TY - JOUR
T1 - Joint modeling of endpoints can be used to answer various research questions in randomized clinical trials
AU - van Eijk, Ruben P A
AU - Roes, Kit C B
AU - van den Berg, Leonard H
AU - Lu, Ying
N1 - Funding Information:
Funding Statement: RPAvE is supported by the Dutch Research Council (Rubicon, 452019301 ); YL is partially supported by the National Institutes of Health Research ( 5UL1TR003142-03, 5R01HL08977810, 3P30CA12443512 ).
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/7
Y1 - 2022/7
N2 - OBJECTIVES: Correlated longitudinal and time-to-event outcomes, such as the rate of cognitive decline and the onset of Alzheimer's disease, are frequent (co-)primary and key secondary endpoints in randomized clinical trials (RCTs). Despite their biological associations, these types of data are often analyzed separately, leading to loss of information and increases in bias. In this paper, we set out how joint modeling of longitudinal and time-to-event endpoints can be used in RCTs to answer various research questions.STUDY DESIGN AND SETTING: The key concepts of joint models are introduced and illustrated for a completed trial in amyotrophic lateral sclerosis.RESULTS: The output of a joint model can be used to answer different clinically relevant research questions, where the interpretation of effect estimates and those obtained from conventional methods are similar. Albeit joint models have the potential to overcome the limitations of commonly used alternatives, they require additional assumptions regarding the distributions, as well as the associations between two endpoints.CONCLUSION: Improving the uptake of joint models in RCTs may start by outlining the exact research question one seeks to answer, thereby determining how best to prespecify the model and defining the parameter that should be of primary interest.
AB - OBJECTIVES: Correlated longitudinal and time-to-event outcomes, such as the rate of cognitive decline and the onset of Alzheimer's disease, are frequent (co-)primary and key secondary endpoints in randomized clinical trials (RCTs). Despite their biological associations, these types of data are often analyzed separately, leading to loss of information and increases in bias. In this paper, we set out how joint modeling of longitudinal and time-to-event endpoints can be used in RCTs to answer various research questions.STUDY DESIGN AND SETTING: The key concepts of joint models are introduced and illustrated for a completed trial in amyotrophic lateral sclerosis.RESULTS: The output of a joint model can be used to answer different clinically relevant research questions, where the interpretation of effect estimates and those obtained from conventional methods are similar. Albeit joint models have the potential to overcome the limitations of commonly used alternatives, they require additional assumptions regarding the distributions, as well as the associations between two endpoints.CONCLUSION: Improving the uptake of joint models in RCTs may start by outlining the exact research question one seeks to answer, thereby determining how best to prespecify the model and defining the parameter that should be of primary interest.
KW - Amyotrophic lateral sclerosis
KW - Clinical trials
KW - Informative censoring
KW - Joint modeling
KW - Longitudinal
KW - Time-to-event
UR - http://www.scopus.com/inward/record.url?scp=85128242275&partnerID=8YFLogxK
U2 - 10.1016/j.jclinepi.2022.03.009
DO - 10.1016/j.jclinepi.2022.03.009
M3 - Article
C2 - 35346783
SN - 0895-4356
VL - 147
SP - 32
EP - 39
JO - Journal of Clinical Epidemiology
JF - Journal of Clinical Epidemiology
ER -