A group of investigators conducted a randomized placebo-controlled clinical trial to assess the effect of a new aldosterone receptor antagonist on the progression of chronic heart failure. The primary outcome was all-cause mortality. A decrease in all-cause mortality in the treatment group was reported, with a relative risk of 0.71 (p = 0.001). Which of the following statements is the best interpretation of the reported association?

Question

A group of investigators conducted a randomized placebo-controlled clinical trial to assess the effect of a new aldosterone receptor antagonist on the progression of chronic heart failure.  The primary outcome was all-cause mortality.  A decrease in all-cause mortality in the treatment group was reported, with a relative risk of 0.71 (p = 0.001).  Which of the following statements is the best interpretation of the reported association?

Quizplus · Accepted Answer

Relative risk (RR) is a point estimate of association, but it does not account for random error. It is always possible that the calculated RR occurred by chance. The p-value is used to strengthen the results of the study and represents the probability of observing a given (or more extreme) result by chance alone, assuming the null hypothesis is true. In this scenario, assuming there were no difference in all-cause mortality between the treatment and placebo groups (null hypothesis), the probability of obtaining a RR of 0.71 or a more extreme value due to chance alone is 0.1% (ie, p = 0.001 because 0.1/100 = 0.001). The commonly accepted upper limit (cut-off point) of the p-value for a result to be considered statistically significant is 0.05 (ie, p <5% is statistically significant). (Choices A and E) Both the p-value and the confidence interval are measures of statistical significance. A 95% confidence interval that contains 1.0 (null value for RR) would mean that the results are not statistically significant. This is not consistent with the obtained p-value of 0.001, which is statistically significant. (Choice C) A RR = 0.71 shows that the drug decreased the risk of mortality by 29% (as 1.0 - 0.71 = 0.29 or 29%). (Choice D) The p-value reflects random variability, not bias (which is systematic error). Educational objective: The p-value is the probability of observing a given (or more extreme) result due to chance alone, assuming the null hypothesis is true. A result is generally considered statistically significant when p <0.05.

A Group of Investigators Conducted a Randomized Placebo-Controlled Clinical Trial