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


CONCLUSIONS
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.
Marschner
Ian C
IC
Asia Biometrics Centre, Pfizer Global Pharmaceuticals, 38 Wharf Road, West Ryde, 2114 New South Wales, Australia. ian.marschner@pfizer.com
Emberson
Jonathan
J
Irwig
Les
L
Walter
Stephen D
SD
D015982:Bias; D003327:Coronary Disease / Q000517:prevention & control; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018401:Sample Size; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors