A multicenter, randomized controlled trial is conducted to evaluate the safety of a novel … — USMLE Step 3

A multicenter, randomized controlled trial is conducted to evaluate the safety of a novel oral anticoagulant (NOAC) compared to standard-of-care warfarin for stroke prevention in patients with nonvalvular atrial fibrillation and concurrent moderate chronic kidney disease. The study enrolls 2,400 patients, who are randomly assigned in a 1:1 ratio to receive either the NOAC or warfarin. All patients are followed for exactly two years. During the follow-up period, the primary safety endpoint of major gastrointestinal bleeding is assessed.

The investigators report the following safety data:
- NOAC group ( $n = 1,200$ ): 54 patients experienced a major gastrointestinal bleed.
- Warfarin group ( $n = 1,200$ ): 30 patients experienced a major gastrointestinal bleed.

Based on these study results, what is the number needed to harm (NNH) for major gastrointestinal bleeding associated with the NOAC compared to warfarin? (Enter your answer as a whole number).

Answer: 50 patients

Answer

The Number Needed to Harm (NNH) represents the number of patients who need to be exposed to a risk factor or experimental treatment to cause one additional adverse event compared to the control group. It is calculated as the inverse of the Absolute Risk Increase (ARI). First, the incidence of major gastrointestinal bleeding in the NOAC group is calculated as

54 / 1200 = 0.045

(

4.5\%

). The incidence in the warfarin group is

30 / 1200 = 0.025

(

2.5\%

). The ARI is the absolute difference between these two rates:

0.045 - 0.025 = 0.020

(

2.0\%

). The NNH is calculated as

1 / \text{ARI}

, which is

1 / 0.020 = 50

. Therefore, for every 50 patients treated with the NOAC instead of warfarin, one additional major gastrointestinal bleed will occur.

Step-by-Step Solution

Calculate experimental event rate

0.045 (4.5%)

Needed to determine the absolute risk increase associated with the new intervention.

Calculate control event rate

0.025 (2.5%)

Needed to determine the baseline risk of the adverse event under standard care.

Calculate Absolute Risk Increase (ARI)

0.020 (2.0%)

ARI represents the excess risk of the adverse event directly attributable to the NOAC.

Calculate Number Needed to Harm (NNH)

NNH is the inverse of the ARI (

1 / 0.020

Key Concept

Calculation and interpretation of the Number Needed to Harm (NNH)

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