The recommended clinical endpoint of nocturia is a reduction in nocturnal voids. This has been shown to translate into improved health-related quality of life (HRQoL). But does this constitute a clinically meaningful improvement in voids and quality of life?
The conventional approach has been to establish a minimally important difference (MID), to see whether the average treatment benefit of a medical intervention is higher than this MID. There are a number of ways to evaluate this, based on group means. A more recent scientific recommendation is to provide evidence of a clinically meaningful treatment benefit on an individual basis. One should conduct responder analyses, as well as present cumulative distribution functions (CDFs). For a nocturia treatment, this translates into:
•	A reduction from baseline of at least 1.2 voids or more per night (corresponds to a “somewhat better” improvement)
•	A reduction from baseline of at least 1.7 voids or more per night (corresponds to a “much better” improvement)
•	A reduction to less than 2 voids per night (threshold for bothersome nocturia according to the scientific literature [1])
•	Complete responders, i.e. dry nights or “cured from nocturia”.

Desmopressin orally disintegrating tablet (ODT) was assessed in two, 3-month phase 3 double-blind randomised placebo-controlled trials of desmopressin ODT in males (50/75µg; NCT01262456) and females (25µg; NCT01223937) at multiple centers across the US and Canada, on adult subjects with nocturia. Eligible patients had ≥2 voids per night determined via a 3-day frequency–volume chart completed immediately prior to randomization to treatment. Patients completed the Nocturia Quality of Life (N-QoL) questionnaire at monthly visits [2]. N-QoL includes 12 questions summarized in a total score ranging from 0 (low QoL) to 100 (high QoL). Our analyses focused on the Nocturnal Polyuria (NP) sub-population (approx. 90% of the study samples).
Prior to each visit, each subject reported the number of voids per night, and based on these the mean number of nocturnal voids was derived. Responders were identified based on their data collected just prior to study visit in question, mirroring how patients’ benefit would be assessed in clinical practice.
For each responder definition, the logit of the responder probability was adjusted for the baseline number of nocturnal voids as covariate and treatment and age stratum at randomization as factors. The adjusted responder probabilities, odds, and the odds ratios between desmopressin ODT and Placebo (with two-sided p-value based on the Chi-square test) are presented below. The estimated difference between responder groups in N-QoL total score is adjusted for baseline N-QoL total score. Two sided p-values are based on the t-test.

Table 1: A. Responder analysis of reduction from baseline of at least 1.2 voids and   
B. Difference between responder groups in N-QoL total score at 3 months (Full Analysis Set – NP population)

A. Treatment 	Adjusted Responder Probability	Odds ratio	P-value
Women			
Desmopressin ODT	75%                                 	        2.33	                0.009
Placebo	                        56%		
			
Men			
Desmopressin ODT	59%	                                                2.66	                0.003
Placebo	                        35%		

B. Responder Group	Mean change N-QoL	Difference (CI)	      P-value
Women			
A responder	                30.34	                    15.14 (10.29;20.00) 	      <0.001
Not a responder	        15.19		
			
Men			
A responder	               22.06	                     8.45 (3.77;13.12)	      <0.001
Not a responder	       13.61

Space only permits a presentation of the responder definition of 1.2 voids but the other three definitions present similar results. More patients in the desmopressin ODT arms met these responder criteria after 3 months of treatment, as compared to placebo. The different voiding responder definitions translate into substantial health-related quality of life benefits. Scientific literature indicates that an N-QoL difference of about 6 points is clinically meaningful [3].

This approach allows the audience to assess whether a new treatment generates a clinically meaningful improvement to the patients, or not. In our case the generally higher voiding response rates with desmopressin ODT compared to Placebo, irrespective of the responder definition, indicate a relevant and important treatment benefit across the nocturnal polyuria patient population. Furthermore, the published literature indicates that the resulting QoL improvement could be considered clinically meaningful.

Tikkinen KA, Johnson TM 2nd, Tammela TL, Sintonen H, Haukka J, Huhtala H, et al. Nocturia frequency, bother, and quality of life: how often is too often? A population-based study in Finland. Eur Urol. 2010, 57:488-96.
Abraham L, Hareendran A, Mills IW, Martin ML, Abrams P, Drake MJ, et al. Development and validation of a quality-of-life measure for men with nocturia. Urology. 2004, 63:481-6.
Yu H-J, Chen F-Y, Huang P-C, Chen T H-H, Chie W-C, Liu C-Y. Impact of nocturia on symptom-specific quality of life among community-dwelling adults aged 40 years and older. Urology 2006, 67:713–8