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

A randomized controlled trial is conducted to evaluate the efficacy and safety of a novel P2Y12 inhibitor added to aspirin, compared to aspirin alone, in patients with a recent transient ischemic attack (TIA) or minor ischemic stroke. The primary efficacy endpoint is the 1-year incidence of recurrent stroke, and the primary safety endpoint is the 1-year incidence of major bleeding.

The 1-year event rates in the aspirin-alone (control) group were:
- Recurrent stroke: $16.0\%$
- Major bleeding: $2.0\%$

In the group receiving the novel P2Y12 inhibitor plus aspirin, the relative risk reduction (RRR) for recurrent stroke was $25.0\%$ compared to the control group. However, this intervention group also had a relative risk (RR) of $2.25$ for major bleeding compared to the control group.

Based on these results, what is the number needed to harm (NNH) for major bleeding? (Enter the exact integer).

Answer: 40 patients

Answer

To calculate the Number Needed to Harm (NNH), the Absolute Risk Increase (ARI) must first be determined. For major bleeding, the baseline Control Event Rate (CER) is

2.0\%

. The Experimental Event Rate (EER) is the CER multiplied by the Relative Risk (RR):

2.0\% \times 2.25 = 4.5\%

. The ARI is the difference between the EER and CER:

4.5\% - 2.0\% = 2.5\%

, or

0.025

. The NNH is the reciprocal of the ARI (

1 / 0.025 = 40

), meaning 40 patients need to be treated with the novel P2Y12 inhibitor to cause one additional major bleeding event.

Step-by-Step Solution

Identify the relevant data for major bleeding.

Control Event Rate (CER) for bleeding is 2.0% and Relative Risk (RR) is 2.25.

The question asks for the Number Needed to Harm (NNH), which applies to the adverse safety endpoint (major bleeding), so efficacy data must be filtered out.

Calculate the Experimental Event Rate (EER) for major bleeding.

EER = 2.0% × 2.25 = 4.5%.

EER must be determined to find the absolute difference in risk between the two groups.

Calculate the Absolute Risk Increase (ARI).

ARI = 4.5% - 2.0% = 2.5% (or 0.025).

ARI represents the excess risk of bleeding attributable to the novel therapy.

Calculate the Number Needed to Harm (NNH).

NNH = 1 / 0.025 = 40.

NNH is the reciprocal of the Absolute Risk Increase.

Key Concept

Number Needed to Harm (NNH) calculation using Control Event Rate and Relative Risk.

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