Inadequate assessment of adherence to maintenance medication leads to loss of power and increased costs in trials of severe asthma therapy: results from a systematic literature review and modelling study.
Eur Respir J
; 53(5)2019 05.
Article
em En
| MEDLINE
| ID: mdl-30846467
ABSTRACT
Adherence to inhaled maintenance therapy in severe asthma is rarely adequately assessed, and its influence on trial outcomes is unknown. We systematically determined how adherence to maintenance therapy is assessed in clinical trials of "add-on" therapy for severe asthma. We model the improvement in trial power that could be achieved by accurately assessing adherence.A systematic search of six major databases identified randomised trials of add-on therapy for severe asthma. The relationship between measuring adherence and study outcomes was assessed. An estimate of potential improvements in statistical power and sample size was derived using digitally recorded adherence trial data.87 randomised controlled trials enrolling 22â173 participants were included. Adherence assessment was not reported in 67 trials (n=13â931, 63%). Studies that reported adherence used a range of self-report and subjective methods. None of the studies employed an objective assessment of adherence. Studies that reported adherence had a significantly reduced pooled variance in forced expiratory volume in 1â
s (FEV1) compared to those that did not assess adherence s2=0.144â
L2 versus s2=0.168â
L2, p<0.0001. Power to detect clinically relevant changes in FEV1 was significantly higher in trials that reported adherence assessment (mean power achieved 59% versus 49%). Modelling suggests that up to 50% of variance in FEV1 outcomes is attributable to undetected variations in adherence. Controlling for such variations could potentially halve the required sample size.Few trials of add-on therapy monitor adherence to maintenance inhaled therapy, resulting in a greater variance in trial outcomes and inadequate power for determining efficacy.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Antiasmáticos
/
Adesão à Medicação
Tipo de estudo:
Clinical_trials
/
Health_economic_evaluation
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
Eur Respir J
Ano de publicação:
2019
Tipo de documento:
Article