Clinical practice requires a complex interplay between experience and training, research, guidelines and judgement, and must not only draw on data from traditional or classical randomised controlled trials (cRCTs), but also from pragmatically designed studies that better reflect real-life clinical practice. To minimise extraneous variables and to optimize their internal validity, cRCTs exclude patients, clinical characteristics and variations in care that could potentially confound outcomes. The result is that respiratory cRCTs often enrol a small, non-representative subset of patients and overlook the important interplay and interactions between patients and the real world, which can effect treatment outcomes. Evidence from real-life studies (e.g. naturalistic or pragmatic clinical trials and observational studies encompassing healthcare database studies and cohort studies) can be combined with cRCT evidence to provide a fuller picture of intervention effectiveness and realistic treatment outcomes, and can provide useful insights into alternative management approaches in more challenging asthma patients. The Respiratory Effectiveness Group (REG), in collaboration with the European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS), is developing quality appraisal tools and methods for integrating different sources of evidence. A REG/EAACI taskforce aims to help support future guideline developers to avoid a one-size-fits-all approach to recommendations and to tailor the conclusions of their meta-analyses to the populations under consideration.