The innovative and trustworthy use of routinely collected healthcare data has enabled a UK company, NorthWest Ehealth, experts in the use of this technology, to become the only organisation in the world to have evaluated the safety and effectiveness of a pre-license medicine in a real-world setting. Its technology can support the whole clinical trial lifecycle and enable more effective feasibility, economic modelling, recruitment, real-time safety monitoring and data analytics.
‘The use of electronic healthcare records for clinical research is helping change the clinical trial landscape’
The EHR and future of clinical trials
The use of electronic healthcare records (EHRs) for clinical research is helping change the clinical trial landscape to be more relevant to everyday practice. Use of the EHR can help in the development of study design and to better understand the trial population and follow-up. The potential data set extends well beyond the period of the clinical trial, which allows a much longer-term assessment of the evolution of chronic conditions and the impact of interventions.
Salford Lung Studies
The Salford Lung Studies have demonstrated how EHRs can be used to support clinical trials. Salford is a community served mainly by a single hospital with an established EHR system that connects primary and secondary care. This setting allowed patients to be observed unobtrusively for effectiveness and safety monitoring, blended into routine clinical care.
The first Salford Lung Study was designed to evaluate the effectiveness and safety of the once-daily inhaled combination of fluticasone furoate and vilanterol (fluticasone furoate–vilanterol) as compared with existing maintenance therapy (usual care) in a large, real-world population of patients with chronic obstructive pulmonary disease (COPD) in conditions of normal care.1 It was a prospective, 12-month, open-label, parallel-group, randomised trial conducted in 77 general practices in Salford and South Manchester. The second Salford Lung Study assessed the same product in asthma with a similar study design.2 Over 7,200 patients were monitored in near real-time for safety and outcomes using city-wide linked EHRs.
Following screening of medical records, patients were asked it they would like to participate in the study and gave written informed consent if they met the inclusion and exclusion criteria. They were randomly assigned to receive the study inhaler or to continue their usual maintenance therapy within the following two months.
The use of existing EHR data was maximised to fulfil protocol and analysis requirements, including total cost of care, care pathways and adherence. The key investigators in the trial were general practitioners, who could choose appropriate therapy according to their clinical opinion. Treatments were dispensed by community pharmacies in the usual way. Patients could switch from the study treatment to usual care, but patients in the usual-care group were not permitted to switch to the study inhaler group.
Importantly, the trial was designed in collaboration with regulators and payers. To preserve the real-world nature of the trial, the patients’ experience was as close to everyday clinical practice care as possible. Contact with trial staff was minimised. If at months 3, 6, and 9, patients had not had any contact with their general practice within the previous eight weeks, then they were contacted by telephone by a trial team member to assess any serious adverse events or non-serious adverse drug reactions; there was no additional intervention at these assessments. At 12 months, trial staff met the patients to make a final assessment of outcomes. Thus, most patients had contact with trial staff only at recruitment, at the baseline visit, and at 12 months.
The safety alerting and reporting system in the Salford Lung Studies
The amount of manually entered data was minimised with primary and secondary care connected through the EHR. This was integrated with a new data recording system, ConneXon, that enabled the collection of a trial-relevant dataset with the highest standards of data management and validation – more than three million lines of data were collected for all the effectiveness and safety outcomes.
Patients were monitored remotely with the use of the EHR for the early detection of safety events. This system was adjusted to ensure that the right amount of data was transmitted to the authorities, as initially the wealth of ‘real-time’ data that could be collected regarding adverse events was overwhelming. A time-delayed submission of adverse event reports was decided upon in order to allow the full resolution and investigation of adverse events to be included in one report.
The Salford Lung Studies challenge the automatic transfer of findings from efficacy studies to clinical guidelines or everyday clinical practice. For any new treatment, it is essential to carry out safety and efficacy randomised, controlled trials. But these are carried out in carefully selected populations, which exclude patients with co-existing conditions. In addition, the frequent face-to-face monitoring seen in randomised, controlled trials ensures high adherence to therapy. Trials conducted using EHRs can be conducted in a largely unsupervised population, which allows important factors in usual clinical care, such as adherence, frequency of dosing, and persistence of good inhaler technique, to come into play.
Articles in the handbook
2. National Institute for Health Research
4. Recent research at the Institute of Cardiovascular Medicine and Science
5. Clinical trials in the UK from a commercial perspective
6. Brexit: threat or opportunity
7. How to initiate a clinical trial in the UK
8. Useful organisations