University of North Carolina at Chapel Hill
School of Public Health
Department of Epidemiology
Fundamentals of Epidemiology (EPID 168)
Midterm Exam, Fall 1996
Answer Key - REVISED
Note: this answer guide is especially detailed in order to provide thorough
explanations of the many concepts that exam touched on (including a few it
touched on unintentionally!).
1. The primary study question for this investigation concerns the
relationship, suggested by previous studies, between exposure to
pesticides and risk of birth anomalies in offspring. The main exposure
is pesticides (assessed by the surrogate measure of being licensed to
apply certain pesticides). The main outcome is birth anomalies in
offspring, as recorded in birth records.
2. Classification of disease using manifestional criteria means grouping
disorders on the basis of their having similar observable
characteristics, e.g., symptoms, signs, behavior, laboratory findings,
onset, course, prognosis, response to treatment. Classification using
causal criteria means grouping disorders on the basis of their having the
same primary etiologic agent, which, of course, must have been previously
identified. The logic for analyzing the data in terms of organ systems
(a manifestational criterion) is that anomalies occurring in the same
organ system may be more likely to have the same (or closely related)
etiology and therefore should exhibit stronger associations with the
relevant exposure than would the more general category of all birth
anomalies.
3. The presentation of data concerning the occurrence of birth defects with
regard to place (crop region) and time (seasons) is basic descriptive
epidemiology. The fact that the study was designed with a view to
examining specific relationships of interest, which were then assessed
with measures of association and statistical tests, derives from an
analytic perspective.
4. C. Passive surveillance
5. This study cannot really establish the temporal sequence of pesticide
exposure and birth defects because a) half of births occurred before the
data used for the pesticide certification (1991); and b) the time of
actual exposure cannot be determined, since exposure is measured so
indirectly and without the ability to establish when it occurred.
6. A. Any answer can be defended - the population attributable risk (PAR) is
equal to the attributable risk multiplied by exposure prevalence or,
equivalently, the crude incidence minus the incidence in unexposed
persons. When incidence is measured as a rate (i.e., ID), then the PAR
is the difference of two rates. When incidence is measured as a
proportion (i.e., CI), then PAR is the difference of two proportions and
therefore cannot exceed 1.0. The resulting value is typically expressed
as a rate or a proportion. So this question is ambiguous -- apologies!
B. Rate - by the definition of ID
C. Proportion - by the definition of prevalence
D. Ratio - relative risk is a ratio of independently-derived risks (or
rates, if "relative risk" is interpreted as applying to the concept,
rather than specifically to the risk ratio).
7. C. prevalence - Although a birth with an anomaly is an "event", there is
no way to establish the population at risk (denominator) for these
events. For example, would the denominator population be couples, fecund
couples, fecund couples trying to conceive, embryos, recognized
pregnancies? Birth anomalies do not arise out of "live births", since
the anomalies already exist in the fetus. Therefore the "rate of
anomalies per 1000 live births" is simply the proportion of live births
in which a birth defect is present.
8. C. Pesticide appliers had a greater proportion of births with anomalies
as compared to the general population.
9. Assuming that prevalence of birth anomalies increases with increasing
maternal age, an increase in the odds ratio due to age-adjustment
indicates that the maternal age distribution in the general population is
shifted toward older ages relative to that distribution in pesticide
applier spouses. The basis for this conclusion is the following. Birth
defect prevalence was greater for pesticide applier couples. If some of
that excess were due to greater age among pesticide applier mothers, then
age-adjustment would diminish the excess, thereby decreasing the odds
ratios. Since instead, age-adjustment increased the odds ratios, then
the older ages of general population mothers must have offset some of the
excess risk due associated with pesticide exposure.
10A. Since the question does not specify absolute or relative impact, either
attributable risk (AR) or attributable risk proportion (ARP) is correct
(actually, attributable prevalence, but the term attributable risk is
typically applied to rates and prevalences as well as risks).
AR = P1 - P0 = [125 / (125 + 4456)] - [3666 / (3666 + 179,265)]
= 0.02728 - 0.02004 = 0.0072466 = 0.0072, or
7.2 per 1000 total live births
Meaning: 7.2 births with anomalies per 1000 live births fathered by
pesticide appliers are attributable to pesticide exposure.
Attributable Risk proportion (ARP) = (RR-1) / RR (using OR for RR)
= (OR - 1) / OR = (1.37 - 1) / 1.37 = 0.270 = 27%
or
ARP = AR / P1 = (0.027283 - 0.02004)/0.027283 = 0.26548 = 27%
Meaning: 27% of the prevalence of births with anomalies among all
live births fathered by pesticide appliers are attributable to
pesticide exposure.
To attribute cases to exposure requires the assumption of a causal
relationship between pesticides exposure and birth defects.
10B. Again, either population attributable risk (PAR) or population
attributable risk proportion (PARP) provide an answer.
Prevalence of paternal exposure among all live births is:
Pe = 4456 / (4456 + 179,265) = 0.02425 = 2.4% of live births
So PAR = AR x Pe = 0.0072466 x 0.02425 = 0.0655 = 0.000176
= 1.8 per 10,000 live births.
or PCrude - P0 = 0.020217 - 0.02004 = 0.000177 = 1.8 / 10,000
Meaning: 1.8 births with anomalies per 10,000 live births to the general
(married) population are attributable to pesticide exposure in pesticide
appliers.
PARP = [Pe (RR-1) ] / [1 + Pe (RR-1)] (using OR for RR)
= [(0.02425) (1.37-1)] / [1+0.02425(1.37)] = 0.0089
= 1% (approximately)
Or, using the case-control formulation,
Pe|d = 125 / ( 125 + 3666 ) = .032973
PARP = Pe|d (OR-1) / OR = (.032973) (1.37-1) / 1.37 = 0.008905
= 1% (approximately)
Or, PARP = Pe x ARP = 0.02425 x 0.26548 = 0.00644, using the ARP
from part a.
Meaning: Approximately 1% of all Minnesota live births with anomalies
are attributable to pesticide exposure in pesticide appliers.
(Note: small differences among the results from the various methods are
primarily due to the fact that the OR of 1.37 has been rounded to fewer
significant digits than are the prevalences computed above.
11. OR = 1.04 (Derivation:
"Corrected" cases in exposed = 127 - (19 + 12) = 96
Proportion in exposed = 96 / (4456 + 96) = 0.0211
"Corrected" cases in control = 3666 + 31 = 3697;
Proportion in control = 3697 / (3697 + 179,265) = 0.0202
0.0211 / 0.0202 = 1.04 = new odds ratio)
Thus, incorrectly classifying those anomalies into the exposed group
overestimates the strength of association.
12. A. False - there is no basis for assuming that all births would be
affected equally.
B. True - The total proportion of harm, including fetal loss, is:
(lost fetuses + birth anomalies)
-----------------------------------------------------
(lost fetuses + birth anomalies + normal live births)
This proportion exceeds the prevalence of birth anomalies among live
births, potentially by a substantial amount.
13. A. ecologic study - exposure is assessed at the community (region) level,
and exposure of persons is inferred based on residence in a geographic
region where pesticides are heavily used.
14. 1) Strength of association, estimated using odds ratios, is modest, and
therefore does not provide strong evidence on which to infer causal
relationships.
2) Biological plausibility - various laboratory studies and a clinical
epidemiologic study show that active ingredients and contaminants in
pesticides can be teratogenic and/or spermatotoxic. Also, several
compounds in the pesticides are endocrine disrupters.
3) Consistency (the authors cite epidemiologic studies [in Iowa,
Nebraska, Colorado] that have found similar relationships).
15. This question underwent a revision to simplify it, but unfortunately some
parts of the previous version remained. The columns labelled
"# live births" should have included the qualifier "Normal", and the
rates for Minnesota needed to be re-computed accordingly. Due to this
problem, two alternate solutions are completely acceptable, one in which
the denominators are the numbers in the "# live births" column and one in
which the denominators equal the sum of these numbers plus the numbers of
births with anomalies. In addition, full credit is given if the rates
for Minnesota were recomputed. Here is the version in which the stated
rates were used and the # of live births column was treated as if it
meant "Total live births":
Birth anomaly prevalences for Illinois, by water type:
Well water: 2/100 = 20.0 per 1000 live births
City water: 6/200 = 30.0 per 1000 live births
Bottled water: 145/7293 = 19.9 per 1000 live births
Overall (crude): 153/7593 = 20.2 per 1000 live births
Thus, the crude prevalence is higher in Minnesota than in Illinois.
Number of live births (both states combined)
--------------------------------------------
Well water 3479
City water 1074
Bottled water 7499
Total 12,052
Standardized prevalence for MN:
3479 x 26.8 + 1074 x 30.0 + 7499 x 23.7
---------------------------------------- = 25.2 per 1,000
12,052 x 1000
Standardized prevalence for IL:
3479 x 20.0 + 1074 x 30.0 + 7499 x 19.9
---------------------------------------- = 20.8 per 1,000
12,052 x 1000
The standardized prevalence for Minnesota also exceeds that for
Illinois, though by a smaller amount than the difference in the crude
prevalences. The difference has been slightly reduced because the
standardized prevalence for Minnesota gives somewhat greater weight to
the prevalence for bottled water (23.7/1000) and less to the
prevalence for well water (26.8/1000) than did the crude prevalence.
16. Yes - it is not clear from these data whether birth anomalies occurred
in people with or without exposure because exposure information was
based on group data.
17. A. False - subjects were selected from birth records for live births
B. False
C. True
D. False
E False
F. True - (however, a correlation coefficient indicates the extent of
association in the sense of two variables moving in tandem; it does
not indicate the strength of association in the epidemiologic sense
of how great a change occurs in the response variable for a change
of a given size in the exposure variable)
G. True
18. [Question removed, 10/7/97]
19. Points in favor of action at this time are the evidence that the
relationship is causal (biological plausibility, consistency between
results of ecologic [by crop-region] and individual-based [pesticide
applier] analyses, pattern of findings (season of conception),
consistency across several epidemiologic studies, and the high
attributable risk percent (27%) among babies with birth anomalies born
to pesticide applier couples. In addition, the substantially
increased prevalences of birth anomalies among all live births in
county clusters with high use of chlorophenoxy herbicides/fungicides
(Table 4), consistent across the four regions, suggest that anomalies
due to pesticides (assuming that the relationship is causal) occur
throughout areas where these pesticides are used. Even though the
population attributable risk proportion is very small (about 1%) for
exposure due to being a pesticide applier, the proportion of all
Minnesota birth anomalies potentially attributable to residence in a
county cluster with high pesticide use is 27% [overall prevalence of
birth anomalies for all Minnesota in-wedlock births was 3791 / 183,721
= 20.63 per 1000 live births (Table 1), prevalence of birth anomalies
in low-pesticide county clusters ("unexposed") was 15 per 1000 (Table
4), so PARP = (PCrude - P0) / PCrude = (20.63 - 15) / 20.63 = .27).
The effects seem to be strongest for chlorophenoxy pesticides,
suggesting that at least this category should be restricted.
Moreover, there are powerful arguments for reducing pesticide use for
environmental reasons as well.
Against taking action other than continuing research are that the
evidence is still not very strong (biological mechanisms not yet
elucidated, relationship is not highly specific, epidemiologic studies
limited and not entirely consistent, experimental evidence not
available), the potential impact on agriculture and therefore food
prices is considerable, and the costs to industry and commerce from
restrictions on a major product are substantial. Moreover, the
relative weakness of the odds ratios (below 2.0) indicates a
significant possibility that other factors could be responsible for
the increase in birth anomaly prevalence seen in association with
pesticide exposure, a possibility whose investigation requires better
data on exposure and other factors that may lead to birth anomalies.
Grading of this question is based on the clarity and support for your
evaluation and recommendation.
10/21/96, 10/7/97 - wr:eml/vs \ mepid168\ exams 1996 Midterm exam - answers rev.