Psychometric validation and interpretation of the Nocturia Impact Diary in a clinical trial setting

Abstract

Purpose: Psychometric evaluation of the Nocturia Impact (NI) Diary was conducted to support its use as a trial endpoint.

Methods: As part of a randomized, controlled Phase 2 clinical trial investigating a novel drug candidate for nocturnal polyuria, adult nocturia patients completed the NI Diary and a voiding diary for three nights preceding their clinic visit at Baseline and Weeks 1, 4, 8, and 12 (end of treatment). Exit interviews were conducted to obtain patient impressions of the NI Diary.

Results: A total of N = 302 participants were included. Confirmatory factor analysis (CFA) indicated that the 11-item measure is unidimensional with values of CFI, TLI, and RMSEA meeting relevant thresholds. Good internal consistency (Cronbach's α 0.941) and test-retest reliability (intra-class correlation coefficients 0.730-0.880). Convergent validity with two reference measures was demonstrated with strong correlations of 0.573-0.730 were shown. Significant differences (P = 0.0018, standardized effect size = 0.372) between groups defined by number of night-time voids supported known-groups validity. Exit interviews in 66 patients indicated all participants experienced improvement in at least 1 NI Diary item and that a 1-point improvement on the item response scale and 1-void reduction per night (associated with an average best cut point on ROC analysis of - 11.6) constituted meaningful improvement. Anchor and distribution-based analyses identified a meaningful change threshold of - 15 to - 18 points on the NI Diary.

Conclusion: The NI Diary is a reliable and valid patient-reported psychometric instrument which is fit-for-purpose to evaluate the impact of nocturia on patient quality of life in the clinical trial setting. Trial registration number and registration date NCT03201419; June 28, 2017.

Keywords: Anchor-based; Meaningful change threshold; NI Diary; Nocturia; Patient-reported outcomes; Quality of life.

Fig. 1

Overview of Psychometric Analyses performed for the current study

Fig. 2

Item discrimination curve for all five response options for Item 5 (irritable or moody). Abscissa represents the Mean NI Diary total score at Baseline and ordinate represents Cumulative Proportion of Subjects. The curves for different response options are well-separated with direct correspondence between higher NI Diary scores below which all subjects score and higher severity of response of the item. For instance, for those responding 0 (Not at all) to indicate how much the experience moodiness or irritability, 100% of patients had a Baseline NI Diary score < 60 with most < 30, whereas for those who scored 4 (A great deal), almost all participants scored 60–100. NI nocturia impact

Fig. 3

Confirmatory factor analysis: standardized factor loadings. CFA confirmatory factor analysis, NI nocturia impact