Safety data in randomised real-world evidence studies: Salford Lung Study learnings

Abstract

Evidence to support clinical decision making must be based on safety data that have been captured, analysed and interpreted in a robust and reliable way. Randomised real-world evidence (RRWE) studies provide the opportunity to evaluate the use of medicines in patients and settings representative of routine clinical practice. However, elements that underpin the design of RRWE studies can have a significant impact upon the analysis, interpretation and implications of safety data. In this narrative review, we use data from the Salford Lung Study; two prospective, 12-month, open-label, parallel-group, phase III randomised controlled trials conducted in primary care in the UK; to highlight the importance of capturing treatment modifications when attempting to evaluate safety events according to actual treatment exposure. We demonstrate that analysing safety data by actual treatment received (i.e. accounting for the treatment modifications that occur routinely in the primary care setting) provides additional insight beyond analysing according to randomised treatment strategy only. It is therefore proposed that understanding of safety data from RRWE trials can be optimised by analysing both by randomised group and by actual treatment received.

FIGURE 1

Overview of design of Salford Lung Study (SLS) COPD and SLS asthma groups. ^#: randomisation stratified by presence/absence of a COPD exacerbation in the previous 12 months and baseline intended COPD maintenance therapy. ⁺: randomisation stratified by baseline Asthma Control Test (ACT) score (≥20, 16–19, ≤15) and baseline intended asthma maintenance therapy. AQLQ: Asthma Quality of Life Questionnaire; BD: bronchodilator; CAT: COPD Assessment Test; EHR: electronic health record; FF/VI: fluticasone furoate/vilanterol; GP: general practitioner; ICS: inhaled corticosteroid; LABA: long-acting β₂-agonist; LAMA: long-acting muscarinic antagonist; MARS-A: Medical Adherence Report Scale for Asthma; UC: usual care; WPAI: asthma: Work Productivity and Activity Impairment questionnaire.

FIGURE 2

Treatment modifications by randomised treatment group during the 12-month study period in Salford Lung Study (SLS) COPD and SLS asthma groups. A key design characteristic of the SLS was the ability for patients’ treatment to be modified during the 12-month study period. Treatment modifications included a change in class of medication, an increase/decrease in medication dose or a change in brand of medication. Patients who initiated treatment with fluticasone furoate/vilanterol (FF/VI) were permitted to modify treatment to usual care (UC); however, patients who initiated treatment with UC were not permitted to initiate treatment with FF/VI. ^#: total study population (intent-to-treat).