ABSTRACT
Background: Innovative information techniques are increasingly used to perform federated analyses in real-world studies. Whether these techniques are suitable for harmonizing patient data from non-standardized registries and evaluating treatment outcomes needs further evidence. Aim(s): To standardize patient-level registry data from SHARP (Severe Heterogeneous Asthma Registry Patientcentred) and evaluate the effectiveness of mepolizumab on frequent (>=2/yr) exacerbations in patients with severe asthma. Method(s): We standardized data from 5,871 adults with severe asthma in 10 European countries using the OMOP Common Data Model (www.ohdsi.org). Patients who had taken mepolizumab >=1 yr (2016-2021) and had exacerbation data available were included. Changes in odds of >=2 exacerbations/yr were evaluated. Result(s): Of 2,109 patients who initiated mepolizumab 563 met inclusion criteria. Analysis showed a reduction of having >=2 (vs 0-1) annual exacerbations after 1 yr mepolizumab therapy: OR (95%CI) 0.18 (0.13-0.25)[N=369] pre and 0.08 (0.05-0.13)[N=194] during the COVID-19 pandemic (Fig). Conclusion(s): By harmonizing non-standardized, patient-level registry data and applying federated analysis we demonstrated that mepolizumab reduced asthma exacerbations, consistent with current knowledge. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof way. (Figure Presented).
ABSTRACT
Aims: The COVID-19 pandemic caused significant disruption to clinical research, reducing the ability of patients to visit clinical sites for face-to-face visits. This has accelerated the trend of initiating decentralised research, where patients complete some, or all, of the study procedures at home. These studies have potential upsides of greater convenience for the patient and possibly lower costs for sponsors. Conversely de-centralised trials bring the challenge of ensuring rigour and high levels of completion when administering PROs via an electronic PRO (ePRO) solution. The methodology and compliance levels of an de-centralised observational validation study are presented. Method(s): A 10-week de-centralised, observation study was completed in US, UK and Germany to assess the psychometric properties of the Asthma Daytime and Night-time Symptoms Diaries (ADSD/ANSD). Following IRB review and approval, multiple PROs were administered via a Bring your Own Device ePRO solution, including the ADSD/ANSD, SGRQ, EQ-5D, PROMIS Sleep Disturbance 8a. Fair-market value honoraria were phased over the period of the study. PRO compliance was monitored throughout the study, with pre-programmed scheduled reminders and escalating triggered alerts implemented to facilitate compliance. Result(s): 235 moderateto-severe asthma patients have been recruited. An interim assessment of the compliance indicates that over 90% of patients completed at least 4 days of daily data each week. The end of study overall compliance will be analysed and stratified by days completed per week. The frequency and distribution pattern of reminders will be assessed. Compliance patterns by country, demographics and baseline characteristics will be reported. Lessons learned will be discussed in detail to inform best practice. Conclusion(s): Decentralised trials are increasing in popularity. PROs are progressively being viewed as fundamental to Patient Focused Drug Development. The interim results from this ongoing study demonstrate that high levels of PRO completion are possible in a decentralised, BYOD study, with numerous and variable PRO administration frequency. This highlights the importance of well designed, patient friendly research protocols, in ensuring high levels of patient compliance in remote settings. On completion of study, compliance and compliance reminder metrics will be presented, stratified by baseline and demographic characteristics.