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Difficulty: HardMeasures of Association and Impact

A randomized, double-blind, placebo-controlled clinical trial evaluates the efficacy and safety of a novel targeted biologic therapy for patients with severe, uncontrolled eosinophilic asthma. A total of 4,000 patients are enrolled and randomized in a 1:1 ratio to receive either the biologic therapy or a placebo over a 52-week period.

The primary efficacy endpoint is the occurrence of a severe asthma exacerbation requiring an emergency department visit or hospitalization. The primary safety endpoint is the occurrence of severe opportunistic infections. The trial results are summarized in the table below:

OutcomeBiologic Therapy (n = 2,000)Placebo (n = 2,000)
Severe asthma exacerbation130250
Severe opportunistic infection5018

Based on these results, which of the following represents the number needed to treat (NNT) to prevent one severe asthma exacerbation and the number needed to harm (NNH) to cause one additional severe opportunistic infection, respectively?

  1. NNT: 17; NNH: 62Answer
  2. B
    NNT: 17; NNH: 63
  3. C
    NNT: 16; NNH: 63
  4. D
    NNT: 34; NNH: 125
  5. E
    NNT: 14; NNH: 60

Answer

The correct answer is NNT: 17; NNH: 62.
The correct answer accurately calculates the absolute risk metrics and correctly applies clinical rounding principles. The absolute risk reduction (ARR) for severe asthma exacerbations is 0.125−0.065=0.0600.125 - 0.065 = 0.060. The NNT is 10.060=16.67\frac{1}{0.060} = 16.67. To avoid overstating efficacy, NNT is always rounded UP to the next whole person, yielding 17. The absolute risk increase (ARI) for severe infections is 0.025−0.009=0.0160.025 - 0.009 = 0.016. The NNH is 10.016=62.5\frac{1}{0.016} = 62.5. To avoid minimizing risk, NNH is always rounded DOWN to the next whole person, yielding 62.

Step-by-Step Solution

1
Calculate Absolute Risk Reduction (ARR) for efficacy.
ARR=2502000−1302000=0.125−0.065=0.06ARR = \frac{250}{2000} - \frac{130}{2000} = 0.125 - 0.065 = 0.06
ARR is the difference in the rate of adverse clinical events between the control group and the treatment group.
2
Calculate Number Needed to Treat (NNT) and apply clinical rounding.
NNT=10.06≈16.67NNT = \frac{1}{0.06} \approx 16.67. Rounded UP to 17.
NNT is the inverse of ARR. Clinically, NNT is always rounded UP to the next whole number to avoid overestimating a drug's benefit.
3
Calculate Absolute Risk Increase (ARI) for harm.
ARI=502000−182000=0.025−0.009=0.016ARI = \frac{50}{2000} - \frac{18}{2000} = 0.025 - 0.009 = 0.016
ARI is the difference in the rate of adverse side effects between the treatment group and the control group.
4
Calculate Number Needed to Harm (NNH) and apply clinical rounding.
NNH=10.016=62.5NNH = \frac{1}{0.016} = 62.5. Rounded DOWN to 62.
NNH is the inverse of ARI. Clinically, NNH is always rounded DOWN to the next whole number to avoid underestimating a drug's potential for harm.

Key Concept

Calculation and appropriate clinical rounding of Number Needed to Treat (NNT) and Number Needed to Harm (NNH).
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Topics

Measures of Association and Impact

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