Reporter, European Medical Journal
In May 2016, the results of the Salford Lung Study (SLS) were first announced. The findings of the study showed that patients with chronic obstructive pulmonary disease (COPD) who received the drug Relvar (a fluticasone furoate-vilanterol combination) over a 12-month period had fewer exacerbations than COPD patients who maintained their usual care. To measure and record these findings, the collaborative network that conducted the SLS implemented a data system linking together patient data from primary care, secondary care, and pharmacy visits. In joining together primary and secondary data, the SLS signalled an important event for bringing clinical research a step closer to ‘real-world’ data.
The SLS was a year-long, Phase IIIb, open label, pragmatic randomised controlled trial (pRCT) that took place in 75 general practices in and around the City of Salford in the North of England. Primarily, it was an efficacy study but one designed in such a way it could capture how this particular medicine would behave in everyday clinical practice, something that more conventional methods might fail to do. Dr David Leather, Global Medical Affairs Leader in the Respiratory Franchise at GlaxoSmithKline (GSK), the company that sponsored the SLS, explained that a double-blind randomised controlled trial is the typical design for an efficacy study. However, this approach can involve strict controls, a wide exclusion criterion, and encourage adherence to the medication. “It’s quite an artificial setting,” he said, “efficacy trials are essential, we need to have them, but they do not actually tell you how a medicine may behave in everyday clinical practice.” So, instead, the recruitment criteria for SLS was made broader and more inclusive. To be enrolled, patients were required to have a COPD diagnosis determined by their general practitioner (GP), be receiving a maintenance treatment, and have had at least one exacerbation in the past 3 years. “Those were essentially the inclusion criteria,” Dr Leather explained, “so very, very broad compared to ‘normal’ studies.”
In their efforts to test whether the number of exacerbations experienced by ‘ordinary people’ with COPD could be reduced by Relvar, 2,802 patients in Salford and the surrounding area were enrolled into the study after being asked by their GP to take part. To minimise intrusion into the study and avoid any difference between the patients receiving usual care and those receiving Relvar, information was extracted from health records in primary and secondary care. The data were then collated into a database designed by NorthWest EHealth (NWEH), a not-for-profit organisation formed as a partnership between the NHS and the University of Manchester, Manchester, UK. Patient behaviours and the effects of Relvar could then be monitored without the need for regular contact between the trial staff and patients. The exceptions for interaction were at recruitment, the baseline visit, and for a final assessment at the end of the trial. A safety protocol was also implemented so that telephone contact would be made to assess whether any serious adverse events had been experienced by a patient who had not been in recent contact with their general practice at months 3, 6, and 9.
Patients were also able to collect their medicines as they normally would, including picking it up from their local pharmacy. “That meant we had to recruit every single pharmacist in the city and the surrounding areas and train them in good clinical practice,” Dr Leather explained. “This had never been done before and meant we trained about 3,000 people in Good Clinical Practice (GCP) to enable that to happen.” He also explained that in order to guide the collaboration between the 132 pharmacy companies operating in the area, GSK created a Pharmacy Steering Group, chaired by Scientific Director in the GSK Respiratory Franchise, Linda Stevens. Part of its remit was to ensure the pharmacy staff involved in the research received the GCP training and that they also understood and were able to carry out the Standard Operative Procedure (SOP). As a result, pharmacy data could be incorporated into the linked database system, allowing researchers to easily monitor whether patients collected their prescribed medication.
The GSK team also provided support and training to general practitioners whose responsibility it was to extend the invitations for eligible patients to take part in the SLS. GSK brought in and allocated teams of research-experienced nurses to aid in the recruitment process. This support was important as there was an awareness that the environments in which the study was being carried out included people who had never undertaken this sort of research before. According to Dr John New, the Chief Clinical Officer at NWEH, and part of the lead team for the SLS, some GPs were very research naïve which showed in their concerns early-on about recruiting patients. “They were worried that the General Medical Council would strike them off if they wrote to the patient twice asking them to take part in the study,” said Dr New, “so having the research nurses being able to help them was very important and useful.” Training was given to the GPs in how to obtain consent from the patients and a majority of them did make contact with the patients themselves. This was felt to have contributed to the success seen in the numbers or patients recruited and to the small number who subsequently dropped out over the course of the study (a rate of 8%, according to Dr Leather). “The people of Salford do not tend to move around,” Dr New said, “so many of these people had a GP there for 20 years and they really trust the GP, it’s not some external researcher who they had never ever seen before. This is why I think we got such a high interest in the study.”