Affiliations: [a] Case Western Reserve School of Medicine, Cleveland, OH, USA | [b] Department of Medicine, Summa Health System, Akron OH, USA | [c] Department of Pediatrics, Rainbow Babies and Children’s Hospital, Case Western Reserve University, Cleveland, OH, USA
Address for correspondence: Brian Corwin, MD, Summa Health System, 55 Arch Street, Ste 1B, Akron, 44304, OH, USA. Tel.: +1 617 966 8257; Fax: +1 330 375 7779; E-mail: [email protected].
Abstract: BACKGROUND:Bronchopulmonary dysplasia (BPD) is used to clinically describe the severity of lung disease and to serve as a common surrogate endpoint for long-term pulmonary morbidity in clinical trials, but its performance as a surrogate end-point warrants evaluation. Our objective was to assess real-world performance of BPD as a surrogate marker for long-term pulmonary outcomes. METHODS:We performed a systematic review of large, multi-centered, blinded, randomized control trials to evaluate the use of BPD as a surrogate marker for long-term pulmonary outcomes. Long-term pulmonary outcomes occurred within two years and included measures of hospital utilization, respiratory illness, respiratory medication, and mortality. Direction and magnitude of effect were evaluated using number needed to treat analysis. RESULTS:Five studies were included in our review. Studies varied in definition of BPD and in long-term outcomes measured. Only one study found a significant, consistent risk reduction in both BPD and any long-term pulmonary outcome. Two studies found significant reductions in long-term pulmonary outcomes with a non-significant reduction in BPD. CONCLUSIONS:BPD is an imperfect surrogate marker for long-term pulmonary outcomes. It did not consistently predict the magnitude or direction of the effect of an intervention on longer-term pulmonary outcomes. Furthermore, there was significant variation in the definitions of BPD and in the long-term pulmonary outcomes used. There is a need for future work to identify more predictive surrogate markers and a need for better standardization of assessments of long-term pulmonary outcomes.