CHAPTER 10: Experimental Studies

CHAPTER 10 EXERCISES

10.1 Fictitious Trial of an HIV Vaccine. Four-hundred (400) high-risk HIV-free volunteers were randomly assigned to either receive an experimental HIV vaccine or saline placebo. Subjects were randomized to form two equally sized groups of 200 each. Because of withdrawals, exclusions, and competing risks, 317 subjects completed the trial. After 5-years of observation, 4 HIV infection were observed in the treatment group (n₁ = 154 completing the study) and 11 HIV infections were observed in the control group (n₀ = 163 completing the trial).

(A) Is this study a clinical trial, field trial, community trial, or cohort study? Explain your answer.

(B) List ethical concerns you might have in performing this trial.

(D) Conduct an intention-to-treat analysis (“analyze as randomized”) by calculating the risk difference using initial cohort sizes as denominators for each of the groups. Does this materially change your conclusion?

10.2 Stanford Five-City Project. Read this abstract carefully, and then answer the questions that follow: Fortmann S. P. & Varady, A. N. (2000). Effects of a community-wide health education program on cardiovascular disease morbidity and mortality: the Stanford Five-City Project. American Journal of Epidemiology, 152(4), 316-23. [Link to full article].

The authors examined changes in morbidity and mortality from 1979 through 1992 during the Stanford Five-City Project, a comprehensive community health education study conducted in northern California. The intervention (1980-1986), a multiple risk factor strategy delivered through multiple educational methods, targeted all residents in two treatment communities. Potentially fatal and nonfatal myocardial infarction and stroke events were identified from death certificates and hospital records. Clinical information was abstracted from hospital charts and coroner records; for fatal events, it was collected from attending physicians and next of kin. Standard diagnostic criteria were used to classify all events, without knowledge of the city of origin. All first definite events were analyzed; denominators were estimated from 1980 and 1990 US Census figures. Mixed model regression analyses were used in statistical comparisons. Over the full 14 years of the study, the combined-event rate declined about 3% per year in all five cities. However, during the first 7-year period (1979-1985), no significant trends were found in any of the cities; during the late period (1986-1992), significant downward trends were found in all except one city. The change in trends between periods was slightly but not significantly greater in the treatment cities. It is most likely that some influence affecting all cities, not the intervention, accounted for the observed change. Explain why this study is experimental in design, and not merely observational.

(A) Explain why this is a community trial, and not a clinical trial or field trial.

(B) Was any form of blinding possible during this study? If so, please explain.

(C) The abstract states “Over the full 14 years of the study, the combined-event rate declined about 3% per year in all five cities.” The abstract also states “The change in trends between periods was slightly but not significantly greater in the treatment cities.” Interpret these statements.

10.3 Randomization. What is the importance of randomization? What does it actually accomplish?

10.4 Improving eating habits in adolescents. Many American adolescents don’t eat well. A study wants to determine if improving school lunches will decrease obesity among middle school students. Twenty middle schools willing to participate in a community trial are identified. The investigators form 10 pairs of schools (matched on SES) and randomize the intervention to one unit in each pair. What does the randomization accomplish in this trial?