Outcomes and endpoints reported in studies of pulmonary exacerbations in people with cystic fibrosis: A systematic review

Abstract

Background: There is no consensus about which outcomes should be evaluated in studies of pulmonary exacerbations in people with cystic fibrosis (CF). Outcomes used for evaluation should be meaningful; that is, they should capture how people feel, function or survive and be acknowledged as important to people with CF, or should be reliable surrogates of those outcomes. We aimed to summarise the outcomes and corresponding endpoints which have been reported in studies of pulmonary exacerbations, and to identify those which are most likely to be meaningful.

Methods: A PROSPERO registered systematic review (CRD42020151785) was conducted in Medline, Embase and Cochrane from inception until July 2020. Registered trials were also included.

Results: 144 studies met the inclusion criteria. A wide range of outcomes and corresponding endpoints were reported. Death, QoL and many patient-reported outcomes are likely to be meaningful as they directly capture how people feel, function or survive. Forced expiratory volume in 1-second [FEV₁] is a validated surrogate of risk of death and reduced QoL. The extent of structural lung disease has also been correlated with lung function, pulmonary exacerbations and risk of death. Since no evidence of a correlation between airway microbiology or biomarkers with clinically meaningful outcomes was found, the value of these as surrogates was unclear.

Conclusions: Death, QoL, patient-reported outcomes, FEV₁, and structural lung changes were identified as outcomes that are most likely to be meaningful. Development of a core outcome set in collaboration with stakeholders including people with CF is recommended.

Keywords: Cystic fibrosis; Endpoint measure; Outcome assessment; Outcome variables; Patient reported outcome measures; Pulmonary exacerbation.