## Abstract

The number needed to treat (NNT) is an efficacy index commonly used in randomized clinical trials. The NNT is the average number of treated patients for each undesirable patient outcome, for example, death, prevented by the treatment. We introduce a systematic theoretically-based framework to model and estimate the conditional and the harmonic mean NNT in the presence of explanatory variables, in various models with dichotomous and nondichotomous outcomes. The conditional NNT is illustrated in a series of four primary examples; logistic regression, linear regression, Kaplan-Meier estimation, and Cox regression models. Also, we establish and prove mathematically the exact relationship between the conditional and the harmonic mean NNT in the presence of explanatory variables. We introduce four different methods to calculate asymptotically-correct confidence intervals for both indices. Finally, we implemented a simulation study to provide numerical demonstrations of the aforementioned theoretical results and the four examples. Numerical analysis showed that the parametric estimators of the NNT with nonparametric bootstrap-based confidence intervals outperformed other examined combinations in most settings. An R package and a web application have been developed and made available online to calculate the conditional and the harmonic mean NNTs with their corresponding confidence intervals.

Original language | English |
---|---|

Pages (from-to) | 3299-3320 |

Number of pages | 22 |

Journal | Statistics in Medicine |

Volume | 41 |

Issue number | 17 |

DOIs | |

State | Published - 30 Jul 2022 |

Externally published | Yes |

### Bibliographical note

Publisher Copyright:© 2022 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

## Keywords

- NNT
- adjusted NNT
- conditional NNT
- harmonic NNT
- the cox model