A randomized, double-blinded clinical trial was conducted to evaluate the effect of a new hypolipidemic drug on the survival of patients after percutaneous coronary intervention (PCI). 1000 patients undergoing PCI were randomly assigned to the drug or placebo group. 500 patients were in each group. The 2 groups were then followed for 3 years for the development of acute coronary syndromes. Severe acute myositis was reported as a rare side effect of the drug therapy, but the difference between the 2 groups in the occurrence of this side effect was not statistically significant (p = 0.09). A review of the literature shows that, in prior clinical trials and case reports, the same side effect was noted in some patients taking this drug. Which of the following is the most likely cause for the failure to detect a significant statistical difference in the occurrence of acute myositis between the treatment and placebo groups in this randomized trial?
A)Ascertainment bias
B)Limited follow-up period
C)Inappropriate patient selection
D)Small sample size
E)Observer bias

Question

A randomized, double-blinded clinical trial was conducted to evaluate the effect of a new hypolipidemic drug on the survival of patients after percutaneous coronary intervention (PCI).  1000 patients undergoing PCI were randomly assigned to the drug or placebo group.  500 patients were in each group.  The 2 groups were then followed for 3 years for the development of acute coronary syndromes.  Severe acute myositis was reported as a rare side effect of the drug therapy, but the difference between the 2 groups in the occurrence of this side effect was not statistically significant (p = 0.09).  A review of the literature shows that, in prior clinical trials and case reports, the same side effect was noted in some patients taking this drug.  Which of the following is the most likely cause for the failure to detect a significant statistical difference in the occurrence of acute myositis between the treatment and placebo groups in this randomized trial?
A)Ascertainment bias
B)Limited follow-up period
C)Inappropriate patient selection
D)Small sample size
E)Observer bias

Quizplus · Accepted Answer

Explanation: Power is the probability to detect a difference in the outcome of interest between 2 groups, if such a difference exists. Acute myositis was previously reported in patients using this new hypolipemic drug; however, in this randomized trial, the difference between the treatment and the placebo group were not statistically significant. The most likely explanation is that, because this side effect is rareand few patients experienced it, the p value for the difference is marginal, approaching but not reaching statistical significance. A larger sample size will increase the power of the study (ie, its ability to detect the difference), and the p value will reach statistical significance. (Choice A) Ascertainment bias occurs when results from an atypical population are extrapolated into the entire population. There is no reason for this study sample to be significantly different from the general population in terms of risk of acute severe myositis. (Choice B) Increasing the follow-up period may not increase the power, because the side effect may occur in susceptible individuals relatively early after starting the therapy. Therefore, longer follow-up would not increase the number of events. (Choice C) No information is given on how the patients were selected for the study. Randomization should help account for known and unknown confounders between the 2 groups studied. (Choice E) The fact that double-blinding techniques were employed in this trial decreases the potential for observer bias. Educational objective: Power is the ability to detect a difference in the outcome of interest between 2 groups, if such a difference exists. Increasing the sample size increases the power of a study.

A Randomized, Double-Blinded Clinical Trial Was Conducted to Evaluate the Effect