Salford Lung Study
Real World Evidence (RWE) studies are increasingly being developed to assess the effectiveness of new drug therapies. For clinical trials to be of value they must reflect a broader, more representative population over a longer timeframe, and provide information on comparators and outcomes that are not normally part of a standard clinical trial protocol.
The Salford Lung Study, was designed to generate evidence on the effectiveness of a Phase III trial of a once-daily treatment, compared to patient’s standard treatment, for Chronic Obstructive Pulmonary Disease (COPD) in routine primary care using patient’s Electronic Health Records (EHR). This study used innovative data collection methods, combining directly extracted routine healthcare data, along with more standard data collection methods for clinical trials.
The broad inclusion criteria and minimal exclusion criteria captured patients with complex co-morbidities who would not normally be selected in Standard Randomised Controlled Trials (RCTs). To maintain the real-world methodology and preserve the external validity, study visits were minimised to resemble routine clinical practice. A total of 2802 patients were randomized to either initiation of therapy or a continuation of their standard treatment. Due to the broad inclusion criteria for this study, it was anticipated that patients would experience more Serious Adverse Events (SAEs) than typically observed in more standard RCTs. Therefore, the safety of patients was of paramount importance due to the limited direct contact and heterogeneous patient population
This presented a significant challenge, which was only overcome by using remote access to primary and secondary care EHR and the development of a bespoke electronic IT infrastructure developed by NorthWest EHealth (NWEH). Robust safety reporting processes were accomplished by the remote monitoring of patients’ EHR. This bespoke IT infrastructure enabled safety events captured in the patient’s EHR to trigger an alert to the research team, which prompted a clinical review of the event. Safety events were then reviewed along with any additional information available to determine whether they met the protocol defined criteria for an SAE. Upon confirmation of an SAE, the clinical research team completed a SAE form as would be expected in standard RCTs.
In comparison to other phase three COPD trials the Salford Lung Study had a higher overall rate of SAEs reported during the study (27% vs 13-24%), which was due to the combination of enrolling patients with complex comorbidities and the method of SAE detection, which sets a precedent for safety monitoring and reporting for future clinical trials.
What the Salford Lung Study has managed to achieve is research methodology as robust as an RCT, whilst managing to bridge the important gap between internal and external validity. This new approach to SAE detection not only provides Sponsors with more accurate and comprehensive safety data for their products, but close to real time safety monitoring improves patient safety and enables faster risk benefit analysis to be performed. Additionally, studies reflecting a broader, more representative patient population have the potential to provide better post-marketing pharmacovigilance than the current conventional reliance on spontaneous event reporting.