Endoscopic sinus surgery in adult patients with Chronic Rhinosinusitis with nasal polyps (PolypESS) - statistical analysis plan for a multicentre randomised controlled trial

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) afflicts 2-4% of the population and comes with a long time burden of disease and high societal costs. The current treatment consists of medical treatment alone or in combination with endoscopic sinus surgery. No consensus exists on the right timing and extent of disease that warrants surgery. Furthermore, there is lack of clinical knowledge about the benefit of surgery over medication only. The current study evaluates the clinical effectiveness and cost-effectiveness of endoscopic sinus surgery in addition to medical treatment versus medication alone in the adult patient group with nasal polyps (CRSwNP). Methods: The PolypESS trial is designed as a prospective, randomised, multicentre trial in adult patients with CRSwNP selected for primary or revision endoscopic sinus surgery by their otorhinolaryngologist. Patients are randomly assigned to endoscopic sinus surgery in addition to medication or medical therapy only. This paper details the statistical analysis plan (SAP) of this trial and was submitted before outcome data were available. Results: The primary outcome of the trial is disease-specific Health-Related Quality of Life quantified by the SNOT-22 at 12-months follow-up. Secondary outcomes consist of generic and disease-specific Health-Related Quality of Life, objective signs of disease and adverse events of treatment. Subgroup analyses will be performed to verify if treatment effects differ among patient phenotypes. Analyses will be completed according to this pre-specified SAP. The main analysis will be performed as a standard ITT analysis. Discussion: The PolypESS trial will show whether addition of endoscopic sinus surgery to medical treatment improves the disease-specific Health-Related Quality of Life quantified by the SNOT-22 at 12-months follow-up. Unforeseen deviations from the SAP at the time of analysis will be motivated and discussed in the final publication of the primary outcome of this study.