Supporting Table 1: Assessment tools and outcome measures of OIC (authors that provided a definition are marked grey)
Study
No.
1
Subjective
Author (year)
Objective measure
Subjective measure
burden measure
Joswick et al.14 (2013)
Proportions and median times to onset of a patient's first SBM were estimated
-
-
using Kaplan-Meier methods in a time-to-event analysis
2
Lichtlen et al.15 (2013)
-
-
-
3
Mareya et al.16 (2013)
Overall change from baseline in CSBM weekly rate;
-
-
BM difficulty;
Constipation distress
weekly and monthly changes in CSBM frequency.
4
Peppin et al.65 (2013)
-
Global Clinical Impression of Change (GCIC)
5
Ahmedzai et al.62 (2012)
-
BFI;
-
PAC-SYM;
EORTC QLQ-C30
6
Anissian et al.17 (2012)
Laxation within 2 and 4 hours of the first dose of study drug;
time to laxation
7
Jamal et al.48 (2012)
Questionnaire assessing patient global
-
satisfaction
Overall SBM response rate, defined as having 3 or more SBMs per week for at
Overall mean changes from baseline in OBD-
least 9 weeks, and at least 1 additional SBM over mean baseline SBM frequency;
related symptoms
-
changes from baseline in weekly, monthly, and overall SBM frequency;
time-to-first SBM
1
Study
No.
8
Subjective
Author (year)
Objective measure
Subjective measure
burden measure
Singla et al.49 (2012)
Change in spontaneous bowel movements (SBMs) over 4 weeks;
-
-
overall SBM responders (patient with ≥3 and ≥1 SBM/week from baseline for 3 of
4 weeks);
spontaneous complete BMs (SCBMs); opioid consumption
9
Wirz et al.18 (2012)
Defecation rates;
number of patients with a stool-free interval longer than 72 h (sfi72);
Subjectively rated intensity of constipation by
-
using the numerical rating scale (NRS, 0–10, 0 =
no symptom, 10 = worst symptom imaginable);
consumption of laxatives;
item 16 (constipation) of the EORTC QLQ (NRS, 1–
the average defecation rate of all patients during the time period of data
collection was calculated (defecations/patient/5 days)
4, 1 = no symptom, 4 = worst symptom
imaginable)
10
Clemens et al.11 (2011)
BSFS
BFI
11
Etropolski et al.36 (2011)
Bowel Function Diary (BFD) - module 1: bowel movement (BM) event log;
Bowel Function Diary (BFD) - module 2: symptom
the primary tolerability endpoint was the difference between each of the
the average 24-hour scores for bloating, pain in
week, calculated pro rata from the total number of SBMs recorded over the 14-
the abdomen, extent of presence of bothersome
day treatment period in which IR formulations were assessed; number of SBMs;
gas, and the level of lack of appetite, the scores
BMs, SBMs, and complete SBMs (CSBM); BSFS; number of days without a BM
-
assessment; module 3: symptom management;
tapentadol IR groups and the oxycodone HCl IR group in the number of SBMs per
total number of all BMs irrespective of spontaneity or completeness; number of
-
for inability to defecate, incomplete bowel
emptying, and BM pain in the rectum
2
Study
No.
12
Subjective
Author (year)
Objective measure
Subjective measure
burden measure
Irving et al.27 (2011)
Proportion of “responders”, with responder defined as a patient experiencing 3
Opioid-induced bowel dysfunction Symptoms
or more SBMs per week over the treatment period;
Improvement Scale (SIS);
average increase from baseline of at least 1 SBM per week
improvements in lower GI symptoms (straining,
-
stool consistency, and incomplete evacuation)
were also evaluated: 4-point scale
13
Iyer et al.12 (2011)
-
PAC-SYM
-
14
Jansen et al.28 (2011)
Proportion of “responders”, with responder defined as a patient experiencing 3
OBD Symptoms Improvement Scale (SIS);
-
or more SBMs per week over the treatment period;
average increase from baseline of at least 1 SBM per week
Improvements in lower GI symptoms (stool
consistency, straining, and incomplete
evacuation) were also evaluated: 4-point scale
15
16
Mercadante et al.52
Time to first bowel movement; percentage of patients who had a bowel
(2011)
movement within 24 hours after administration of AM dose
Michna et al.47 (2011)
Proportion of patients having a RFBM within 4 hours of the first dose;
percentage of active injections per patient resulting in a RFBM within 4 hours;
time to first RFBM after injection; change in weekly number of RFBMs; number
and time of bowel movements; BSFS; use of rescue laxatives
17
Moss et al.53 (2011)
Time to first bowel movement
-
-
Straining Scale (assessed as 0 [none] to 4 [very
PAC-QOL
severe]);
Sense of Complete Evacuation Scale (assessed as
either 0 [no] or 1 [yes])
-
-
3
Study
No.
18
Subjective
Author (year)
Objective measure
Subjective measure
burden measure
Webster et al.50 (2011)
Percentage of injections resulting in a bowel movement within 4 hours;
-
-
-
-
change from baseline in number of weekly bowel movements
19
Duerden et al.56 (2010)
Proportion of patients with a RFBM within 4 hours of the first dose of study
medication;
the percentage of all active doses resulting in a RFBM within 4 hours of dosing
20
Ishihara et al.29 (2010)
The number of days with stool in a week
-
-
21
Sandner-Kiesling et al.63
-
Bowel Function Index (BFI)
-
(2010)
22
Sawh et al.54 (2010)
Time to laxation
-
-
23
Sloots et al.35 (2010)
Average increase from baseline of ≥1 SCBM per week during the 4-week study
Patient Assessment of Constipation Symptoms
Patient Assessment of
period;
PAC-SYM
Constipation–Qualify of
Life (PAC-QOL)
proportion of patients having, on average, ≥3 SCBM per week during the 4-week
trial period;
average weekly frequency of SCBMs, SBMs, and all BMs
24
Webster et al.51 (2010)
Increase of spontaneous bowel movements/week
-
-
25
Blonsky et al.57 (2009)
Rescue-free laxation response within 4 hours of first dose;
-
-
rescue-free laxation response within 4 hours after all active doses
4
Study
No.
26
27
Subjective
Author (year)
Objective measure
Subjective measure
burden measure
Chamberlain et al.30
Bowel movements were assessed and concomitant medications were recorded
Patient- and clinician-reported Global Clinical
Constipation distress
(2009)
daily
Impression of Change (GCIC) on a seven-point
(on a five-point scale, 1
balanced scale (1 = much worse to 7 = much
= none to 5 = very
better)
much)
BFI; global patient satisfaction was assessed with
-
Clemens et al.61 (2009)
BSFS
Patient Global Impression of Change Scale (PGIC)
28
Loewenstein37 (2009)
Number of CSBMs a week; BSFS; frequency of laxative use
BFI; PAC-SYM
-
29
Meissner et al.64 (2009)
-
BFI
-
30
Slatkin et al.55 (2009)
Proportion of patients with laxation within 4 hours after administration of the
Improvement in Global Clinical Impression of
Constipation distress
double-blind dose;
Change (GCIC) scale (defined as a rating of
(on 5-point scale, 1 =
proportion of patients with rescue-free laxation within 24 hours post dosing;
slightly better, somewhat better, or much better) none to 5 = very much)
 improvement
improvement in stool consistency (1 = very hard; 2 = hard; 3 = slightly hard; 4 =
defined as a change >
firm; 5 = soft/formed; 6 = watery)
31
Wirz et al.21 (2009)
Use of analgesics, laxatives or antiemetics was recorded;
incidence of emesis and defecation
1 toward none)
The intensity of pain at rest, the intensity of
-
nausea, and constipation was assessed once daily
using the numerical rating scale (NRS, 0–10, 0 =
no symptom, 10 = worst symptom imaginable)
5
Study
No.
Subjective
Author (year)
Objective measure
Subjective measure
burden measure
32
Netzer et al.59 (2008)
Colonic transit time indices (CTIs) were calculated using a ROI (region of interest)
-
-
33
Portenoy et al.33 (2008)
‘‘Laxation response,’’ which was defined as a bowel movement within four hours
Constipation severity on five-point categorical
Constipation distress
of the initial dose
scales: Severity was described as none, mild,
on 5-point categorical
moderate, severe, or very severe;
scale: distress was
laxation within four hours of subsequent doses, during the 24-hour period after
each dose;
time to laxation;
BM: consistency (diarrhea, soft formed, firm,
slightly hard, hard, very hard) and difficulty
passing stool (no difficulty, slight, moderate,
the use of rescue laxatives
considerable, great)
described as none, a
little bit, somewhat,
quite a bit, or very
much
34
Simpson et al.38 (2008)
Number and mean number per week of CSBMs
BFI; PAC-SYM
-
35
Thomas et al.39 (2008)
Proportion of patients with rescue-free laxation
-
-
a. within 4 hours after the first dose of the study drug;
b. within 4 hours after two or more of the first four doses;
c. within 4 hours after four or more of seven doses;
d. within 4 or 24 hours after each dose;
the proportion of patients with > 3 laxations per week; the time to laxation
6
Study
No.
36
Subjective
Author (year)
Objective measure
Subjective measure
burden measure
Webster et al.13 (2008)
Change in weekly spontaneous bowel movement frequency;
PAC-SYM;
changes in weekly number of doses of rescue laxative used: impact of the rescue
weekly changes in bowel movement symptom
laxative on bowel movement frequency;
rating scores (proportion of stools leaving subject
responders for spontaneous bowel movement frequency (defined as subjects
PAC-QOL
with a sense of incomplete evacuation;
with ≥3 spontaneous bowel movements per week or subjects with an increase
stool consistency [loose/watery, semi-solid/soft,
from baseline of ≥1 spontaneous bowel movement per week)
lumpy/hard, or small pellets]; and
straining [none, mild, moderate or severe])
37
Wirz et al.34 (2008)
Stool free interval >72 h
Constipation was assessed once daily by using
-
the numerical rating scale (NRS, 0–10, 0 = no
symptom, 10 = worst symptom imaginable)
38
Twycross et al.40 (2006)
Frequency and consistency of bowel movements (each on a 4-point scale);
Level of discomfort; need to strain
-
requirement for suppositories, enemas or manual evacuation;
time to first bowel movement
39
Liu et al.41 (2002)
Bowel frequency
-
-
40
Yuan et al.42 (2000)
Stool frequency; stool consistency;
Subjective opinion of patients to rate subjects'
-
OCTT
satisfaction with bowel movement
41
Yuan et al.43 (1999)
Frequency; consistency; OCTT
-
-
42
Ramesh et al.44 (1998)
Bowel movement
Assessment of Laxative Efficacy (0-3)
-
7
Study
No.
Subjective
Author (year)
Objective measure
Subjective measure
burden measure
43
Latasch et al.58 (1997)
Bowel evacuation 1 to 4 h after the first intake
-
-
44
Freye et al.60 (1996)
Gastrocecal transit time
-
-
45
Sykes45 (1996)
Stool frequency;
Ease of defecation (1-4); day's bowel function
-
stool form by comparison of photographs
46
Sykes46 (1996)
Small bowel transit time (SBTT); stool frequency
using ten-point discrete visual scale
Ease of defecation; stool consistency
-
AM: Amidotrizoate; BFD: Bowel Function Diary; BFI: Bowel Function Index; BM: Bowel movement; BSFS: Bristol Stool Form Scale; CTIs: Colonic transit time indices; CSBM: Complete spontaneous bowel movement;
EORTC: European Organization for Research and Treatment of Cancer; GI: Gastrointestinal; GCIC: Global Clinical Impression of Change; HCl: Hydrochloride; IR: Immediate release; NRS: Numerical Rating Scale; OBD:
Opioid-induced bowel dysfunction; OCTT: Oral-cecal transit time; PAC-QOL: Patient Assessment of Constipation–Qualify of Life; PAC-SYM: Patient Assessment of Constipation-Symptoms; RFBM: Rescue-free bowel
movement; ROI: Region of interest; SBM: Spontaneous bowel movement; SBTT: Small bowel transit time; SCBM: Spontaneous complete; SBTT: Small bowel transit time; Stool-free interval longer than 72 h; SIS:
Symptoms Improvement Scale
8