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 |
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Keywords
- Linear mixed models
- Longitudinal data
- Marginal linear models
- Power
- Survival analysis
ASJC Scopus subject areas
- Pharmacology (medical)
- Medicine(all)
Cite this
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, Laurel A; Petersen, R. C.; Weiner, M. W.; Aisen, P.
In: Contemporary Clinical Trials, Vol. 32, No. 5, 09.2011, p. 685-693.Research output: Contribution to journal › Article
}
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, Laurel A
AU - Petersen, R. C.
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 -