Nawar Diar Bakerly

Effectiveness of Fluticasone Furoate–Vilanterol for COPD in Clinical Practice

BACKGROUND Evidence for the management of chronic obstructive pulmonary disease (COPD) comes from closely monitored efficacy trials involving groups of patients who were selected on the basis of restricted entry criteria. There is a need for randomized trials to be conducted in conditions that are closer to usual clinical practice. METHODS In a controlled effectiveness trial conducted in 75 general practices, we randomly assigned 2799 patients with COPD to a once-daily inhaled combination of fluticasone furoate at a dose of 100 μg and vilanterol at a dose of 25 μg (the fluticasone furoate-vilanterol group) or to usual care (the usual-care group). The primary outcome was the rate of moderate or severe exacerbations among patients who had had an exacerbation within 1 year before the trial. Secondary outcomes were the rates of primary care contact (contact with a general practitioner, nurse, or other health care professional) and secondary care contact (inpatient admission, outpatient visit with a specialist, or visit to the emergency department), modification of the initial trial treatment for COPD, and the rate of exacerbations among patients who had had an exacerbation within 3 years before the trial, as assessed in a time-to-event analysis. RESULTS The rate of moderate or severe exacerbations was significantly lower, by 8.4% (95% confidence interval, 1.1 to 15.2), with fluticasone furoate-vilanterol therapy than with usual care (P=0.02). There was no significant difference in the annual rate of COPD-related contacts to primary or secondary care. There were no significant between-group differences in the rates of the first moderate or severe exacerbation and the first severe exacerbation in the time-to-event analyses. There were no excess serious adverse events of pneumonia in the fluticasone furoate-vilanterol group. The numbers of other serious adverse events were similar in the two groups. CONCLUSIONS In patients with COPD and a history of exacerbations, a once-daily treatment regimen of combined fluticasone furoate and vilanterol was associated with a lower rate of exacerbations than usual care, without a greater risk of serious adverse events. (Funded by GlaxoSmithKline; Salford Lung Study ClinicalTrials.gov number, NCT01551758 .).

Obtaining real-world evidence: the Salford Lung Study.

We need to assess clinical treatments in real-life settings outside of randomised controlled trials (RCTs). Pragmatic RCT (pRCT) data can supplement RCTs by providing effectiveness information to support healthcare decisions. Electronic health records can facilitate concurrent safety monitoring and data collection without direct patient contact for large randomised study populations in pRCTs. The Salford Lung Study is the worlds first phase III pRCT in asthma and chronic obstructive pulmonary disease (COPD), which aims to randomise over 7000 patients. This paper describes the hurdles overcome and the enormous effort and resource required to establish this comparative effectiveness study of a prelicence intervention. GlaxoSmithKline protocol HZC115151 Asthma study clinicaltrials.gov registration NCT01706198 COPD study clinicaltrials.gov registration NCT01551758

Using an electronic medical record (EMR) to conduct clinical trials: Salford Lung Study feasibility

BackgroundReal-world data on the benefit/risk profile of medicines is needed, particularly in patients who are ineligible for randomised controlled trials conducted for registration purposes. This paper describes the methodology and source data verification which enables the conduct of pre-licensing clinical trials of COPD and asthma in the community using the electronic medical record (EMR), NorthWest EHealth linked database (NWEH-LDB) and alert systems.MethodsDual verification of extracts into NWEH-LDB was performed using two independent data sources (Salford Integrated Record [SIR] and Apollo database) from one primary care practice in Salford (N = 3504). A feasibility study was conducted to test the reliability of the NWEH-LDB to support longitudinal data analysis and pragmatic clinical trials in asthma and COPD. This involved a retrospective extraction of data from all registered practices in Salford to identify a cohort of patients with a diagnosis of asthma (aged ≥18) and/or COPD (aged ≥40) and ≥2 prescriptions for inhaled bronchodilators during 2008. Health care resource utilisation (HRU) outcomes during 2009 were assessed. Exacerbations were defined as: prescription for oral corticosteroids (OCS) in asthma and prescription of OCS or antibiotics in COPD; and/or hospitalisation for a respiratory cause.ResultsDual verification demonstrated consistency between SIR and Apollo data sources: 3453 (98.6%) patients were common to both systems; 99.9% of prescription records were matched and of 29,830 diagnosis records, one record was missing from Apollo and 272 (0.9%) from SIR. Identified COPD patients were also highly concordant (Kappa coefficient = 0.98).A total of 7981 asthma patients and 4478 COPD patients were identified within the NWEH-LDB. Cohort analyses enumerated the most commonly prescribed respiratory medication classes to be: inhaled corticosteroids (ICS) (42%) and ICS plus long-acting β2-agonist (LABA) (40%) in asthma; ICS plus LABA (55%) and long-acting muscarinic antagonists (36%) in COPD. During 2009 HRU was greater in the COPD versus asthma cohorts, and exacerbation rates in 2009 were higher in patients who had ≥2 exacerbations versus ≤1 exacerbation in 2008 for both asthma (137.5 vs. 20.3 per 100 person-years, respectively) and COPD (144.6 vs. 41.0, respectively).ConclusionApollo and SIR data extracts into NWEH-LDB showed a high level of concordance for asthma and COPD patients. Longitudinal data analysis characterized the COPD and asthma populations in Salford including medications prescribed and health care utilisation outcomes suitable for clinical trial planning.

Risk of Pneumonia with Inhaled Corticosteroid versus Long-Acting Bronchodilator Regimens in Chronic Obstructive Pulmonary Disease: A New-User Cohort Study

Introduction Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD). New-user observational cohort designs may minimize biases associated with previous case-control designs. Objective To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy. Methods Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding. Setting: United Kingdom electronic medical records with linked hospitalization and mortality data (2002–2010). New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up. Outcomes: severe pneumonia (primary) and any pneumonia (secondary). Results Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83). Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively. Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use. There was an apparent dose-related effect, with greater risk at higher daily doses of ICS. There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted. Conclusions The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20–50% increased risk of pneumonia in COPD, which reduced with exposure time. This risk must be weighed against the benefits when prescribing ICS to patients with COPD.

Development of an integrated chronic obstructive pulmonary disease service model in an inner-city region in the UK: initial findings and 12-month results

AIMS To improve the management of chronic obstructive pulmonary disease (COPD) in Salford, UK, and to evaluate the impact of an integrated service model after one year. METHODS A health needs analysis and benchmarking exercise was undertaken in 2007. These activities were used to develop an integrated service model in order to improve the diagnosis and management of COPD and reduce unscheduled hospital admissions and length of stay. RESULTS Following implementation of the model, 811 further patients were diagnosed. Unscheduled hospital admissions for COPD fell from 935 to 840, length of stay was reduced from 8.3 to 7.7 days, and associated costs fell from £1,772, 865 to £1,528,080. The number of patients who completed pulmonary rehabilitation increased from 84 to 143. CONCLUSIONS An integrated COPD service model was successful in increasing diagnosis, reducing hospital admissions and reducing length of hospital stay - in line with the proposed National Strategy for COPD Services in England. It also promoted management according to National Institute of Health and Clinical Excellence (NICE) guidelines.

Effectiveness of fluticasone furoate plus vilanterol on asthma control in clinical practice: an open-label, parallel group, randomised controlled trial

BACKGROUND Evidence for management of asthma comes from closely monitored efficacy trials done in highly selected patient groups. There is a need for randomised trials that are closer to usual clinical practice. METHODS We did an open-label, randomised, controlled, two-arm effectiveness trial at 74 general practice clinics in Salford and South Manchester, UK. Patients aged 18 years or older with a general practitioners diagnosis of symptomatic asthma and on maintenance inhaler therapy were randomly assigned to initiate treatment with a once-daily inhaled combination of either 100 μg or 200 μg fluticasone furoate with 25 μg vilanterol or optimised usual care and followed up for 12 months. The primary endpoint was the percentage of patients who achieved an asthma control test (ACT) score of 20 or greater or an increase in ACT score from baseline of 3 or greater at 24 weeks (termed responders), in patients with a baseline ACT score less than 20 (the primary effectiveness analysis population). All effectiveness analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01706198. FINDINGS Between Nov 12, 2012, and Dec 16, 2016, 4725 patients were enrolled and 4233 randomly assigned to initiate treatment with fluticasone furoate and vilanterol (n=2114) or usual care (n=2119). 1207 patients (605 assigned to usual care, 602 to fluticasone furoate and vilanterol) had a baseline ACT score greater than or equal to 20 and were thus excluded from the primary effectiveness analysis population. At week 24, the odds of being a responder were higher for patients who initiated treatment with fluticasone furoate and vilanterol than for those on usual care (977 [71%] of 1373 in the fluticasone furoate and vilanterol group vs 784 [56%] of 1399 in the usual care group; odds ratio [OR] 2·00 [95% CI 1·70-2·34], p<0·0001). At week 24, the adjusted mean ACT score increased by 4·4 points from baseline in patients initiated with fluticasone furoate and vilanterol, compared with 2·8 points in the usual care group (difference 1·6 [95% CI 1·3-2·0], p<0·0001). This result was consistent for the duration of the study. Pneumonia was uncommon, with no differences between groups; there was no difference in other serious adverse events between the groups. INTERPRETATION In patients with a general practitioners diagnosis of symptomatic asthma and on maintenance inhaler therapy, initiation of a once-daily treatment regimen of combined fluticasone furoate and vilanterol improved asthma control without increasing the risk of serious adverse events when compared with optimised usual care. FUNDING GlaxoSmithKline.

Perseverative negative cognitive processes are associated with depression in people with long-term conditions

Background: Perseverative negative cognitive processes, such as worry, suppression and avoidance of undesirable thoughts, have been linked to persistence and relapse of depression. Such processes could account for poor treatment response though they have received little research attention in people with long-term conditions (LTCs). Method: We conducted a cross-sectional study to investigate the associations of perseverative negative cognitive processes with depression among medical outpatients with LTCs. In 190 patients, we recorded levels of depression (Hospital Anxiety and Depression Scale), worry (Penn State Worry Questionnaire), suppression (White Bear Suppression Inventory) and avoidance of undesirable thoughts (Acceptance and Action Questionnaire). Associations between these constructs were assessed using linear correlation and logistic regression. Results: Both depression (32%) and anxiety (40%) were common in patients recruited. After controlling for demographic and medical confounders, subjects in the top tertile of worry, suppression and avoidance of undesirable thoughts were 20 (95% CIs, 6.6–58.3), 10 (95% CIs, 3.5–25.9) and 22 (95% CIs, 6.0–80.0) times more likely to have possible depression compared to those in the lowest tertile. Conclusions: Prospective research is required to investigate causal relationships between these constructs, and to assess the potential of psychological interventions that target these processes to improve outcomes in patients with LTCs.

Putting patients in control of data from electronic health records

Research using data from electronic health records offers great potential in healthcare, but patients must be informed about how their data are to be used and for what purpose, argue John New and colleagues

The effectiveness of a social marketing model on case-finding for COPD in a deprived inner city population.

AIM To evaluate the effectiveness of a social marketing model on case-finding for COPD in a population with high smoking rates and COPD prevalence. METHODS A two-week marketing campaign was conducted using high visibility posters, leaflets distributed with the local newspaper, and the creation of a free automated COPD information line. The primary outcome measure was the number of newly-diagnosed cases of COPD as a result of the campaign. Secondary outcomes measures were: the number of phone calls to the information line up to four weeks after the end of the campaign; the number of individuals who presented to their general practitioner (GP) for spirometry as a result of the campaign; and responses to a questionnaire sent to members of the public to analyse and assess the visibility and impact of the campaign. RESULTS Ten people came forward to have spirometry performed and all had non-obstructive results. Nine calls were made to the dedicated COPD phone line. 135 out of 400 members of the public (34%) responded to the questionnaire; of these, only 34 (25%) recalled seeing a campaign poster. CONCLUSIONS Posters and leaflets from this campaign were visible but only led to 10 individuals coming forward for spirometry, none of whom had COPD. This form of healthcare marketing was costly and not effective for COPD case-finding in our area.

Effectiveness versus Efficacy Trials in COPD: How study design influences outcomes and applicability.

Guidelines for chronic obstructive pulmonary disease (COPD) management are based largely on results from double-blind randomised controlled trials (RCTs) of efficacy. These trials have high internal validity and test whether a drug is efficacious, but they are conducted in highly selected populations that may differ significantly from patients with COPD seen in routine practice. We compared the baseline characteristics, healthcare use and outcomes between the Salford Lung Study (SLS), an open-label effectiveness RCT, with six recent large-scale efficacy RCTs. We also calculated the proportion of SLS patients who would have been eligible for inclusion in an efficacy RCT by applying the inclusion criteria used in efficacy trials of combination treatments. SLS patients were older, included more females and more current smokers, had more comorbidities (including asthma), and had more often experienced exacerbations prior to inclusion. In the SLS, rates of moderate or severe exacerbations, incidence of overall serious adverse events (SAEs), and SAEs of pneumonia were more frequent. A maximum of 30% of patients enrolled in the SLS would have been eligible for a phase IIIa regulatory exacerbation study. Patients in large COPD efficacy RCTs have limited representativeness compared with an effectiveness trial. This should be considered when interpreting efficacy RCT outcomes and their inclusion into guidelines. Efficacy trials are less representative than effectiveness trials and both are required when evaluating treatments http://ow.ly/plwd30he4a2