University of North Carolina School of Public Health Department of Epidemiology EPID 168 - Fundamentals of Epidemiology Copyright, 1997, Victor Schoenbach and Wayne Rosamond <!-- Note: Adjust margins or pagination before printing. !> Note: The scores on this examination were on the high side, and some of the questions on this exam were problematic. MIDTERM EXAMINATION, Fall 1997 -- Answer Guide 1. Matching (1 pt each): Column A - Terms Column B - Topics 7 cumulative incidence (11 is ok) 1. Case-control studies 12 incidence density 2. Causal inference 11 prevalence (7 is ok) 3. Confounds cross-sectional data 2 dose response 4. Death certificate 9 induction period 5. Descriptive epidemiology 1 odds ratio 6. Diagnostic tests 8 preventive fraction in the exposed 7. Estimates risk 4 underlying cause of death 8. Measures impact 6 positive predictive value 9. Natural history of disease 10 detectable, pre-clinical phase 10. Population screening 5 migrant studies 11. Proportion 3 cohort effect 12. Relative rate (Credit was also given for some other pairings.) 2. Diagnosis of myocardial infarction is based on manifestational criteria. (4 pts) 3. a. community, person, community (units of assignment, observation, analysis, respectively, in the Minnesota Heart Health Program. (4 pts) 4. a. to create two treatment groups that are similar at baseline on both known and unknown factors associated with myocardial infarction (4 pt) 5. Age standardization, True or False (2 pts each): T a. The indirect method of age standardization uses data from the stratum specific rates from an external population applied to the age distribution of the study population. F b. A standardized mortality ratio is an example of a stratum specific crude rate. F c. Standardized mortality ratios are useful when the number of events is small and multiple comparisons among populations are to be made. T d. Direct age standardization can be characterized as applying the same set of weights to the age-specific rates between populations to be compared. 6. Predictive value depends both on specificity and on prevalence. For a given specificity, higher prevalence means higher positive predictive value, lower prevalence means higher negative predictive value. Prevalence of coronary artery disease is lower in women who are younger and have few risk factors, so negative predictive value is higher in this group. (3 pts) -2- 7A. a. proportion -- The "transmission rate" is the number of HIV-infected infants divided by the total number of births in that group. The proportion estimates the prevalence of HIV infection in these infants. The proportion also estimates cumulative incidence of HIV-infected babies among 2nd trimester, HIV-infected pregnant women. Cumulative incidence measures for birth outcomes are a complex matter, because of the great opportunity for selection bias due to impaired fecundity and fertility, and unrecognized pregnancy loss. In this case, however, the exposure occurs after the pregnancy has been recognized. (4 pts) 7B. Relative risk of HIV infection for zidovudine vs. placebo: Relative risk (RR) = CI1 / CI0 = 7.4% / 25.6% = 0.29 The transmission rates serve as estimates of CI1 and CI0 (the incidences can be estimated from the transmission rates even if the former are regarded as prevalences, since there is a restricted risk period and duration is not a factor). (4 pts) 7C. Proportion of potential cases of perinatal HIV transmission that could be prevented by zidovudine, i.e., the preventive fraction in the exposed, PF1 (all women take zidovudine, so all are exposed) (4 pts): PF1 = 1 - RR = 1 - 0.29 = 0.71 or 71% By diagram: H _ _ _ _ _ _ _ _ _ _ _ _ 25.6% transmission rate in women I | who do not take zidovudine (based on V | ^ the placebo group) | | T | | Amount of the transmission rate that r | | is prevented by zidovudine a | v n |_______________________ 7.4% transmission rate in women m | who took zidovudine i | s |_______________________ 0 . (25.6% - 7.4%) / 25.6% = 1 - 7.4% / 25.6% = 0.71 (= 1 - RR) 7D. b. Cases are HIV-infected infants; controls are uninfected infants of HIV-seropositive mothers. Using all uninfected infants as controls would make zidovudine appear to be a risk factor for HIV transmission, since most mothers do not have HIV so their infants will be uninfected. Choices c. and d. choose the control and/or case group partly on the basis of exposure, which completely undermines a case- control design. (4 pts) 8A. c. Range -- the range is in fact completely determined by the highest and lowest values. (4 pts) 8B. a. Age at first coitus -- its mean and mean are both close together and not very far from the middle of the range. Although the mean and median are also close together for the number of partners in the past 4 months, but they are no where near the middle of the range. (4 pts) -3- 8C. a. Incidence of gonorrhea is lower than that of chlamydia -- if duration is the same for both diseases, the prevalence odds are proportional to the incidence density, so gonorrhea's smaller prevalence (42/940 vs. 66/957) implies a lower incidence. (3 pts) 8D. a. Duration of gonorrhea is shorter than that of chlamydia -- if incidence rates are the same, chlamydia must last longer in order for its prevalence to be higher. (2 pts) 8E. (3 pts) Prevalence odds = duration x incidence density. Therefore: prevalence odds (gonorrhea) duration(G) x incidence density ----------------------------- = -------------------------------- prevalence odds (chlaymdia) duration(C) x incidence density Since both diseases have the same incidence, the ratio of their durations equals the ratio of their prevalence odds: prev. odds for gonorrea 42 / 898 0.468 ------------------------ = -------- = ------- = 0.63 prev. odds for chlamydia 66 / 891 0.741 (Credit was also given for "prevalence = incidence x duration", though this true only approximately.) 9A. School absence from acute asthma and cigarette smoking (4 pts): School absence due to acute asthma in middle school by cigarette smoking status Smokers Nonsmokers Total ------- ---------- ----- AA-10* 100 300 400 Absent fewer than 1,100 6,500 7,600 10 days ------ ----- ----- Total 1,200** 6,800 8,000 * AA-10 refers to absence 10+ days due to acute asthma. ** Based on 15% smoking prevalance 9B. Cumulative incidence of AA-10: a. Crude CI = 400 / 8,000 = 50 per 1,000 or 5% b. CI in smokers = 100 / 1,200 = 83 per 1,000 or 8.3% c. CI in nonsmokers = 300 / 6,800 = 44 per 1,000 or 4.4% 9C. Strength of association (4 pts): CI in smokers 8.3% Cumulative incidence ratio = ----------------- = ------ = 1.89 CI in nonsmokers 4.4% d. The cumulative incidence ratio (CIR) of 1.9 indicates a moderate association between cigarettes and extended school absence. -4- 9D. Number of cases of excessive absence due to acute asthma (AA-10) that (assuming causation) are attributable to smoking. This question asks for the size of the shaded box in the diagram in the "evolving text". That diagram, with numbers instead of variables is: | 8.3% | 8.3% = incidence | |XXXXXXXXXXXXXXX| in exposed Incidence | | | persons | | 3.9% x 1,200 | | | = 47 | 3.9% = "attributable 4.4% | |XXX XXXX| risk" | |\\\\\\\\\\\\\\\| | 300 | 4.4% x 1,200 | 4.4% = incidence 0 | |\\ = 53 \\| in unexposed 6,800 1,200 (15%) persons Nonsmokers Smokers So the number of cases attributable is 47 (after rounding). This number can be obtained in various ways: Number of cases in smokers - "expected" cases in smokers 100 - 1,200 x 4.4% Attributable risk x Number of smokers (I1 - I0) x 1,200 (8.3% - 4.4%) x 1,200 Number of cases in smokers x Attributable risk proportion (ARP) 100 x (1.89 - 1 ) / 1.89 Overall number of cases x Pop. attributable risk proportion (PARP) 400 x (I - I0) / I 400 x (5% - 4.4%) / 5% 400 x 12% All these methods come up with approximately the same answer, the differences being due to the rounding of intermediate results in obtaining some of the incidences and the CIR. When the numbers from the table are used and intermediate results not rounded, the number of cases attributable to smoking is 47.0588 Assuming causation, cigarette smoking is responsible for heavy absence (10 days or more during the fall quarter) due to acute asthma in about 47 middle schoolers in the district, or 12% of all students with heavy absence due to acute asthma. 10A Prevalence of chlamydia at the 12-month follow-up (3 pts): Cases 18 cases found at 12-month follow-up Prevalence = ----- = -------------------------------------- = 2.2% PAR 810 youth tested at 12-month follow-up -5- 10B Average incidence density of chlamydia (average simply means one number that applies to the entire two-year interval, rather than one rate for each three-month interval - if you compute the latter rates, however, and take the average, you should obtain the same result as the overall incidence density) (3 pts): (Total) Cases Prevalence = --------------------- (Total) person-time (15 + 23 + 8 + 18 + 17 + 17 + 14 + 11) cases = ------------------------------------------------------------ (890 + 870 + 850 + 820 + 780 + 760 + 710 + 630) x 3 months 123 cases = ------------------ = 0.65/100 person-months = 7.8/100 person-yrs 18,930 person-months 10C Reasons for preferring incidence density in this case (6 pts): These diseases have an extended risk period (i.e., one longer than the period of observation) People can acquire these diseases more than once Different lengths of follow-up time per subject 11A. Inherent weaknesses in this design that make it susceptible to obtaining inaccurate data are the potential for problems of recall, reporting, and recording in medical records; also, there is considerable opportunity for alcohol abuse status to influence diagnosis of depression. (3 pts) 11B. Criteria for causal inference (6 pts) Strength of association -- in this regard the study provides strong evidence of causation due to its very high odds ratio ([(76)(80)]/[(20)(24)] = 12.7 -- assuming for this discussion that the OR is not biased by design problems) Temporality (antecedant-consequent) -- there is no indication here that alcohol abuse preceded major depression, and the reverse seems just as possible. Other criteria (e.g., dose-response, biological plausibility, experiment, analogy, consistency, coherence) either do not apply to a single study or cannot be evaluated with the information provided. 10/19/97 EPID 168 Midterm, Fall 1997, Answer guide