Jørgen Vestbo - University of Manchester

From randomised and controlled to clinical reality

The randomised clinical trial (RCT) is the gold standard for drug evaluation. RCTs provide the core for drug development and subsequent drug approval – often in the form of rigorously designed efficacy trials in carefully selected subjects. In fact, in- and exclusion criteria are often so restrictive that only 1–7% of patients from outpatient clinics would be eligible for trials in asthma and chronic obstructive pulmonary disease (COPD).

Lately, the discrepancy between patients on whom medicines are tested and patients who are subsequently prescribed these drugs has been highlighted. Whereas drug developers want to know what a new drug can do, clinicians managing everyday patients want to know what a drug does do. Particularly with regard to chronic conditions, patients very often have multiple comorbid diseases, and this is generally ignored in efficacy trials where multimorbid patients are usually excluded, in order to have as “clean” a signal as possible. As a consequence, a flurry of mainly register-based pharmacoepidemiological studies have appeared, purporting to study “real-life effects” of drug treatment. Although methodologies exist to counter some of the biases that are invariably present in these observational studies, it will never be possible to fully adjust for the fact that for each individual patient a doctor has made a conscious choice as to why that patient should receive that particular drug that she or he has been prescribed. For this very reason, randomisation is often seen as the essential part of ensuring internal validity in an RCT.

Recently, the results of the COPD part of the Salford Lung Study were published. This is a randomised study carried out in everyday clinical practice with very limited in- and exclusion criteria and minimal study-related intervention, the latter in spite of the fact that the combination inhaled drug under study was not approved when starting the trial. The availability of a joint electronic health record synchronised in real-time between primary and secondary care, as well as a productive collaboration between university academics, general practitioners, visionary data managers, and a brave pharmaceutical company sponsor, made this possible.

The Salford Lung Study is setting a new standard, and, as a consequence, there is no longer a need for fighting over RCTs on the one side, and “real-world studies” on the other. The Salford Lung Study has shown that RCTs are getting real.