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 or not receive an experimental HIV vaccine. Subjects are randomized to form two equally sized groups. Because of withdrawals, exclusions, and competing risks, 317 subjects complete the trial. After 5-years of study, 4 onsets of HIV infection are observed in the treatment group (n1 = 154 completing the study) and 11 HIV onsets are observed in the control group (n0 = 163).
(A) Is this study a clinical trial, field trial, community trial, or cohort study? Explain.
(B) List ethical concerns you might have in performing this trial.
(C) Calculate the risk difference associated with the vaccine. Interpret your results.
(D) Conduct an intention-to-treat analysis, again estimating the risk difference associated with the vaccine. Does this materially change your interpretation of the results?

10.2 Stanford Five-City Project. Read this abstract: 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. 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.

(A) Explain why this study is experimental and not observational.
(B) Is this a clinical trial, community trial, or field trial? Explain.
(C) Was any form of blinding possible during this study? If so, at what level?
(D) 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 this statement.

10.3  Randomization. What does randomization actually accomplish? 

10.4 Improving eating habits in adolescents. Many American adolescents don't eat well. We want to determine if improving school lunches will decrease obesity among middle school students and identify 20 middle schools willing to participate in a community trial. We decide to form 10 pairs of schools (matched on SES) and randomize the intervention to one unit per pair. What is the importance of randomization in this trial? What does it accomplish? 

Key                            Version: 5/10/05