Dynamic predictive probabilities to monitor rapid cystic fibrosis disease progression
Open accessAbstract
Cystic fibrosis (CF) is a progressive, genetic disease characterized by frequent, prolonged drops in lung function. Accurately predicting rapid underlying lung-function decline is essential for clinical decision support and timely intervention. Determining whether an individual is experiencing a period of rapid decline is complicated due to its heterogeneous timing and extent, and error component of the measured lung function. We construct individualized predictive probabilities for "nowcasting" rapid decline. We assume each patient's true longitudinal lung function, S(t), follows a nonlinear, nonstationary stochastic process, and accommodate between-patient heterogeneity through random effects. Corresponding lung-function decline at time t is defined as the rate of change, S'(t). We predict S'(t) conditional on observed covariate and measurement history by modeling a measured lung function as a noisy version of S(t). The method is applied to data on 30 879 US CF Registry patients. Results are contrasted with a currently employed decision rule using single-center data on 212 individuals. Rapid decline is identified earlier using predictive probabilities than the center's currently employed decision rule (mean difference: 0.65 years; 95% confidence interval (CI): 0.41, 0.89). We constructed a bootstrapping algorithm to obtain CIs for predictive probabilities. We illustrate real-time implementation with R Shiny. Predictive accuracy is investigated using empirical simulations, which suggest this approach more accurately detects peak decline, compared with a uniform threshold of rapid decline. Median area under the ROC curve estimates (Q1-Q3) were 0.817 (0.814-0.822) and 0.745 (0.741-0.747), respectively, implying reasonable accuracy for both. This article demonstrates how individualized rate of change estimates can be coupled with probabilistic predictive inference and implementation for a useful medical-monitoring approach.
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Predictive models have been studied in CF in the past.
“Predictive models have been studied in CF in the past (30, 31).”
From Virtual monitoring in CF – the importance of continuous monitoring in a multi-organ chronic condition (2023) · cites this paper as [31]
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Cites
Random-Effects Models for Longitudinal Data
Laird, N. M., & Ware, J. H. (1982) · Biometrics · doi:10.2307/2529876 · Cited by 8,923 · see citing works
Diggle, P. J., Heagerty, P. J., Liang, K., & Zeger, S. L. (2002) · doi:10.1093/oso/9780198524847.001.0001 · Cited by 3,388 · see citing works
Ruppert, D., WAND, M. P., & Carroll, R. J. (2003) · Cambridge University Press eBooks · doi:10.1017/cbo9780511755453 · Cited by 2,153 · see citing works
Joint modelling of longitudinal measurements and event time data
Henderson, R. (2000) · Biostatistics · doi:10.1093/biostatistics/1.4.465 · Cited by 919 · see citing works
Knapp, E. A., Fink, A. K., Goss, C. H., Sewall, A., Ostrenga, J., Dowd, C., Elbert, A., Petren, K., & Marshall, B. C. (2016) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201511-781oc · Cited by 467 · see citing works
Konstan, M. W., Morgan, W. J., Butler, S. M., Pasta, D. J., Craib, M. L., Silva, S. J., Stokes, D. C., Wohl, M. E. B., Wagener, J. S., Regelmann, W. E., et al. (2007) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2007.03.006 · Cited by 436 · see citing works
The prevalence of cystic fibrosis in the European Union
Farrell, P. M. (2008) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2008.03.007 · Cited by 395 · see citing works
Galovic, M., Döhler, N., Erdélyi‐Canavese, B., Felbecker, A., Siebel, P., Conrad, J., Evers, S., Winklehner, M., von Oertzen, T. J., Haring, H., et al. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30404-0 · Cited by 336 · see citing works
Risk and Uncertainty Communication
Spiegelhalter, D. (2017) · Annual Review of Statistics and Its Application · doi:10.1146/annurev-statistics-010814-020148 · Cited by 248 · see citing works
Lung Transplantation and Survival in Children with Cystic Fibrosis
Liou, T. G., Adler, F. R., Cox, D. R., & Cahill, B. C. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa066359 · Cited by 196 · see citing works
Taylor-Robinson, D. C., Whitehead, M. M., Diderichsen, F., Olesen, H. V., Pressler, T., Smyth, R. L., & Diggle, P. J. (2012) · Thorax · doi:10.1136/thoraxjnl-2011-200953 · Cited by 180 · see citing works
Lung function decline from adolescence to young adulthood in cystic fibrosis
VandenBranden, S. L., McMullen, A., Schechter, M. S., Pasta, D. J., Michaelis, R. L., Konstan, M. W., Wagener, J. S., Morgan, W. J., McColley, S. A., & for the Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis (2012) · Pediatric Pulmonology · doi:10.1002/ppul.21526 · Cited by 128 · see citing works
Bayesian predictive approach to interim monitoring in clinical trials
Dmitrienko, A. A., & Wang, M. (2005) · Statistics in Medicine · doi:10.1002/sim.2204 · Cited by 127 · see citing works
Lechtzin, N., Mayer-Hamblett, N., West, N. E., Allgood, S., Wilhelm, E., Khan, U., Aitken, M. L., Ramsey, B. W., Boyle, M. P., Mogayzel, P. J., et al. (2017) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201610-2172oc · Cited by 127 · see citing works
Szczesniak, R. D., Heltshe, S. L., Stanojevic, S., & Mayer-Hamblett, N. (2017) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2017.01.002 · Cited by 126 · see citing works
Real‐Time Individual Predictions of Prostate Cancer Recurrence Using Joint Models
Taylor, J. M. G., Park, Y., Ankerst, D. P., Proust‐Lima, C., Williams, S., Kestin, L. L., Bae, K., Pickles, T., & Sandler, H. M. (2013) · Biometrics · doi:10.1111/j.1541-0420.2012.01823.x · Cited by 116 · see citing works
Risk factors for rate of decline in FEV1 in adults with cystic fibrosis
Konstan, M. W., Wagener, J. S., VanDevanter, D. R., Pasta, D. J., Yegin, A., Rasouliyan, L., & Morgan, W. J. (2012) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2012.03.009 · Cited by 115 · see citing works
Harun, S. N., Wainwright, C. E., Klein, K., & Hennig, S. (2016) · Paediatric Respiratory Reviews · doi:10.1016/j.prrv.2016.03.002 · Cited by 112 · see citing works
Epidemiology of CF: How registries can be used to advance our understanding of the CF population
Jackson, A. D., & Goss, C. H. (2017) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2017.11.013 · Cited by 92 · see citing works
Simulation-Based Confidence Intervals for Functions With Complicated Derivatives
Mandel, M. (2013) · The American Statistician · doi:10.1080/00031305.2013.783880 · Cited by 77 · see citing works
A semiparametric approach to estimate rapid lung function decline in cystic fibrosis
Szczesniak, R. D., McPhail, G. L., Duan, L. L., Macaluso, M., Amin, R. S., & Clancy, J. P. (2013) · Annals of Epidemiology · doi:10.1016/j.annepidem.2013.08.009 · Cited by 60 · see citing works
Marshall, B. C., & Nelson, E. C. (2014) · BMJ Quality & Safety · doi:10.1136/bmjqs-2013-002790 · Cited by 55 · see citing works
Phenotypes of Rapid Cystic Fibrosis Lung Disease Progression during Adolescence and Young Adulthood
Szczesniak, R. D., Li, D., Su, W., Brokamp, C., Pestian, J. P., Seid, M., & Clancy, J. P. (2017) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201612-2574oc · Cited by 54 · see citing works
Real-time monitoring of progression towards renal failure in primary care patients
Diggle, P. J., Sousa, I., & Asar, Ö. (2014) · Biostatistics · doi:10.1093/biostatistics/kxu053 · Cited by 50 · see citing works
Schechter, M. S., Schmidt, H. J., Williams, R., Norton, R., Taylor, D., & Molzhon, A. (2018) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2018.06.003 · Cited by 36 · see citing works
Neuhaus, J. M., McCulloch, C. E., & Boylan, R. D. (2018) · Statistics in Medicine · doi:10.1002/sim.7932 · Cited by 32 · see citing works
Siracusa, C. M., Weiland, J., Acton, J. D., Chima, A. K., Chini, B. A., Hoberman, A. J., Wetzel, J. D., Amin, R. S., & McPhail, G. L. (2014) · BMJ Quality & Safety · doi:10.1136/bmjqs-2013-002361 · Cited by 30 · see citing works
Moss, A. F. D., Juarez‐Colunga, E., Nathoo, F. S., Wagner, B. D., & Sagel, S. D. (2016) · Statistics in Medicine · doi:10.1002/sim.6845 · Cited by 24 · see citing works
Correction: Lung Transplantation and Survival in Children with Cystic Fibrosis
Liou, T. G., Adler, F. R., Cahill, B. C., & Cox, D. R. (2008) · New England Journal of Medicine · doi:10.1056/nejmc086289 · Cited by 15 · see citing works
Szczesniak, R. D., Brokamp, C., Su, W., Mcphail, G. L., Pestian, J., & Clancy, J. P. (2019) · IEEE Journal of Translational Engineering in Health and Medicine · doi:10.1109/jtehm.2018.2878534 · Cited by 15 · see citing works
Prediction-based classification for longitudinal biomarkers
Foulkes, A. S., Azzoni, L., Li, X., Johnson, M. A., Smith, C. J., Mounzer, K., & Montaner, L. J. (2010) · The Annals of Applied Statistics · doi:10.1214/10-aoas326 · Cited by 14 · see citing works
Prediction-Based Classification for Longitudinal Biomarkers
Foulkes, A. S., Azzoni, L., Li, X., Johnson, M. A., Smith, C. J., Mounzer, K., & Montaner, L. J. (2010) · ScholarWorks@UMassAmherst (University of Massachusetts Amherst) · Cited by 13 · see citing works
Albert, P. S. (2018) · Statistics in Medicine · doi:10.1002/sim.8011 · Cited by 10 · see citing works
Salvatore, D., Buzzetti, R., & Mastella, G. (2016) · Pediatric Pulmonology · doi:10.1002/ppul.23473 · Cited by 8 · see citing works
Li, H., & Gatsonis, C. (2018) · Statistics in Medicine · doi:10.1002/sim.8079 · Cited by 1 · see citing works
Flagged first, then by citations
1 of the 36 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- [17]De Finetti B. Theory of Probability. Vol 1 New York, NY: Wiley; 1974.
- [32]McPhail GL, Weiland J, Hoberman AJ, et al. Improving rapid FEV1 decline through quality improvement. Pediatr Pulmonol. 2013; 48: 394.
Cited by
Sorted by citations
Linear Mixed Effects Models for Non-Gaussian Continuous Repeated Measurement Data
Asar, Ö., Bolin, D., Diggle, P. J., & Wallin, J. (2020) · Journal of the Royal Statistical Society Series C (Applied Statistics) · doi:10.1111/rssc.12405 · Cited by 26 · see citing works
Schlüter, D. K., Ostrenga, J., Carr, S. B., Fink, A. K., Faro, A., Szczesniak, R. D., Keogh, R. H., Charman, S. C., Marshall, B. C., Goss, C. H., et al. (2021) · Thorax · doi:10.1136/thoraxjnl-2021-216849 · Cited by 23 · see citing works
Functional data analysis and prediction tools for continuous glucose-monitoring studies
Gecili, E., Huang, R., Khoury, J. C., King, E. C., Altaye, M., Bowers, K. A., & Szczesniak, R. D. (2020) · Journal of Clinical and Translational Science · doi:10.1017/cts.2020.545 · Cited by 15 · see citing works
Built environment factors predictive of early rapid lung function decline in cystic fibrosis
Gecili, E., Brokamp, C., Rasnick, E., Afonso, P. M., Andrinopoulou, E., Dexheimer, J. W., Clancy, J. P., Keogh, R. H., Ni, Y., Palipana, A., et al. (2023) · Pediatric Pulmonology · doi:10.1002/ppul.26352 · Cited by 13 · see citing works
Palipana, A., Gecili, E., Song, S., Johnson, S. R., Szczesniak, R. D., & Gupta, N. (2023) · CHEST Journal · doi:10.1016/j.chest.2022.12.027 · Cited by 12 · see citing works
Bayesian regularization for a non-stationary Gaussian linear mixed effects model
Gecili, E., Sivaganesan, S., Asar, O., Clancy, J., Ziady, A., & Szczesniak, R. (2021) · Statistics in Medicine · doi:10.1002/sim.9279 · Cited by 9 · see citing works
Gecili, E., Brokamp, C., Palipana, A., Huang, R., Andrinopoulou, E., Pestian, T., Rasnick, E., Keogh, R. H., Ni, Y., Clancy, J. P., et al. (2021) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2021.145905 · Cited by 9 · see citing works
Cystic Fibrosis Point of Personalized Detection (CFPOPD): An Interactive Web Application
Wolfe, C., Pestian, T., Gecili, E., Su, W., Keogh, R. H., Pestian, J. P., Seid, M., Diggle, P. J., Ziady, A. G., Clancy, J. P., et al. (2020) · JMIR Medical Informatics · doi:10.2196/23530 · Cited by 7 · see citing works
Su, W., Gecili, E., Wang, X., & Szczesniak, R. D. (2021) · Statistics in Biopharmaceutical Research · doi:10.1080/19466315.2020.1870546 · Cited by 6 · see citing works
Gecili, E., Brokamp, C., Asar, Ö., Andrinopoulou, E., Brewington, J. J., & Szczesniak, R. D. (2024) · Environmetrics · doi:10.1002/env.2884 · Cited by 4 · see citing works
Palma, M., Keogh, R. H., Carr, S. B., Szczesniak, R. D., Taylor-Robinson, D. C., Wood, A., Terrera, G. M., & Barrett, J. (2024) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2024.05.013 · Cited by 3 · see citing works
Pratt, J. M., Su, W., Hayes, D., Clancy, J. P., & Szczesniak, R. D. (2021) · Journal of Healthcare Engineering · doi:10.1155/2021/6671833 · Cited by 3 · see citing works
Peterson, C. J., Rao, M. B., Palipana, A., Rasnick, E., Vancil, A., Ryan, P., Brokamp, C., Kramer, E. L., Szczesniak, R. D., & Gecili, E. (2024) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2024.175348 · Cited by 2 · see citing works
Evaluating precision medicine tools in cystic fibrosis for racial and ethnic fairness
Colegate, S. P., Palipana, A., Gecili, E., Szczesniak, R. D., & Brokamp, C. (2024) · Journal of Clinical and Translational Science · doi:10.1017/cts.2024.532 · Cited by 2 · see citing works
Vagg, T., Deasy, K. F., Chapman, W. W., Ranganathan, S. C., Plant, B. J., & Shanthikumar, S. (2023) · Frontiers in Digital Health · doi:10.3389/fdgth.2023.1196442 · Cited by 1 · see citing works
“Predictive models have been studied in CF in the past (30, 31).”
BackgroundSu, W., Wang, X., Afonso, P. M., Andrinopoulou, E., & Szczesniak, R. D. (2026) · The New England Journal of Statistics in Data Science · doi:10.51387/26-nejsds99 · Cited by 1 · see citing works
Palipana, A., Song, S., Gupta, N., & Szczesniak, R. D. (2024) · Biometrics · doi:10.1093/biomtc/ujae011 · Cited by 1 · see citing works
Predicting lung function decline in cystic fibrosis: the impact of initiating ivacaftor therapy
Zhou, G. C., Wang, Z., Palipana, A., Andrinopoulou, E., Afonso, P. M., McPhail, G. L., Siracusa, C. M., Gecili, E., & Szczesniak, R. D. (2024) · Respiratory Research · doi:10.1186/s12931-024-02794-2 · Cited by 1 · see citing works
Palma, M., Keogh, R. H., Carr, S. B., Szczesniak, R. D., Taylor-Robinson, D. C., Wood, A., Terrera, G. M., & Barrett, J. (2023) · medRxiv · doi:10.1101/2023.05.12.23289768 · Cited by 1 · see citing works
Predicting the course of nutrition and lung disease in infants and children with cystic fibrosis
McColley, S. A. (2020) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2020.07.006
(2020) · Statistics in Medicine · doi:10.1002/sim.8229
Varkki, S. D., Medhi, P., Mathai, S., Kumar, S., & Paul, G. (2023) · Journal of Cystic Fibrosis · doi:10.1016/s1569-1993(23)01547-3
624 Evaluating precision medicine tools in cystic fibrosis for racial and ethnic fairness
Colegate, S. P., Palipana, A., Szczesniak, R. D., & Brokamp, C. (2023) · Journal of Cystic Fibrosis · doi:10.1016/s1569-1993(23)01546-1
Dagenais, R., Karlsen, E., Lee, K., & Bradley, Q. (2023) · Journal of Cystic Fibrosis · doi:10.1016/s1569-1993(23)01545-x
Wang, Z., Zhou, G. C., Palipana, A., Gecili, E., Dexheimer, J. W., Siracusa, C. M., & Szczesniak, R. D. (2024) · Discover Data · doi:10.1007/s44248-024-00014-2
Hypercubes to identify geomarkers of rapid cystic fibrosis lung disease progression
Cheng, Y., Brokamp, C., Rasnick, E., Kramer, E. L., Ryan, P., Szczesniak, R. D., & Gecili, E. (2025) · BMC Medical Informatics and Decision Making · doi:10.1186/s12911-025-03097-2
Zhou, G. C., Wang, Z., Palipana, A., Andrinopoulou, E.-R., Afonso, P. M., McPhail, G. L., Siracusa, C. M., Gecili, E., & Szczesniak, R. D. (2024) · Figshare · doi:10.6084/m9.figshare.26713634
Pandagale, A. A., & Pandagale, L. V. P. A. A. (2026) · Statistical Applications in Genetics and Molecular Biology · doi:10.1515/sagmb-2025-0042
Garter, A., Gecili, E., Hossain, M. M., Nakamura, A., Wackler, M., Boat, T. F., & Szczesniak, R. D. (2026) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2026.103448
- Authors
- Szczesniak, R. D., Su, W., Brokamp, C., Keogh, R. H., Pestian, J. P., Seid, M., Diggle, P. J., & Clancy, J. P.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- University of Cincinnati (US)
- London School of Hygiene & Tropical Medicine (GB)
- Health Data Research UK (GB)
- Corresponding author
- Szczesniak, Rhonda D.
- ORCID
- Venue
- Statistics in Medicine
- Publisher
- Wiley
- Published
- 2019-12-09
- Volume
- 39
- Issue
- 6
- Pages
- 740-756
- ISSN
- 0277-6715 (ISSN-L)
- 1097-0258
- PMC
- PMC7028099
- OpenAlex
- W2995206395
- Cited by
- 30
- References
- 36
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 8 · 2023: 7 · 2021: 5 · 2020: 5 · 2019: 1
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Statistics in Medicine (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Lancaster EPrints (Lancaster University) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (K25 HL125954, R01 HL141286)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- cystic fibrosis, lung function decline, predictive probability, nowcasting, random effects, measurement error, bootstrap confidence intervals, clinical decision support, real-time monitoring
- MeSH terms
- Cystic Fibrosis, Forced Expiratory Volume, Humans, Lung, Probability, Disease Progression
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