A physician is critically appraising a multi-page drug advertisement for a novel oral anti… — USMLE Step 3

A physician is critically appraising a multi-page drug advertisement for a novel oral anticoagulant, rivatran, targeted at patients with atrial fibrillation and a high risk of recurrent ischemic stroke.

The headline of the advertisement proclaims in large font: *"Rivatran significantly lowers the risk of recurrent stroke, demonstrating a $20\%$ relative risk reduction compared to standard warfarin therapy!"*

Upon reviewing the fine print in the supplemental prescribing information, the physician examines the following safety and efficacy data from the 3-year pivotal trial:

Outcome at 3 Years	Rivatran ( $n=4000$ )	Warfarin ( $n=4000$ )
Recurrent ischemic stroke	$16.0\%$	Not provided
Major bleeding events	$4.5\%$	$2.5\%$

Based on the data provided, how many patients would need to be treated with rivatran instead of warfarin for 3 years to prevent one recurrent stroke?

Answer: 25 patients

Answer

To determine the Number Needed to Treat (NNT), the Absolute Risk Reduction (ARR) must first be calculated, as

NNT = 1 / ARR

. The ARR is the difference between the Control Event Rate (CER) and the Experimental Event Rate (EER). The advertisement provides the Relative Risk Reduction (RRR) as

20\%

(

0.20

) and the EER for the intervention as

16.0\%

(

0.16

). The relative risk (RR) can be derived from the RRR because

RRR = 1 - RR

, making the

RR = 1 - 0.20 = 0.80

. Since

RR = EER / CER

, we can determine the omitted baseline risk in the warfarin group:

0.80 = 0.16 / CER

, which yields a CER of

0.20

(

20\%

). The ARR is therefore

0.20 - 0.16 = 0.04

(

4\%

). Finally, the NNT is

1 / 0.04 = 25

. This means 25 patients need to be treated with rivatran instead of warfarin for 3 years to prevent one recurrent ischemic stroke.

Step-by-Step Solution

Identify the provided epidemiological metrics from the advertisement.

Relative Risk Reduction (RRR) = 20% (0.20). Experimental Event Rate (EER) for recurrent stroke = 16.0% (0.16).

Accurate extraction of relative and absolute measures is the crucial first step in interpreting drug advertisements.

Calculate the Relative Risk (RR) and use it to find the Control Event Rate (CER).

RR = 1 - RRR = 1 - 0.20 = 0.80

. Since

RR = \frac{EER}{CER}

, we solve for CER:

0.80 = \frac{0.16}{CER} \Rightarrow CER = 0.20

(20%).

The absolute baseline risk (CER) is hidden in the advertisement but is required to calculate the absolute clinical benefit.

Calculate the Absolute Risk Reduction (ARR).

ARR = CER - EER = 0.20 - 0.16 = 0.04

(4%).

ARR represents the actual difference in risk between the two interventions and provides a true measure of clinical impact.

Calculate the Number Needed to Treat (NNT).

NNT = \frac{1}{ARR} = \frac{1}{0.04} = 25

NNT is the inverse of the ARR and represents the number of patients needed to receive the intervention to prevent one additional adverse outcome.

Key Concept

Calculating Number Needed to Treat (NNT) by first deriving the baseline risk and Absolute Risk Reduction (ARR) from a reported Relative Risk Reduction (RRR).

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