CFTR and cystic fibrosis: Most RCTs have also excluded CF individuals with severe lung disease (ppFEV1 < 40%), individuals colonized/infected with bacteria associated with rapid lung function decline (e.g. Burkholderia cenocepacia, Mycobacterium abscessus), and individuals with very frequent pulmonary exacerbations requiring continuous or near continuous systemic antibiotics by virtue of requiring clinical stability and no systemic antibiotics 4 weeks prior to randomization and therefore the efficacy and safety of CFTR modulators in these sub-groups remain unclear.