Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website https://gr.elmerpub.com

Original Article

Volume 000, Number 000, January 2026, pages 000-000

Early Therapeutic Response Predicts Outcome in Chronic Constipation: A Multicenter Prospective Observational Study

Figure 2. Correlation between treatment reactivity at 2 and 4 weeks of treatments. (a) Responder defined by patient’s impression of improved or better (Q18). (b) Responder defined by numeric rating scale ≤ 5 (Q19). (c) Responder defined by spontaneous bowel movement (SBM) responder.

Table 1. Structure of CC-TEST

Domain

Subdomain

Item number

Items

Response form

Subscale

Definitions of SS

CC-TEST: Chronic Constipation-Therapeutic Efficacy and Satisfaction Test; LS: Likert scale; Sx: symptom; SS: subscale.

Symptoms

Item 1 - 7

Item 1

Infrequent bowel movements

7-point LS

Stool Sx-SS

Mean of items 1and 2

Item 2

Hard stool

Defecation Sx-SS

Mean of items 3, 4 and 7

Item 3

Difficulty in defecation

Abdominal Sx-SS

Mean of items 5 and 6

Item 4

Feeling of incomplete bowel movements

Total symptom score

Mean of stool Sx-SS, defecation Sx-SS and abdominal Sx-SS

Item 5

Abdominal pain

Item 6

Abdominal discomfort

Item 7

Anal pain during defecation

Defecation status

Item 8 - 12

Item 8

Number of bowel movements during the past week

Number

Item 9

Number of forced bowel movements during the past week

Number of spontaneous bowel movements during the past week (item 8 - item 9)

Item 10

Bristol Stool Form Scale

7-point LS

Item 11

Time to defecate

6-point LS

Item 12

Defecation assistance

5-point LS

Impact for daily life

Item 13 - 16

Item 13

Dissatisfaction with daily activity

5-point LS

Dissatisfaction for daily life-SS

Mean of items 13, 14, 15 and 16

Item 14

Dissatisfaction with the mood

Item 15

Dissatisfaction with eating

Item 16

Dissatisfaction with overall constipation symptoms

Therapeutic response

Item 17 - 20

Item 17

Desire for additional medication

5-point LS

Item 18

Patient’s impression of the therapy

Item 19

Numeric rating scale

0 - 10 scale

Item 20

Compliance with the medication

5-point LS

**Table 2.** Patient Characteristics
BMI: body mass index; OTCM: over-the-counter medication; SD: standard deviation.
Age (mean ± SD)	66.4 ± 15.4
Sex
Female	69 (71%)
Male	28 (29%)
BMI (mean ± SD)	21.7 ± 3.2
Duration of constipation, month (mean ± SD) (month)	165.6 ± 169.7
History of hospital visit due to constipation, yes	69 (71%)
Severity of constipation
Severe	8 (8%)
Moderate	89 (92%)
OTCM, yes	22 (23%)
Pre-study medication, yes	70 (72%)
Magnesium oxide	33
New constipation treatment medication	26
Stimulant laxatives	18
Kampo medicine	13
Others	21
Number of pre-study medication
1	36
2	23
3	6
4	2
5	2
Abdominal surgery, yes	40 (41%)
Open	28
Laparoscopic surgery	8
Unclear	4
Childbirth, yes	42 (61%)
Vaginal delivery	35
Cesarean section	6
Unclear	1
Coexisting disorders, yes	71 (73%)
Endocrine and metabolic disorders	35
Neurological disorders	8
Collagen disease	5
Degenerative disorders	1
Mental disorders	13
Colorectal and anal disorders	33
Others	11
Number of coexisting conditions
1	44
2	20
3	6
4	1
Medications causing constipation, yes	57 (60%)
Number of medications causing constipation
1	29
2	22
3	6
Types of study prescription medications
New constipation treatment medication	87
Stimulant laxatives	20
Magnesium oxide	23
Kampo medicine	7
Others	25
Number of study medication
1	55
2	22
3	14
4	3
5	3

Table 2. Patient Characteristics

BMI: body mass index; OTCM: over-the-counter medication; SD: standard deviation.

Age (mean ± SD)

66.4 ± 15.4

Sex

Female

69 (71%)

Male

28 (29%)

BMI (mean ± SD)

21.7 ± 3.2

Duration of constipation, month (mean ± SD) (month)

165.6 ± 169.7

History of hospital visit due to constipation, yes

69 (71%)

Severity of constipation

Severe

8 (8%)

Moderate

89 (92%)

OTCM, yes

22 (23%)

Pre-study medication, yes

70 (72%)

Magnesium oxide

New constipation treatment medication

Stimulant laxatives

Kampo medicine

Others

Number of pre-study medication

Abdominal surgery, yes

40 (41%)

Open

Laparoscopic surgery

Unclear

Childbirth, yes

42 (61%)

Vaginal delivery

Cesarean section

Unclear

Coexisting disorders, yes

71 (73%)

Endocrine and metabolic disorders

Neurological disorders

Collagen disease

Degenerative disorders

Mental disorders

Colorectal and anal disorders

Others

Number of coexisting conditions

Medications causing constipation, yes

57 (60%)

Number of medications causing constipation

Types of study prescription medications

New constipation treatment medication

Stimulant laxatives

Magnesium oxide

Kampo medicine

Others

Number of study medication

**Table 3.** Effectiveness of Treatment
Items/subscales	Baseline (n = 109)	2 W (n = 109)	0 W vs. 2 W	4 W (n = 107)	0 W vs. 4 W
Interpretation of effect size (Cohen’s d): small ≥ 0.20, medium ≥ 0.50, large ≥ 0.80. W: week; SD: standard deviation; Sx: symptom; SS: subscale; BSFS: Bristol Stool Form Scale; SBM: spontaneous bowel movement.
Infrequent bowel movements	4.1	1.3	3.1	1.4	-1.0	< 0.001	0.73	2.8	1.4	-1.3	< 0.001	0.94
Hard stool	4.4	1.5	3.0	1.6	-1.4	< 0.001	0.89	2.7	1.7	-1.7	< 0.001	1.07
Difficulty in defecation	4.5	1.5	3.1	1.6	-1.5	< 0.001	0.95	2.9	1.7	-1.6	< 0.001	1.00
Feeling of incomplete bowel movements	3.8	1.4	3.2	1.5	-0.6	< 0.001	0.43	3.1	1.5	-0.7	< 0.001	0.47
Abdominal pain	2.9	1.7	2.3	1.2	-0.6	0.001	0.39	2.3	1.3	-0.6	< 0.001	0.38
Abdominal discomfort	4.1	1.5	3.2	1.5	-0.8	< 0.001	0.54	3.1	1.5	-0.9	< 0.001	0.63
Anal pain during defecation	2.9	1.7	2.3	1.4	-0.6	0.002	0.42	2.2	1.3	-0.8	< 0.001	0.51
Stool Sx-SS	4.3	1.3	3.1	1.4	-1.2	< 0.001	0.89	2.8	1.4	-1.5	< 0.001	1.12
Defecation Sx-SS	3.8	1.2	2.8	1.2	-0.9	< 0.001	0.75	2.7	1.3	-1.0	< 0.001	0.81
Abdominal Sx-SS	3.5	1.4	2.8	1.2	-0.7	< 0.001	0.54	2.7	1.2	-0.8	< 0.001	0.57
Total symptom score	3.8	1.1	2.9	1.1	-0.9	< 0.001	0.84	2.7	1.2	-1.1	< 0.001	0.95
Number of bowel movements during the past week	4.4	4.7	6.9	10.5	2.5	0.020	0.30	6.1	5.1	1.7	0.001	0.34
Number of forced bowel movements during the past week	2.2	3.8	3.0	5.2	0.8	0.102	0.17	2.9	4.6	0.7	0.133	0.16
Number of spontaneous bowel movements during the past week	2.2	3.9	3.9	7.2	1.5	0.016	0.29	3.2	4.0	1.0	0.012	0.25
\|SBM-7\|	5.6	2.6	5.6	5.4	0.1	0.916	0.01	4.7	2.9	-0.9	0.012	0.31
Bristol Stool Form Scale	2.7	1.8	4.0	1.7	1.3	< 0.001	0.73	4.1	1.7	1.3	< 0.001	0.75
\|BSFS-4\|	1.9	1.1	1.4	1.0	-0.5	< 0.001	0.48	1.3	1.1	-0.6	< 0.001	0.52
Time to defecate	2.6	1.3	2.0	1.1	-0.6	< 0.001	0.45	1.9	1.1	-0.7	< 0.001	0.56
Defecation assistance	2.3	1.2	1.7	1.1	-0.6	< 0.001	0.48	1.6	1.0	-0.7	< 0.001	0.60
Dissatisfaction with daily activity	2.6	1.1	2.4	1.2	-0.2	0.034	0.19	2.2	1.1	-0.4	< 0.001	0.33
Dissatisfaction with the mood	2.8	1.2	2.4	1.2	-0.3	0.004	0.27	2.3	1.1	-0.5	0.004	0.40
Dissatisfaction with eating	2.3	1.3	1.9	1.2	-0.4	0.001	0.35	1.9	1.1	-0.4	< 0.001	0.34
Dissatisfaction with overall constipation symptoms	3.6	1.1	2.9	1.1	-0.7	< 0.001	0.61	2.7	1.3	-0.8	< 0.001	0.71
Dissatisfaction with daily life-SS	2.8	0.9	2.4	1.0	-0.4	< 0.001	0.46	2.3	0.9	-0.5	< 0.001	0.58

Table 3. Effectiveness of Treatment

Items/subscales

Baseline (n = 109)

2 W (n = 109)

0 W vs. 2 W

4 W (n = 107)

0 W vs. 4 W

Mean

Δscore (2 W - 0 W)

P value

Cohen’s d

Mean

Δscore (4 W - 0 W)

P value

Cohen’s d

Interpretation of effect size (Cohen’s d): small ≥ 0.20, medium ≥ 0.50, large ≥ 0.80. W: week; SD: standard deviation; Sx: symptom; SS: subscale; BSFS: Bristol Stool Form Scale; SBM: spontaneous bowel movement.

Infrequent bowel movements

4.1

1.3

3.1

1.4

-1.0

< 0.001

0.73

2.8

1.4

-1.3

< 0.001

0.94

Hard stool

4.4

1.5

3.0

1.6

-1.4

< 0.001

0.89

2.7

1.7

-1.7

< 0.001

1.07

Difficulty in defecation

4.5

1.5

3.1

1.6

-1.5

< 0.001

0.95

2.9

1.7

-1.6

< 0.001

1.00

Feeling of incomplete bowel movements

3.8

1.4

3.2

1.5

-0.6

< 0.001

0.43

3.1

1.5

-0.7

< 0.001

0.47

Abdominal pain

2.9

1.7

2.3

1.2

-0.6

0.001

0.39

2.3

1.3

-0.6

< 0.001

0.38

Abdominal discomfort

4.1

1.5

3.2

1.5

-0.8

< 0.001

0.54

3.1

1.5

-0.9

< 0.001

0.63

Anal pain during defecation

2.9

1.7

2.3

1.4

-0.6

0.002

0.42

2.2

1.3

-0.8

< 0.001

0.51

Stool Sx-SS

4.3

1.3

3.1

1.4

-1.2

< 0.001

0.89

2.8

1.4

-1.5

< 0.001

1.12

Defecation Sx-SS

3.8

1.2

2.8

1.2

-0.9

< 0.001

0.75

2.7

1.3

-1.0

< 0.001

0.81

Abdominal Sx-SS

3.5

1.4

2.8

1.2

-0.7

< 0.001

0.54

2.7

1.2

-0.8

< 0.001

0.57

Total symptom score

3.8

1.1

2.9

1.1

-0.9

< 0.001

0.84

2.7

1.2

-1.1

< 0.001

0.95

Number of bowel movements during the past week

4.4

4.7

6.9

10.5

2.5

0.020

0.30

6.1

5.1

1.7

0.001

0.34

Number of forced bowel movements during the past week

2.2

3.8

3.0

5.2

0.8

0.102

0.17

2.9

4.6

0.7

0.133

0.16

Number of spontaneous bowel movements during the past week

2.2

3.9

7.2

1.5

0.016

0.29

3.2

4.0

1.0

0.012

0.25

|SBM-7|

5.6

2.6

5.6

5.4

0.1

0.916

0.01

4.7

2.9

-0.9

0.012

0.31

Bristol Stool Form Scale

2.7

1.8

4.0

1.7

1.3

< 0.001

0.73

4.1

1.7

1.3

< 0.001

0.75

|BSFS-4|

1.9

1.1

1.4

1.0

-0.5

< 0.001

0.48

1.3

1.1

-0.6

< 0.001

0.52

Time to defecate

2.6

1.3

2.0

1.1

-0.6

< 0.001

0.45

1.9

1.1

-0.7

< 0.001

0.56

Defecation assistance

2.3

1.2

1.7

1.1

-0.6

< 0.001

0.48

1.6

1.0

-0.7

< 0.001

0.60

Dissatisfaction with daily activity

2.6

1.1

2.4

1.2

-0.2

0.034

0.19

2.2

1.1

-0.4

< 0.001

0.33

Dissatisfaction with the mood

2.8

1.2

2.4

1.2

-0.3

0.004

0.27

2.3

1.1

-0.5

0.004

0.40

Dissatisfaction with eating

2.3

1.3

1.9

1.2

-0.4

0.001

0.35

1.9

1.1

-0.4

< 0.001

0.34

Dissatisfaction with overall constipation symptoms

3.6

1.1

2.9

1.1

-0.7

< 0.001

0.61

2.7

1.3

-0.8

< 0.001

0.71

Dissatisfaction with daily life-SS

2.8

0.9

2.4

1.0

-0.4

< 0.001

0.46

2.3

0.9

-0.5

< 0.001

0.58

**Table 4.** Clinical Factors Associated With Therapeutic Response at 4 Weeks (Multiple Regression Analysis)
Factor	Patient’s impression	NRS	SBM frequency
BSFS: Bristol Stool Form Scale; BMI: body mass index; NRS: numerical rating scale; SBM: spontaneous bowel movement; Sx: symptom; SS: subscale.
Age	-0.292	0.022	0.037	0.778	0.069	0.577
Sex (female)	-0.117	0.368	-0.001	0.997	0.047	0.713
BMI	-0.040	0.717	0.106	0.364	0.003	0.980
Duration of constipation	-0.009	0.938	-0.023	0.848	0.168	0.145
Stool Sx-SS	-0.263	0.125	-0.214	0.217	-0.149	0.371
Defecation Sx-SS	0.028	0.875	0.008	0.963	-0.022	0.900
Abdominal Sx-SS	-0.011	0.937	0.089	0.557	-0.027	0.854
\|SBM-7\|	0.158	0.170	0.268	0.029	0.116	0.313
\|BSFS-4\|	-0.085	0.472	-0.002	0.987	0.133	0.251
R²	0.146	0.186	0.118	0.385	0.086	0.580
Interpretation (effect size)	β	R²
Small	≥ 0.1	≥ 0.02
Medium	≥ 0.3	≥ 0.13
Large	≥ 0.5	≥ 0.26

Table 4. Clinical Factors Associated With Therapeutic Response at 4 Weeks (Multiple Regression Analysis)

Factor

Patient’s impression

NRS

SBM frequency

P value

BSFS: Bristol Stool Form Scale; BMI: body mass index; NRS: numerical rating scale; SBM: spontaneous bowel movement; Sx: symptom; SS: subscale.

Age

-0.292

0.022

0.037

0.778

0.069

0.577

Sex (female)

-0.117

0.368

-0.001

0.997

0.047

0.713

BMI

-0.040

0.717

0.106

0.364

0.003

0.980

Duration of constipation

-0.009

0.938

-0.023

0.848

0.168

0.145

Stool Sx-SS

-0.263

0.125

-0.214

0.217

-0.149

0.371

Defecation Sx-SS

0.028

0.875

0.008

0.963

-0.022

0.900

Abdominal Sx-SS

-0.011

0.937

0.089

0.557

-0.027

0.854

|SBM-7|

0.158

0.170

0.268

0.029

0.116

0.313

|BSFS-4|

-0.085

0.472

-0.002

0.987

0.133

0.251

R²

0.146

0.186

0.118

0.385

0.086

0.580

Interpretation (effect size)

R²

Small

≥ 0.1

≥ 0.02

Medium

≥ 0.3

≥ 0.13

Large

≥ 0.5

≥ 0.26

**Table 5.** Effect of Adding Non-Response at Week 2 on the Prediction of Therapeutic Response at 4 Weeks (Multiple Regression Analysis)
Factor	Patient’s impression	NRS	SBM frequency
BSFS: Bristol Stool Form Scale; BMI: body mass index; NRS: numerical rating scale; SBM: spontaneous bowel movement; Sx: symptom; SS: subscale.
Age	-0.271	0.016	-0.018	0.882	0.083	0.460
Sex (female)	-0.138	0.228	0.020	0.876	0.001	0.996
BMI	-0.136	0.174	0.043	0.695	0.062	0.537
Duration of constipation	0.073	0.464	0.040	0.715	0.142	0.173
Stool Sx-SS	-0.344	0.024	-0.315	0.053	-0.072	0.638
Defecation Sx-SS	0.064	0.680	0.007	0.965	-0.093	0.572
Abdominal Sx-SS	0.030	0.815	0.085	0.549	0.026	0.844
\|SBM-7\|	-0.039	0.716	0.217	0.06	0.165	0.115
\|BSFS-4\|	-0.015	0.885	-0.010	0.927	0.098	0.349
Non-responder at week 2	0.558	< 0.001	0.429	< 0.001	-0.451	< 0.001
R²	0.392	< 0.0001	0.279	0.009	0.274	0.003
Interpretation (effect size)	β	R²
Small	≥ 0.1	≥ 0.02
Medium	≥ 0.3	≥ 0.13
Large	≥ 0.5	≥ 0.26

Table 5. Effect of Adding Non-Response at Week 2 on the Prediction of Therapeutic Response at 4 Weeks (Multiple Regression Analysis)

Factor

Patient’s impression

NRS

SBM frequency

P value

BSFS: Bristol Stool Form Scale; BMI: body mass index; NRS: numerical rating scale; SBM: spontaneous bowel movement; Sx: symptom; SS: subscale.

Age

-0.271

0.016

-0.018

0.882

0.083

0.460

Sex (female)

-0.138

0.228

0.020

0.876

0.001

0.996

BMI

-0.136

0.174

0.043

0.695

0.062

0.537

Duration of constipation

0.073

0.464

0.040

0.715

0.142

0.173

Stool Sx-SS

-0.344

0.024

-0.315

0.053

-0.072

0.638

Defecation Sx-SS

0.064

0.680

0.007

0.965

-0.093

0.572

Abdominal Sx-SS

0.030

0.815

0.085

0.549

0.026

0.844

|SBM-7|

-0.039

0.716

0.217

0.06

0.165

0.115

|BSFS-4|

-0.015

0.885

-0.010

0.927

0.098

0.349

Non-responder at week 2

0.558

< 0.001

0.429

< 0.001

-0.451

< 0.001

R²

0.392

< 0.0001

0.279

0.009

0.274

0.003

Interpretation (effect size)

R²

Small

≥ 0.1

≥ 0.02

Medium

≥ 0.3

≥ 0.13

Large

≥ 0.5

≥ 0.26