A great article in BioWorld explaining the benefits of e-sourced data in clinical research.
Ignite Data is working with its integrated record partner in the UK to find all kind of different benefits to patients using the technologies applied in the Salford Lung Study:
Glaxosmithkline plc has reported statistically significant results in what it claims is the world’s first real-world randomized control trial, the Salford lung study (SLS).
The trial showed that patients taking its new treatment for chronic obstructive pulmonary disease (COPD), Relvar/Ellipta (fluticasone furoate/vilanterol), were 8.4 percent (p=0.025) less likely to suffer a moderate or severe exacerbation than patients receiving “usual care,” including inhaled corticosteroids, long-acting muscarinic antagonists (LAMA), long-acting beta2-agonists (LABA) and inhaled corticosteroids, administered as monotherapy, dual or triple combinations.
The results were presented at the European Respiratory Congress in London and have been published in the New England Journal of Medicine.
In contrast to a formal randomized controlled trial with multiple grounds for exclusion, the 2,802-patient open-label SLS recruited anyone older than 40 with COPD who had suffered an exacerbation in the previous three years and who was being treated at any one of 80 primary care centers in the city of Salford in northwest England.
All COPD patients in the city who met the criteria were invited to take part. Recruits had co-morbidities including heart disease, cancer and diabetes.
The all-comers trial was initiated by GSK in response to the pressure all pharma companies are coming under to demonstrate the value new treatments offer to health care systems as early as possible in the life cycle of a drug.
In addition to being open to all, the trial reflected real life by minimizing interventions. Rather than being required to attend specialist centers for review, patients were recruited by their general practitioners and tracked via their electronic health records (EHRs).
In Salford, EHRs are integrated and can be accessed by both general practitioners in primary care and hospital clinicians in the emergency room and outpatient clinics. Once patients were recruited to the trial and randomly assigned to Relvar/Ellipta, or to remain on usual care, their EHRs were tagged and all subsequent interactions with health care providers monitored.
During the study physicians were allowed to modify or switch treatment at any point as would happen in normal clinical practice, the only exception being a switch from usual care to Relvar/Ellipta.
When SLS started in 2012, Relvar/Ellipta was not licensed in the U.K. Now, just two years after U.K. approval, GSK has 12-month treatment data confirming the effectiveness of the product in a real-world setting, compared to usual care with corticosteroids and compared to patients who were taking another corticosteroid/LABA combination therapy.
Neil Barnes, global medical head of GSK’s respiratory franchise, said the results “provide robust evidence that will enable the health care community to begin understanding how the choice of COPD treatment can significantly influence patient outcomes.”
SLS involved a large-scale collaboration across hospitals, general practitioners, pharmacies and health informatics experts at Manchester University. The trial used bespoke software developed by Northwest Electronic Health, a not-for-profit set up by the university and Salford hospital, which integrates the EHRs of patients across all interactions with the health care service.
That allowed monitoring of patients in near real time, but with minimum intrusion.
“This is not about big data,” said Martin Gibson, chief executive of Northwest Electronic Health. “This is about understanding the way patients interact with medications in their everyday lives.”
A NEW APPROACH
The real-world, yet randomized control design used in SLS represents a new approach to conducting clinical trials. The study methodology could be used in other trials, not only in Salford, but anywhere else in the world where EHRs are in use, according to the clinical partners in SLS.
For the primary effectiveness analysis, the patient population was restricted to patients who had exacerbated in the previous 12 months prior to randomization, rather than in the previous three years prior to randomization.
While delivering statistical significance on the primary endpoint, there were no differences between Relvar/Ellipta and usual care on secondary endpoints, including the time to the first moderate or severe exacerbation and the rate of severe exacerbations, the rate of secondary health care contacts and COPD-related primary care contacts.
A moderate exacerbation is defined as a patient receiving an exacerbation-related prescription to treat an acute worsening of COPD symptoms, of oral corticosteroid and/or antibiotic with or without contact with a health care provider, not requiring hospitalization.
A severe exacerbation is defined as an exacerbation-related hospitalization required as a direct result of an acute worsening of symptoms of COPD, or a prolonged hospitalization as a result of a COPD exacerbation.
In the COPD assessment test, which measures the impact of disease on health status, 45 percent of patients in the Relvar/Ellipta arm improved their scores by a clinically relevant two or more points, compared to 36 percent in the usual care group.
The incidence of serious adverse events was similar, at 29 percent in Relvar/Ellipta and 27 percent in usual care.
In the formal clinical trials of Relvar/Ellipta that led to the regulatory approval of the product, there was an increase in the incidence of pneumonia in COPD patients in the active arms. SLS demonstrated the risk of pneumonia was similar in Relvar/Ellipta, at 7 percent, to usual care, where the incidence was 6 percent.
That finding enabled GSK to comply with a post-authorization measure requested by the EMA.
The all-comers, open-label approach improved recruitment, with up to 200 patients per month joining once the study was up and running. In another trial of Relvar/Ellipta in asthma, 4,236 patients have been recruited.
Patient safety was increased through the near real-time monitoring by a central clinical group, which reviewed all instances of patients attending health care facilities. The resulting data offer breadth and depth, providing information on all primary, secondary and pharmacy EHR data for participants both before and during their time on the trial.
Iain Buchan, professor of public health informatics at Manchester University, said SLS “has broken the mold” of randomized control trials by harnessing an approach to health care data and computing that “focuses on populations, not hospitals or other organizations.”