Item Response Theory Modeling of the International Prostate Symptom Score in Patients with Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia

Yassine Kamal Lyauk,Trine Meldgaard Lund,Daniël M Jonker,Mats O Karlsson,Andrew C Hooker

doi:10.1208/s12248-020-00500-w

Abstract

Item response theory (IRT) was used to characterize the time course of lower urinary tract symptoms due to benign prostatic hyperplasia (BPH-LUTS) measured by item-level International Prostate Symptom Scores (IPSS). The Fisher information content of IPSS items was determined and the power to detect a drug effect using the IRT approach was examined. Data from 403 patients with moderate-to-severe BPH-LUTS in a placebo-controlled phase II trial studying the effect of degarelix over 6 months were used for modeling. Three pharmacometric models were developed: a model for total IPSS, a unidimensional IRT model, and a bidimensional IRT model, the latter separating voiding and storage items. The population-level time course of BPH-LUTS in all models was described by initial improvement followed by worsening. In the unidimensional IRT model, the combined information content of IPSS voiding items represented 72% of the total information content, indicating that the voiding subscore may be more sensitive to changes in BPH-LUTS compared with the storage subscore. The pharmacometric models showed considerably higher power to detect a drug effect compared with a cross-sectional and while-on-treatment analysis of covariance, respectively. Compared with the sample size required to detect a drug effect at 80% power with the total IPSS model, a reduction of 5.9% and 11.7% was obtained with the unidimensional and bidimensional IPSS IRT model, respectively. Pharmacometric IRT analysis of the IPSS within BPH-LUTS may increase the precision and efficiency of treatment effect assessment, albeit to a more limited extent compared with applications in other therapeutic areas.

Highlights

Benign prostate hyperplasia (BPH) is a common condition in the aging male and is estimated to affect 50% of males by age 60 years and 90% by age 85 years [1,2]
The severity of BPH-LUTS is commonly measured by the International Prostate Symptom Score (IPSS) [7], which consists of seven questions describing the severity of each of the clinical manifestations of LUTS
A marked drop in total IPSS was observed in all treatment arms following dosing, and there was a similar distribution of itemlevel IPSS responses at the three key trial visits in both the placebo arm and the pooled treatment arms

Summary

Introduction

Benign prostate hyperplasia (BPH) is a common condition in the aging male and is estimated to affect 50% of males by age 60 years and 90% by age 85 years [1,2]. The clinical manifestations of BPH are known as lower. The severity of BPH-LUTS is commonly measured by the International Prostate Symptom Score (IPSS) ( known as the American Urological Association score) [7], which consists of seven questions describing the severity of each of the clinical manifestations of LUTS. The IPSS questionnaire is considered the gold standard measure for assessing BPH-LUTS, and its use is widespread in the clinic, as a primary or secondary endpoint in clinical trials, and in urology research [8]

Methods

Results

Conclusion