@article{82f110c52c1b416f9ae009a99ce6efbc,
title = "A semiparametric joint model for terminal trend of quality of life and survival in palliative care research",
abstract = "Palliative medicine is an interdisciplinary specialty focusing on improving quality of life (QOL) for patients with serious illness and their families. Palliative care programs are available or under development at over 80% of large US hospitals (300+ beds). Palliative care clinical trials present unique analytic challenges relative to evaluating the palliative care treatment efficacy which is to improve patients{\textquoteright} diminishing QOL as disease progresses towards end of life (EOL). A unique feature of palliative care clinical trials is that patients will experience decreasing QOL during the trial despite potentially beneficial treatment. Often longitudinal QOL and survival data are highly correlated which, in the face of censoring, makes it challenging to properly analyze and interpret terminal QOL trend. To address these issues, we propose a novel semiparametric statistical approach to jointly model the terminal trend of QOL and survival data. There are two sub-models in our approach: a semiparametric mixed effects model for longitudinal QOL and a Cox model for survival. We use regression splines method to estimate the nonparametric curves and AIC to select knots. We assess the model performance through simulation to establish a novel modeling approach that could be used in future palliative care research trials. Application of our approach in a recently completed palliative care clinical trial is also presented.",
keywords = "end-of-life, joint modeling, palliative care, semiparametric, terminal trend",
author = "Zhigang Li and Frost, {H. R.} and Tosteson, {Tor D.} and Lihui Zhao and Lei Liu and Kathleen Lyons and Huaihou Chen and Bernard Cole and David Currow and Marie Bakitas",
note = "Funding Information: We thank the referees for their review comments. Funding: Zhigang Li, H. R. Frost and Tor D. Tosteson were partially supported by R03NR014915. Zhigang Li is also partially supported by P01ES022832 and P20GM104416. H. R. Frost is also partially supported by K01LM012426 and P20GM103534. Tor D. Tosteson was also partially supported by the Dartmouth Clinical and Translational Science Institute, under award number UL1TR001086, and award number P30CA023108 to the Norris Cotton Cancer Center. Lei Liu was partially supported by AHRQ R01HS020263. Kathleen D. Lyons was supported by a Mentored Research Scholar Grant in Applied and Clinical Research (MRSG 12‐113‐01 – CPPB) from the American Cancer Society. Marie Bakitas was supported by the National Institute for Nursing Research (R01NR011871), National Cancer Institute (R01 CA101704), Foundation for Informed Medical Decision‐Making and a Cancer and Leukemia Group B Foundation Clinical Scholar Award. Funding Information: Funding information: National Institute of Nursing Research, Grant/Award Number: R01NR011871 and R03NR014915; American Cancer Society, Grant/Award Number: MRSG 12‐113‐01 ‐ CPPB; National Institute of General Medical Sciences, Grant/Award Number: P20GM104416; National Cancer Institute, Grant/Award Number: P30CA023108, R01CA101704 and R01 CA101704; Cancer and Leukemia Group B Foundation, Grant/ Award Number: Clinical Scholar Award; National Institute for Nursing Research, Grant/Award Number: R01NR011871; Mentored Research Scholar Grant in Applied and Clinical Research, Grant/Award Number: MRSG 12‐113‐01 – CPPB; Dartmouth Clinical and Translational Science Institute, Grant/Award Number: P30CA023108, UL1TR001086. Zhigang Li and H.R. Frost contributed equally to the paper. Publisher Copyright: Copyright {\textcopyright} 2017 John Wiley & Sons, Ltd.",
year = "2017",
month = dec,
day = "20",
doi = "10.1002/sim.7445",
language = "English",
volume = "36",
pages = "4692--4704",
journal = "Statistics in Medicine",
issn = "0277-6715",
number = "29",
}