Randomised controlled trials evaluating phenotype targeted biological therapies in severe asthma do not reflect real-world populations and are poorly generalisable to clinical practice, a new study shows.
Comparing data for 342 severe asthma patients within the Wessex Severe Asthma Cohort (WSAC) against comprehensive trial eligibility criteria for 37 randomised controlled trials (RCTs) in severe asthma, the researchers showed that only 9.8% of the patients would have been eligible for enrolment.
Significant numbers of patients were excluded by stipulations for airflow obstruction, bronchodilator reversibility and smoking history, show results published in European Respiratory Journal by consultant respiratory physician Dr Thomas Brown from the Portsmouth Hospitals NHS Trust.
Their study also found that almost 80% of the patients with severe eosinophilic asthma would have been excluded from participating in the Phase III licensing trials of IL-5/5R targeted therapies.
“Our findings show the RCTs in severe asthma lack external validity with the majority of patients excluded by criteria designed to re-confirm ‘arbitrary diagnostic labels’ rather than by biomarker criteria that predict the characteristic or ‘trait’ addressed by the treatment,” say the researchers.
RCTs of type-2 targeted therapies excluded significantly more participants on the basis of diagnostic criteria than those evaluating non-type 2 and non-biological therapies, which the researchers say suggests hyper-selection within this population, further limiting generalisability of the results.
They suggest that avoiding eligibility criteria that are not relevant to the biological trait targeted would allow a more inclusive trial population better generalisable to the subsequent treatment population.
“Failure to adopt an exclusively phenotypic approach to trial inclusion will perpetuate the limited generalisability of effectiveness and health economic evidence used by regulatory bodies. This risks missing opportunities for application of novel therapies and propagating the vast unmet need in severe asthma,” say Dr Brown and colleagues.
“Pragmatic phase III RCTs which better reflect real-world populations and clinical practice may improve external validity and equity of access. This will require engagement between clinicians, licensing authorities, funding bodies and the pharmaceutical industry.”