Date of Award
Selective Evidence-Based Medicine Review
Master of Science in Health Sciences - Physician Assistant
Physician Assistant Studies
Objective: The objective of this selective EBM review is to determine whether or not “Is triple combination CFTR modulator therapy effective in improving the quality of life of patients with cystic fibrosis who have one Phe508del allele?”
Study Design: A systematic review of three, double-blind, randomized controlled trials (RCTs) published in 2018 and 2019.
Data Sources: All RCTs were found using PubMed. All articles were published in peer-reviewed journals and selected based on credibility, relevance to the clinical question, date of publication, population, and evaluation of patient-oriented evidence that matters (POEMs).
Outcome measured: All three studies utilized the CFQ-R respiratory domain score, a 50-item questionnaire that assesses the impact of cystic fibrosis on health-related quality of life (HRQoL). Scores range from 0 – 100 with higher scores indicating a higher patient-reported HRQoL with respect to respiratory status. 4 points is considered a minimal clinical importance. The absolute change from baseline CFQ-R scores were determined at the end of each intervention period.
Results: Clinically significant improvements in CFQ-R scores from baseline were revealed in all three studies. CFQ-R scores increased 17.1 points in the Davies et al. study (N Engl J Med. 2018;379(17):1599-1611. doi: 10.1056/NEJMoa1807119 [doi]), 24.4 points in the Keating et al. study (N Engl J Med. 2018;379(17):1612-1620. doi: 10.1056/NEJMoa1807120 [doi]), and 17.5 points in the Middleton et al study (N Engl J Med. 2019;381(19):1809-1819. doi:10.1056/nejmoa1908639). However, the Davies et al. study revealed clinically significant improvements in CFQ-R scores in both the intervention and placebo group rendering these results inconclusive. The Middleton et al. study provided statistically significant results and a mean treatment difference of 20.2 points with a statistically significant p-value (<0.001).
Conclusion: Triple combination CFTR modulator therapy demonstrated clinically significant improvements in CFQ-R scores from baseline in patients with cystic fibrosis who have one Phe508del allele, indicating an improvement in quality of life. However, the evidence is inconclusive as one of the studies revealed clinically significant improvements in both the intervention and placebo group. Further research is needed to demonstrate the potential of this therapy using larger intervention groups and longer treatment periods in order to assess for statistically significant findings.
Avallone, Gia, "Is Triple Combination CFTR Modulator Therapy Effective in Improving the Quality of Life of Patients with Cystic Fibrosis Who Have One Phe508del Allele?" (2020). PCOM Physician Assistant Studies Student Scholarship. 519.