Longitudinal model for a dose-finding study for a rare disease treatment

被引:0
作者
Chen, Younan [1 ]
Fries, Michael [1 ]
Leonov, Sergei [1 ]
机构
[1] CSL Behring, Biostat Quantitat Clin Sci & Reporting, 1020 1st Ave, King Of Prussia, PA 19406 USA
关键词
Dose-finding; Nonlinear mixed effects model; Longitudinal model; Optimal design; D-optimality; EDP-optimality; OPTIMAL DESIGNS;
D O I
10.1007/s00362-023-01424-1
中图分类号
O21 [概率论与数理统计]; C8 [统计学];
学科分类号
020208 ; 070103 ; 0714 ;
摘要
Dose-finding studies in rare diseases are faced with unique challenges including low patient numbers, limited understanding of the dose-exposure-response relationship, variability around the endpoints. In addition, patient exposure to placebo is often not feasible. To describe the disease progression for different dose groups, we introduce a longitudinal model for the change from baseline for a clinical endpoint. We build a nonlinear mixed effects model using the techniques which have become popular over the past two decades in the design and analysis of population pharmacokinetic/pharmacodynamics studies. To evaluate operating characteristics of the proposed design, we derive the Fisher information matrix and validate analytical results via simulations. Alternative considerations, such as trend analysis, are discussed as well.
引用
收藏
页码:1343 / 1360
页数:18
相关论文
共 50 条
[41]   A hybrid design for dose-finding oncology clinical trials [J].
Liao, Jason J. Z. ;
Zhou, Feng ;
Zhou, Heng ;
Petruzzelli, Lilli ;
Hou, Kevin ;
Asatiani, Ekaterine .
INTERNATIONAL JOURNAL OF CANCER, 2022, 151 (09) :1602-1610
[42]   Dose-finding design and benchmark for a right censored endpoint [J].
Andrillon, Anais ;
Chevret, Sylvie ;
Lee, Shing M. ;
Biard, Lucie .
JOURNAL OF BIOPHARMACEUTICAL STATISTICS, 2020, 30 (06) :948-963
[43]   An approach to meta-analysis of dose-finding studies [J].
Zohar, Sarah ;
Katsahian, Sandrine ;
O'Quigley, John .
STATISTICS IN MEDICINE, 2011, 30 (17) :2109-2116
[44]   Proportional odds model for dose-finding clinical trial designs with ordinal toxicity grading [J].
Van Meter, Emily M. ;
Garrett-Mayer, Elizabeth ;
Bandyopadhyay, Dipankar .
STATISTICS IN MEDICINE, 2011, 30 (17) :2070-2080
[45]   Revisiting isotonic phase I design in the era of model-assisted dose-finding [J].
Wages, Nolan A. ;
Conaway, Mark R. .
CLINICAL TRIALS, 2018, 15 (05) :524-529
[46]   Target toxicity design for phase I dose-finding [J].
Guo, Wenchuan ;
Zhong, Bob .
STATISTICAL THEORY AND RELATED FIELDS, 2021, 5 (02) :149-161
[47]   MISSING DATA MECHANISMS IN A DOSE-FINDING ADAPTIVE TRIAL [J].
Liu, Kenneth ;
Entsuah, Richard .
JOURNAL OF BIOPHARMACEUTICAL STATISTICS, 2012, 22 (02) :329-337
[48]   An adaptive design for identifying the dose with the best efficacy/tolerability profile with application to a crossover dose-finding study [J].
Ivanova, Anastasia ;
Liu, Ken ;
Snyder, Ellen ;
Snavely, Duane .
STATISTICS IN MEDICINE, 2009, 28 (24) :2941-2951
[49]   Calculation of Phase 2 dose-finding study sample size for reliable Phase 3 dose selection [J].
Liu, Fang ;
Zhao, Qing ;
Rodgers, Anthony J. ;
Mehrotra, Devan V. .
PHARMACEUTICAL STATISTICS, 2023, 22 (06) :1076-1088
[50]   Implementation of maximin efficient designs in dose-finding studies [J].
Fackle-Fornius, Ellinor ;
Miller, Frank ;
Nyquist, Hans .
PHARMACEUTICAL STATISTICS, 2015, 14 (01) :63-73