University of North Carolina School of Public Health

                        Department of Epidemiology

                  EPID 168 - Fundamentals of Epidemiology

          Copyright, 1997, Victor Schoenbach and Wayne Rosamond

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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