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A1402 - Inhaled Corticosteroid (ICS) and Long Acting Beta-Adrenoceptor Agonist (LABA) Therapy Adherence Reporting and Monitoring in Clinical Trials of Severe Adult Asthma Drug Treatments: A Systematic Review
Author Block: M. Mokoka1, M. J. McDonnell2, S. Cormican1, F. Boland3, F. Doyle4, R. W. Costello5; 1Clinical Research Centre, Royal College of Surgeons, Dublin, Ireland, 2Respiratory Medicine, Galway University Hospitals, Galway, Ireland, 3Data Science Centre, Royal College of Surgeons, Dublin, Ireland, 4Psychology, Royal College of Surgeons, Dublin, Ireland, 5Medicine, Royal College of Surgeons, Dublin 9, Ireland.
Rationale
Identifying refractory asthma in clinical practise and in the conduct of clinical trials is crucial because it ensures that appropriate patients eligible for expensive potential add-on therapies are enrolled in the clinical trials. Adherence monitoring during the conduct of clinical trials allows accurate sample size calculations, adjusting for suboptimal adherence and ensuring true treatment effects sizes. We hypothesised that adherence to inhaled corticosteroids (ICS) and long-acting beta-agonist (LABA) is under-assessed and under-reported in clinical trials of add-on drug treatment interventions in adolescent and adult patients with severe asthma.
Methods
A systematic electronic literature search of six major databases including the Cochrane Central Register of Controlled Trials was performed to identify randomised controlled trials (RCTs) of asthma drug treatment interventions conducted in severe adolescent and adult asthma patients taking ICS alone or in combination with LABA therapy (ICS/LABA). Identified studies were reviewed concerning characteristics of the trial and the intervention; reporting and monitoring of adherence to ICS/LABA and the relationship between measuring adherence and study outcomes was assessed. Studies eligible for inclusion were assessed for quality using the Cochrane methodology for assessing risk of bias. This systematic review has been registered on PROSPERO; registration number CRD42015029611.
Results
8686 articles were identified, 4350 duplicate records were excluded, 4336 records were screened for eligibility of which 4007 were excluded and 329 full-texts articles were assessed for eligibility. 88 RCTs were included and underwent data extraction and quality scoring. Of these, 20 RCTs reported adherence to ICS or ICS/LABA therapy. Measures of adherence used included; self-report, n=12; self-report and inhaler technique, n=1; inhaler technique, n=1; inhaler technique and fractional exhaled nitric oxide, n= 1; dose counting, n=1; electronic monitoring, n=1; prescription records, n=1; weighing inhaler canister, n=1; assumption that primary respiratory physician had assessed adherence, n=1; and method of adherence assessment not reported but measure of adherence included in n=2 studies. A placebo-effect meta-analysis was conducted for available data in the primary studies. The overall pooled mean post bronchodilator forced expiratory volume in one second was 0.08 litres/second (95% CI; 0.00, 0.22), whilst the overall mean difference in peak expiratory flow rate was 6.19 litres/minute (95% CI;-11.10, 23.48) and the pooled mean asthma quality of life was 0.56 (95% CI; 0.28, 0.85).
Conclusion
Adherence monitoring to standard therapy in clinical trials is essential. Future studies should use standardized objective methodology to assess adherence and inhaler technique.