A group of psychiatrists conducts a double-blind placebo-controlled randomized trial to determine the efficacy and safety of cariprazine for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults. The treatment response rate was 46% for cariprazine versus 32% for placebo, and the rate for all adverse events was 7% for cariprazine versus 5% for placebo. The differences in rates were statistically significant. Which of the following is the approximate number of patients who must be exposed to cariprazine to cause harm to 1 person who otherwise would not have been harmed?
The number of people who must be exposed to a treatment to cause harm to 1 person who otherwise would not have been harmed is known as the number needed to harm (NNH). It is calculated in a manner similar to the number needed to treat (NNT) but using the absolute risk increase (ARI) instead of the absolute risk reduction:
NNH = (1 / ARI)
ARI is the difference in the rate (risk) of the adverse event (AE) between the treatment group (eg, cariprazine) and the control group (eg, placebo):
ARI = (Rate AEcariprazine − Rate AEplacebo)
In this study, the rate of any AE in the treatment group (ie, cariprazine) is 0.07 (ie, 7%) and in the control (ie, placebo) group is 0.05 (5%). Therefore, the ARI in adverse events of cariprazine versus placebo is:
ARI = (Rate AEcariprazine − Rate AEplacebo) = 0.07 − 0.05 = 0.02 (or 2%) (Choice A)
Consequently, the NNH is:
NNH = (1 / ARI) = 1 / 0.02 = 50
Therefore, approximately 50 patients would need to be treated with cariprazine to cause harm to 1 person who otherwise would not have been harmed. The lower the NNH, the more risk of harm; an NNH of 1 means that every patient treated is harmed.
(Choices B, C, and D) The absolute risk reduction (ARR) is the difference in risk of an unfavorable event (eg, treatment nonresponse) between the cariprazine and placebo groups: ARR = (Rateplacebo − Ratecariprazine). In this case, the rate of no response in the cariprazine group is 100% − 46% = 54% and in the placebo group is 100% − 32% = 68%, so ARR = 0.68 − 0.54 = 0.14 (ie, 14%). The relative risk reduction (RRR) is (Rateplacebo − Ratecariprazine ) / Rateplacebo, so RRR = (0.68 − 0.54) / 0.68 ≈ 0.21 (ie, 21%). The number needed to treat (NNT) to avoid 1 additional negative event (ie, no treatment response) compared to placebo is the inverse of the absolute risk reduction (ARR): NNT = 1 / ARR = 1 / 0.14 ≈ 8.
Educational objective:
The number needed to harm (NNH) is the number of people who must be exposed to a treatment to cause harm to 1 person who otherwise would not have been harmed. To calculate NNH, the absolute risk increase (ARI) between the treatment and control groups must be known: NNH = 1 / ARI.