Traditional efficacy trials for chronic obstructive pulmonary disease (COPD) have limited relevance to everyday clinical practice and should be changed, according to the authors of a University of Manchester study.
The report details a new method of testing effectiveness of drugs which puts the patients’ clinical experience at the heart of the process.
Led by Professors Jorgen Vestbo and Ashley Woodcock from The University of Manchester’s School of Biological Sciences, the research team conducted an effectiveness and safety trial of fluticasone furoate-vilanterol to manage COPD. Instead of a traditional randomised cohort selected using strict criteria, the new study used specific, representative patients drawn directly from GP practices in which they were receiving care for COPD.
Entitled the Salford Lung Study, the clinical trial recruited 2799 patients with COPD from 75 GP practices in and around Salford in Greater Manchester. The GP practices were involved in ensuring the study not only had access to specific COPD patients but also that the usual clinical care provided by the practices was built into the trials – the study was therefore rooted in a real clinical environment unlike tradition efficacy trial model.
“Our findings challenge the automatic transfer of findings from efficacy studies to clinical guidelines or everyday clinical practice,” said Vestbo. “Involving the GP practices in the Salford Lung Study allowed the team to create an unsupervised environment for the patients, enabling important factors in usual clinical care – such as adherence, frequency of dosing and persistence of good inhaler technique – to rightly influence the trial outcomes.
“This is a major deviation from the traditional model, but one we believe will deliver a more accurate set of results regarding effectiveness and safety of new medicines and treatments.”
The trial proved that broad populations of patients with COPD benefit from treatment with a once-daily treatment regimen of combined fluticasone furoate and vilanterol was associated with a lower rate of COPD exacerbations than usual care, without a greater risk of serious adverse events.
The 2,799 patients in the study were randomly assigned either a combination of fluticasone furoate at a dose of 100 μg and vilanterol at a dose of 25 μg or requested to remain on their usual care regime as identified by their GP.
The year-long study concluded that the fluticasone furoate and vilanterol cohort had an 8.4% less frequent occurrence of moderate to severe exacerbations than the usual care group, leading the team to state that the fluticasone furoate and vilanterol combination was superior to usual COPD care – with no significantly higher risk of serious adverse effects.
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.
Jørgen Vestbo, David Leather, Nawar Diar Bakerly, John New, J Martin Gibson, Sheila McCorkindale, Susan Collier, Jodie Crawford, Lucy Frith, Catherine Harvey, Henrik Svedsater, Ashley Woodcock