Monitoring safety in a phase III real-world effectiveness trial: use of novel methodology in the Salford Lung Study.
BACKGROUND
The Salford Lung Study (SLS) programme, encompassing two phase III pragmatic randomised controlled trials, was designed to generate evidence on the effectiveness of a once-daily treatment for asthma and chronic obstructive pulmonary disease in routine primary care using electronic health records.


OBJECTIVE
The objective of this study was to describe and discuss the safety monitoring methodology and the challenges associated with ensuring patient safety in the SLS. Refinements to safety monitoring processes and infrastructure are also discussed. The study results are outside the remit of this paper. The results of the COPD study were published recently and a more in-depth exploration of the safety results will be the subject of future publications.


RESULTS
The SLS used a linked database system to capture relevant data from primary care practices in Salford and South Manchester, two university hospitals and other national databases. Patient data were collated and analysed to create daily summaries that were used to alert a specialist safety team to potential safety events. Clinical research teams at participating general practitioner sites and pharmacies also captured safety events during routine consultations. Confidence in the safety monitoring processes over time allowed the methodology to be refined and streamlined without compromising patient safety or the timely collection of data. The information technology infrastructure also allowed additional details of safety information to be collected.


CONCLUSIONS
Integration of multiple data sources in the SLS may provide more comprehensive safety information than usually collected in standard randomised controlled trials. Application of the principles of safety monitoring methodology from the SLS could facilitate safety monitoring processes for future pragmatic randomised controlled trials and yield important complementary safety and effectiveness data. © 2016 The Authors Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.
Respiratory Research and Development, GlaxoSmithKline UK Ltd, Uxbridge, UK.
Sue
S
Collier
Global Clinical Safety & Pharmacovigilance, Safety Evaluation and Risk Management, GlaxoSmithKline UK Ltd, Uxbridge, UK.
Catherine
C
Harvey
Respiratory Centre of Excellence, GlaxoSmithKline UK Ltd, Uxbridge, UK.
Jill
J
Brewster
Salford Royal NHS Foundation Trust, Salford, UK.
Nawar Diar
ND
Bakerly
Salford Royal NHS Foundation Trust, Salford, UK.
Hanaa F
HF
Elkhenini
Salford Royal NHS Foundation Trust, Salford, UK.|Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Roxana
R
Stanciu
CK Aspire, Chesterfield, UK.
Claire
C
Williams
CK Aspire, Chesterfield, UK.
Jacqui
J
Brereton
Salford Royal NHS Foundation Trust, Salford, UK.|Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
John P
JP
New
Salford Royal NHS Foundation Trust, Salford, UK.
John
J
McCrae
NHS Salford Clinical Commissioning Group, UK and NIHR Clinical Research Network: Greater Manchester, UK.
Sheila
S
McCorkindale
Global Respiratory Franchise, GlaxoSmithKline UK Ltd, Uxbridge, UK.
David
D
Leather
D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy*; D001592:Benzyl Alcohols / Q000008:administration & dosage / Q000009:adverse effects; D002722:Chlorobenzenes / Q000008:administration & dosage / Q000009:adverse effects; D016208:Databases, Factual; D004338:Drug Combinations; D057286:Electronic Health Records / Q000706:statistics & numerical data*; D006801:Humans; D008498:Medical Record Linkage; D011320:Primary Health Care; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012107:Research Design
D000730:Androstadienes; D001592:Benzyl Alcohols; D002722:Chlorobenzenes; D004338:Drug Combinations; C000611924:fluticasone furoate-vilanterol trifenatate
Salford Lung Study; data linkage; electronic health records; pharmacoepidemiology; pragmatic randomised controlled trial; real-world evidence; safety reporting