Explaining the sex effect on survival in cystic fibrosis:A joint modeling study of UK registry data

Taylor-Robinson, D. and Schlüter, D.K. and Diggle, P.J. and Barrett, J.K. (2020) Explaining the sex effect on survival in cystic fibrosis:A joint modeling study of UK registry data. Epidemiology, 31 (6). pp. 872-879. ISSN 1044-3983

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Abstract

Background: Male sex is associated with better lung function and survival in people with cystic fibrosis but it is unclear whether the survival benefit is solely due to the sex-effect on lung function. Methods: This study analyzes data between 1996 and 2015 from the longitudinal registry study of the UK Cystic Fibrosis Registry. We jointly analyze repeated measurements and time-to-event outcomes to assess how much of the sex effect on lung function also explains survival. These novel methods allow examination of association between percent of forced expiratory volume in 1 second (%FEV1) and covariates such as sex and genotype, and survival, in the same modeling framework. We estimate the probability of surviving one more year with a probit model. Results: The dataset includes 81,129 lung function measurements of %FEV1 on 9,741 patients seen between 1996 and 2015 and captures 1,543 deaths. Males compared with females experienced a more gradual decline in %FEV1 (difference 0.11 per year 95% confidence interval [CI] = 0.08, 0.14). After adjusting for confounders, both overall level of %FEV1 and %FEV1 rate of change are associated with the concurrent hazard for death. There was evidence of a male survival advantage (probit coefficient 0.15; 95% CI = 0.10, 0.19) which changed little after adjustment for %FEV1 using conventional approaches but was attenuated by 37% on adjustment for %FEV1 level and slope in the joint model (0.09; 95% CI = 0.06, 0.12). Conclusions: We estimate that about 37% of the association of sex on survival in cystic fibrosis is mediated through lung function.

Item Type:
Journal Article
Journal or Publication Title:
Epidemiology
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700/2713
Subjects:
ID Code:
148640
Deposited By:
Deposited On:
02 Nov 2020 16:55
Refereed?:
Yes
Published?:
Published
Last Modified:
23 Nov 2020 15:16