### Abstract

Randomized, placebo-controlled trials often use time-to-event as the primary endpoint, even when a continuous measure of disease severity is available. We compare the power to detect a treatment effect using either rate of change, as estimated by linear models of longitudinal continuous data, or time-to-event estimated by Cox proportional hazards models. We propose an analytic inflation factor for comparing the two types of analyses assuming that the time-to-event can be expressed as a time-to-threshold of the continuous measure. We conduct simulations based on a publicly available Alzheimer's disease data set in which the time-to-event is algorithmically defined based on a battery of assessments. A Cox proportional hazards model of the time-to-event endpoint is compared to a linear model of a single assessment from the battery. The simulations also explore the impact of baseline covariates in either analysis.

Original language | English (US) |
---|---|

Pages (from-to) | 685-693 |

Number of pages | 9 |

Journal | Contemporary Clinical Trials |

Volume | 32 |

Issue number | 5 |

DOIs | |

State | Published - Sep 2011 |

### Fingerprint

### Keywords

- Linear mixed models
- Longitudinal data
- Marginal linear models
- Power
- Survival analysis

### ASJC Scopus subject areas

- Pharmacology (medical)
- Medicine(all)

### Cite this

*Contemporary Clinical Trials*,

*32*(5), 685-693. https://doi.org/10.1016/j.cct.2011.04.007

**The relative efficiency of time-to-threshold and rate of change in longitudinal data.** / Donohue, M. C.; Gamst, A. C.; Thomas, R. G.; Xu, R.; Beckett, L.; Petersen, Ronald Carl; Weiner, M. W.; Aisen, P.

Research output: Contribution to journal › Article

*Contemporary Clinical Trials*, vol. 32, no. 5, pp. 685-693. https://doi.org/10.1016/j.cct.2011.04.007

}

TY - JOUR

T1 - The relative efficiency of time-to-threshold and rate of change in longitudinal data

AU - Donohue, M. C.

AU - Gamst, A. C.

AU - Thomas, R. G.

AU - Xu, R.

AU - Beckett, L.

AU - Petersen, Ronald Carl

AU - Weiner, M. W.

AU - Aisen, P.

PY - 2011/9

Y1 - 2011/9

N2 - Randomized, placebo-controlled trials often use time-to-event as the primary endpoint, even when a continuous measure of disease severity is available. We compare the power to detect a treatment effect using either rate of change, as estimated by linear models of longitudinal continuous data, or time-to-event estimated by Cox proportional hazards models. We propose an analytic inflation factor for comparing the two types of analyses assuming that the time-to-event can be expressed as a time-to-threshold of the continuous measure. We conduct simulations based on a publicly available Alzheimer's disease data set in which the time-to-event is algorithmically defined based on a battery of assessments. A Cox proportional hazards model of the time-to-event endpoint is compared to a linear model of a single assessment from the battery. The simulations also explore the impact of baseline covariates in either analysis.

AB - Randomized, placebo-controlled trials often use time-to-event as the primary endpoint, even when a continuous measure of disease severity is available. We compare the power to detect a treatment effect using either rate of change, as estimated by linear models of longitudinal continuous data, or time-to-event estimated by Cox proportional hazards models. We propose an analytic inflation factor for comparing the two types of analyses assuming that the time-to-event can be expressed as a time-to-threshold of the continuous measure. We conduct simulations based on a publicly available Alzheimer's disease data set in which the time-to-event is algorithmically defined based on a battery of assessments. A Cox proportional hazards model of the time-to-event endpoint is compared to a linear model of a single assessment from the battery. The simulations also explore the impact of baseline covariates in either analysis.

KW - Linear mixed models

KW - Longitudinal data

KW - Marginal linear models

KW - Power

KW - Survival analysis

UR - http://www.scopus.com/inward/record.url?scp=79960894260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960894260&partnerID=8YFLogxK

U2 - 10.1016/j.cct.2011.04.007

DO - 10.1016/j.cct.2011.04.007

M3 - Article

VL - 32

SP - 685

EP - 693

JO - Contemporary Clinical Trials

JF - Contemporary Clinical Trials

SN - 1551-7144

IS - 5

ER -