCE: Number of individuals in a : Number of individuals in a population that become ill in a stated population that become ill in a stated period of timeperiod of time
• CUMULATIVE INCIDENCECUMULATIVE INCIDENCE: Proportion of : Proportion of a fixed population that becomes ill in a a fixed population that becomes ill in a stated period of timestated period of time
• PREVALENCEPREVALENCE: Proportion of a population : Proportion of a population affected by a disease at a given point of affected by a disease at a given point of timetime
• MORTALITYMORTALITY: Number of individuals in a : Number of individuals in a population died for a disease in a stated population died for a disease in a stated period of timeperiod of time
PREVALENCE AND PREVALENCE AND INCIDENCEINCIDENCE
MigratingMigratinginin
MigratingMigratingoutout
RecoveryRecoveryDeathDeath
IncidenceIncidence
PrevalenPrevalencece
Prevalence = Incidence Prevalence = Incidence x average durationx average duration
DIAGNOSIS
• In the presence of diagnostic markers, the diagnostic process is simplified
• In the absence of diagnostic markers, the diagnosis is based on criteria implying a validation process and consensus among caring physicians
VALIDITY & RELIABILITY OF A DIAGNOSTIC TEST
• VALIDITY: capability to identify as positive those affected by the disease and as negative those not affected by the disease
• RELIABILITY: capability to obtain the same results in different occasions (1. Assessment of the same patient at different times; 2. Assessment of the same patient by different investigators)
VALIDITY OR ACCURACYVALIDITY OR ACCURACY
True True positives positives (a)(a)
False False positives positives (b)(b)
False False negatives negatives (c)(c)
True True negatives negatives (d)(d)
TestTest
DiseaseDisease
PositivPositivee
NegativeNegative
PositiPositiveve
NegativeNegative
Sensitivity = Sensitivity = True positivesTrue positives___ ___ a__a__ PPV = PPV = True True positives__ positives__ a__a__
Total with dis Total with dis a+ca+c Total Total tested pos tested pos a+ba+b
Specificity = Specificity = Total negatives_Total negatives__ _ d d NPV = NPV = True True negatives_ negatives_ d__d__ Total without dis Total without dis b+d b+d Total Total tested neg tested neg c+dc+d
EPILEPTIFORM ABNORMALITIES
General Population (n=1000)
55 334040
955955
Goodin & Aminoff, Goodin & Aminoff, 19841984
Sens = 60% Spec = Sens = 60% Spec = 96%96%PPV = 7% NPV = 99%PPV = 7% NPV = 99%
EPILEPTIFORM ABNORMALITIES
Epilepsy Center (n=1000)
Goodin & Aminoff, Goodin & Aminoff, 19841984
260 260 240240
2020
480480
Sens = 52% Spec = 96%Sens = 52% Spec = 96%VPP = 93% VPN = 67%VPP = 93% VPN = 67%
RELIABILITYRELIABILITY
RepeatabilityRepeatabilityor or
AgreementAgreement
InterobserverInterobserver
IntraobserverIntraobserver
ObserverObserver InstrumentInstrument ObjectObject
RELIABILITYRELIABILITY
True True positives positives (a)(a)
False False positives positives (b)(b)
False False negatives negatives (c)(c)
True True negatives negatives (d)(d)
Observer 1Observer 1
Observer 2Observer 2
PositivPositivee
NegativeNegative
PositiPositiveve
NegativeNegative
Percent Percent = = Positive + negative agreementsPositive + negative agreements x 100 = x 100 = a+da+d x 100 x 100Agreement All observations Agreement All observations NN
Kappa = Kappa = Observed % agreement – Expected % Observed % agreement – Expected % agreementagreement
100% - expected % agreement100% - expected % agreement
KAPPA STATISTIC
• Parameter quantifying inter-rater agreement adjusting for chance agreement
• Its value ranges from 0 (chance agreement) to 1 (perfect agreement)
• As measured by kappa, agreement is poor (<0.25), fair (0.25-0.50), good (0.50-0.75), almost perfect (>0.75)
INTER-OBSERVER INTER-OBSERVER AGREEMENT ON EEG AGREEMENT ON EEG
CONCLUSIONSCONCLUSIONS(Dichotomous Scale)(*)(Dichotomous Scale)(*)
ReportReport ObserveObserved d agreemeagreementnt
Expected Expected agreemeagreementnt
K (SE)K (SE)
NormalNormal
Standard EEGStandard EEG
Sleep-depr Sleep-depr EEGEEG
0.730.73
0.730.730.500.50
0.540.54.47 .47 (12)(12)
.42 .42 (13)(13)
EpileptiformEpileptiform
Standard EEGStandard EEG
Sleep-depr Sleep-depr EEGEEG
0.840.84
0.730.730.610.61
0.550.55.59 .59 (13)(13)
.41 .41 (13)(13)
Van Donselaar et al, Van Donselaar et al, 19921992
(*)(*) Epileptiform = Epileptiform =
yes/noyes/no
OBSERVATIONAL OBSERVATIONAL CRITERIA FOR CRITERIA FOR CAUSATIONCAUSATION
• Temporal sequence• Consistency of association• Strength of association• Biological gradient• Specificity of association• Biological plausibility
Bradford-Hill, Bradford-Hill, modifiedmodified
DESIGN OF STUDIES ASSESSING DESIGN OF STUDIES ASSESSING DISEASE ETIOLOGYDISEASE ETIOLOGY
Schoenberg, 1983Schoenberg, 1983
ODDS RATIO (OR)
• Is a measure of association closely related to the relative risk (RR)
• Approximates the RR for rare diseases• In the 2 x 2 table Disease
Exposure Yes NoYes A BNo C D Odds of exposure A/C among the cases and B/D in the controls; the ratio of the odds of exposure is:OR = (A/C) : (B/D) = AD / BC
RELATIVE RISK (RR)RELATIVE RISK (RR)
• The relative risk is the The relative risk is the ratioratio between the rate (risk) of between the rate (risk) of disease in disease in those with the those with the exposure factorexposure factor and the rate and the rate (risk) of disease in (risk) of disease in those without those without the factorthe factor
RR = RR = R (exp) / R (nexp)R (exp) / R (nexp)
RELEVANCE OF CAUSAL RELEVANCE OF CAUSAL ASSOCIATIONASSOCIATION
• Relative Risk or Odds RatioRelative Risk or Odds Ratio
- - DefiniteDefinite> 10> 10 - - Highly Highly probableprobable 4-104-10 - - ProbableProbable 2.5-3.92.5-3.9- - PossiblePossible 1.1-2.41.1-2.4
Considerations When Considerations When Studying MortalityStudying Mortality
• Death among people with the conditionDeath among people with the condition
• Death due to the conditionDeath due to the condition
Courtesy of Giancarlo LogroscinoCourtesy of Giancarlo Logroscino
STANDARDIZED MORTALITY RATIO
• The standardized mortality ratio or SMR, is a quantity, expressed as either a ratio or percentage quantifying the increase or decrease in mortality of a study cohort with respect to the general population
WHY TO CALCULATE THE WHY TO CALCULATE THE STUDY POWERSTUDY POWER
• A study should be sufficiently large to A study should be sufficiently large to avoid two important statistical errors:avoid two important statistical errors:
- Assuming - Assuming that a difference between groups is real that a difference between groups is real while it is a chance finding (while it is a chance finding (alpha erroralpha error))
- Assuming - Assuming that there are no differences between that there are no differences between groups when a difference is actually groups when a difference is actually present (present (beta errorbeta error))