University of North Carolina at Chapel Hill
School of Public Health
Department of Epidemiology

Fundamentals of Epidemiology (EPID 168)

Final Examination, Fall 1999
The questions on this examination are largely based on Cantor KP, Lynch CF, Hildesheim ME, Dosemeci M, Lubin J, Alavanja M, Craun G. Drinking water source and chlorination byproducts in Iowa. III. Risk of brain cancer. Am J Epidemiol 1999;150:552-60. You may refer to an unannotated copy of this article during the examination.
  1. Briefly discuss two reasons why a case-control study is (or is not) well suited to examine risk factors for brain cancer. (3 pts)

 

  1. The authors describe the study design they used as a "population-based case-control study". Briefly explain how this is different than a non-population based case-control study. Include in your answer issues regarding the selection of cases, selection of controls, and validity. (3 pts)

    2.  

  2. Cases were identified by the State Health Registry of Iowa. Which of the following categories of study design best describes this method of case finding? Choose one best answer. (3 pts)
    1. Prospective follow-up
    2. Passive surveillance
    3. Cross-sectional survey
    4. Community-based screening
    5. Hospital-based surveillance
  1. The authors state that cases had to be newly diagnosed with histologically confirmed glioma without previous diagnosis of a maligant neoplasm. Which of the following best describes an advantage of using incident cases instead of prevalent cases? Choose one best answer. (3 pts)
    1. Using incident cases allows the investigators to directly compute relative risks.
    2. Using incident cases reduces the non-systematic error of case-control studies.
    3. Estimates of exposure from incident cases may be less influenced by disease status.
    4. Using incident cases allows for the investigation of effects on risk versus those effecting duration.
    5. Incident cases are less likely to be lost to follow up than prevalent cases.
  1. Even if the investigators are careful in the selection of cases and controls, selection bias can make interpretation of results difficult. Which of the following is NOT a situation that can produce selection bias? Choose one best answer. (3 pts)
    1. The exposure has some influence on the process by which controls are selected.
    2. The exposure has some influence on the process of case ascertainment.
    3. The disease status has some influence on the recall of exposures.
    4. The exposed cases are reported to registries more than unexposed.
    5. All of the above will produce selection bias.
  1. In this study, exposre information for many of the brain cancer cases was provided by proxy respondents. The authors did not have information from independent sources that could be used to directly verify information provided by these surrogates. However, suppose a follow-up questionnaire was administered to cases, and for 85 of the cases, the investigators were able to obtained information about whether or not they used a private well directly for the cases (self report). Assuming that self report is the best available assessment of whether they used a private well or not, complete the table below so that it reflects a sensitivity, specificity, and positive predictive value of a proxy response of 77%, 75%, and 57%, respectively. Assume that 26 of cases reported that they used private wells. Show your calculation. (6 pts)
    2.

    Proxy report

    Self Report = YES

    Self report = NO

    YES

    		    

    NO

    		    

  2. Cases in this study were histologically confirmed. This is an example of which of the following disease classification criteria? Choose one best answer. (3 pts)
    1. Causal criteria
    2. Ecologic criteria
    3. Manifestational criteria
    4. Etiologic criteria
    5. None of the above
  1. Consider the data presented in Table 1 of this article. Which of the following best represents the proportion of the risk of brain cancer in the population that is attributable to working on a farm (farm occupation). Assume that a farm occupation is causally related to brain cancer risk. Choose one best answer. (4 pts)
    1. 33%
    2. 57%
    3. 10%
    4. 29%
    5. Cannot be calculated from case-control studies
  1. A case-control study like the one described in this paper is most useful when it helps us understand what is happening in the study base (underlying population). Which of the following best describes the study base in this article? Choose one best answer. (3 pts)
    1. The study base is those who if they developed brain cancer could have been selected as a case.
    2. The study base is those who have an equal probability to be selected as a case or control.
    3. The study base is those who are identified as cases or controls after excluding non-responders.
    4. The study base is those who if exposed would have been identified as exposed.
    5. None of the above.
  1. In Table 3 the odds ratios for incident brain cancer by duration of chlorinated surface water exposure are given. The odds ratio (95% confidence interval) in men estimating the risk of brain cancer with 1-19 years of exposure is 1.3 (0.8, 2.1) and 2.5 (1.2, 5.0) for 40 years or more of exposure. Which of the following best describes the role of chance in observing these two estimates? Choose one best answer. (3 pts).
    1. The odds ratio for ³ 40 years exposure is more likely due to chance because it is based on fewer cases and controls.
    2. The odds for 1-19 years of exposure is more likely due to chance because the point estimate is closer to the null value (1.0).
    3. The odds ratio for ³ 40 years exposure is more likely due to chance because the confidence interval is so wide.
    4. The odds ratio for 1-19 years of exposure is less likely due to chance because the confidence interval is narrower.
    5. The odds ratio for ³ 40 years exposure is less likely due to chance because the confidence interval does not include 1.0.
  1. Table 3 presents odds ratios for the association of incident brain cancer with various levels of lifetime average THM exposure. The odds ratio (95% confidence interval) for lifetime average THM concentration of 0.8-2.2 m g/liter for men was 0.9 (0.6, 1.6). The odds ratio (95% confidence interval) for lifetime average THM concentration of ³ 32.6 m g/liter for woman was 0.9 (0.4, 1.8). Which of the following best describes the precision of these two estimates of risk? Choose one best answer. (3 pts)
    1. The estimate is equal because the point estimates are the same.
    2. The estimate is equal because neither confidence interval excludes 1.0.
    3. The estimate in men is slightly more precise because the confidence interval is narrower.
    4. The estimate in women is slightly more precise because the exposure level is much higher.
    5. The precision of the estimates cannot be compared because they are from different exposure groups.
  1. Using the data in Table 4, which of the following best describes the crude unadjusted odds ratios estimating the risk of brain associated with ³ 40 years exposure to chlorinated surface water in men with above median tap water intake? Use the category of 0 years exposure to chlorinated surface water as the reference group. Choose one best answer. (4 pts)
    1. 4.0
    2. 1.5
    3. 3.6
    4. 2.6
    5. Cannot be computed from data in Table 4.
  1. Table 1 shows the adjusted odds ratio estimating the risk of brain cancer by population size. Using the £ 25,000 population size as a reference calculate the crude (unadjusted) odds ratio associated with the > 50,100 population. In 2 sentences or less explain why the two estimate agree or disagree. (4 pts)

    2.  

  2. The authors state that they "found a dose-response relationship among men between brain cancer and duration of consuming drinking water from chlorinated surface water…". Using 3 Bradford Hill criteria, in 3-4 sentences, address causality (or the lack of causality) of the relationship of drinking water to brain cancer. (4 pts)

    3.  

  3. An early study of drinking water and brain cancer was an ecological study conducted by the lead author of the present article. In this study, brain cancer mortality rates in 923 U.S. counties were compared with average levels of THM measured in the drinking water supplies of those counties. For counties in which the sampled water supply served at least 85% of the residents of that county, the correlation coefficient between county-specific mortality rates from brain cancer and trihalomethane levels was 0.24 in White men and 0.19 in White women. After reviewing this paper, your colleague concluded that THM in drinking water are causally related to brain cancer. However, you are more cautious in your interpretation, citing the "ecological fallacy." Please define the ecologic fallacy (2 pts) and describe why it limits the causal inferences that can be made from the ecological study described above (2 pts).

    4.  

  4. The authors used information provided by cases and controls on place of residence, primary source of drinking water, and tap water and total fluid consumption to create an index of cumulative lifetime exposure. However, the natural history of cancer (initiation, promotion, conversion, and progression) may encompass many years. If drinking water is involved at the earliest stages of brain cancer (initiation), then drinking water exposures in the recent past may be more important than present exposures or those in the distant past (e.g., in childhood). As defined in class, which of the following periods would be important in defining the minimal and maximal length of time expected between drinking water exposure and diagnosis with histologically confirmed glioma? Choose one best answer. (3 pts)
    1. Induction period
    2. One year case fatality
    3. Latent period
    4. Both a and c
    5. None of above
  1. The authors included all cases of histologically confirmed malignant brain cancers, including glioblastoma, fibrillary and gemistocytic astrocytoma, and mixed glioma. If authors suspected that drinking water exposure was associated with only certain subtypes of brain cancer (i.e., disease heterogeneity), which of the following strategies could they employ at the analysis stage? (3 pts)
    1. Adjustment for cancer type using mathematical modeling (e.g., logistic regression)
    2. Stratification of cases by brain cancer type
    3. Direct standardization by brain cancer type
    4. Indirect standardization by brain cancer type
    5. Matching cases and control by brain cancer type
  1. The authors restricted their analysis to those cases and controls with at least 70 percent of their lifetime years with a known source of drinking water. This approach was used to reduce which type of bias? Choose one best answer (3 pts)
    1. Confounding bias
    2. Selection bias
    3. Information bias
    4. Random error
    5. None of the above
  1. (question was not asked)


  2.  
    1. Using the data in Table 3, label and complete a 2x2 table for the association between brain cancer and >=40 years’ residence with a chlorinated surface water source (versus 0 years), collapsing over sex (i.e., combine the data for men and women). (4 pts)

      2.  

    2. Calculate the odds ratio for your 2x2 table in part a. Show your work. (3 pts)

      3.  

    3. Suppose that the sex-adjusted OR for the relationship between brain cancer and >=40 years’ residence with a chlorinated surface water source is 1.1. Is sex a confounder of this relationship? Justify your answer. (3 pts)

      4.  

    4. Is sex an effect modifier (assuming a multiplicative model for joint effects) of the relationship between brain cancer and >=40 years’ residence with a chlorinated surface water source? Justify your answer. (3 pts)

      5.  

    5. According to Table 1, having a farming occupation (ever vs. never) is a risk factor for brain cancer (OR=1.5). Assume that among the controls, farming occupation is associated with duration of residence with a chlorinated surface water source. Could farming occupation be a confounder of the associations reported under the Total column in Table 3? Explain your answer. (3 pts)

     

  1. Characteristics of cases and controls included in this study are shown in Table 1. Using this information answer the following questions.
  1. Calculate the appropriate crude (unadjusted) measure of association between farm occupation and brain cancer. Consider those ever working on a farm as sufficient to be classified as having a farm occupation. In 2 sentences or less interpret what this odds ratio means. (4 pts)

    2. Farm Occupation

    CASE

    CONTROL

    YES

    		    

    NO

    		    

     

  2. Assume that 10% of the cases that were labeled as never having worked on a farm truly had worked in such an environment. Furthermore assume that 15% of the controls that were labeled as having ever worked on a farm, in fact never really did work on a farm. What would the true association be between farm occupation and brain cancer? Assume that the classification of disease status is valid. (4 pts)

    3.  

  3. Which of the following best describes a comparison of the odds ratios you computed in parts (a) and (b)? Choose one best answer. (3 pts)
    1. The odds ratios are different as a result of differential misclassification of exposure.
    2. The odds ratios are different as a result of nondifferential misclassification of exposure.
    3. The odds ratios are different as a result of differential misclassification of disease status.
    4. The odds ratios are different as a result of nondifferential misclassification of disease status.
    5. The odds ratios are different as a result of random variation in the exposure assessment.
  1. Which of the following is a measure of the validity of methods used to classify exposures such as having worked on a farm? Choose one best answer. (3 pts)
    1. interclass correlation coefficient
    2. kappa statistic
    3. standard error
    4. sensitivity
    5. none of the above
    1. Using data in Table 1, assess whether the crude OR of brain cancer associated with farm occupation is confounded by age and/or sex. Support your answer with relevant calculations. Table 1 shows the adjusted odds ratios estimating the risk of brain cancer due to having farm occupation. (2 pts)

      2.  

    2. What feature of the study design could have contributed to the crude OR’s in Table 1 being confounded by age and/or sex? (2 pts)

 

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Format 7/27/2000 vs, 8/4/2000 vs, 11/20/2000