Real-World Data and Randomised Controlled Trials: The Salford Lung Study

Abstract

Traditional efficacy double-blind randomised controlled trials (DBRCTs) measure the benefit a treatment produces under near-ideal test conditions in highly selected patient populations; however, the behaviour of patients and investigators in such trials is highly controlled, highly compliant and adherent, and non-representative of routine clinical practice. Pragmatic effectiveness trials measure the benefit a treatment produces in patients in everyday ''real-world'' practice. Ideally, effectiveness trials should recruit patients as similar as possible to those who will ultimately be prescribed the medicine, and create freedom within the study design to allow normal behaviours of patients and healthcare professionals (HCPs) to be expressed. The Salford Lung Study (SLS) was a world-first, prospective, phase III, pragmatic randomised controlled trial (RCT) programme in patients with chronic obstructive pulmonary disease and asthma to evaluate the effectiveness of a pre-licensed medication (fluticasone furoate/vilanterol) in real-world practice using electronic health records and through collaboratively engaging general practitioners and community pharmacists in clinical research. The real-world aspect of SLS was unique, requiring careful planning and attention to the goals of maximising the external validity of the Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.11336171.

Outcomes of patients with solid tumour malignancies treated with first-line immuno-oncology agents who do not meet eligibility criteria for clinical trials

“…To reduce bias while maintaining a high external validity, prospective pragmatic effectiveness RCTs with broad inclusion criteria and minimal exclusion criteria may be an option. One such example is the Salford Lung Chronic Obstructive Pulmonary Disease and Asthma Study, and the application of a similar trial design in oncology trials remains to be seen [31]. Finally, our findings may serve as a moderator in tempering treatment expectations in routine clinical practice and day-to-day physician-patient discussion of treatment options and outcome expectations.…”

Moving towards a Treatable Traits model of care for the management of obstructive airways diseases

“…Yet, further supportive evidence is needed. Here, real-world trials such as the innovative Salford Lung Study, a prospective, phase 3, pragmatic RCT in patients with COPD and asthma [73,74], could be used to evaluate the effectiveness and safety of treatments in a setting reflective of real clinical practice, while maintaining the scientific rigor of RCTs [74]. The next consideration should therefore be how evidence supporting a TTs model of care can be incorporated into current guidelines and future management strategies, following the example of the proposed joint guidelines on chronic asthma from the British Thoracic Society, Scottish Intercollegiate Guideline Network, and National Institute for Health and Care Excellence (https://www.brit-thoracic.org.uk/about-us /pressmedia/2019/bts-sign-and-nice-to-produce-joint-guideline-on-chr onic-asthma).…”

Practical and Relevant Guidelines for the Management of Psoriasis: An Inference-Based Methodology

“…Real-world evidence may better reflect actual clinical environments and patient populations in which medical treatments are used [ 34 ]; however, this data is subject to numerous biases: prescriber bias, enrollment bias, confounder bias, survivor bias, observer bias, assessment bias, lack of precision, collection bias, enrichment bias, and absence of appropriate control populations [ 35 ]. Label restrictions may preclude patients with specific underlying conditions from enrolling in pragmatic studies [ 36 ]. In the case of uncommon conditions, many years of observations or large numbers of patients are required before the number of events in the population of interest provides sufficient power to estimate a sound statistic.…”