Calibration and validation of modeled 5-year survival predictions among people with cystic fibrosis treated with the cystic fibrosis transmembrane conductance regulator modulator ivacaftor using United States registry data
Copyright: © 2023 McGarry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..
OBJECTIVES: Cystic fibrosis (CF) is a rare genetic disease characterized by life-shortening lung function decline. Ivacaftor, a CF transmembrane conductance regulator modulator (CFTRm), was approved in 2012 for people with CF with specific gene mutations. We used real-world evidence of 5-year mortality impacts of ivacaftor in a US registry population to validate a CF disease-progression model that estimates the impact of ivacaftor on survival.
METHODS: The model projects the impact of ivacaftor vs. standard care in people with CF aged ≥6 years with CFTR gating mutations by combining parametric equations fitted to historical registry survival data, with mortality hazards adjusted for fixed and time-varying person-level characteristics. Disease progression with standard care was derived from published registry studies and the expected impact of ivacaftor on clinical characteristics was derived from clinical trials. Individual-level baseline characteristics of the registry ivacaftor-treated population were entered into the model; 5-year model-projected mortality with credible intervals (CrIs) was compared with registry mortality to evaluate the model's validity.
RESULTS: Post-calibration 5-year mortality projections closely approximated registry mortality in populations treated with standard care (6.4% modeled [95% CrI: 5.3% to 7.6%] vs. 6.0% observed) and ivacaftor (3.4% modeled [95% CrI: 2.7% to 4.4%] vs. 3.1% observed). The model accurately predicted 5-year relative risk of mortality (0.53 modeled [0.47 to 0.60] vs. 0.51 observed) in people treated with ivacaftor vs. standard care.
CONCLUSIONS: Modeled 5-year survival projections for people with CF initiating ivacaftor vs. standard care align closely with real-world registry data. Findings support the validity of modeling CF to predict long-term survival and estimate clinical and economic outcomes of CFTRm.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
PloS one - 18(2023), 4 vom: 11., Seite e0283479 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
McGarry, Lisa J [VerfasserIn] |
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| Links: |
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| Themen: |
126880-72-6 |
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| Anmerkungen: |
Date Completed 14.04.2023 Date Revised 19.03.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0283479 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM355479230 |
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| 100 | 1 | |a McGarry, Lisa J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Calibration and validation of modeled 5-year survival predictions among people with cystic fibrosis treated with the cystic fibrosis transmembrane conductance regulator modulator ivacaftor using United States registry data |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 19.03.2024 | ||
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| 520 | |a Copyright: © 2023 McGarry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||
| 520 | |a OBJECTIVES: Cystic fibrosis (CF) is a rare genetic disease characterized by life-shortening lung function decline. Ivacaftor, a CF transmembrane conductance regulator modulator (CFTRm), was approved in 2012 for people with CF with specific gene mutations. We used real-world evidence of 5-year mortality impacts of ivacaftor in a US registry population to validate a CF disease-progression model that estimates the impact of ivacaftor on survival | ||
| 520 | |a METHODS: The model projects the impact of ivacaftor vs. standard care in people with CF aged ≥6 years with CFTR gating mutations by combining parametric equations fitted to historical registry survival data, with mortality hazards adjusted for fixed and time-varying person-level characteristics. Disease progression with standard care was derived from published registry studies and the expected impact of ivacaftor on clinical characteristics was derived from clinical trials. Individual-level baseline characteristics of the registry ivacaftor-treated population were entered into the model; 5-year model-projected mortality with credible intervals (CrIs) was compared with registry mortality to evaluate the model's validity | ||
| 520 | |a RESULTS: Post-calibration 5-year mortality projections closely approximated registry mortality in populations treated with standard care (6.4% modeled [95% CrI: 5.3% to 7.6%] vs. 6.0% observed) and ivacaftor (3.4% modeled [95% CrI: 2.7% to 4.4%] vs. 3.1% observed). The model accurately predicted 5-year relative risk of mortality (0.53 modeled [0.47 to 0.60] vs. 0.51 observed) in people treated with ivacaftor vs. standard care | ||
| 520 | |a CONCLUSIONS: Modeled 5-year survival projections for people with CF initiating ivacaftor vs. standard care align closely with real-world registry data. Findings support the validity of modeling CF to predict long-term survival and estimate clinical and economic outcomes of CFTRm | ||
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