Basic Ideas and TerminologyEttore BeghiInstitute for Pharmacological Research Mario Negri, Milano, Italy

EPIDEMIOLOGYDiscipline which studies the frequency and the determinants of a given disease in a well-defined population

PRINCIPAL AIMS OF EPIDEMIOLOGYCalculation of the distribution of a disease in a given population Definition of risk factors and etiological factorsDevelopment of strategies for disease prevention Planning of health assistance

RELEVANT ISSUES IN EPIDEMIOLOGICAL STUDIESRepresentativeness of the study populationSources of casesDiagnosis (disease definition)Criteria for the assessment of causalityCriteria for the assessment of disease course and impact of treatments

CLASSIFICATION OF EPIDEMIOLOGICAL STUDIESDESCRIPTIVE (Population Survey)

In populationsFrequency of diseaseDistribution of disease- time- place- personANALYTIC (Case-control & Cohort Studies)

In individualsTest casual hypothesesUncontrolled assignment

SAMPLING AND BIASTargetpopulationIntendedsampleActualsampleMeasurementsHypothesistestingSampling biases

BIASAny systematic error in the design, conduct, or analysis of a study that results in a mistaken estimate of an exposures effect on the risk of diseaseSchlesselman, 1982

DIAGRAM OF THE IDENTIFICATION OF A DISEASE IN THE GENERAL POPULATIONKurtzke, 1978

SOURCES OF NEUROLOGICAL DISEASES IN EPIDEMIOLOGICAL STUDIES Hospital recordsAmbulatory recordsElectrophysiological (EMG) recordsGeneral practitioners filesDisability recordsLay associationsTertiary centersDeath certificatesDiagnosis related groups (DRGs)Disease registries

MEASURES OF DISEASE FREQUENCYINCIDENCE: Number of individuals in a population that become ill in a stated period of timeCUMULATIVE INCIDENCE: Proportion of a fixed population that becomes ill in a stated period of timePREVALENCE: Proportion of a population affected by a disease at a given point of timeMORTALITY: Number of individuals in a population died for a disease in a stated period of time

PREVALENCE AND INCIDENCEMigratinginMigratingoutRecoveryDeathIncidencePrevalencePrevalence = Incidence x average duration

DIAGNOSISIn 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 TESTVALIDITY: capability to identify as positive those affected by the disease and as negative those not affected by the diseaseRELIABILITY: 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 ACCURACYTestDiseasePositiveNegativePositiveNegativeSensitivity = True positives___ a__ PPV = True positives__ a__ Total with dis a+c Total tested pos a+b

Specificity = Total negatives__ d NPV = True negatives_ d__ Total without dis b+d Total tested neg c+d

True positives (a)False positives (b)False negatives (c)True negatives (d)

EPILEPTIFORM ABNORMALITIES General Population (n=1000)5340955Goodin & Aminoff, 1984Sens = 60% Spec = 96%PPV = 7% NPV = 99%

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40955

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EpilepsyNormal

EEG +340

EEG -2955

EPILEPTIFORM ABNORMALITIES Epilepsy Center (n=1000)Goodin & Aminoff, 1984260 24020480Sens = 52% Spec = 96%VPP = 93% VPN = 67%

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260240

20480

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EpilepsyNormal

EEG +26020

EEG -240480

RELIABILITYRepeatabilityor AgreementInterobserverIntraobserverObserverInstrumentObject

RELIABILITYObserver 1Observer 2PositiveNegativePositiveNegativePercent = Positive + negative agreements x 100 = a+d x 100Agreement All observations N

Kappa = Observed % agreement Expected % agreement 100% - expected % agreement

True positives (a)False positives (b)False negatives (c)True negatives (d)

KAPPA STATISTICParameter quantifying inter-rater agreement adjusting for chance agreementIts value ranges from 0 (chance agreement) to 1 (perfect agreement) As measured by kappa, agreement is poor (0.75)

INTER-OBSERVER AGREEMENT ON EEG CONCLUSIONS(Dichotomous Scale)(*)Van Donselaar et al, 1992(*) Epileptiform = yes/no

ReportObserved agreementExpected agreementK (SE)NormalStandard EEGSleep-depr EEG0.730.730.500.54.47 (12).42 (13)EpileptiformStandard EEGSleep-depr EEG0.840.730.610.55.59 (13).41 (13)

OBSERVATIONAL CRITERIA FOR CAUSATIONTemporal sequenceConsistency of associationStrength of associationBiological gradientSpecificity of associationBiological plausibilityBradford-Hill, modified

DESIGN OF STUDIES ASSESSING DISEASE ETIOLOGYSchoenberg, 1983

ODDS RATIO (OR)Is a measure of association closely related to the relative risk (RR)Approximates the RR for rare diseasesIn the 2 x 2 tableDiseaseExposureYes NoYesABNoCDOdds 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)The relative risk is the ratio between the rate (risk) of disease in those with the exposure factor and the rate (risk) of disease in those without the factorRR = R (exp) / R (nexp)

RELEVANCE OF CAUSAL ASSOCIATIONRelative Risk or Odds Ratio- Definite> 10 - Highly probable4-10 - Probable2.5-3.9- Possible1.1-2.4

Considerations When Studying MortalityDeath among people with the condition

Death due to the condition

Courtesy of Giancarlo Logroscino

STANDARDIZED MORTALITY RATIOThe 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 STUDY POWERA study should be sufficiently large to avoid two important statistical errors:- Assuming that a difference between groups is real while it is a chance finding (alpha error)- Assuming that there are no differences between groups when a difference is actually present (beta error)

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