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

E.S Lourijsen,M Vleming,S Reitsma,W.J Fokkens

doi:10.4193/rhinol/20.092

Abstract

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.

Highlights

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 Sinonasal Outcome Test 22 (SNOT-22) at 12-months follow-up
Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) experience a significant impact on most aspects of their Healthrelated Quality of Life (HrQOL) . [1-3] Together with the high prevalence of disease (1-4%), the diagnosis and treatment give high healthcare costs . [4-6] The current treatment exists of medical treatment alone or in combination with endoscopic sinus surgery (ESS) (5, . 7-11) It is unclear what the benefit is of the addition of surgical treatment on top of on-going medical treatment and at what time point in the disease course a patient should be offered surgery
The PolypESS study is the first multicentre, randomised controlled trial investigating the impact of ESS on Statistical analysis plan for the PolypESS trial disease-specific HrQOL in adult patients suffering from Chronic rhinosinusitis with nasal polyps (CRSwNP) in comparison to on-going medical treatment

Summary

Methods

A questionnaire comprising five domains/questions: mobility, self-care, usual activities, pain or discomfort and anxiety or depression. A VAS for health status is applied (0-100). Nasal blockage, symptoms of rhinorrhoea, symptoms of postnasal drip, facial pain / headache and loss of smell are measured with a Visual Analogue Scale (VAS) ranging from 0-10. Asthma Control Test (2002 TM QualityMetric Incorporated) is used in the subpopulation of patients with asthma. It contains five individual questions (total score 5-25 points). Left and right side of the nose is scored for size of nasal polyps (0-4 on both sides). Left and right side of the nose is scored for presence or absence of polyp, oedema and discharge (total score 0-12). Ethmoid, sphenoid, frontal sinuses and olfactory fossa are scored for mucosal inflammation, mucus and purulent discharge (total score 0-100). Mean delta SNOT-22 will be reported (change from baseline)

Results

Discussion

Introduction

Difference between treatment groups in VAS calculated from EQ-5D-5L