Zeracizumab is an experimental angiogenesis inhibitor targeting vascular endothelial growth factor that is being tested for the treatment of advanced, chemotherapy-naive, non-squamous non-small cell lung cancer (NSCLC). Part of the drug company's evaluation process is to analyze the 1-year survival after treatment to determine the clinical efficacy of the experimental treatment. The results are given in the table below.
| Zeracizumab-containing regimen | Standard chemotherapy | |
| Alive at 1 year | 40 | 51 |
| Dead at 1 year | 60 | 69 |
Which of the following best represents the number needed to harm for the zeracizumab-containing regimen?
Unfortunately, not all interventions or new treatments end up helping patients. The number needed to harm (NNH) represents the number of people who must be treated before 1 additional adverse event occurs. It is calculated in a manner similar to the number needed to treat (NNT) but using the absolute risk increase (attributable risk) instead of the absolute risk reduction:
NNH = 1 / Absolute risk increase
To determine the absolute risk increase, first calculate the adverse event rate (eg, death) in the experimental and control groups. In this case, the adverse event of interest is death at 1 year. There were 40 + 60 = 100 people treated with the experimental treatment (ie, zeracizumab-containing regimen); of those, 60 were dead at 1 year. Similarly, there were 51 + 69 = 120 people treated with standard chemotherapy; of those, 69 were dead at 1 year. Therefore:
Adverse event rate in experimental group = 60 / 100 = 0.60 (ie, 60%)
Adverse event rate in control group = 69 / 120 = 0.575 (ie, 57.5%)
The absolute risk increase can then be calculated by subtracting the adverse event rate in the control group from the adverse event rate in the treatment group:
Absolute risk increase = 0.60 – 0.575 = 0.025 (ie, 2.5%)
The absolute risk increase attributable to the treatment is 2.5% (60% risk of being dead at 1 year in the treatment group compared to 57.5% in the control group). The NNH then is simply the inverse of the absolute risk increase:
NNH = 1 / 0.025 = 40
This result indicates that, on average, 40 patients need to be treated with a zeracizumab-containing regimen for 1 additional person to experience an adverse event (ie, death in 1 year).
Note that the data is NOT presented in the standard format of a contingency (2 × 2) table, so care should be exercised in selecting the appropriate values and applying the formulas (see alternate solution).
Educational objective:
The number needed to harm (NNH) represents the number of people who must be treated before 1 additional adverse event occurs. In order to calculate NNH, the absolute risk increase between the treatment and control groups must be known: NNH = 1 / Absolute risk increase