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Epidemiologylat 1
Epidemiologylat 1
Competency Examination
Questions (with answers)
January 2002
(for details on which specific topic areas you will be tested on please
refer to the PhD guidelines booklet)
1. (2 points) You’ve been asked to use conditional logistic regression to analyze these data,
but
in principle you could have used cross-tabulation techniques. For these data, why is it
advantageous to use logistic regression modeling rather than cross-tabulation techniques to
study the relationship between glycemic control and neuropathy?
We would have to stratify the Duration variable in order to use it in cross-tabulation. We can
keep it continuous in a conditional logistic regression analysis.
For matched data, we can only use those pairs that are concordant for the exposure if we want
to
look at interaction of exposure and another variable in cross-tabulation. In conditional logistic
regression approach, pairs discordant for exposure still contribute to parameter estimates.
Simultaneous assessment of serveral confounders and/or effect modifiers can be difficult or
impossible using cross-tabulation due to small stratum-specific sample sizes. If the over-all
sample size sufficient, several confounders and effect modifiers can be considered jointly in
conditional logistic regression.
2. (4 points) As part of your investigation, you computed the following models:
Model I:
Parameter DF Estimate Standard Error -2lnL
-----------------------------------------------------------------------------------------------------------
Control 1 -0.6359 0.1844 334.06
Model II:
Parameter DF Estimate Standard Error -2lnL
-----------------------------------------------------------------------------------------------------------
Control 1 -0.5295 0.1934 304.72
Duration 1 0.4471 0.0873
Model III:
Parameter DF Estimate Standard Error -2lnL
-----------------------------------------------------------------------------------------------------------
Control 1 -0.2814 0.2048 292.79
Duration 1 0.5540 0.0972
Control*Duration 1 0.0236 0.0115
a) Using the information provided to you for each model, describe how you would
decide, in pure statistical terms, which of these three models is most appropriate to
use when you report the effect of glycemic control on the odds of having neuropathy.
The best way is to compare nested models using a chi-square likelihood ratio test (1st and 2nd
are
nested in 3rd, 1st nested in 2nd). The chi-square likelihood ratio test is comput ed as
[-2*ln(likelihood for reduced model)]– [-2*ln(likelihood for full model)]. The correct number
of
degrees of freedom for each test is equal to the difference in the number of parameters
between
the full and reduced models.
For each test, the null hypothesis is that the parameters included in the full model but not in
the
reduced model are equal to zero. The alternative hypothesis is that those parameters are
different
from zero. For example, to compare the 1st model to the 2nd, the null hypothesis is that the
parameter for Duration is equal to zero. The alternative is that the parameter for Duration is
different from zero. If the p-value for the likelihood ratio test is less than some significance
level
(most commonly, 0.05), then the null hypothesis is rejected.
The exact order of testing the models will likely differ between students. It is important that in
any case, the student indicate some systematic way to choose between the 3 models. For
instance, the student may first test for the presence of a statistically significant interaction by
comparing the 2nd model to the 3rd. If the 3rd is the better model according to the likelihood
ratio
test, then they may conclude that no more testing is necessary and that the best model is the
3rd.
If instead the 2nd is best, they would then compare the 2nd to the 1st, etc. Others may not
choose
the reductionist approach, but would instead compare the 1st and 2nd models as the first step.
Still others may test for an over-all affect of duration first by comparing the 1st and 3rd models.
Student may also indicate that examination of changes in parameter estimates after inclusion
of
additional variable(s) would guide choice of model.
Description of and use of t-tests acceptable except in the case that the student would use them
to
try to compare the 1st and 3rd models.
b) Assume that you found model II to be the best model. Interpret the coefficients for
control and duration. You do not need to include confidence intervals or p- values.
The coefficient for Control is the log of the ratio of the odds of neuropathy for those with
glycemic control to those without glycemic control after controlling for Duration. The odds of
neuropathy for those with glycemic control are 0.59 (e –0.5295.) the odds for those without
glycemic control.
The coefficient for Duration is the change in the log of the odds ratio for neuropathy
associated
with a one-year increase in the duration of disease after controlling for Control. The odds of
neuropathy for those who have had diabetes for 9 years are 1.56 (e 0.4471) the odds for those
who
have had diabetes for 8 years. (9 vs. 8 is arbitrary).
c) Assume instead that you found model III to be the best model.
i. Calculate the odds ratio for those with glycemic control to those without for
those with a duration of 5 years. You do not need to include a confidence
intervals or p- value.
The OR associated with glycemic control to those without for those with a duration of 5
years:
e –0.2814 + 0.0236*5 = e –0.1634 = 0.85
ii. Write a summary of the relationship between glycemic control and the odds of
developing neuropathy for an audience without statistical training. You do not
need to include confidence intervals or p- values.
An example: Demonstration of glycemic control is associated with a reduction in the odds of
having neuropathy among type 2 diabetics after controlling for the effect of duration of the
type
2 diabetes. The magnitude of this reduction depends on the duration of type 2 diabetes. The
reduction in the odds of neuropathy due to glycemic control is attenuated with increasing
duration. Specifically, the odds of having neuropathy for those with glycemic control were
85%
of the odds for those that did not demonstrate glycemic control for those with a duration of
diabetes of 5 years. For those with a duration of 10 years, the odds of having neuropathy for
those with glycemic control were 95% of the odds for those that did not demonstrate such
control.
3. (2 points)
a) A collaborator would like to know if increasing age is associated with the odds of
neuropathy in your sample
Is it possible for you to assess this relationship in this sample? If it is possible to
assess the relationship, write out the model(s) and describe the statistical test that you
would use to do so. If is not possible to assess the relationship, explain to your
collaborator why this is the case.
It is not possible to test for association with a matching factor, in this case age, since age will
not
differ in any stratum (each matched case and control form one stratum). We can test for
association with a factor only when that factor differs among at least one matched case and
control pair.
b) The collaborator would also like to know if the effect of glucose control on the odds
of neuropathy is modified by age.
Is it possible for you to assess this relationship in this sample? If it is possible to
assess the relationship, write out the model(s) and describe the statistical test that you
would use to do so. If is not possible to assess the relationship, explain to your
collaborator why this is the case.
Yes, it is possible to assess whether or not age is a modifying factor for glycemic control in
this
sample. One set of possible models:
Model A:
Logit(p) = 1 + 2 + …+ 250 +1Control + 2Age1 + 3Age2 +4Age3 + 5Age4 + 6Age5 +
7Age6 + 8Age7 + 9Age8
Model B:
Logit(p) = 1 + 2 + …+ 250 +1Control + 2Age1 + 3Age2 +4Age3 + 5Age4 + 6Age5 +
7Age6 + 8Age7 + 9Age8 + 10Control*Age1 + 11Control*Age2 + … + 17Control*Age8.
Use a likelihood ratio test to compare the model with the interaction(s) between Age and
Control
to the model without the interaction. The likelihood ratio test is defined as above in (1). If the
pvalue
for the test is less than 0.05 (or some other student-defined and justified significance level),
then conclude that there is a statistically significant interaction. Models may look different
between students depending on how they enter Age into the model (linear or dummy
variable).
If they use a linear term, then t-test acceptable.
4. (1 point) Your collaborator would also like to know if the effect of glycemic control on the
odds of neuropathy is modified by blood pressure. Is it possible or not possible for you to
assess this relationship in this sample? Explain your answer to your collaborator who has
little statistical training.
Yes, it is possible to assess whether or not the effect of glycemic control on neuropathy is
modified by blood pressure in pure statistical terms since it is likely that blood pressure status
varies between at least one case and control pair.
An example: It is possible to do so because we have not matched on blood pressure. Because
we
did not match on blood pressure, each case and control pair has the potential to differ in
whether
or not they have high blood pressure. As long as some pairs differ, we can test the interaction
between blood pressure and glycemic control. Whether or not this will have biological
meaning
will need further investigation.
METHODOLOGY QUESTION
Limit your answer to 6-8 double spaced pages done in 12 pt. font
Primary liver cancer is a significant global public health problem. The causal agents are
multiple, but you have been asked to design a study that evaluates the independent causal
significance of infection with hepatitis C virus, transmitted primarily by contaminated blood
or
blood products. You are asked to evaluate potential confounding by infection with hepatitis B
virus and exposure to alcohol. The setting for your study is the United States. The study
design
may be case-control, cohort, case-control nested in a cohort, cross-sectional, etc. You are
asked
to choose one design that will enable you to respond to the questions below:
1.) (4 points) Describe an appropriate design with consideration of:
a. selection criteria of study subjects;
b. measures of the exposures to hepatitis C, hepatitis B, alcohol. Please note that the
diagnosis of chronic infection with hepatitis C virus is based on demonstration of
antibody (anti-HCV) using an enzyme-linked immunosorbent assay.
c. potential sources of bias and confounding.
d. strengths and limitations of the chosen study design
2.) (2 points) Effects of non-participation:
Not all potential participants will be available or agree to participate. It is generally
recognized that substantial nonparticipation may affect external validity or generalizability.
Discuss the effect that nonparticipation may have on biased assessment of rate ratios, risk
ratios, or odds ratios when:
a. The proportions participating and nonparticipating differ according to the likelihood of
exposure but not the risk or probability of disease.
b. Individuals who are exposed and develop subsequently the disease are less likely to
participate than other subgroup members.
3.) (2 points) Consider an appropriate statistical model to assess relative risk of exposure to
hepatitis C virus. Write the model in the form y = 0 + 1X1 + 2X2 + ….. , describe the
parameters and describe how will interpret the statistical model that you will employ.
4.) (1 point) The development of cirrhosis may represent an important intervening event and
manifestation of susceptibility for future liver cancer. In your consideration of the research
design and statistical method of analysis, how would you assess the association of cirrhosis
in the natural history of chronic hepatitis C infection?
The analysis attempts to associate hrt with tooth loss over a two-year period. The amount of tooth loss
experienced is small relative to the secular changes that are occurring in the US population (1.5 points).
ANSWER 3:
Residual confounding (1.5 points).
(Tooth loss is largely a behavioral phenomenon. Women who choose to use hrt are possibly also less likely
to choose extraction to treat a tooth that could be maintained with an alternative treatment.)
ANSWER 4:
If hrt is a major player in tooth loss, and health behavior is not, then there should be large differences in hrt
between these subjects and the rest of the female population. The authors have presented no evidence of
this kind of difference. Residual confounding is more likely. (1.5 points)
(The evidence is overwhelming that tooth loss is driven my cultural and behavioral forces, arguably even
more than by disease states. Especially in these generally health conscious women, the likelihood that
disease would be so advanced that they would have no other choice than extraction is extremely unlikely.
Only if they had neglected their oral health for a long period of time would tooth loss be likely to be the
only available option. Thus, the choice of extraction (tooth loss) instead of an alternative treatment is likely
to be behavioral, not disease driven.)
ANSWER 5:
While no difference between males and females does not rule out a hrt effect, it is clear that there are
substantial reductions occurring in both males and females that are, at least in the case of males, not related
to hrt (0.75 points).
Further, the absence of a difference between males and females calls into question the magnitude and thus the
practical importance of and causal effect of estrogen loss and tooth loss (0.75 points).
ANSWER 6:
With so much less tooth loss in this group than in women overall, there is a clear suggestion that factors other
than
hormone replacement play a substantial role. That all of these other effects are eliminated by selecting a
relatively
homogeneous group seems unlikely. Residual confounding could remain. Also, the rationale for studying a
condition in a group in which it relatively infrequently occurs is not obvious. (0.75 points)
Some strengths in using this group are that they are relatively well-educated and generally aware of their health,
and
thus will be better able than most women to report accurately on their health and related activities. Also, it is
relatively inexpensive to add this analysis on to an existing, ongoing study (0.75 points).
1
ECOLOGY; BSC 201
STUDY GUIDE; THIRD EXAMINATION
FALL 2004
The following questions are intended to be a general guide for you to use in studying the
material
presented after the second examination. All possible examination topics/questions are not
included, nor is it guaranteed that questions directly related to the study questions will be on
the
examination. You should use these questions to help you learn the specific information
indicated, and to learn how to think about ecological and evolutionary questions. Be sure to
consult both your lecture notes and the reading assignments.
1. Define and explain the terms R0, r, and G. How are they derived from life tables?
2. What is reproductive value? How is it calculated?
3. What is reproductive effort? Give an example.
4. What is Lack’s hypothesis? Are the house wren data presented in class consistent with the
hypothesis? Why?
5. Design an experiment that tests Lack’s hypothesis. Design another experiment that tests for
the existence of a cost of reproduction in some organism.
6. What is the cost of reproduction? How is it related to Lack’s hypothesis?
7. What is the difference between current reproductive value and residual reproductive value?
8) What are the columns in a life table and how are the columns related to each other?
9) How are life tables obtained, and what are the different types of life tables?
10) What is the difference between crude density and ecological density?
11) What are the relative advantages of using numbers, biomass, and standing crop of energy
as
measures of abundance?
12) What is the difference between a static and a cohort life table?
13) How are distribution and abundance related?
14) What is the evidence that distribution is limited by abiotic and biotic factors?
15) What is the hypothetico-deductive method of science? Design a study that employs this
approach.
16) What role does experimentation play in science and, if any, in the hypothetico-deductive
method?
17) What is the Principle of Allocation?