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Frequency and measures of association. Center for Clinical Epidemiology and Evidence-Based Medicine (CEEBM) Faculty of Medicine, University of Indonesia – Cipto Mangunkusumo Hospital. Frequency measures. Two types: Someone has the disease already: prevalence
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Frequency and measures of association Center for Clinical Epidemiology and Evidence-Based Medicine (CEEBM) Faculty of Medicine, University of Indonesia – Cipto Mangunkusumo Hospital
Frequency measures • Two types: • Someone has the disease already: prevalence = measure population disease status • Someone gets the disease in the future: incidence =measure frequency of disease onset
Measure of disease occurrence (example) • Incidence: the rain arriving • Prevalence: the water in the puddle, new and old • Period prevalence: the water in the puddle, during a period • Point prevalence: at one point of time The water draining away into the soil or into drains reduce the puddle (i.e. the prevalence) just as recovery or death reduce the number of patients with a problem
Prevalence Number of cases of disease at a specific time Population exposed at that time • Proportion of population affected by the disease at a given point in time • Expressed as a percentage: (number of diseased)/(population) * 100
Frequency measures: prevalence • Cross-sectional studies • Determinant and disease measured at the same time • Used in diagnostic research • Prevalence • Number of persons with the disease at a certain moment • Prevalence (%) • Number of persons with the disease / total population
Frequency measures: prevalence • Examples • 50% of the persons with a suspicion of lung cancer had a lesion on the thorax X-ray • In a general practice population of 2500 persons, 50 had asthma • 30% of the Indonesian people smoke
Frequency measures: prevalence • Interpretation / relevance • Quantification amount of disease: a priori probability • public health planning • Issues • non-response • prevalence of MI • prevalence of dementia • selective mortality
New events… • Incidence • Incidence rate • Incidence density • Attack rate • Cumulative incidence • Risk • ……
Frequency measures: Incidence • Incidence • number of new cases • in the population at risk • Two types of incidence • Cumulative incidence • Incidence density (incidence rate)
Frequency measures: Incidence • Used in prognostic research • Incidence density • The number of new disease cases in the population divided by the observation time • Cumulative incidence • new cases in a certain time period in the population at risk (free of the disease at the start) • proportion / probability • varies between 0 and 1 • within certain time period
Frequency measures: Incidence • Cumulative incidence: examples • 5-year risk of a second MI • 10-year survival for women with breast cancer • 1-year risk of a fracture for osteoporotic women
Exercise 1 Ad question 1: tonsillitis • Dutch population • 1 year • incidence • 19/1000 or 1.9%
Exercise 1 Ad question 2: asthma • Children in the general practice • Certain moment (look into practice data at a certain moment) • (point) prevalence
Exercise 1 Ad question 3: breast cancer • Women • Life • Incidence
Exercise 1 Ad question 4: vertebral collapse • 9% • 55-59 year-old men and women • Certain moment • (point) prevalence
Exercise 1 Ad question 5: fractures • Post-menopausal women • Follow-up duration of the study • Incidence
Frequency measures: Incidence • How do we calculate an incidence?
Frequency measures: Incidence • Cohort approach • Group of persons with the same characteristics • All participants have the same starting point (start cohort) • However, baseline can differ in time • All participants are followed during a certain time period
Cumulative incidence • Cumulative incidence excludes prevalence at baseline • Example: Population 350.000 New cases 1.250 Cumulative incidence 3.6/1000 per year Number of NEW cases of disease during a period Population exposed during the period
Frequency measuresIncidence density • # new patients / person-years of the population at risk • 10 per 1000 person-years • between 0 and infinity Number of new/incident cases Amount of at-risk experience time
Frequency measures:Incidence: cohort • 5 persons followed during a year • (N at risk = 5) • A------------------------------ • B------------------------------ • C-------------breast cancer • D------------------------------ • E------------------------------ • 1-year risk of breast cancer = CI = 1/5=20% per year • ID = 1/4.5 person-years = 222/ 1000 person-years
Frequency measures: example cohort • 13 persons followed for 5 years for mortality • A-----------------------------x--Moves away t=2.5 • B-----------------------------x-------------Death t=3.0 • C-------breast cancer/death t=1.0 • D-----------------------------x------------------------------------------- alive t=5.0 • E-----------------------------x--------lost to follow-up t=3.0 • F-----------------------------x--------------------------------------------alive t=5.0 • G-----------------------------x---------------------------breast cancer/death t=4.0 • H-----------------------------x-Myocardial infarction/death t=2.5 • I--------death t=1.0 • J------------------------------x-------------------------------------------alive t=5.0 • K-------------lost to follow-up t=1.5 • L-----------------------------x----------------moves from the area t=3.5 • M--------1---------------2--x----------3---------------4-------------------alive t=5.0 • Total amount time at-risk = 42 years
Frequency measures: example cohort • CI = 5/13 = 38% • ID = 5/42 x 1000 = 199/1000 person-years
Measures of association • Epidemiology • Disease = f (determinants) • Is the determinant associated with the disease? • Is the probability of disease different for exposed and non-exposed?
Measures of association • Research question? Is smoking associated with lung cancer? • Cohort approach • divide the cohort in smokers and non-smokers • estimate the incidence density (or CI) in each group • prior: ID smokers > ID not smokers
Measures of association Disease Yes No Yes a - PY1 Determinant No c - PY0 ID1 a/py1 ID0 c/py0 RR = =
Measures of association • Smoking and lung cancer Disease Yes No Yes 440 - 22.008 py Determinant No 212 - 21.235 py RR = (440/22.008) / (212/21.235) = 2.0
Measures of association • Risk difference between exposed and non-exposed • CI or ID • public health impact • Risk difference smoking and lung cancer • 20/1000 py - 10/1000 py = 10 / 1000 personyears
Measures of association • Research question: Does smoking increase the risk of lung cancer ? • Case-control study • select cases and controls • Estimate the frequency of smoking among cases and controls • prior: % smokers among cases > % smokers among controls
Measures of association Disease Yes No Yes a b Determinant No c d • RR? • Odds ratio = (a/c) / (b/d) = ad / bc • Odds= the chance of something happening/the chance of it not happening • Odds Ratio - a ratio of two odds
Measures of association • Smoking and lung cancer (controls = 10% random sampling from cohort) Disease Yes No Yes 440 300 740 Determinant No 212 350 562 • Odds ratio (440/212) / (300/350) = 2.42
Measures of association • Smoking and lung cancer Disease Yes No Yes 440 300 740 Determinant No 212 350 562 • RR = (440/740) / (212/562) = 1.57 (shouldn’t be calculated) • Odds ratio (440/212) / (300/350) = 2.42
Measures of association • Smoking and lung cancer Disease Yes No Yes 440 3000 3440 Determinant No 212 3500 3712 • Now entire cohort as control • RR = (440/3440) / (212/3712) = 2.23 • Odds ratio =(440/212) / (3000/3500) = 2.42 • RR (a/(a+b)) / (c/(c+d)) ~ (a/c) / (b/d)
Frequency measures:Therapeutic research • Suppose: you see a patient with an increased blood pressure who you want to treat with blood pressure decreasing drugs. He asks about the effect of this treatment on the prognosis • Research question: Does treatment decrease the probability of CVD?
Frequency measures:Incidence • Intervention study (RCT) • Estimate incidence density (or CI) for each group • prior: ID treated < ID not treated
Exercise 2 • People of age 55 years and older • 5 years • Incidence (probably cumulative) • Relative risk and risk difference
Exercise 2 Risksmokers = 41/1736 = 0.024 Risknon-smokers = 107/5949 = 0.018 - RR = 0.024/0.018 = 1.3 Smokers have a 1.3 x higher probability of CVD than non-smokers • RD = 0.024 - 0.018 = 0.006 Smokers have a 5-year risk of CVD that is 0.6% higher than that of non-smokers
Exercise 3 • Case-control study • Severe head injury • Population • Alzheimer’s disease • Odds ratio
Exercise 3 Severe head injury in the past Alzheimer Yes No Severe Yes 33 31 Head injury No 165 167 OR = (33x167)/(31x165)=1.1
SummaryFrequency and measures of association • Frequency • Prevalence • Incidence • cumulative • density • Association • - Relative risk • - Rate ratio • - Risk ratio • - Odds ratio • - Risk difference
Outcome measures • Diagnostics? • Prognostics? • Etiology? • Intervention?
Outcome measures • Diagnostics • Prevalence (abs. risk), posterior probability, Se, Sp, PV+, PV-, OR, AUC • Prognostics • Incidence (abs. risk), OR, AUC • Etiology • Incidence (abs. risk), RR, OR • Intervention • Incidence (abs. risk), RR, RD, mean difference, NNT
Effect estimate • Does a single effect estimate, e.g. RR=1.5 or RR=1.0 give sufficient information?
Effect estimate • No, because it does not tell anything about precision
P-values versus confidence intervals • P-value: The probability that the found association (or more extreme) occurs given the nullhypothesis is true (often with arbitrary cut-off of 5%) • Confidence interval: Range of possible effect estimates that you would find if you would repeat the research (infinitely) often
P-values • Statistical significance (is not the same as clinical relevance) • Dependent on • Size of the effect • Size of the study population
Example • American study on losing weight in obese people • Intervention: • Half an hour per day sports+ diet advice • only half an hour sports • Numbers: 2 x 10.000 people