The Salford Lung Study: a pioneering comparative effectiveness approach to COPD and asthma in clinical trials

Abstract

The Salford Lung Study (SLS) of patients with asthma and chronic obstructive pulmonary disease (COPD) is a practical, community-based, randomized, open-label pragmatic study on the efficacy and safety of the once-daily dry powder inhaler that combines the inhaled corticosteroid fluticasone furoate (FF) with the long-acting beta2 agonist vilanterol (VI). The asthma component of the SLS is not yet reported but the COPD component, done over a 12-month period, found a statistically significant 8.4% reduction in COPD exacerbations when compared to usual care. No differences in adverse events, including serious adverse events and pneumonia, were noted. The importance of real-world findings, such as those found in the SLS COPD trial with inhaled FF/VI, is discussed in comparison to classical randomized controlled trials (RCTs) with inhaled FF/VI in COPD patients. The real-world, community-based pragmatic RCT like the SLS provides additional generalizable data with direct clinical applicability and potential usefulness in the development of practice guidelines. The results from the SLS, along with those of large and small RCTs, are supportive of the use of once-daily FF/VI in COPD maintenance therapy.

GOLD Reports on Chronic Obstructive Pulmonary Disease (COPD): Evolutions, Revolutions and Controversies

“…But despite all efforts to decrease the risk of bias through matching and adjustments, there is always a risk of hidden residual confounding that prevents from qualifying these studies as "high-level evidence". Pragmatic RCTs could be a solution to this dilemma and some attempts have been made recently 57 , but progresses remain necessary to improve the reliability and understandability of their results.…”

Innovation in Regulatory Science Is Meeting Evolution of Clinical Evidence Generation

“…The need to seize opportunities in the areas of greatest unmet need—including domains lacking an established pathway to regulatory approval—has pressed pharmaceutical companies to modify their established clinical trial designs and to experiment with entirely novel trial designs. Innovative trial designs have been previously categorized and fall into three broad categories: biomarker‐led design, adaptive design, and cohort‐led design ( Table ) . Biomarker‐led designs incorporate a genetic or other biomarker to either stratify patients or to select the best treatment for the patient based on their genetic profiling (e.g., umbrella, basket trials).…”

“…GlaxoSmithKline's Salford lung study provides one example of how pharmaceutical companies are trying to use pragmatic trials. The Salford lung study was an open‐label, randomized, real‐world trial comparing a once‐daily inhaler containing the long‐acting beta2 agonist vilanterol and the inhaled corticosteroid fluticasone furoate against existing therapy . The trial design included relatively broad inclusion criteria and compared the fluticasone furoate/vilanterol combination inhaler against patients’ existing therapy, with the goal of producing results that can be more confidently generalized to real‐world medical practice and patient populations.…”

“…( c ) Number of approved submissions that included studies with patient‐reported outcomes and/or real‐world data. Source data: ClinicalTrials.gov, FDA , Bhatt et al ., Zang et al ., TrialTrove, Bateman et al ., Yelland et al ., Albertson et al ., and Batten Disease News…”

Efficacy and safety of once-daily fluticasone furoate/vilanterol (FF/VI) versus twice-daily inhaled corticosteroids/long-acting β2-agonists (ICS/LABA) in patients with uncontrolled asthma: An open-label, randomized, controlled trial

“…Due to the long duration of action of the monocomponents [16][17][18][19], the fixed-dose combination of the inhaled corticosteroid fluticasone furoate (FF) with the LABA vilanterol (VI) is approved for once-daily use at doses of 100/25 or 200/25 μg in more than 70 countries, including Europe (in adults and adolescents aged ≥12 years) and the USA (in adults), for the maintenance treatment of asthma [19][20][21]. Extensive reviews have summarized data from multiple randomized controlled trials, which support the use of inhaled dry-powder FF/VI as maintenance treatment in patients with asthma who are not well controlled on an ICS alone [19,[22][23][24][25]. In addition, real-world data from the Salford Lung Study (SLS), a large study conducted in everyday clinical practice, demonstrated improved asthma control without an increased risk of serious adverse events in those who initiated treatment with FF/ VI compared with those who continued usual care [26].…”