Rationalizing endpoints for prospective studies of pulmonary exacerbation treatment response in cystic fibrosis
Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved..
BACKGROUND: Given the variability in pulmonary exacerbation (PEx) management within and between Cystic Fibrosis (CF) Care Centers, it is possible that some approaches may be superior to others. A challenge with comparing different PEx management approaches is lack of a community consensus with respect to treatment-response metrics. In this analysis, we assess the feasibility of using different response metrics in prospective randomized studies comparing PEx treatment protocols.
METHODS: Response parameters were compiled from the recent STOP (Standardized Treatment of PEx) feasibility study. Pulmonary function responses (recovery of best prior 6-month and 12-month FEV1% predicted and absolute and relative FEV1% predicted improvement from treatment initiation) and sign and symptom recovery from treatment initiation (measured by the Chronic Respiratory Infection Symptom Score [CRISS]) were studied as categorical and continuous variables. The proportion of patients retreated within 30days after the end of initial treatment was studied as a categorical variable. Sample sizes required to adequately power prospective 1:1 randomized superiority and non-inferiority studies employing candidate endpoints were explored.
RESULTS: The most sensitive endpoint was mean change in CRISS from treatment initiation, followed by mean absolute FEV1% predicted change from initiation, with the two responses only modestly correlated (R2=.157; P<0.0001). Recovery of previous best FEV1 was a problematic endpoint due to missing data and a substantial proportion of patients beginning PEx treatment with FEV1 exceeding their previous best measures (12.1% >12-month best, 19.6% >6-month best). Although mean outcome measures deteriorated approximately 2-weeks post-treatment follow-up, the effect was non-uniform: 62.7% of patients experienced an FEV1 worsening versus 49.0% who experienced a CRISS worsening.
CONCLUSIONS: Results from randomized prospective superiority and non-inferiority studies employing mean CRISS and FEV1 change from treatment initiation should prove compelling to the community. They will need to be large, but appear feasible.
| Errataetall: |
CommentIn: J Cyst Fibros. 2017 Sep;16(5):529-531. - PMID 28865768 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society - 16(2017), 5 vom: 20. Sept., Seite 607-615 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
VanDevanter, D R [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Bacterial Agents |
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| Anmerkungen: |
Date Completed 23.05.2018 Date Revised 25.02.2020 published: Print-Electronic CommentIn: J Cyst Fibros. 2017 Sep;16(5):529-531. - PMID 28865768 Citation Status MEDLINE |
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| doi: |
10.1016/j.jcf.2017.04.004 |
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| PPN (Katalog-ID): |
NLM271248858 |
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| 500 | |a CommentIn: J Cyst Fibros. 2017 Sep;16(5):529-531. - PMID 28865768 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Given the variability in pulmonary exacerbation (PEx) management within and between Cystic Fibrosis (CF) Care Centers, it is possible that some approaches may be superior to others. A challenge with comparing different PEx management approaches is lack of a community consensus with respect to treatment-response metrics. In this analysis, we assess the feasibility of using different response metrics in prospective randomized studies comparing PEx treatment protocols | ||
| 520 | |a METHODS: Response parameters were compiled from the recent STOP (Standardized Treatment of PEx) feasibility study. Pulmonary function responses (recovery of best prior 6-month and 12-month FEV1% predicted and absolute and relative FEV1% predicted improvement from treatment initiation) and sign and symptom recovery from treatment initiation (measured by the Chronic Respiratory Infection Symptom Score [CRISS]) were studied as categorical and continuous variables. The proportion of patients retreated within 30days after the end of initial treatment was studied as a categorical variable. Sample sizes required to adequately power prospective 1:1 randomized superiority and non-inferiority studies employing candidate endpoints were explored | ||
| 520 | |a RESULTS: The most sensitive endpoint was mean change in CRISS from treatment initiation, followed by mean absolute FEV1% predicted change from initiation, with the two responses only modestly correlated (R2=.157; P<0.0001). Recovery of previous best FEV1 was a problematic endpoint due to missing data and a substantial proportion of patients beginning PEx treatment with FEV1 exceeding their previous best measures (12.1% >12-month best, 19.6% >6-month best). Although mean outcome measures deteriorated approximately 2-weeks post-treatment follow-up, the effect was non-uniform: 62.7% of patients experienced an FEV1 worsening versus 49.0% who experienced a CRISS worsening | ||
| 520 | |a CONCLUSIONS: Results from randomized prospective superiority and non-inferiority studies employing mean CRISS and FEV1 change from treatment initiation should prove compelling to the community. They will need to be large, but appear feasible | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Spahr, J |e verfasserin |4 aut | |
| 700 | 1 | |a Beckett, V V |e verfasserin |4 aut | |
| 700 | 1 | |a Daines, C L |e verfasserin |4 aut | |
| 700 | 1 | |a Dasenbrook, E C |e verfasserin |4 aut | |
| 700 | 1 | |a Gibson, R L |e verfasserin |4 aut | |
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