title: Population model of longitudinal FEV1 data in asthmatics: meta-analysis and predictability of placebo response.
abstract: Asthma is an obstructive lung disease where the mechanism of disease progression is not fully understood hence motivating the use of empirical models to describe the evolution of the patient's health state. With reference to placebo response, measured in terms of FEV1 (Forced Expiratory Volume in 1 s), a range of empirical models taken from the literature were compared at a single trial level. In particular, eleven GSK trials lasting 12 weeks in mild-to-moderate asthma were used for the modelling of longitudinal placebo responses. Then, the chosen exponential model was used to carry out an individual participant data meta-analysis on eleven trials. A covariate analysis was also performed to find relevant covariates in asthma to be accounted for in the meta-analysis model. Age, gender, and height were found statistically significant (e.g. the taller the patients the higher the FEV1, the older the patients the lower the FEV1, and females have lower FEV1). By truncating each trial at week 4, the predictive properties of the meta-analysis model were also investigated, showing its ability to predict long-term FEV1 response from truncated trials. Summarizing, the study suggests that: (i) the exponential model effectively describes the placebo response; (ii) the meta-analysis approach may prove helpful to simulate new trials as well as to reduce trial duration in view of its predictive properties; (iii) the inclusion of available covariates within the meta-analysis model provides a reduction of the inter-individual variability.
authors.affiliation: Department of Industrial and Information Engineering, University of Pavia, Via Ferrata 1, 27100 , Pavia, Italy, eleonora.marostica@unipv.it.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Marostica
authors.forename: Alberto
authors.initials: A
authors.lastname: Russu
authors.forename: Shuying
authors.initials: S
authors.lastname: Yang
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Nicolao
authors.forename: Stefano
authors.initials: S
authors.lastname: Zamuner
authors.forename: Misba
authors.initials: M
authors.lastname: Beerahee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D002986:Clinical Trials as Topic; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D015990:Placebo Effect; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D055815:Young Adult