Epidemiology 200B: Winter 2010
Homework 5: “Practice Quiz”
Name:
TA: Joni / Doug
Questions 1-10 address: Wilcox AJ et al. Folic acid supplements and risk of facial clefts: national
population based case-control study. BMJ 2007 Mar 3; 334(7591):464.
1. a) What is the objective of the study?
b) Which study design did the investigators use for this purpose?
c) What are the source population and the control-sampling design?
d) Why did they choose this study design?
2. a. Describe the different sources of information bias in the study.
b. Which sources are most likely leading to non-differential misclassification?
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Epidemiology 200B: Winter 2010
Homework 5: “Practice Quiz”
c. What is recall bias? What kind of misclassification is likely to result from recall bias?
d. Considering the definition of recall bias that you have just given, comment on the statement from
page 4 of 6 at the end of the “Bias” section the authors write, “The fact that folic acid less than 400
microgram a day showed no association with clefts suggests a lack of recall bias.”
3. a. Is selection bias a likely problem in this study? Explain.
b. In the methods section describing the intake of folic acid supplements the authors write that
“…Among women who reported taking folic acid, we were able to confirm intake for 99% by
using the product name or pill bottle label…”
Comment on the authors’ use of the term “confirmed”.
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Epidemiology 200B: Winter 2010
Homework 5: “Practice Quiz”
c. If you dichotomize the exposure data in Table 1 for cleft lip+/- palate at 400 micrograms folic acid
and now assume that participations rates were 76% for both exposed (>400 micrograms) and
unexposed (<400 micrograms) controls but all the non participating cases (12% of those invited) were
unexposed, what is then the expected OR among all who were selected for the study (no other bias or
random variation)? Comment on any difference between the observed and the calculated OR using
these assumptions.
4. a) From Table 1 calculate the two crude odds ratios for the effect measure of different doses of
folic acid supplements on the risk of cleft lip  cleft palate. What do you infer from your results?
b) For the analysis of “isolated clefts,” the investigators excluded cases with a non-cleft birth defect.
Under which conditions would this affect the validity of the study?
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Epidemiology 200B: Winter 2010
Homework 5: “Practice Quiz”
5. The authors have adjusted for potential confounders in the study. Is there any change in observed
estimates after adjusting for confounders?
6. a. Pick two from the list of potential confounders and discuss briefly how and why you agree or
disagree with the investigator’s choice.
b. Supply a DAG for each to illustrate and support your choice.
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Epidemiology 200B: Winter 2010
Homework 5: “Practice Quiz”
7. Let’s assume now that increased homocysteine levels are known to be associated with increased
risk of cleft lip with or without cleft palate, but you would like to avoid doing a randomized trial to
demonstrate this. Can you think of other techniques that utilize the MTHFR gene discussed in class
and in question 10 that could be used to control for potential confounders both measured and
unmeasured? Briefly discuss what information you would need to have to utilize this technique.
8. a. Describe a case-crossover design to study this association. (HINT: The exposure period is already
described in the article.)
b. Assume that in a case-crossover study with 196 cases of cleft palette only, the exposure of >/= 400
µg of folic acid supplements was as given below. Calculate the odds ratio.
Exp (w)
+
+
-
Exp
(ref)
+
+
-
5
31
41
119
196
c. The point estimate for the crude OR in Table 2 for cleft palette only is given as 0.81. Explain a
possible reason for the difference in point estimates between these 2 study designs.
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Epidemiology 200B: Winter 2010
Homework 5: “Practice Quiz”
9. a. Draw a 2 x 2 table where exposure is >/= 400 µg of folic acid supplements (unexposed is < 400 µg)
and outcome is cleft palate only. Calculate the odds ratio.
b. Stratify this 2 x 2 table across 2 levels of smoking (1. None/Passive 2. Active at any level) and
calculate an odds ratio for each.
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