Use of Nonmedicated Control Substances in Randomized Clinical Trials of Patients With Chronic Rhinosinusitis A Systematic Review and Single-Arm Meta-analysis

Importance The effect of nonmedicated control substances in chronic rhinosinusitis remains unclear. Objective To assess the association of nonmedicated control substances in randomized clinical trials with disease outcomes in patients diagnosed with chronic rhinosinusitis. Data Sources and Study Selection In this single-arm systematic review and meta-analysis, the Cochrane Library of Systematic Reviews, Ovid MEDLINE, Embase, PubMed, and ClinicalTrials.gov databases were searched for randomized clinical trials with a preintervention and postintervention design for chronic rhinosinusitis that were published between 1946 and January 23, 2019. Data Extraction and Synthesis Paired reviewers independently extracted data. The analyses used random-effects models and the Cochrane risk of bias assessment to rate the quality of the evidence. Main Outcomes and Measures The primary outcomes were the association of nonmedicated control substances with 22-item Sinonasal Outcome Test (SNOT-22) scores or nasal symptom scores when SNOT-22 was not available. Results A total of 2305 abstracts were identified and screened, 725 articles were reviewed in full text, and 38 articles met the study criteria and were included in the meta-analysis. Among the 38 included studies, a total of 2258 adults (mean age range, 27-53 years; 20.0%-72.5% women) were randomized to receive nonmedicated control substances or sham interventions. Topical nonmedicated control substances were associated with significant reduction in SNOT-22 scores (mean difference [MD], -8.81; 95% CI, -12.60 to -5.03). A subgroup analysis of topical therapies, limited to saline irrigation and nasal spray diluents, found that topical diluents were associated with a greater reduction in SNOT-22 scores (MD, -11.45; 95% CI, -13.50 to -9.41) compared with saline irrigation (MD, -13.60; 95% CI, -19.95 to -7.25). Nonmedicated control substances were associated with a significant reduction in nasal obstruction scores (standardized MD [SMD], -0.42; 95% CI, -0.81 to -0.03). No significant change was found in rhinorrhea scores (SMD, -0.34; 95% CI, -1.37 to 0.69), postnasal drip scores (SMD, -0.96; 95% CI, -2.18 to 0.25), facial pain scores (SMD, -0.57; 95% CI, -1.68 to 0.55), or loss of smell scores (SMD, -0.18; 95% CI, -0.68 to 0.32). Conclusions and Relevance This systematic review and meta-analysis of the use of nonmedicated control substances in randomized clinical trials of chronic rhinosinusitis outcomes suggests that the use of nonmedicated control substances is associated with limited improvements in SNOT-22 and nasal obstruction scores. These findings highlight potential areas of future research directions and the importance of randomized clinical trials to accurately estimate treatment effect. Question Can nonmedicated control substances improve patient-reported and observer-reported outcomes in chronic rhinosinusitis? Findings This systematic review and meta-analysis of the use of nonmedicated control substances in 38 randomized clinical trials of patients with chronic rhinosinusitis found an improvement in quality-of-life measures (6.21 of 110 points) and in nasal obstruction scores reported using a visual analog scale (0.42 standardized points). Meaning This study suggests that nonmedicated control substances are associated with limited improvements in the 22-item Sinonasal Outcome Test and nasal obstruction scores. This systematic review and meta-analysis assesses the association of nonmedicated control substances in randomized clinical trials with disease outcomes in patients diagnosed with chronic rhinosinusitis.