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The relationship of an attribute to the disease is examined by comparing the diseased and nondiseased with regard to how frequently the attribute is present or, if quantitative, the levels of the attribute in each of the groups. — Last JM, A dictionary of epidemiology. 2nd edition, NY, Oxford, 1988 Synonyms: case comparison study, case compeer study, case history study, case referent study, retrospective study Defining characteristic Subjects are selected on the basis of the outcome variable. Key advantages � Statistically efficient for rare conditions � Logistically efficient for prolonged induction or latency diseases � Can examine many exposures in one study � Ethical - cannot affect onset of disease Basic procedure 1. Identify cases, determine their characteristics - cases estimate the prevalence of the exposure in people who get the disease. 2. Select controls (noncases), determine their characteristics - controls estimate the prevalence of the exposure in people who have not developed the disease. 3. Compare the characteristics of cases with characteristics of noncases. 4. Draw inferences about the underlying processes that led to differences in characteristics of cases and controls. Odds ratio (OR = odds of exposure in cases/odds of exposure in controls) estimates the incidence density ratio (IDR = rate of disease in exposed persons/rate of disease in unexposed persons). For rare disease, IDR closely approximates cumulative incidence ratio (CIR, RR) of the disease for that exposure. _____________________________________________________________________________________________ www.sph.unc.edu/courses/EPID168, © Victor J. Schoenbach 1999 8. Analytic study designs - 231 rev. 9/6/1999, 10/7/1999, 12/17/1999
Example Cases Case-control studies Controls If we want to test the hypothesis that exogenous estrogen is an etiologic factor in cancer of the uterine endometrium, we assemble a (case) group of women who have developed endometrial cancer (preferably newly-detected cases) and a (control) group of women whom we believe accurately reflect the population from which the cases have come. The case group will be used to estimate usage of estrogen by women who developed endometrial cancer; the control group will be used to estimate usage of estrogen by women in the source population (the "study base") which gave rise to the case group. Estrogen Endometrial cancer Yes No Total Case a b m1 (a + b) Control c d m2 (c + d) Total n1 n0 n (a + c) (b + d) _____________________________________________________________________________________________ www.sph.unc.edu/courses/EPID168, © Victor J. Schoenbach 1999 8. Analytic study designs - 232 rev. 9/6/1999, 10/7/1999, 12/17/1999
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Understanding the Fundamentals of E
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Preface Introductory epidemiology c
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Table of Contents Chapter (in Acrob
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1. Introduction Definition, charact
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problems (Schwartz and Carpenter, 1
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HIV - a new or newly-recognized vir
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d = principal investigator's degree
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Analytic studies typically involve
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Observational sciences especially a
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McGavran EG. What is public health?
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2. An evolving historical perspecti
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Time line for the history of public
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as a one-room bacteriology laborato
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− Health surveys − Research fun
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his scientific peers of the correct
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Kuhn, Thomas S. The structure of sc
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3. Studying populations - basic dem
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The demographic balancing equation
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ates. Similarly, bulges in the repr
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When the baby boom cohort retires 1
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The pervasiveness, strength, viciou
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Total fertility rate (TFR) Standard
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Life expectancy The technique, of u
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Excerpt from the U.S. 1993 abridged
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At the other end of the life table,
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to change, hopefully to decline. If
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Thought question: Professors typica
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Descriptive studies and surveillanc
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4. The Phenomenon of Disease Concep
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Classification is the foundation As
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As we gain more sophisticated under
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To recapitulate the above discussio
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Classifying cause of death Since mo
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Laboratory and other objectively me
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distribution but are not diabetic (
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program in the general population,
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Infectious disease Incubation "time
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the direct effects of carcinogenic
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patient outcomes. The design and ev
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detected by screening will appear b
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Morrison, Alan S. Screening in chro
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e relevant. Compromises might be fo
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educational attainment by the numbe
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Distributions - the fuller picture
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Per capita income: Should health ca
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Deaths of children < 1 year of age
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No. of persons with senile dementia
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Incidence Immigration Relationship
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Examples: arthritis, cholelithiasis
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Cohort - entrance into the populati
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Sample calculation: 200 people free
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• The units of time must be state
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Calculation of person-time in a coh
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Original Calculation of person-time
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average risk for a member of the co
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However: Nurses: 601 cases/89,538 w
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treated. If the rate at which patie
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Incidence and prevalence in a popul
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small prevalence. So if the seropre
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Appendix on weighted averages Becau
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Appendix on exponents and logarithm
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and epidemiology. The notation ln(x
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3. For the following hypothetical d
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c. ________________ 6 fatalities /
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Measuring disease and exposure - As
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5. a. Flow Diagram Population of si
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New cases Q ID = ------------------
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Overview 6. Standardization of rate
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differences between the groups in f
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∑ (stratum-specific rates �× s
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especially important when comparing
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copy this cell to the other columns
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where the RR k are the stratum-spec
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and the observed number of deaths i
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Directly standardized rate for A =
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5,022 Indirectly standardized = —
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the situation among older age group
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Appendix on Standardized Mortality
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across age strata, then the damage
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d. How would you feel about the con
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Cases per 100,000 Mean annual incid
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d. dt Indirectly standardized rates
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The second ingredient for an standa
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Group US rate /100,000 County pop.
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Crude rates are comparable because
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The "Big Picture" 7. Relating risk
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Consider first the table on the lef
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The epidemiologist first arranges t
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(I1 - I0)/I0 = (0.01200-0.00800 / 0
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Descriptive adjectives for magnitud
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Odds ratio The odds ratio (OR) is a
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Duncan C. Thomas, "On the need for
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6. Odds of exposure in controls Pro
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CID = CI1 - CI0 = .20 - .10 = .10 (
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When both disease and exposure have
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variables is linear. An r of zero m
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Page 195 and 196: Incidence Diagrammatic representati
Page 197 and 198: PAR = AR × P1 = (I1 - I0)P1 = I -
Page 199 and 200: expresses the prevented cases as a
Page 201 and 202: Incidence Diagrammatic representati
Page 203 and 204: The result, (NHIH)/(NLIL+NHIH), is
Page 205 and 206: Proportion with = 0.5 ( 22 --- ) +
Page 207 and 208: CI may be preferred: � if the hea
Page 209 and 210: Appendix — Relating risk factors
Page 211 and 212: By definition, oddsr = risk / (1 -
Page 213 and 214: Bibliography Measures of effect: Te
Page 215 and 216: Relating risk factors to health - A
Page 217 and 218: 4. In a study of adverse effects of
Page 219 and 220: number of "permanent" quits (define
Page 221 and 222: = I1n1- I0n1 + I0n0 - I0n0 ——
Page 223 and 224: 2. Imprecision in determining the t
Page 225 and 226: Sometimes the appearance of a new s
Page 227 and 228: Case-control (case-referent, etc.)
Page 229 and 230: ealistic setting and results may th
Page 231 and 232: "ecologic fallacy", the erroneous i
Page 233 and 234: can vary substantially among indivi
Page 235 and 236: e estimated from that study since t
Page 237 and 238: Risk ratio Consider the example of
Page 239 and 240: Dietary Salt Intake and hypertensio
Page 241 and 242: Intervention trials can include tes
Page 243: Treatment allocation can be 1) fixe
Page 247 and 248: Cases Controls ____________________
Page 249 and 250: population and that the controls we
Page 251 and 252: Estrogen users (N1) Nonusers (N0) N
Page 253 and 254: In the 3 × 10 6 unexposed women-ye
Page 255 and 256: similar to that in the case group t
Page 257 and 258: A modern perspective In general, de
Page 259 and 260: of exposed to unexposed persons sam
Page 261 and 262: Case-control studies: Armenian, Har
Page 263 and 264: Wingo, Phyllis A.; Howard W. Ory, P
Page 265 and 266: Part I Analytic study designs - Ass
Page 267 and 268: 1. Doll and Hill state (page 1451,
Page 269 and 270: Part I Analytic study designs - Ass
Page 271 and 272: � Possible motivation to change b
Page 273 and 274: 9. Causal inference * The desire to
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Page 277 and 278: The mother who replaced the burned-
Page 279 and 280: As presented in Kleinbaum, Kupper,
Page 281 and 282: Popper maintains that it is fundame
Page 283 and 284: 1. Is the association real or artef
Page 285 and 286: Temporality First exposure, then di
Page 287 and 288: confer upon us a freedom to ignore
Page 289 and 290: Lave, Lester B.; E.P. Seskin. Epide
Page 291 and 292: Precision The presence of random va
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methodological literature. Validity
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disease detection may be mistakenly
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In cohort studies, the primary sour
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present, then the D&C would detect
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Controls in an experiment In a true
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Southern endometrial cancer and est
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Cases ` The ` "detection bias" hypo
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from ETS, then a cohort study of ha
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employing lead exposure measures fr
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which the both measures increase in
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coefficient (slope) is to 1.0 and t
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_ _ Se = Pr(D'|D) Sp = PR(D'|D) _ _
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Differential misclassification, how
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subject plus or minus a random nois
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Appendix 2 More on the concern to a
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Bibliography Henneckens and Buring.
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Sackett, D.L.: Bias in analytic res
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e. OPTIONAL: If the reported cumula
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Results from the Evans County Cardi
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2. I1 = incidence in the exposed P1
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makes most sense to view detection
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Sensitivity × cases + (1 - Specifi
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In the factual world, however, we c
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Hypertensive SI participants were t
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3,154 male managers and white colla
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Table 2 Relationship of CHD to Beha
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a group did indeed have higher CHD
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Confounding - comparison of weighte
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Type A smokers) are not very meanin
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Different control groups for hypoth
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Confounding, then, is a function of
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Since the OR is the crossproduct ra
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Case-control study In a case-contro
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First and foremost, a potential con
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is defined in relation to the count
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poor. A scientific basis linking ra
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One way to obtain a better balance
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Stratified analysis is intuitively
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attributed to the exposure of inter
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Bibliography Rothman and Greenland
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Senior P, Bhopal RS. Ethnicity as a
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Some of the relationships just pres
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n1i _______________________________
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2. A 20-year retrospective cohort s
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No. of urinary tract infections Tab
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2. completely attributable to obesi
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5. a. C -- the adjusted relative ri
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of dietary antioxidants. However, c
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epidemiologic research is to identi
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Since the indicator variable (POP)
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Over two decades ago (Causes, Am J
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In this diagram, G and H exhibit ab
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In this situation, the first suffic
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Crude rates as weighted averages Re
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Lung cancer rates by smoking and as
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{B0} Smk Smk Asb. Asb. {B1} {B2} {B
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Notation for joint effects R1 risk
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and R111 = R000 + RD100 + RD010 + R
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RR11 = RR10 × RR01 [End of aside]
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multiplicative model supports the u
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Effect modification as a reflection
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4. Defining subgroups for preventiv
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Bibliography Rothman and Greenland,
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Multicausality: Effect modification
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4. Several studies have shown a syn
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1. Multicausality: Effect modificat
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In these data, or, Expected ROC,SMK
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to drinking in the absence of smoki
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we determine that confounding is pr
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Association between reserpine and b
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R11 R10 × R01 R10 —— = ——
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Hypothetical data on incidence of m
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1. Data conform to an additive mode
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Difference measure - the CID The va
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Distribution of CIR, IDR, OR 0 +1 M
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1 wi = ---------------------------
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5 Y n B 3 n Y C 8 n Y C 4 Y Y D 7 Y
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R11 - R00 = (R10 - R00) + (R01 - R0
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You may well wonder what is the val
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Moreover, the logistic model, we wi
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Key epidemiologic assumptions in th
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a + b1X1 + b2X2 + b3X3 + …) on th
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Wilcosky, Timothy C. and Lloyd E. C
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Data analysis and interpretation Ep
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Range checks Range checks compare e
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� Decisions deferred have to be m
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� Simpler is better � Avoid ext
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educe bias and tend to introduce ad
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data. Perhaps too often generalitie
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When this "analogous experiment" is
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tests are based (e.g., see Sander G
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The probability associated with bei
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conclude that the association is su
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Exposed to diethylstilbesterol? Yes
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For example, suppose that we are co
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The idea behind small studies bias
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Confidence intervals address the qu
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Computing a confidence interval for
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Bibliography General Ahlbom, Anders
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Thompson, W. Douglas. Statistical c
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Appendix Estimating sample size to
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p1 (1 - p1) p2 (1 - p2) σ 2 1 σ 2
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Margin of error (rounded) Point Sam
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Meditations on hypothesis testing a
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Independent replication is the corn
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More meditations on interpreting st
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Part I Data analysis and interpreta
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Part I 1. (a) Restriction Data anal
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9. ORCIG,HYP,OC [multiplicative mod
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15. Practical aspects of epidemiolo
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(CDC, which includes the National I
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cardiovascular area -- notably the
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Disease Control (CDC) decided again
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After submission but before the awa
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Journal of Medicine, Jan 14, 1999,
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Explore the data � Look at data (
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Recently, standardization has come
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Riesenberg, Don; Goerge D. Lundberg
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16. Data management and data analys
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implications, or suspicions or char
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1.4.1.2 Consistency Consistency is
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1.4.5.1.2 Series Runs in series are
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Obviously it will be easier to asse
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2.1.2.1 Statistical There are forma
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2.3.5 Bivariate displays If the sam
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errors. Related to this concern is
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3.3 Expected values Perhaps, the si
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Despite the best efforts, however,
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Complete data cases % distribution
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3.5 Outliers Outliers are now exami
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Bibliography Davidson, Fred. Princi
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attrib ckd length=$1 label='Check d
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17. Epidemiology and public health
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� Geneva - " . . . IFV and allied
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public health, since the best oppor
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Individual-level versus societal le
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14%, so that the burden of the envi
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1. exhausting various non-renewable
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O'Hare WP, Pollard KM, Mann TL, Ken
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� Health for all What contributes
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Challenges in the environment for e
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� What kind of population is requ
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Bibliography American College of Ep
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