Psychometric validation of patient-reported outcome measures assessing chronic constipation

Figures & data

Table 1 Baseline demographics and characteristics of study participants

Demographic/characteristic	Phase IIb N=307	Phase III N=1,272
Average age in years, mean (SD)	47.3 (13.7)	47.8 (13.6)
Age range in years	18–86	18–85
Sex, n (%)
Female	282 (91.9)	1,131 (88.9)
Race, n (%)
White	259 (84.4)	969 (76.2)
Language,a n (%)
English	307 (100)	1,242 (97.6)
Average body mass index, mean (SD)	27.3 (5.3)	28.0 (6.0)
Body mass index range	18.5 to 46.4	15.1 to 72.3
CC Symptom Severity Measures, baseline meanb (SD)
CSBM Frequency	0.4 (0.7)	0.3 (0.5)
SBM Frequency	2.3 (1.5)	2.0 (1.6)
Stool Consistency	2.4 (1.0)	2.4 (1.0)
Straining	3.1 (0.8)	3.2 (0.9)
Bloating	2.8 (0.9)	2.8 (0.9)
Abdominal Discomfort	2.4 (0.9)	2.5 (0.8)
Abdominal Pain	2.0 (0.9)	2.2(0.9)
Constipation Severity	3.4 (0.8)	3.3 (0.7)

Notes:

a The non-English speakers were Spanish speakers

b baseline is the average of the pretreatment weeks.

Abbreviations: CC, chronic constipation; CSBM, complete spontaneous bowel movement; SBM, spontaneous bowel movement; SD, standard deviation.

Table 2 Inter-item correlations and correlations with Constipation Severity (treatment period averages)

CC Symptom Severity Measure	Bowel symptoms				Abdominal symptoms
	CSBM Frequency	SBM Frequency	Stool Consistency	Straining	Bloating	Abdominal Discomfort	Abdominal Pain
Phase IIb
Bowel symptoms
CSBM Frequency	–
SBM Frequency	0.60*	–
Stool Consistency	0.37*	0.39*	–
Straining	−0.45*	−0.28*	−0.50*	–
Abdominal symptoms
Bloating	−0.45*	−0.24*	−0.12	0.42*	–
Abdominal Discomfort	−0.42*	−0.23*	−0.02	0.42*	0.81*	–
Abdominal Pain	−0.30*	−0.12	0.02	0.37*	0.65*	0.81*	–
Constipation Severity	−0.60*	−0.52*	−0.37*	0.53*	0.58*	0.54*	0.42*
Phase III
Bowel symptoms
CSBM Frequency	–
SBM Frequency	0.73*	–
Stool Consistency	0.43*	0.46*	–
Straining	−0.49*	−0.40*	−0.62*	–
Abdominal symptoms
Bloating	−0.40*	−0.26*	−0.22*	0.53*	–
Abdominal Discomfort	−0.33*	−0.21*	−0.18*	0.51*	0.81*	–
Abdominal Pain	−0.29*	−0.20*	−0.16*	0.48*	0.71*	0.90*	–
Constipation Severity	−0.59*	−0.54*	−0.49*	0.70*	0.63*	0.59*	0.52*

Notes:

* P<0.01. – signifies not computed.

Abbreviations: CC, chronic constipation; CSBM, complete spontaneous bowel movement; SBM, spontaneous bowel movement.

Table 3 Correlations between Constipation Relief and change in CC Symptom Severity Measures

Change in CC Symptom Severity Measure	BL to week 1	BL to week 2	BL to week 4	BL to week 8	BL to week 12	BL to treatment average
Phase IIb
CSBM Frequency	−0.52	−0.54	−0.58	–	–	−0.59
SBM Frequency	−0.45	−0.39	−0.41	–	–	−0.46
Stool Consistency	−0.38	−0.36	−0.51	–	–	−0.39
Straining	0.38	0.38	0.45	–	–	0.40
Bloating	0.36	0.43	0.40	–	–	0.45
Abdominal Discomfort	0.33	0.37	0.41	–	–	0.43
Abdominal Pain	0.30	0.31	0.34	–	–	0.37
Phase III
CSBM Frequency	−0.49	−0.53	−0.49	−0.52	−0.52	−0.60
SBM Frequency	−0.39	−0.48	−0.45	−0.43	−0.46	−0.51
Stool Consistency	−0.39	−0.43	−0.40	−0.42	−0.39	−0.48
Straining	0.40	0.38	0.41	0.41	0.42	0.48
Bloating	0.35	0.39	0.42	0.44	0.44	0.48
Abdominal Discomfort	0.29	0.36	0.36	0.40	0.44	0.43
Abdominal Pain	0.26	0.31	0.31	0.35	0.39	0.38

Notes: All correlations are statistically significant (P<0.001). – signifies data not available.

Abbreviations: BL, baseline; CC, chronic constipation; CSBM, complete spontaneous bowel movement; SBM, spontaneous bowel movement.

Table 4 Correlations between change in PAC-QOL scores and change in CC Symptom Severity Measures

Phase	Bowel symptoms				Abdominal symptoms
	CSBM Frequency	SBM Frequency	Stool Consistency	Straining	Bloating	Abdominal Discomfort	Abdominal Pain
PAC-QOL overall
Phase IIb	−0.47	−0.37	−0.44	0.54	0.53	0.56	0.50
Phase III	−0.43	−0.40	−0.33	0.46	0.57	0.57	0.53
Physical Discomfort
Phase IIb	−0.46	−0.36	−0.48	0.59	0.56	0.56	0.47
Phase III	−0.42	−0.37	−0.32	0.45	0.63	0.61	0.56
Psychosocial Discomfort
Phase IIb	−0.29	−0.21	−0.24	0.34	0.36	0.42	0.41
Phase III	−0.26	−0.23	−0.18	0.31	0.42	0.42	0.40
Satisfaction
Phase IIb	−0.52	−0.48	−0.48	0.47	0.47	0.44	0.37
Phase III	−0.48	−0.44	−0.40	0.44	0.47	0.44	0.39
Worries and Concerns
Phase IIb	−0.35	−0.25	−0.32	0.46	0.44	0.50	0.45
Phase III	−0.34	−0.33	−0.25	0.39	0.48	0.50	0.46

Notes: The change in PAC-QOL subscale scores from day 1 to end of treatment was correlated with the change in the CC Symptom Severity Measures between baseline and the average over the last 2 weeks of treatment. All correlations are statistically significant (P<0.01).

Abbreviations: CC, chronic constipation; CSBM, complete spontaneous bowel movement; PAC-QOL, Patient Assessment of Constipation Quality of Life questionnaire; SBM, spontaneous bowel movement.

Figure 1 Illustration of the two-factor confirmatory factor analysis model for CC Symptom Severity Measures, with factor loadings.

Notes: The confirmatory factor analysis solution includes correlated residuals that are not shown between the following: CSBM Frequency and SBM Frequency, Straining and Stool Consistency, Abdominal Pain and Abdominal Discomfort.
Abbreviations: CC, chronic constipation; CSBM, complete spontaneous bowel movement; SBM, spontaneous bowel movement.

Table 5 Known-groups analyses – subgroup means on CC Symptom Severity Measures (treatment period average)

CC Symptom Severity Measures	Overall CSBM known groupa		Constipation Severity known groupa,b
	Nonresponder, mean (SD)	Responder, mean (SD)	Severe/very severe, mean (SD)	None/mild mean (SD)
Phase IIb	(n=231–238)c	(n=69)	(n =53–56)c	(n=123)
Bowel symptoms
CSBM Frequency	1.2 (1.2)	5.4 (2.2)	0.5 (0.9)	3.5 (2.7)
SBM Frequency	4.7 (2.9)	8.1 (3.3)	2.9 (2.4)	7.1 (3.3)
Stool Consistency	3.7 (1.5)	4.7 (1.0)	3.5 (1.6)	4.5 (1.2)
Straining	2.3 (0.8)	1.7 (0.5)	2.7 (0.9)	1.8 (0.6)
Abdominal symptoms
Bloating	2.7 (0.9)	1.8 (0.6)	3.2 (0.8)	2.0 (0.7)
Abdominal Discomfort	2.3 (0.8)	1.6 (0.6)	2.8 (0.8)	1.8 (0.6)
Abdominal Pain	1.9 (0.8)	1.4 (0.5)	2.3 (0.9)	1.5 (0.6)
Phase III	(n=1,034–1,087)c	(n=185)	(n=185–200)c	(n=568–583)c
Bowel symptoms
CSBM Frequency	1.2 (1.9)	6.3 (2.8)	0.3 (0.6)	3.3 (3.0)
SBM Frequency	3.9 (3.2)	8.6 (3.6)	1.8 (1.8)	6.1 (3.8)
Stool Consistency	3.7 (1.3)	4.9 (1.0)	3.0 (1.3)	4.4 (1.2)
Straining	2.4 (0.8)	1.6 (0.5)	3.2 (0.9)	1.8 (0.5)
Abdominal symptoms
Bloating	2.5 (0.8)	1.8 (0.6)	3.2 (0.9)	1.9 (0.6)
Abdominal Discomfort	2.2 (0.8)	1.6 (0.5)	2.8 (0.9)	1.7 (0.5)
Abdominal Pain	1.9 (0.8)	1.4 (0.4)	2.4 (1.0)	1.5 (0.5)

Notes:

a Responder and nonresponder means are statistically different for all CC Symptom Severity Measures in Phase IIb and Phase III (P<0.001)

b averaged across treatment period. Higher mean values represent improvement for CSBM Frequency, SBM Frequency, and Stool Consistency, while lower values represent improvement for Straining, Bloating, Abdominal Discomfort, and Abdominal Pain.

c Subgroup number may vary due to missing data.

Abbreviations: CC, chronic constipation; CSBM, complete spontaneous bowel movement; SBM, spontaneous bowel movement; SD, standard deviation.

Table 6 Responsiveness analyses – subgroup mean changes on CC Symptom Severity Measures and effect sizes

CC Symptom Severity Measures	Overall CSBM Responder status			Constipation Reliefa
	Nonresponder, mean (SD)	Responder, mean (SD)	Guyatt’s statistic (effect size)	Worsened, mean (SD)	Improved, mean (SD)	Guyatt’s statistic (effect size)
Phase IIb	(n=231–238)b	(n=69)		(n=12–19)b	(n=82–87)b
CSBM Frequency	0.82 (1.20)	4.77 (2.31)	3.29	0.15 (0.55)	3.67 (2.52)	6.36
SBM Frequency	2.52 (2.67)	5.59 (3.53)	1.14	1.85 (3.10)	5.28 (3.35)	1.11
Stool Consistency	1.20 (1.42)	2.47 (1.24)	0.89	1.10 (1.86)	2.36 (1.30)	0.68
Straining	−0.75 (0.94)	−1.55 (0.84)	−0.86	−0.57 (1.34)	−1.53 (0.87)	−0.72
Bloating	−0.19 (0.64)	−0.67 (0.65)	−0.74	0.22 (0.45)	−0.69 (0.67)	−2.02
Abdominal Discomfort	−0.18 (0.66)	−0.53 (0.70)	−0.54	0.34 (0.50)	−0.60 (0.68)	−1.88
Abdominal Pain	−0.19 (0.62)	−0.39 (0.68)	−0.31	0.27 (0.51)	−0.52 (0.69)	−1.57
Phase III	(n=1,034–1,087)b	(n=185)		(n=47–70)b	(n=382–424)b
CSBM Frequency	0.97 (1.80)	5.80 (2.91)	2.68	0.19 (0.63)	3.54 (3.16)	5.34
SBM Frequency	2.00 (2.94)	6.14 (3.54)	1.41	0.65 (2.26)	4.48 (3.72)	1.69
Stool Consistency	1.28 (1.37)	2.36 (1.23)	0.79	0.51 (1.05)	2.18 (1.35)	1.59
Straining	−0.84 (0.90)	−1.59 (0.87)	−0.83	−0.20 (0.67)	−1.45 (0.88)	−1.89
Bloating	−0.28 (0.59)	−0.90 (0.69)	−1.05	−0.05 (0.47)	−0.76 (0.69)	−1.51
Abdominal Discomfort	−0.34 (0.56)	−0.91 (0.70)	−1.02	−0.02 (0.49)	−0.75 (0.69)	−1.50
Abdominal Pain	−0.31 (0.53)	−0.77 (0.71)	−0.87	−0.07 (0.47)	−0.66 (0.66)	1.26

Notes:

a Improved = completely relieved or considerably relieved; worsened = somewhat worse, considerably worse, or “as bad as I can imagine”. Higher mean values represent improvement for CSBM Frequency, SBM Frequency, and Stool Consistency, while lower values represent improvement for Straining, Bloating, Abdominal Discomfort, and Abdominal Pain. Change is computed as treatment period average minus baseline, and mean difference is computed as responder minus nonresponder; therefore, effect sizes associated with CSBM Frequency, SBM Frequency, and Stool Consistency are positive, and effect sizes associated with Straining, Bloating, Abdominal Discomfort, and Abdominal Pain are negative.

b Subgroup number may vary due to missing data.

Abbreviations: CC, chronic constipation; CSBM, complete spontaneous bowel movement; SBM, spontaneous bowel movement; SD, standard deviation.