University of North Carolina at Chapel Hill
School of Public Health
Department of Epidemiology
Fundamentals of Epidemiology (EPID 168)
Final Examination, Fall 1998
Most of the questions on this examination relate to the article "Individual risk factors for hip osteoarthritis: obesity, hip injury, and physical activity" (Cyrus Cooper, Hazel Inskip, Peter Croft, Lesley Campbell, Gillian Smith, Magnus McLaren, and David Coggon. Am J Epidemiol 1998; 147:516-22). You may refer to this article during the examination.
1. Briefly list two reasons why a case control study is (or is not) appropriate to examine individual risk factors for hip osteoarthritis. (2 pts)
2. The authors state that their cases come from a defined population. List four features of the population or the study design that support this statement or helped the authors to achieve it? (4 pts)
3. Considering the study population, study design, and other information in the article, which of the following statements is (are) TRUE and which is (are) FALSE. (2 pts each)
a. In these two health districts, the incidence density of symptomatic hip osteoarthritis of sufficient severity to warrant hip arthroplasty exceeds 40 per 100,000 person-years.
b. If about 12% of the population was age 65 years or older, then about 12,000 people age 65 years or older in the two districts have radiographic evidence of hip osteoarthritis.
c. The data in Table 1 demonstrate that women are 1.9 times as likely to develop severe symptomatic hip osteoarthritis as are men.
d. The data in Table 2 indicate that female gender is not a risk factor for hip osteoarthritis.
e. In this study, matching the control group to the cases on age, as opposed to a random sample of the general adult population, probably resulted in greater statistical power and precision.
4. The case identification process was based on a register in each district made up of persons on a waiting list for a total hip arthoplasty (surgical reformation of the hip joint). Waiting lists for procedures are common in societies with a nationa l or social medicine system. In the United States, a region wide waiting list for a hip arthoplasty is unlikely, as the availability of receiving this procedure would be more related to insurance status or ability to afford such a procedure. Explain how using the register system in the Untied Kingdom to select cases either increases or decreases the possibility of selection bias as compared to a study conducted in the United States. (4 pts)
5. How was the diagnosis of hip osteoarthritis made in this study? Was this based on manifestional or causal criteria? Explain your answer. (3 pts)
6. According to the authors: "For each case, a control of the same sex and age was selected from the list of the same general practice held by the county Family Health Service Association". State in one sentence the rationale for using a list from ge neral practioners? (3pts)
7. Eighty-four percent of the patients listed for total hip arthroplasty fulfilled the criteria for entry into the study as cases. Which of the following best describes the criteria: (3 pts)
a. age > 45 years, being on the waiting list for hip arthroplasty, and the presence of Heberden’s nodes.
b. age > 45 years, pain duration at least for 36 months, and presence of Heberden’s nodes.
c. history of hip fracture within the past year, being on the waiting list for hip arthroplasty and reside in the study area.
d. presence of Heberden’s nodes, history of hip fracture within the past year, and reside in the study area.
e. being on the waiting list for hip arthroplasty, reside in the study area, and age > 45 years
8. The authors report that 89% of the eligible cases agreed to participate and 60% of the 1060 controls approached agreed to participate. Which of the following best states a condition regarding the non-responders that could lead to an odds ratio re ported for the risk of osteoarthritis associated with previous hip injury that is biased away from the null (>1). Choose one best answer. (3 pts)
a. control non-responders are more likely to have a history of hip injury compared to case non-responders.
b. control non-responders are less likely to have a history of hip injury compared to case non-responders.
c. being a non-respondent is not related to previous hip injury.
d. none of the above
9. What was accomplished by replacing controls who refused to participate? (Choose one best answer) (3 pts)
If controls who refused had not been replaced:
a. selection bias would have been greater;
b. the control group would have been less representative of the study base;
c. probability of a Type I error would have been greater;
d. probabillty of a Type II error would have been greater;
e. nondifferential misclassification bias would have been greater.
f. it would have been necessary to control for age and sex in the analysis.
10. The authors selected controls who were individually matched to cases by age, gender, and family practitioner. Matching in the design stage is usually considered only for those variables that are known to be confounders. Under which of the follow ing circumstances could gender be a confounder of the association between a risk factor (obesity) and the outcome (hip osteoarthritis)? Circle all that apply. (4 pts)
a. the prevalence of obesity and the prevalence of hip osteoarthritis are both higher in men that in women
b. the prevalence of obesity is lower in men than women, but the prevalence of hip osteoarthritis is higher in men than women.
c. the prevalence of obesity is higher in men than women, but the prevalence of hip osteoarthritis is the same in men and women.
d. the prevalence of obesity is the same in men and women, but the prevalence of hip osteoarthritis is higher in men than women.
11. The odds ratios in Table 2 are "mutually adjusted for the other two variables" by logistic regression. The following questions concern the models used to estimate the odds ratios in the table (ignore the fact that it was "condit ional" logistic regression and ignore the middle categories for body mass index and presence of Heberden’s nodes) (2 pts each):
a. How many logistic models were necessary to estimate the odds ratios for body mass index >28.0, definite Heberden’s nodes, and previous hip injury among women.
b. The odds ratio estimate for hip injury in women was 2.8. What must the logistic coefficient have been?
c. From this table, estimate the odds ratio for women who had both definite Heberden’s nodes and previous hip injury compared to women who had neither.
12. In this study, information on medical history, life style, and leisure time physical activities was obtained through a "structured interviewer-administered questionnaire". (page 517). It is possible that persons on a waiting list for a hip arthoplasty would be more keenly aware of hip injuries they may have had in the past than controls. If true, this is an example of which of the following? Choose one best answer. (3 pts)
a. differential case ascertainment bias
b. differential misclassification bias
c. differential selection bias
d. differential precision bias
e. none of the above
13. Among women, the odds of previous hip injury is higher among cases than controls (Table 2; OR=2.8). As indicated in the footnotes for Table 2, the odds ratio for pervious hip injury is adjusted or controlled for the other two variables in the Ta ble (body mass index and Heberden’s nodes). Using the counts shown in Table 2, calculate an unadjusted (crude) odds ratio for previous hip injury in women. (3 pts)
Unadjusted (crude) odds ratio = _________
14. Which of the following conclusions can be made from the above results? (choose one best answer) (3 pts)
a. the unadjusted (crude) association between hip injury and hip osteoarthritis in women is completely confounded by body mass index and Heberden’s nodes.
b. since the unadjusted and adjusted odds ratios are similar, the risk factor (hip injury) must not be associated with the adjustment variables (body mass index and Heberden’s nodes)
c. since the unadjusted and adjusted odds ratios are similar, there is no effect-measure modification of the association between hip injury and hip osteoarthritis.
d. none of the above
15. The odds ratios presented in Table 5 are adjusted for previous hip injury. Why might they still be confounded by hip injury? (3 pts)
16. In Table 6, is the crude association between previous hip injury and risk of unilateral hip osteoarthritis biased towards the null or away from the null? (2 pts)
17. Based on the data in Table 3, what is the odds ratio for Heberden's nodes (definite versus none) for persons in the Upper tertile of body mass index? (3 pts)
18. Rothman has proposed that "public health synergism" is present when an observed joint effect exceeds that expected under the additive model. Do the odds ratios in Table 3 indicate the presence of "public health synergism" for effect of Heberden 's nodes and elevated body mass index on hip osteoarthiritis? If not, do the odds ratios conform to a multiplicative model? Include in your answer a 1-2 sentence assessment of whether these data indicate "public health synergism". (For this question, ignore the row for "Possible" Heberden's nodes and the column for the middle tertile of body mass index, and assume that both Heberden’s nodes and elevated BMI reflect casual risk factors for hip osteoarthritis. Note: do not necessarily rely on the autho rs' description of this table.) (6 pts)
19. The authors investigated the association of specific sporting activities with risk of hip osteoarthritis. Their data are presented in Table 5. Using their data, compute separately the unadjusted (crude) risk of osteoarthritis associated with pla ying golf and for swimming in men and women combined. Consider those who do not participate in any sport as the reference group and assume no missing data. Show two appropriate 2x2 table and your calculations. (4 pts)
19a. Compare these unadjusted (crude) odds ratios with the ones presented in Table 3. Briefly describe and explain the comparison. (3 pts)
19b. Consider the possibility that golfers who have hip osteoarthritis are reluctant to seek medical attention for their condition for fear it will mean the end of their ability to play golf. Therefore, cases who golf are less likely to be se lected for this study than cases who do not golf. If the true OR associated with golf is 2.0, then which of the following best describes the selection bias and its impact on the odds ratio you computed. (3 pts)
a. non-differential selection bias resulting in an odds ratio biased toward the null.
b. non-differential selection bias resulting in an odds ratio biased away from the Null.
c. differential selection bias resulting in an odds ratio biased away from the null.
d. differential selection bias resulting in an odds ratio biased toward the null.
e. none of the above
19c. The authors state that "...the association with swimming may have arisen because patients with hip osteoarthritis were advised to swim..." (page 521). Suppose that 25% of the cases had been incorrectly classified as swimmers and assume that the misclassified cases had not participated in any other sporting activity, either. Re-compute the odds ratio for the association of hip osteoarthritis and swimming, after re-classifying these individuals, using the number from the 2x2 table in question 19 above. Briefly discuss how your conclusion about the role of swimming does (or does not) change. In what direction did misclassification bias the study OR? (3 pts)
20. The odds ratio (95% confidence interval) estimating the risk of osteoarthritis associated with a previous hip injury was 24.8 (3.1-199.3) in men and 2.8 (1.4-5.8) in women (see Table 2).
a. Which estimate indicates a stronger association? (2 pts)
b. Which estimate is more precise? (2 pts)
c. Which estimate is more compatible with a population odds ratio of 4.0? (2 pts)
21. Which one of the statements best interprets the following passage? (3 pts)
"In a previous case-control study (17) of men aged 60-76 years, we observed a doubling of risk for hip osteoarthritis among those in the highest third of body mass index distribution, as compared with those in the lowest third, although the increased risk was not statistically significant." (p519 bottom of right column)
a. Hip osteoarthritis is not as significant when it occurs in obese older patients, because it is expected that overweight that lasts for many years will lead to damage to the joints.
b. A doubling of risk is not significant from a statistical perspective, because it represents only a moderate association.
c. The doubling of risk was not statistically significant because a p-value was not computed, so it is not possible for the authors to know whether the increased risk was due to chance.
d. If 1,000 independent random samples the same size as that study population were drawn from a population with no increased risk of hip osteoarthritis, fewer than 950 would have an OR between 0.5 and 2.0.
e. If 1,000 independent random samples the same size as that study population were drawn from a population with a doubling of risk of hip osteoarthritis for the highest third of the body mass distribution, as compared with the lowest third, more th an 5% of the samples would display no elevation in risk.
f. If 1,000 independent random samples the same size as that study population were drawn from a population with a doubling of risk of hip osteoarthritis for the highest third of the body mass distribution, as compared with the lowest third, fewer t han 80% would display an association of that magnitude.
22. A medical journalist, confused by the thrust of this article, comes to you and says: "I've read this article several times, but I can't figure out what it shows about the relationship of body mass index, Heberden's nodes, and hip osteoarthri tis. The authors explain that 'two broad mechanisms are believed to underlie the pathogenesis of osteoarthritis at any joint site: mechanical stress and a generalized predisposition to the disorder' as indexed by Heberden’s nodes [p519 right column]. T hat seems straightforward enough, and they later conclude that the analysis 'supports the notion that this condition arises through an interaction between a generalized predisposition to the disorder and specific mechanical insults to the hip' [p521]. Y et on page 518 [right column], the authors state that there was 'no statistically significant interaction' between body mass index and Heberden's nodes, and on page 519 [left column] they refer to obesity and a tendency to polyarticular involvement as 'i ndependent risk factors for hip osteoarthritis'. Would you please assess for me what this article shows about the relationship among body mass index, Heberden's nodes, and hip osteoarthritis? I have room for 40-60 words. Thanks!" (6 pts)
23. Write a brief statement for or against a causal relationship between hip injury and risk of osteoarthritis. Comment specifically on at least two of Bradford Hill’s criteria for causal inference. Support your conclusion with data or statements f rom the article. (4 pts)
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Last changed 4/10/1999 by Victor_Schoenbach@unc.edu, links 8/4/2000vs, reworded #19c on 12/14/2000vs