The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in chronic obstructive pulmonary disease.
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SUBMITTER: Bakerly ND
PROVIDER: S-EPMC4558879 | biostudies-literature | 2015 Sep
REPOSITORIES: biostudies-literature
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The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in chronic obstructive pulmonary disease.
Bakerly Nawar Diar ND Woodcock Ashley A New John P JP Gibson J Martin JM Wu Wei W Leather David D Vestbo Jørgen J
Respiratory research 20150904
<h4>Background</h4>New treatments need to be evaluated in real-world clinical practice to account for co-morbidities, adherence and polypharmacy.<h4>Methods</h4>Patients with chronic obstructive pulmonary disease (COPD), ≥ 40 years old, with exacerbation in the previous 3 years are randomised 1:1 to once-daily fluticasone furoate 100 μg/vilanterol 25 μg in a novel dry-powder inhaler versus continuing their existing therapy. The primary endpoint is the mean annual rate of COPD exacerbations; an e ...[more]
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Project description:Novel therapies need to be evaluated in normal clinical practice to allow a true representation of the treatment effectiveness in real-world settings.The Salford Lung Study is a pragmatic randomised controlled trial in adult asthma, evaluating the clinical effectiveness and safety of once-daily fluticasone furoate (100 ?g or 200 ?g)/vilanterol 25 ?g in a novel dry-powder inhaler, versus existing asthma maintenance therapy. The study was initiated before this investigational treatment was licensed and conducted in real-world clinical practice to consider adherence, co-morbidities, polypharmacy, and real-world factors.Asthma Control Test at week 24; safety endpoints include the incidence of serious pneumonias. The study utilises the Salford electronic medical record, which allows near to real-time collection and monitoring of safety data.The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in asthma. Use of patients' linked electronic health records to collect clinical endpoints offers minimal disruption to patients and investigators, and also ensures patient safety. This highly innovative study will complement standard double-blind randomised controlled trials in order to improve our understanding of the risk/benefit profile of fluticasone furoate/vilanterol in patients with asthma in real-world settings.Clinicaltrials.gov, NCT01706198; 04 October 2012.
| S-EPMC4676141 | biostudies-literature
Project description: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.
| S-EPMC8165374 | biostudies-literature
Project description:BackgroundThe Salford Lung Study (SLS) programme, encompassing two phase III pragmatic randomised controlled trials, was designed to generate evidence on the effectiveness of a once-daily treatment for asthma and chronic obstructive pulmonary disease in routine primary care using electronic health records.ObjectiveThe objective of this study was to describe and discuss the safety monitoring methodology and the challenges associated with ensuring patient safety in the SLS. Refinements to safety monitoring processes and infrastructure are also discussed. The study results are outside the remit of this paper. The results of the COPD study were published recently and a more in-depth exploration of the safety results will be the subject of future publications.AchievementsThe SLS used a linked database system to capture relevant data from primary care practices in Salford and South Manchester, two university hospitals and other national databases. Patient data were collated and analysed to create daily summaries that were used to alert a specialist safety team to potential safety events. Clinical research teams at participating general practitioner sites and pharmacies also captured safety events during routine consultations. Confidence in the safety monitoring processes over time allowed the methodology to be refined and streamlined without compromising patient safety or the timely collection of data. The information technology infrastructure also allowed additional details of safety information to be collected.ConclusionIntegration of multiple data sources in the SLS may provide more comprehensive safety information than usually collected in standard randomised controlled trials. Application of the principles of safety monitoring methodology from the SLS could facilitate safety monitoring processes for future pragmatic randomised controlled trials and yield important complementary safety and effectiveness data. © 2016 The Authors Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.
| S-EPMC5347861 | biostudies-literature
Project description:IntroductionThe Salford Lung Studies (SLS) were real-world randomised controlled trials set within UK primary care that assessed the effectiveness and safety of initiating once-daily fluticasone furoate/vilanterol versus continuing usual care in patients with chronic obstructive pulmonary disease or asthma. Data were collected for a relatively short period, limiting the study of long-term outcomes. To broaden the capture of SLS patients' data, we undertook the Extended SLS (Ext-SLS), aiming to better understand the patient disease journey and the effects of treatment in a real-world setting, through collection of patient-level data. Here, we present study design information and the challenges and learnings gathered in creating the Ext-SLS.MethodsThe Ext-SLS was intended to augment the SLS by collecting retrospective and prospective (up to 10 years from consent) primary and secondary care electronic health record (EHR) data and patient questionnaires. After ethics approval, general practitioners (GPs) obtained consent from SLS patients remotely (mean 3.2 years post-SLS completion). To facilitate GPs identifying eligible patients, a novel EHR-based approach flagged SLS patients who were alive and registered with their original GP. An automated system sent consent forms/questionnaires to patients. Medical data were collected via EHRs; primary care data were extracted from GPs' systems whilst secondary care data were sourced from the UK NHS.ResultsOf the 75 GP sites from the SLS, 35 (47%) declined Ext-SLS participation leaving 4158 potentially eligible patients; 1169 (28%) patients were excluded as GPs could not confirm them as SLS participants or due to incapacity. Of 2989 patients invited, 1189 (40%) consented.ConclusionsDeveloping an EHR-based trial extension was achieved, with reasonable consent rates amongst invited patients. The resulting Ext-SLS is a unique and valuable research resource. Leveraging EHRs and technology reduced GP burden, facilitating participation. Initiation of extension studies prior to study close-out may help increase GP and patient participation.
| S-EPMC8344325 | biostudies-literature
Project description:IntroductionChronic obstructive pulmonary disease (COPD) is a progressive disease affecting 3?million people in the UK, in which patients exhibit airflow obstruction that is not fully reversible. COPD treatment guidelines are largely informed by randomised controlled trial results, but it is unclear if these findings apply to large patient populations not studied in trials. Non-interventional studies could be used to study patient groups excluded from trials, but the use of these studies to estimate treatment effectiveness is in its infancy. In this study, we will use individual trial data to validate non-interventional methods for assessing COPD treatment effectiveness, before applying these methods to the analysis of treatment effectiveness within people excluded from, or under-represented in COPD trials.Methods and analysisUsing individual patient data from the landmark COPD Towards a Revolution in COPD Health (TORCH) trial and validated methods for detecting COPD and exacerbations in routinely collected primary care data, we will assemble a cohort in the UK Clinical Practice Research Datalink (selecting people between 1 January 2004 and 1 January 2017) with similar characteristics to TORCH participants and test whether non-interventional data can generate comparable results to trials, using cohort methodology with propensity score techniques to adjust for potential confounding. We will then use the methodological template we have developed to determine risks and benefits of COPD treatments in people excluded from TORCH. Outcomes are pneumonia, COPD exacerbation, mortality and time to treatment change. Groups to be studied include the elderly (>80 years), people with substantial comorbidity, people with and without underlying cardiovascular disease and people with mild COPD.Ethics and disseminationEthical approval has been granted by the London School of Hygiene & Tropical Medicine Ethics Committee (Ref: 11997). The study has been approved by the Independent Scientific Advisory Committee of the UK Medicines and Healthcare Products Regulatory Agency (protocol no. 17_114R). An application to use the TORCH trial data made to clinicalstudydatarequest.com has been approved. In addition to scientific publications, dissemination methods will be developed based on discussions with patient groups with COPD.
| S-EPMC5875594 | biostudies-literature
Project description:INTRODUCTION:In the UK and Ireland, severe and complex obesity is managed in specialist weight management services (SWMS), which provide multicomponent lifestyle interventions to support weight loss, and use of medication if available. Liraglutide 3 mg (LIRA 3 mg) is an effective weight-loss medication, but weight loss in individual patients is variable, and its efficacy has not been assessed in SWMS. This study aims to investigate whether a targeted prescribing pathway for LIRA 3 mg with multiple prespecified stopping rules could help people with severe obesity and established complications achieve ?15% weight loss in order to determine whether this could be considered a clinically effective and cost-effective strategy for managing severe and complex obesity in SWMS. METHODS AND ANALYSIS:In this 2-year, multicentre, open-label, real-world randomised controlled trial, 384 adults with severe and complex obesity (defined as body mass index ?35 kg/m2 plus either prediabetes, type 2 diabetes, hypertension or sleep apnoea) will be randomised via a 2:1 ratio to receive either standard SWMS care (n=128) or standard SWMS care plus a targeted prescribing pathway for LIRA 3 mg with prespecified stopping rules at 16, 32 and 52 weeks (n=256).The primary outcome is to compare the proportion of participants achieving a weight loss of ?15% at 52 weeks with a targeted prescribing pathway versus standard care. Secondary outcomes include a comparison of (1) the weight loss maintenance at 104 weeks and (2) the budget impact and cost effectiveness between the two groups in a real-world setting. ETHICS AND DISSEMINATION:The Health Research Authority and the Medicines and Healthcare products Regulatory Authority in UK, the Health Products Regulatory Authority in Ireland, the North West Deanery Research Ethics Committee (UK) and the St Vincent's University Hospital European Research Ethics Committee (Ireland) have approved the study. The findings of the study will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov-Identifier: NCT03036800.European Clinical Trials Database-Identifier: EudraCT Number 2017-002998-20.
| S-EPMC7044994 | biostudies-literature
Project description:ObjectivesBudesonide/formoterol (BF) Spiromax ® is an inhaled corticosteroid/long-acting ?2-agonist fixed-dose combination (FDC) inhaler, designed to minimise common inhaler errors and provide reliable and consistent dose delivery in asthma and chronic obstructive pulmonary disease (COPD). We evaluated non-inferiority of BF Spiromax after changing from another FDC inhaler, compared with continuing the original inhaler.MethodsPatients with asthma and/or COPD who switched to BF Spiromax were matched (1:3) with non-switchers. Data were obtained from the Optimum Patient Care Research Database and Clinical Practice Research Datalink in the UK. The primary end point was the proportion of patients achieving disease control (using the risk domain control (RDC) algorithm); secondary end points were: exacerbation rate, short-acting ?2-agonist (SABA) use and treatment stability (achieved RDC; no maintenance treatment change). Non-inferiority was defined as having 95% CI lower bound above -10%, using conditional logistic regression and adjusted for relevant confounders.ResultsComparing 385 matched patients (asthma 253; COPD 132) who switched to BF Spiromax with 1091 (asthma 743; COPD 348) non-switchers, non-inferiority of BF Spiromax in RDC was demonstrated (adjusted difference: +6.6%; 95%?CI -0.3 to 13.5). Among patients with asthma, switchers to BF Spiromax versus BF Turbuhaler® reported fewer exacerbations (adjusted rate ratio (RR) 0.76;95% CI 0.60 to 0.99; p=0.044); were less likely to use high daily doses of SABA (adjusted OR 0.71;95% CI 0.52 to 0.98; p=0.034); used fewer SABA inhalers (adjusted RR 0.92;95% CI 0.86 to 0.99; p=0.019); and were more likely to achieve treatment stability (adjusted OR 1.44;95% CI 1.02 to 2.04; p=0.037). No significant differences in these end points were seen among patients with COPD.ConclusionsAmong UK patients with asthma and COPD, real-world use of BF Spiromax was non-inferior to BF Turbuhaler in terms of disease control. Among patients with asthma, switching to BF Spiromax was associated with reduced exacerbations, reduced SABA use and improved treatment stability versus continuing on BF Turbuhaler.
| S-EPMC6224753 | biostudies-literature
Project description:This study investigated patient perceptions, experiences and management of COPD throughout the SLS COPD study. Follow-up interviews were conducted with 400 patients who completed SLS COPD; a mixed-methods approach was used to collect quantitative and qualitative information. Structured interviews using closed-ended questions were conducted with 360 patients, detailing aspects of background/lifestyle information and COPD. Extended interviews containing open-ended questions on perceptions of COPD and quality of life (QoL) in addition to the closed-ended questions were completed by 40 further patients. Participants also completed the Adherence Starts with Knowledge-12 (ASK-12) and the COPD and Asthma Sleep Impact Scale (CASIS) questionnaire. Quantitative data were analysed descriptively; qualitative data were analysed using qualitative description. The participants (n?=?400) were reasonably representative of the SLS COPD population; mean age was 66.2 years. Breathlessness was the most commonly recalled symptom of/associated with COPD (88.5% of patients) and was the symptom that changed the most (improved, 26.8%/worsened, 20.9%) throughout the study. Participants' daily functioning and activities were most affected by symptoms of/associated with COPD, followed by relationships and psychological issues. 66.5% of participants experienced exacerbations, 60.5% of whom reported self-management as their first treatment strategy (taking antibiotics, resting and/or corticosteroids). Qualitative analysis revealed COPD symptoms, breathlessness in particular, to have a significant impact on mobility and in turn QoL. In conclusion, breathlessness was cited in these interviews as the COPD symptom with the greatest impact on participants' daily functioning, activities and self-care. The findings provided significant additional knowledge to the SLS COPD study findings.
| S-EPMC5732268 | biostudies-literature
Project description:BackgroundGiven access barriers to cognitive behavioral therapy for chronic pain (CBT-CP), this pragmatic superiority trial will determine whether a remotely delivered CBT-CP intervention that addresses these barriers outperforms in-person and other synchronous forms of CBT-CP for veterans with musculoskeletal pain.DesignThis pragmatic trial compares an asynchronous form of CBT-CP that uses interactive voice response (IVR) to allow patients to participate from their home (IVR CBT-CP) with synchronous CBT-CP delivered by a Department of Veterans Affairs (VA) clinician. Veterans (n=764; 50% male) with chronic musculoskeletal pain throughout nine VA medical centers will participate. The primary outcome is pain interference after treatment (4 months). Secondary outcomes, including pain intensity, depression symptom severity, sleep, self-efficacy, and global impression of change, are also measured after treatment. Where possible, outcomes are collected via electronic health record extraction, with remaining measures collected via IVR calls to maintain blinding. Quantitative and qualitative process evaluation metrics will be collected to evaluate factors related to implementation. A budget impact analysis will be performed.SummaryThis pragmatic trial compares the outcomes, cost, and implementation of two forms of CBT-CP as delivered in the real-world setting. Findings from the trial can be used to guide future policy and implementation efforts related to these interventions and their use in the health system. If one of the interventions emerges as superior, resources can be directed to this modality. If both treatments are effective, patient preferences and health care system factors will take precedence when making referrals. Implications of COVID-19 on treatment provision and trial outcomes are discussed.
| S-EPMC7734659 | biostudies-literature
Project description:AimDespite the potential benefits of e-health interventions for patients with psychosis, the integration of these applications into the clinical workflow and analysis of their long-term effects still face significant challenges. To address these issues, we developed the ReMindCare app. This app aims to improve the treatment quality for patients with psychosis. We chose to study the app in real world and pragmatic manner to ensure results will be generalizable.MethodsThis is a naturalistic empirical study of patients in a first episode of psychosis programme. The app was purpose-designed based on two previous studies, and it offers the following assessments: (a) three daily questions regarding anxiety, sadness and irritability; and (b) 18 weekly questions about medication adherence, medication side effects, medication attitudes and prodromal symptoms. The app offers preset alerts, reminders and the ability for patients to reach out to their clinicians. Data captured by the app are linked to the electronic medical record of the patient. Patients will use the app as part of their ongoing care for a maximum period of 5 years, and assessments will occur at baseline and at the end of the first, second and fifth years of app use.ResultsRecruitment started in October 2018 and is still ongoing.ConclusionsThe ReMindCare app represents early real-world use of digital mental health tools that offer direct integration into clinical care. High retention and compliance rates are expected, and this will in turn lead to improved quality of assessments and communication between patients and clinicians.
| S-EPMC7891598 | biostudies-literature