The number needed to treat (NNT) can be adjusted for bias when the outcome is measured with error

Abstract

Background and objective We consider the number needed to treat (NNT) when the event of interest is defined by dichotomizing a continuous response at a threshold level. If the response is measured with error, the resulting NNT is biased. We consider methods to reduce this bias. Methods Bias adjustment was studied using simulations in which we varied the distributions of the underlying response and measurement error, including both normal and nonnormal distributions. We studied a maximum likelihood estimate (MLE) based on normality assumptions, and also considered a simulation–extrapolation estimate (SIMEX) without such assumptions. The treatment effect across all potential thresholds was summarized using an NNT threshold curve. Results Crude NNT estimation was substantially biased due to measurement error. The MLE performed well under normality, and it continued to perform well with nonnormal measurement error, but when the underlying response was nonnormal the MLE was unacceptably biased and was outperformed by the SIMEX estimate. The simulation results were also reflected in empirical data from a randomized study of cholesterol-lowering therapy. Conclusion Ignoring measurement error can lead to substantial bias in NNT, which can have an important practical effect on the interpretation of analyses. Analysis methods that adjust for measurement error bias can be used to assess the sensitivity of NNT estimates to this effect.