Projecting the impact of triple CFTR modulator therapy on intravenous antibiotic requirements in cystic fibrosis using patient registry data combined with treatment effects from randomised trials
Projecting the impact of triple CFTR modulator therapy on intravenous antibiotic requirements in cystic fibrosis using patient registry data combined with treatment effects from randomised trials
Background: cystic fibrosis (CF) is a life-threatening genetic disease, affecting around 10 500 people in the UK. Precision medicines have been developed to treat specific CF-gene mutations. The newest, elexacaftor/tezacaftor/ivacaftor (ELEX/TEZ/IVA), has been found to be highly effective in randomised controlled trials (RCTs) and became available to a large proportion of UK CF patients in 2020. Understanding the potential health economic impacts of ELEX/TEZ/IVA is vital to planning service provision.
Methods: we combined observational UK CF Registry data with RCT results to project the impact of ELEX/TEZ/IVA on total days of intravenous (IV) antibiotic treatment at a population level. Registry data from 2015 to 2017 were used to develop prediction models for IV days over a 1-year period using several predictors, and to estimate 1-year population total IV days based on standards of care pre-ELEX/TEZ/IVA. We considered two approaches to imposing the impact of ELEX/TEZ/IVA on projected outcomes using effect estimates from RCTs: approach 1 based on effect estimates on FEV1% and approach 2 based on effect estimates on exacerbation rate.
Results: ELEX/TEZ/IVA is expected to result in significant reductions in population-level requirements for IV antibiotics of 16.1% (~17 800 days) using approach 1 and 43.6% (~39 500 days) using approach 2. The two approaches require different assumptions. Increased understanding of the mechanisms through which ELEX/TEZ/IVA acts on these outcomes would enable further refinements to our projections.
Conclusions: this work contributes to increased understanding of the changing healthcare needs of people with CF and illustrates how Registry data can be used in combination with RCT evidence to estimate population-level treatment impacts.
Keogh, Ruth H
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Cosgriff, Rebecca
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Andrinopoulou, Eleni-Rosalina
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Brownlee, Keith G
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Carr, Siobhán B
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Diaz-Ordaz, Karla
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Granger, Emily
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Jewell, Nicholas P
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Lewin, Alex
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Leyrat, Clemence
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Schlüter, Daniela K
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van Smeden, Maarten
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Szczesniak, Rhonda D
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Connett, Gary J
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23 September 2021
Keogh, Ruth H
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Cosgriff, Rebecca
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Andrinopoulou, Eleni-Rosalina
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Brownlee, Keith G
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Carr, Siobhán B
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Diaz-Ordaz, Karla
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Granger, Emily
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Jewell, Nicholas P
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Lewin, Alex
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Leyrat, Clemence
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Schlüter, Daniela K
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van Smeden, Maarten
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Szczesniak, Rhonda D
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Connett, Gary J
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Keogh, Ruth H, Cosgriff, Rebecca, Andrinopoulou, Eleni-Rosalina, Brownlee, Keith G, Carr, Siobhán B, Diaz-Ordaz, Karla, Granger, Emily, Jewell, Nicholas P, Lewin, Alex, Leyrat, Clemence, Schlüter, Daniela K, van Smeden, Maarten, Szczesniak, Rhonda D and Connett, Gary J
(2021)
Projecting the impact of triple CFTR modulator therapy on intravenous antibiotic requirements in cystic fibrosis using patient registry data combined with treatment effects from randomised trials.
Thorax.
(doi:10.1136/thoraxjnl-2020-216265).
Abstract
Background: cystic fibrosis (CF) is a life-threatening genetic disease, affecting around 10 500 people in the UK. Precision medicines have been developed to treat specific CF-gene mutations. The newest, elexacaftor/tezacaftor/ivacaftor (ELEX/TEZ/IVA), has been found to be highly effective in randomised controlled trials (RCTs) and became available to a large proportion of UK CF patients in 2020. Understanding the potential health economic impacts of ELEX/TEZ/IVA is vital to planning service provision.
Methods: we combined observational UK CF Registry data with RCT results to project the impact of ELEX/TEZ/IVA on total days of intravenous (IV) antibiotic treatment at a population level. Registry data from 2015 to 2017 were used to develop prediction models for IV days over a 1-year period using several predictors, and to estimate 1-year population total IV days based on standards of care pre-ELEX/TEZ/IVA. We considered two approaches to imposing the impact of ELEX/TEZ/IVA on projected outcomes using effect estimates from RCTs: approach 1 based on effect estimates on FEV1% and approach 2 based on effect estimates on exacerbation rate.
Results: ELEX/TEZ/IVA is expected to result in significant reductions in population-level requirements for IV antibiotics of 16.1% (~17 800 days) using approach 1 and 43.6% (~39 500 days) using approach 2. The two approaches require different assumptions. Increased understanding of the mechanisms through which ELEX/TEZ/IVA acts on these outcomes would enable further refinements to our projections.
Conclusions: this work contributes to increased understanding of the changing healthcare needs of people with CF and illustrates how Registry data can be used in combination with RCT evidence to estimate population-level treatment impacts.
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thoraxjnl-2020-216265.full
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Accepted/In Press date: 12 August 2021
e-pub ahead of print date: 23 September 2021
Published date: 23 September 2021
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Local EPrints ID: 452221
URI: http://eprints.soton.ac.uk/id/eprint/452221
ISSN: 0040-6376
PURE UUID: e6acfddc-4cc1-48af-90f8-be9830d1ed28
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Date deposited: 30 Nov 2021 17:32
Last modified: 16 Apr 2024 01:54
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Contributors
Author:
Ruth H Keogh
Author:
Rebecca Cosgriff
Author:
Eleni-Rosalina Andrinopoulou
Author:
Keith G Brownlee
Author:
Siobhán B Carr
Author:
Karla Diaz-Ordaz
Author:
Emily Granger
Author:
Nicholas P Jewell
Author:
Alex Lewin
Author:
Clemence Leyrat
Author:
Daniela K Schlüter
Author:
Maarten van Smeden
Author:
Rhonda D Szczesniak
Author:
Gary J Connett
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