# NAPLEX Question of the Week: Biostatistics Challenge!

Statistics evaluation of clinical studies is an important part of clinical practice. This week's question focuses on an important calculation. In the clinical trial assessing the effects on morbidity and mortality of spironolactone in heart failure with reduced ejection fraction (RALES trial), there were 841 patients assigned to receive placebo and 822 patients assigned to receive spironolactone. The primary outcome was all-cause mortality. In the placebo group,  386 patients died and in the spironolactone group,  284 patients died (relative risk of death, 0.70; 95 percent confidence interval, 0.60 to 0.82; P<0.001). What is the number needed to treat with spironolactone to prevent one death in this study?

A. 6

B. 9

C. 22

D. 30

The correct answer is B. The number needed to treat is calculated by the formula:

Number needed to treat (NNT) = 1/ Absolute risk reduction

Absolute risk reduction (ARR) is calculated by subtracting the treatment group’s absolute risk from the control group’s absolute risk. In this case, the treatment group’s absolute risk is

284 / 822 = 0.345 and the control  group’s absolute risk is 386 / 841 = 0.459. Subtracting the treatment group’s absolute risk from the control group’s gives 0.459 - 0.345 = 0.114. From here, we can plug the absolute risk reduction into the formula NNT = 1 / 0.114 = 8.8. Because the NNT is in people needed to treat, and we cannot treat 0.8 people, we round up the NNT to the nearest whole number, or in this case 9, making the answer B.

Don’t get absolute risk reduction confused with relative risk reduction, which is found by the formula:

Relative risk reduction = 1 - relative risk

In this case, relative risk was (284/822) / (386/841) = 0.75, and the relative risk reduction was then 0.25 or 25% for spironolactone vs. placebo. The relative risk of death statistic in the question was referencing the risk of death in the spironolactone group and was calculated using a Cox proportional-hazards model, and is not referring to the overall relative risk of death in the trial.

Source:

Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341(10):709-717. doi:10.1056/NEJM199909023411001