Question: The paper The Effect of an Endothelin Receptor Antagonist Bosentan

The paper “ The Effect of an Endothelin-Receptor Antagonist, Bosentan, on Blood Pressure in Patients with Essential Hypertension’’ [The New England Journal of Medicine (1998)] discussed the contribution of bosentan to blood pressure regulation in patients with essential ­hypertension. The study involved 243 patients with mild-to-moderate essential hypertension. After a placebo run-in period, patients were randomly assigned to receive one of four oral doses of bosentan (100, 500, or 1,000 mg once daily or 1,000 mg twice daily) or a placebo. The blood pressure was measured before treatment began and after a 4-week treatment period. The primary end point of the study was the change in blood pressure from the baseline obtained prior to treatment to the blood pressure at the conclusion of the 4-week treatment period. A summary of the data is given in the following table.
a. Which of the dose levels were associated with a significantly greater reduction in the diastolic pressure in comparison to the placebo? Use a = .05.
b. Why was it important to include a placebo treatment in the study?
c. Using just the four treatments (ignore the placebo), construct a contrast to test for an increasing linear trend in the size of the systolic pressure reductions as the dose levels are increased. See Exercise 9.25 for the method for creating such a contrast.
d. Use Tukey’s W procedure to test for pairwise differences in the mean systolic blood pressure reductions for the four treatment doses. Use a 5 .05.
e. The researchers referred to their study as a double-blind study. Explain the mean-ing of this terminology.

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