A physician is reviewing data from a recent randomized, placebo-controlled clinical trial … — USMLE Step 3

A physician is reviewing data from a recent randomized, placebo-controlled clinical trial evaluating a novel oral therapeutic agent for the prevention of chronic kidney disease progression in high-risk patients. The trial followed two cohorts of patients over a 3-year period to assess both efficacy and safety. The physician is evaluating the net clinical benefit of the medication to prepare for a patient consultation.

The following raw data were reported at the end of the trial:

Outcome	Novel Therapeutic Agent ( $n = 1000$ )	Placebo ( $n = 1000$ )
Primary outcome (disease progression)	$80$ events	$150$ events
Severe mycotic infection (adverse event)	$90$ events	$27$ events

Applying conservative clinical epidemiological rounding principles, which of the following correctly pairs the Number Needed to Treat (NNT) to prevent one primary outcome with the Number Needed to Harm (NNH) for one severe mycotic infection?

NNT: 15; NNH: 15Answer
B
NNT: 14; NNH: 16
C
NNT: 15; NNH: 16
D
NNT: 14; NNH: 15
E
NNT: 13; NNH: 11

Answer

NNT: 15; NNH: 15

The correct answer accurately calculates the Number Needed to Treat (NNT) and Number Needed to Harm (NNH) and correctly applies conservative clinical rounding principles. The ARR is

0.07

, yielding an unrounded NNT of

14.28

. To avoid overestimating clinical benefit, NNT is always rounded UP to the next whole integer (

15

). The ARI is

0.063

, yielding an unrounded NNH of

15.87

. To avoid underestimating clinical risk, NNH is always rounded DOWN to the next whole integer (

15

Step-by-Step Solution

Calculate the Absolute Risk Reduction (ARR) for the primary outcome.

Control Event Rate (CER) =

150/1000 = 0.15

(15%). Experimental Event Rate (EER) =

80/1000 = 0.08

(8%). ARR =

0.15 - 0.08 = 0.07

(7%).

ARR is the absolute difference in the rates of bad outcomes between the control and experimental groups.

Calculate the Number Needed to Treat (NNT) and apply conservative rounding.

NNT =

1 / ARR = 1 / 0.07 \approx 14.28

. Rounding UP to the next whole number gives an NNT of 15.

NNT should always be rounded up to the next highest whole number to avoid overstating the drug's benefit (you cannot treat a fraction of a patient, so 15 patients must be treated to guarantee the prevention of one event).

Calculate the Absolute Risk Increase (ARI) for the adverse event.

Control Adverse Event Rate =

27/1000 = 0.027

(2.7%). Experimental Adverse Event Rate =

90/1000 = 0.090

(9%). ARI =

0.090 - 0.027 = 0.063

(6.3%).

ARI is the absolute difference in the rates of adverse events between the experimental and control groups.

Calculate the Number Needed to Harm (NNH) and apply conservative rounding.

NNH =

1 / ARI = 1 / 0.063 \approx 15.87

. Rounding DOWN to the next whole number gives an NNH of 15.

NNH should always be rounded down to the next lowest whole number to avoid understating the risk of harm (a conservative estimate implies harm occurs sooner, after treating 15 patients instead of 16).

Key Concept

Calculation and conservative clinical rounding principles for Number Needed to Treat (NNT) and Number Needed to Harm (NNH).

Estimated Time:1m 30s

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