Development of an internet-based Cohort of patients with Inflammatory Bowel Diseases (CCFA Partners®): Methodology and initial results

Article (PDF Available)inInflammatory Bowel Diseases 18(11):2099-106 · December 2011with51 Reads
DOI: 10.1002/ibd.22895 · Source: PubMed
Abstract
The widespread use of the Internet allows for unique research opportunities. We aimed to develop and follow an Internet-based cohort (e-cohort) of patients with self-reported inflammatory bowel diseases (IBD) over time. We established an e-cohort of adults with IBD (CCFA Partners) by recruiting through Crohn's and Colitis Foundation of America (CCFA) email rosters, CCFA Website promotion, social media, and other publicity mechanisms. The baseline survey included modules on disease course and activity, diet and exercise, and patient-reported outcomes (PROs). Baseline characteristics of the cohort are summarized using descriptive statistics. A total of 7819 adults with IBD joined CCFA Partners through August, 2011. The median age was 42 years (interquartile range [IQR] 30-54), 5074 (72.3%) were female. A total of 4933 (63.1%) had Crohn's disease (CD), 2675 (34.2%) had ulcerative colitis (UC), and 211 (2.7%) had IBD unspecified. For CD, the mean short CD Activity Index (CDAI) was 151.9 (standard deviation [SD] 106.4), with 2274 (59.4%) in remission. For UC, the mean simple clinical colitis activity index (SCCAI) was 3.6 (SD 2.8), with 937 (42.9%) in remission. The mean short IBD questionnaire (SIBDQ) score was 48.7 (SD 11.8). SIBDQ was inversely correlated with disease activity (P < 0.01). The mean Morisky medication adherence score (MMAS) was 5.7 (SD 2.0). MMAS scores were inversely correlated with disease activity (P < 0.01). CCFA Partners is a novel e-cohort. Enrollment is ongoing, with surveys twice yearly. CCFA Partners represents a unique resource to study PROs and changes in disease management over time. (Inflamm Bowel Dis 2012;).
ORIGINAL ARTICLE
Development of an Internet-based Cohort of Patients with
Inflammatory Bowel Diseases (CCFA Partners):
Methodology and Initial Results
Millie D. Long, MD, MPH,*
,†
Michael D. Kappelman, MD, MPH,
†,‡
Christopher F. Martin, MSPH,*
,†
James D. Lewis, MD, MSCE,
§
Lloyd Mayer, MD,
k
Patricia M. Kinneer, MA,
and Robert S. Sandler, MD, MPH*
,†
Background: The widespread use of the Internet allows for unique research opportunities. We aimed to develop and follow an Internet-based
cohort (e-cohort) of patients with self-reported inflammatory bowel diseases (IBD) over time.
Methods: We established an e-cohort of adults with IBD (CCFA Partners) by recruiting through Crohn’s and Colitis Foundation of America
(CCFA) email rosters, CCFA Website promotion, social media, and other publicity mechanisms. The baseline survey included modules on dis-
ease course and activity, diet and exercise, and patient-reported outcomes (PROs). Baseline characteristics of the cohort are summarized using
descriptive statistics.
Results: A total of 7819 adults with IBD joined CCFA Partners through August, 2011. The median age was 42 years (interquartile range [IQR]
30–54), 5074 (72.3%) were female. A total of 4933 (63.1%) had Crohn’s disease (CD), 2675 (34.2%) had ulcerative colitis (UC), and 211
(2.7%) had IBD unspecified. For CD, the mean short CD Activity Index (CDAI) was 151.9 (standard deviation [SD] 106.4), with 2274 (59.4%)
in remission. For UC, the mean simple clinical colitis activity index (SCCAI) was 3.6 (SD 2.8), with 937 (42.9%) in remission. The mean short
IBD questionnaire (SIBDQ) score was 48.7 (SD 11.8). SIBDQ was inversely correlated with disease activity (P < 0.01). The mean Morisky
medication adherence score (MMAS) was 5.7 (SD 2.0). MMAS scores were inversely correlated with disease activity (P < 0.01).
Conclusions: CCFA Partners is a novel e-cohort. Enrollment is ongoing, with surveys twice yearly. CCFA Partners represents a unique
resource to study PROs and changes in disease management over time.
(Inflamm Bowel Dis 2012;18:2099–2106)
Key Words: inflammatory bowel disease, patient reported outcomes, quality of life, Internet, cohort, disease activity
C
rohn’s disease (CD) and ulcerative colitis (UC) are
chronic, relapsing inflammatory disorders that exact a
considerable personal and economic burden on affected
individuals. Despite extensive research, the etiology
remains largely unknown. There is considerable variation
in healthcare utilization by age, gender, geographic region,
and insurance type that is poorly understood.
1–3
Most longitudinal cohort studies of CD and UC have
relied on administrative data or retrospective review of
clinical records. Such studies often lack important clinical
data that can only be collected directly from the patient.
Examples include detailed smoking history, use of over-
the-counter medications, dietary patterns, exercise, and
quality of life (QoL). Other important patient-reported out-
comes (PROs) such as depression, well-being, sleep, and
fatigue are often lacking. Traditionally, prospective cohort
studies have been extraordinarily expensive to conduct due
to the need for large personnel resources to recruit and fol-
low patients over time. The availability and widespread use
of the Internet creates an unparalleled opportunity to create
an online community of inflammatory bowel disease (IBD)
patients that could be used for education programs and
research at dramatically reduced costs.
Here we describe the development of CCFA Partners,
a longitudinal Internet-based cohort (e-cohort) of IBD
Additional Supporting Information may be found in the online version of
this article.
Received for publication Novem ber 23, 2011; Accepted January 3, 2012.
From the *University of North Carolina, Department of Medicine, Division of
Gastroenterology and Hepatology, Chapel Hill, North Carolina,
Center for
Gastrointestinal Biology and Disease, Chapel Hill, North Carolina,
University of
North Carolina, Department of Pediatrics, Division of Gastroenterology and
Hepatology, Chapel Hill, North Carolina,
§
University of Pennsylvania, Raymond
and Ruth Perelman School of Medicine, Philadelphia, Pennsylvania,
k
Mount
Sinai School of Medicine, New York, NY.
Supported, in part, by grants from the Crohn’s and Colitis Foundation of
America and the National Institutes of Health (P30 Dk34987).
Reprints: Dr. Millie Long, CB #7080, University of North Carolina-Chapel
Hill, Chapel Hill, NC 27599 (e-mail: millie_long@med.unc.edu).
This article was published online on January 27, 2012. Some errors were
subsequently identified. This note is included in the online and print versions
to indicate that both have been corrected August 6, 2012.
Copyright
V
C
2012 Crohn’s & Colitis Foundation of America, Inc.
DOI 10.1002/ibd.22895
Published online 27 January 2012 in Wiley Online Library (wileyonlinelibrary.
com).
Inflamm Bowel Dis
Volume 18, Number 11, November 2012
2099
patients established to 1) facilitate studies of the natural
history of disease in a large, diverse population; 2) serve as
a platform for additional studies of disease mechanisms,
treatments, and outcomes; and 3) potentially influence dis-
ease management through educational interventions focus-
ing on quality improvement and prevention.
MATERIALS AND M ETHODS
We first developed a survey including important infor-
mation on various patient-reported components of living with
IBD that we piloted in 1000 individuals on the Crohn’s and
Colitis Foundation of America (CCFA) email roster to det er-
mine feasibility of recruitment for an Internet-based cohort.
We then expanded the invitation to include all individuals on
CCFA rosters, and employed additional means of recruitment
including social media and print advertisements, a link from
the CCFA Website, word of mouth from other participants,
and promotion at local CCFA chapter meetings. The email
invitations to join the cohort were released in waves in June
and July 2011. For those who did not join the cohort, or who
did not complete a total of two modules, email reminders
were sent at 2 weeks after the initial invitation and again at 3
months. Any individual could access the cohort entry portal
through the Website www.ccfapartners.or g or through a spe-
cific email link if they were on CCFA email rosters. How the
individual jo ined the cohort (via email link vs. direct Website
access) was also tracked. Only those who met inclusion crite-
ria were able to join the cohort.
Eligibility and Inclusion Criteria
During the first recruitment wave we excluded individu-
als under age 18 and those who did not have self-reported IBD
(CD, UC, or indeterminate colitis). Individuals also had to have
Internet access to join the e-cohort and complete the surveys.
There were no other exclusion criteria for participation.
Baseline Survey
The complete CCFA Partners baseline survey is avail-
able online at the CCFA Partners website: www.ccfapartners.
org, under the ‘‘For Researchers’ tab. The survey was available
only in English. The baseline survey instrument featured three
modules that each targeted different aspects of living with IBD.
All participants received Module 1. Participants were then
randomized to receive either Module 2 or Module 3 in equal
proportions. After completion of their second module, all patients
were given the opportunity to complete an optional third module
(whichever module they did not receive as #2) (see Fig. 1).
Module 1
Module 1 included information on demographics, dis-
ease phenotype, prior and current medication use, health-
related behaviors, family history of IBD, extraintestinal mani-
festations of IBD, disease activity, and prevention. Validated
disease activity measurements were used, including the Simple
Clinical Colitis Activity Index (SCCAI)
4
for UC and the short
Crohn’s Disease Activity Index (sCDAI) for CD.
5
The SCCAI
has been validated in a longitudinal cohort study of patients
with UC undergoing colonoscopy. It was found to have excel-
lent psychometric validity and moderate to good performance
validity.
6
A SCCAI score of 5 or more defines a relapse of
UC.
7
A SCCAI score of 2 is associate d with UC remission.
8
The SCCAI has also been validated with self-report.
7
The
validity, reliability, and responsiveness of the sCDAI has been
shown to be comparable to the original CDAI using data from
nine clinical trials of budesonide. The sCDAI accounted for
82.4% of the variance of the original CDAI in this validation
study.
5
Also within this module, patients reported prevention
activities such as vaccine utilization, calcium and vitamin D
supplementation for bone health, skin testing for tuberculosis
(TB), Pap smears for women, skin examinations and sunscreen
use, and colonoscopy surveillance in those with colonic dis-
ease of greater than 10 years duration.
Module 2
Module 2 consisted of questions on diet and exercise.
This module used a National Cancer Institute (NCI) food fre-
quency questionnaire developed in 2010 and a separate food
avoidance questionnaire developed specifically for the IBD pop-
ulation. The dietary results will be reported separately. Exercise
was assessed via the validated Godin Leisure Time Exercise
Index.
9,10
The Godin Index contains questions on frequency of
strenuous, moderate, and mild exercise, with one question on
how often the individual ‘works up a sweat.’ Increasing points
are awarded based on levels of strenuous exercise. The Godin
Index has been validated with self-report.
11
Module 3
Module 3 consisted of patient-reported outcomes
(PROs). PRO is the term used to describe health data provided
by the patient through a system of reporting. A PRO consists
of a patient’s feedback on their feelings or how they function
as they deal with chronic diseases or conditions. We measured
three separate PRO scales on medication adherence, QoL, and
other physical and emotional domains. We collected self-
reported medication adherence using the Morisky Medication
Adherence Scale (MMAS). The MMAS consists of eight
FIGURE 1. CCFA Partners study flow.
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Volume 18, Number 11, November 2012Long et al
2100
questions, each worth 1 point. Each question focuses on a dif-
ferent aspect of adherence, such as forgetfulness and actual
self-reported missing of doses over various time periods (i .e.
yesterday, or over the past 2 weeks). The MMAS is catego-
rized as 1–5 (low), 6–7 (medium), an d 8 (high) adherence.
12
This scale has been validated in the IBD population.
13
We
also collected data from an IBD-specific QoL instrument: the
validated Short IBD Questionnaire (SIBDQ).
14
This scale has
been previously shown to correlate with disease activity in the
IBD population. The scores for the SIBDQ range from 10–70.
A score of 10 correlates with poor health-related quality of
life (HRQOL) and a score of 70 correlates with optim um
HRQOL. Finally, we asked questions on the specific domains
of fatigue, sleep, physical function, and emotional distress .
These questions were taken from the Pati ent Reported Out-
come Measurement Information System (PROMIS). PROMIS
is a system of highly reliable, precise measures of patient-
reported health status for physical, mental, and social well-
being (http://www.nihpromis.org/). The questions have been
validated in the general population and population-based norms
are available.
15–17
The PROMIS results will be reported separately.
Data Collection and Management
The data were collected entirely in a Web-based format,
allowing for real-time implementation of range and consis-
tency checks. Therefore, missing data were minimized at point
of entry. The data management system was implem ented using
a suite of reusable metadata-driven tools that facilitated rapid
development of the protocol and good computing practice.
Some examples of these tools include questionnaire version
change auditing, data change auditing, dynamic form genera-
tion, and data validation. The program provided important vali-
dation including single-variable range checks and cross-variable
and cross-form logic checks that identified logical inconsisten-
cies in the data. For example, an individual would be prompted
if they reported IBD duration as longer than their current age.
The user interfaces for the Web-based system were generated
dynamically from metadata and programmed within the central
database. The Web forms were accessible from any machine
running a modern Internet browser with an active connection to
the Internet; no special software was required.
Statistical Analysis
Descriptive statistics were used to characterize the popu-
lation, including proportions and 95% confidence intervals,
medians and interquartile ranges, means and standard deviations
(SD) as appropriate. Bivariate statistics were used to compare
outcomes by CD versus UC when applicable, including Pear-
son’s chi-square test statistic, Fisher’s exact, Wilcoxon rank
sum, and Student’s t-test as appropriate. Spearman’s correlation
was used to evaluate the association between scales of ordinal
data. STATA v. 10.0 (College Station, TX) was used for all
analyses and P < 0.05 was considered statistically significant.
The study protocol was approved by the Institutional Review
Board at the University of North Carolina at Chapel Hill.
RESULTS
A total of 7819 individuals with self-reported IBD
joined CCFA Partners through August 19, 2011. Of these,
the majority 7609 (97.3%) entered the survey through a
direct email link sent to the CCFA email roster and 210
(2.7%) entered independently via the CCFA Partners Web-
site. Among those who entered independently, reported
mechanisms or recruitment included: an Internet search
(10), CCFA Website advertisement (92), their physician
(13), CCFA newsletter (40), CCFA social media outlet
(27), a friend (7), a family member (8), or a CCFA meet-
ing or event (3). Cohort members included individuals
from over 250 nations and territories throughout the world;
however, the vast majority (96.4) were from within the
United States. The median age within the cohort was 42
years (interquartile range [IQR] 30–54). The majority of
the population were female, 5074 (72.3%). A total of 4933
(63.1%) had CD, 2675 (34.2%) had UC, and 211 (2.7%)
had indeterminate colitis (IC) / IBD unspecified. The char-
acteristics of the population are shown in Table 1 by CD
or UC status. While age was similar for CD and UC popu-
lations, those with CD had longer duration of disease.
Medication Use
The most common class of medications used in the
cohort was the 5-aminosalicyl ate (5-ASA) class. A total of
1465 (34.3%) of the CD patients were currently using oral
5-ASA medications, while 1421 (60.4%) of the UC popula-
tion were currently using oral 5-ASA medications. The
cohort also demonstrated considerable use of immunosup-
pressant and biologic medications for both CD and UC.
Approximately a quarter of patients with CD and UC were
currently on thiopurines. Forty percent of CD patients and
17% of UC patients reported current biologic use (Table 1).
Distribution of Involvement and Extraintestinal
Manifestations
The distribution of involvement by CD is shown in
Table 2. The majority of individuals had colonic and/or
ileal involvement, although upper tract involvement was
also represented in the cohort in up to 24% of individuals.
Painful joints were the most common extraintestinal mani-
festation among the CD population. Table 3 shows disease
location and extraintestinal manifestations among the UC
patients. A total of 34% of those with UC reported pancoli-
tis. Again, painful joints were the most common extraintes-
tinal manifestation.
Disease Activity
When the population was categorized into remission
versus active disease based on validated cutoffs for the
SCCAI and the sCDAI, slightly less than half of the CD
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Development of CCFA Partners
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population was in remission, and slightly greater than half
of the UC population was in remission. These differences
in remission rates between CD and UC are shown in
Table 4. Within the CD population, the mean short CD
activity index (CDAI) was 151.9 (SD 106.4). Within the
UC population, the mean SCCAI was 3.6 (SD 2.8). We
also asked patients to self-report their own level of disease
activity in a separate question. For those with CD, 1064
(25.4%) reported remission, 1478 (35.3%) reported mini-
mal activity, 858 (20.5%) reported mild activity, 573
(13.7%) reported moderate activity, and 211 (5.0%) reported
severe activity. For UC, 821 (35.2%) reported remission,
726 (31.1%) reported minimal activity, 495 (17.4%) reported
mild activity, 273 (11.7%) reported moderate activity, and
109 (4.7%) reported severe activity. When the validated
indices, SCDAI and SCCAI, were compared with the indi-
vidual question on grading of disease activity, there was sig-
nificant correlation for both CD and UC. For CD, the Spear-
man’s correlation was 0.77, P < 0.001. For UC, the
Spearman’s correlation was 0.69, P < 0.001.
Prevention
The status of prevention within both the CD and UC
populations is shown in Table 5. Less than two-thirds of
the population received an influenza vaccine over the prior
year and approximately one-third had ever received a pneu-
mococcal vaccination. We also investigated reasons for
lack of influenza vaccine in the IBD population as a whole.
These reasons included: personal refusal 1044 (45.7%),
never offered the vaccine 267 (11.7%), other 602 (26.4%),
allergy to eggs 78 (3.4%), and don’t know 292 (12.8%).
With regard to bone health, among the population of prior
or current corticosteroid users (n ¼ 5841), approximately
half of individuals with IBD had ever had a dual-ener gy
x-ray absorptiometry (DEXA) scan test (n ¼ 3007, 55.1%).
In this population of prior or current corticosteroid users, a
TABLE 1. Characteristics of the Population by Crohn’s Disease vs. Ulcerative Colitis Within CCFA Partners Cohort
Characteristic
Crohn’s Disease (n¼4933) Ulcerative Colitis (n¼2675)
n %, Median (IQR) n %, Median (IQR)
Age 4389 42 (30-54) 2411 42 (31-54)
Age at IBD diagnosis 4321 24 (18-34) 2373 28 (21-40)
Disease duration of IBD (yrs) 4300 12 (6-24) 2357 9 (4-17)
Gender (% female) 3195 72.7 1739 71.7
Heath care visits in prior year
Primary care physician (% yes) 1885 71.6 1140 73.6
Gastroenterologist (% yes) 3863 90.3 2017 85.1
Ever smoking (% yes) 1720 39.5 881 36.8
Current smoking 419 9.7 104 4.4
Prior bowel surgery 2242 53.0 392 16.6
Current ostomy 366 8.8 81 3.5
Current medications
5-ASA (oral) 1465 34.3 1421 60.4
5-ASA (rectal) 108 2.6 347 15.0
Prednisone 404 9.5 253 10.8
Entocort (budesonide) 268 6.3 39 1.7
Ciprofloxacin 123 2.9 52 2.3
Metronidazole 131 3.1 34 1.5
Thiopurine (6-MP/azathioprine) 1071 25.7 465 20.4
Methotrexate 179 4.3 37 1.6
Cyclosporine 22 0.5 14 0.6
Biologic (any) 1648 40.3 373 16.9
Adalimumab 725 17.7 91 4.1
Infliximab 703 17.1 282 12.6
Certolizumab pegol 240 5.9 21 0.9
Natalizumab 32 0.8 12 0.6
Medication in a clinical trial 48 1.2 27 1.2
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Volume 18, Number 11, November 2012Long et al
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total of 53.6% were on calcium, 60.7% vitamin D supple-
mentation, and 7.4% on a bisphosphonate. We also
assessed skin examination among those on current or prior
immunosuppression (including immunomodulators or bio-
logic medications). In the past 3 years, less than half of
these individuals had a skin examination by a dermatolo-
gist. We additionally asked about skin protective measures
in those on immunosuppression, such as sunscreen use. A
total of 661 (16.0%) reported always wearing sunscreen,
while 1529 (37.1%) only wore sunscreen most of the time,
1496 (36.3%) sometimes, and 438 (10.6%) never. Among
those with current or prior biologic medication use the ma-
jority reported a prior screening test for TB (88.3%). In the
population of patients with prior colonic inflammation and
disease duration >10 years, nearly 80% of both CD and
UC patients reported a colonoscopy within the past 2 years.
In those with a history of primary sclerosing cholangitis
(PSC) and IBD, without prior colectomy, yearly surveil-
lance colonoscopy is recommended. In this group, 69.0%
had a colonoscopy within the past year.
Exercise
The overall median total energy score (ENERT)
score on the Godin scale in the IBD population was 26
(IQR 12–25). There was a significantly lower median score
of 25 (IQR 10–44) in those with CD as compared with
those with UC 29.5 (IQR 15–49), P < 0.01.
Medication Adherence
The MMAS is categorized as 1–5 (low), 6–7 (me-
dium), and 8 (high). Within the overall IBD population a
total of 1651 (40.6%) had low adherence, 1364 (33.5%)
had medium adherence, and 1055 (25.9%) had high adher-
ence on the MMAS scale. The overall mean MMAS was
5.7 (SD 2.0). When evaluated by IBD subtype, there was
no difference in adherence by CD or UC status (5.7 [SD
2.1] for CD vs. 5.8 [SD 2.0] for UC, P ¼ 0.08). [Correc-
tions made to above sentence, after initial online publica-
tion]. We then evaluated medication adherence in quartiles
of disease activity for both CD and UC populations. For
both CD and UC, medication adherence rates were better
in the lowest quartile of disease activity, and worsened sig-
nificantly with higher levels of disease activity (P < 0.01
for both CD and UC; Fig. 2). Additional analyses evaluat-
ing categories of medication adherence by the clinically
TABLE 3. Disease Location (Ever Involvement) and
Extraintestinal Manifestations in Patients with
Ulcerative Colitis Within CCFA Partners Cohort
Characteristic n Percent
Disease location
Rectum (‘‘proctitis’’) 125 5.0
Rectum and sigmoid (‘‘proctosigmoiditis’’) 337 13.4
Rectum/sigmoid/descending (‘‘left’’) 635 25.2
Rectum/sigmoid/descending/transverse
(‘‘extensive’’)
171 6.8
Entire colon (‘‘pancolitis’’) 857 34.0
Don’t know 394 15.6
Extraintestinal manifestations
Painful joints 1132 47.2
Erythema nodosm 95 4.0
Pyoderma gangrenosm 35 1.5
Aphthous ulcerations 212 8.9
Eye inflammation 192 8.0
Primary sclerosing cholangitis 42 1.8
TABLE 4. Disease Activity in Crohn’s Disease and
Ulcerative Colitis Within CCFA Partners Cohort
Disease Activity
a
Crohn’s
Disease
Ulcerative
Colitis
P value
b
n % n %
Remission 937 42.9 2274 59.4 <0.01
Active Disease 1249 57.1 1554 40.6
a
Measured by short CDAI for CD and simple clinical colitis activity index
(SCCAI) for UC, scores of <150 and 2 associated with remission,
respectively, patients with ostomy excluded.
b
Pearson’s chi-square test statistic.
TABLE 2. Disease Location (Ever Involvement) and Extra-
intestinal Manifestations in Patients with Crohns Disease
Within CCFA Partners Cohort
Characteristic n Percent
Disease location
Esophagus 526 12.6
Stomach 720 17.3
Duodenum 1006 24.2
Jejunum 945 22.8
Ileum 2872 68.0
Terminal ileum 2968 70.8
Colon 2577 61.7
Rectum 1675 40.6
Extraintestinal manifestations
Painful joints 2170 52.3
Erythema nodosm 273 6.6
Pyoderma gangrenosm 99 2.4
Aphthous ulcerations 437 10.6
Eye inflammation 432 10.4
Primary sclerosing cholangitis 37 0.9
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Development of CCFA Partners
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significant cutpoint of active disease as compared with
remission (defined as sCDAI <150 for CD and SCCAI 2
for UC) also showed that active disease was associated
with significantly lower medication adherence for CD and
UC (P < 0.01).
Quality of Life
The SIBDQ ranges from 10 (poor) to 70 (optimum).
In the overall IBD population, the median SIBDQ score
was 50 (IQR 41-58). For those wit h CD, the median
SIBDQ score was 50 (IQR 40–58) and for those with UC,
the median score was 52 (42–59), P < 0.01. When evaluated
in quartiles of disease activity, higher QoL was inversely
correlated with disease activity (P < 0.01 for both CD and
UC; Fig. 3). When QoL was compared within quartiles of
disease duration, the SIBDQ significantly increased with
increasing duration of disease (data now shown). Using
logistic regression to control for disease activity, disease du-
ration remained significantly associated with SIBDQ for both
CD and UC (beta coefficient 0.07, 0.06 respectively, P <
0.01). SIBDQ in UC patients with more active disease
(defined as SCCAI > median) was significantly lower than
SIBDQ in UC patients status postcolectomy with pouch for-
mation; 40.8 (SD 10.2) vs. 50.1 (SD 11.9), P < 0.01.
DISCUSSION
We have demonstrated the feasibility of developing
and recruiting an online cohort of IBD patients to study
important patient-reported exposures and outcomes.
Recruitment of almost 8000 participants from 250 nations
over a 2-month period provides strong evidence of the in-
terest in participation by the IBD patient community.
TABLE 5. Status of Prevention in Patients with IBD, Overall, and by Crohn’s Disease vs. Ulcerative Colitis Within CCFA
Partners Cohort
Preventive Measure
IBD Overall CD UC
P value
a
n % yes n % yes n % yes
Vaccinations
Pneumococcal
b
2521 37.8 1695 40.6 757 32.7 <0.01
Influenza
c
4244 63.9 2725 66.1 1399 60.9 <0.01
DEXA
d
3007 55.1 2071 59.4 867 47.3
Pap smear
e
3926 94.0 2466 94.2 1351 93.8 0.60
Skin exam
f
1623 39.6 1170 39.7 423 39.5 0.91
TB skin test
g
2628 88.3 2052 89.2 520 85.5 0.02
Colonoscopy
h
Colonic CD 1017 79.8 NA
UC 739 79.0 NA
PSC 20 69.0 NA
a
Pearson’s chi square comparing CD to UC.
b
Ever.
c
Within the past year.
d
Ever, among those with prior or current corticosteroid use.
e
Among women, within the past 3 years.
f
Within the past 3 years, among those on current or prior immunosuppression.
g
Ever, among those on current or prior biologic anti-TNF.
h
Within past 2 years among those with intact colon, prior colonic inflammation, disease duration of >10 years, or within past 1 year with intact colon and
ever diagnosis of PSC.
NA, not applicable.
FIGURE 2. Self-reported medication adherence by levels of disease
activity (in quartiles) within the CCFA Par tners cohort. [corrected
figure replaced after initial online publication].
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Volume 18, Number 11, November 2012Long et al
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Longitudinal follow-up of this large, div erse cohort of
invested participants will facilitate studies eval uating the
complex associations between health behaviors, medical
treatments, and disease course measured by patient-reported
outcomes. Additionally, we also designed the CCFA Part-
ners to be a scalable and modular platform upon which
interventional studies and translational studies can be built.
By maintaining the contact information of study partici-
pants, we have the ability to evaluate health behavior inter-
ventions, request biospecimens to study genetic, microbio-
logical, and immunological factors, and combine the
patient-reported data from CCFA Partners with physician-
reported data from medical records, research registries, and
clinical trials.
Given widespread Internet access (68.7% of U.S.
households according to 2009 census
18
; 81% of IBD
patients
19
), Web-based epidemiological studies offer a
number of advantages over traditional print survey meth-
ods, including cost savings, efficiency in data collection
and management, convenience for the participant, improve-
ments in data quality, and a greater degree of anonymity
for the participant.
20
Completion rates of sur veys have
been reported to be similar, regardless of Internet or print-
based format.
21
Although individuals without Internet
access may be different from those with access, therefore
limiting the external generalizability of e-cohorts, many
suggest that the bias associated with collecting information
over the Web is no greater than that introduced by tradi-
tional paper methods.
21
As a result, e-cohorts such as ours
have become an increasingly well-accepted study design.
Examples include a military cohort with over 20 years of
planned follow-up
20
and Black Women’s Health study,
which substituted Web-based surveys for paper surveys as
an alternate means of follow-up.
22
Prior studies in IBD
have utilized the Internet for various phases of follow-up
within cohort studies. Wolters et al
23
used an Internet-
based data acquisition tool to successfully attain follow-up
information on a Western-European and Israeli multicenter
10-year study of patients with IBD. Others have used the
Internet to share data acquisition tools within studies of
IBD.
24
To our knowledge, we are among the first to under-
take a large, prospective cohort of patients with IBD
entirely via the Internet.
The strengths of this study include the large sample
size, geographic diversity of the study population, the use of
validated indices, and the ease of participation for individu-
als within the cohort. Additionally, the Web-based format
allowed for enhancement of data quality through point of
entry quality and range checks and electronic skip patterns.
A limitation of this e-cohort is that all data are based
on participant self-reporting. We are unable to confirm the
diagnosis of IBD itself, nor any of the other clinical or
phenotypical aspects of disease. However, we believe that
the strong focus on patient-reported exposures, health
behaviors, and outcomes is an important complement to
more traditional research that has relied solely on physi-
cian-reported data via retrospective chart reviews or pro-
spective clinical registries. Additionally, it will be possible
to combine the patient-reported data collected here with
other data sources including medical records or data col-
lected in other observational or interventional studies.
Reassuringly, we were also able to confirm previously
reported associations within this e-cohort, thus supporting
the internal validity of patient-reported data. For example,
Irvine et al
14
previously reported reductions in QoL scales
with increased disease activity. We found this same associ-
ation within our study. Prior studies have demonstrated that
QoL improves for individuals with active UC after under-
going colectomy for refractory disease.
25,26
We found simi-
lar results within our e-cohort, where QoL scores were
higher for individuals after colectomy than for those with
more active UC (SCCAI > median). We also found a
strong positive correlation between patient global assess-
ment rating of disease severity and symptom-based indices
such as the sCDAI and SCCAI.
Due to methods of recruitment, interest in participat-
ing, requirement for English language, and the technology
required to join our e-cohort, this sample is not necessarily
representative of the IBD population as a whole. As
expected, our study contains relatively few elderly partici-
pants; however, we did recruit a total of 556 over the age
of 65. Additionally, over 70% of those enrolled in the
cohort are female, whereas gender frequencies of CD and
UC in the U.S. are more equal. Regardless of potential for
enrolment bias, internal comparisons and longitudinal anal-
yses will be valid as long as there is not differential loss to
follow-up. Indeed, the selection bias in this cohort is essen-
tially no different than in traditional cohorts such as
FIGURE 3. Quality of life measurements by levels of disease activity
(in quartiles) within the CCFA Par tners cohort.
Inflamm Bowel Dis
Volume 18, Number 11, November 2012
Development of CCFA Partners
2105
Framingham
27
or Nurses Health Study,
28
where the value
lies with continued follow-up. We have learned a great
deal from the aforementioned traditional cohorts, and have
the potential to similarly learn from this IBD-specific e-
cohort at a fraction of the cost.
In summary, this is the first large-scale Internet-based
cohort of individuals living with IBD. This cohort repre-
sents a unique method of recruiting and following individu-
als with IBD over time. Every 6 month s, individuals will
be contacted to update their status within the cohort. CCFA
Partners has been designed to be both modular and scal-
able. In this regard, we anticipate that it will be a valuable
research platform for the scientific community. We antici-
pate this platform will support a variety of research designs
including: 1) survey-based research administered to the
entire cohort, or subpopulations selected on the basis of
prespecified criteria; 2) translational studies combining
CCFA Partners data and with biospecimens collected from
subpopulations of the cohort; 3) additional clinical studies
and trials facilitated by merging CCFA Partners patient-
reported data with medical record, registry, or trial data;
and 4) studies of Internet-based health behavior interven-
tions to promote adherence, preventive measures, and
patient-activation. Researchers interested in utilizing the
CCFA Partners cohort in future studies should register at
the ‘for researchers’ section at www.ccfapartners.org. The
possibilities for future collaborative epidemiologic studies
within this population are extraordinary.
REFERENCES
1. Herrinton LJ, Liu L, Fireman B, et al. Time trends in therapies and
outcomes for adult inflammatory bowel disease, Northern California,
1998–2005. Gastroenterology. 2009;137:502–511.
2. Hilsden RJ, Verhoef MJ, Best A, et al. A national survey on the pat-
terns of treatment of inflammatory bowel disease in Canada. BMC
Gastroenterol. 2003;3:10.
3. Colletti RB, Baldassano RN, Milov DE, et al. Variation in care in pe-
diatric Crohn disease. J Pediatr Gastroenterol Nutr. 2009;49:297–303.
4. Walmsley RS, Ayres RC, Pounder RE, et al. A simple clinical colitis
activity index. Gut. 1998;43:29–32.
5. Thia K, Faubion WA Jr, Loftus EV Jr, et al. Short CDAI: develop-
ment and validation of a shortened and simplified Crohn’s disease ac-
tivity index. Inflamm Bowel Dis. 2011;17:105–111.
6. Higgins PD, Leung J, Schwartz M, et al. The quantitative validation
of non-endoscopic disease activity indices in ulcerative colitis. Aliment
Pharmacol Ther. 2007;25:333–342.
7. Jowett SL, Seal CJ, Phillips E, et al. Defining relapse of ulcerative co-
litis using a symptom-based activity index. Scand J Gastroenterol.
2003;38:164–171.
8. Turner D, Seow CH, Greenberg GR, et al. A systematic prospective
comparison of noninvasive disease activity indices in ulcerative coli-
tis. Clin Gastroenterol Hepatol. 2009;7:1081–1088.
9. Godin G, Shephard RJ. A simple method to assess exercise behavior
in the community. Can J Appl Sport Sci. 1985;10:141–146.
10. Godin G, Jobin J, Bouillon J. Assessment of leisure time exercise
behavior by self-report: a concurrent validity study. Can J Public
Health. 1986;77:359–362.
11. Gionet NJ, Godin G. Self-reported exercise behavior of employees: a
validity study. J Occup Med. 1989;31:969–973.
12. Morisky DE, Ang A, Krousel-Wood M, et al. Predictive validity of a
medication adherence measure in an outpatient setting. J Clin Hyper-
tens (Greenwich). 2008;10:348–354.
13. Trindade AJ, Ehrlich A, Kornbluth A, et al. Are your patients taking
their medicine? Validation of a new adherence scale in patients with
inflammatory bowel disease and comparison with physician perception
of adherence. Inflamm Bowel Dis. 2011;17:599–604.
14. Irvine EJ, Zhou Q, Thompson AK. The Short Inflammatory Bowel
Disease Questionnaire: a quality of life instrument for community
physicians managing inflammatory bowel disease. CCRPT Investiga-
tors. Canadian Crohn’s Relapse Prevention Trial. Am J Gastroenterol.
1996;91:1571–1578.
15. Cella D, Riley W, Stone A, et al. The Patient-Reported Outcomes
Measurement Information System (PROMIS) developed and tested its
first wave of adult self-reported health outcome item banks: 2005–
2008. J Clin Epidemiol. 2010;63:1179–1194.
16. Liu H, Cella D, Gershon R, et al. Representativeness of the Patient-
Reported Outcomes Measurement Information System Internet panel.
J Clin Epidemiol. 2010;63:1169–1178.
17. Rothrock NE, Hays RD, Spritzer K, et al. Relative to the general US
population, chronic diseases are associated with poorer health-related
quality of life as measured by the Patient-Reported Outcomes Mea-
surement Information System (PROMIS). J Clin Epidemiol. 2010;63:
1195–1204.
18. http://www.census.gov/hhes/computer/ Accessed 11/1/2011.
19. Cima RR, Anderson KJ, Larson DW, et al. Internet use by patients in
an inflammatory bowel disease specialty clinic. Inflamm Bowel Dis.
2007;13:1266–1270.
20. Smith B, Smith TC, Gray GC, et al. When epidemiology meets the
Internet: Web-based surveys in the Millennium Cohort Study. Am J
Epidemiol. 2007;166:1345–1354.
21. Ekman A, Dickman PW, Klint A, et al. Feasibility of using Web-
based questionnaires in large population-based epidemiological stud-
ies. Eur J Epidemiol. 2006;21:103–111.
22. Russell CW, Boggs DA, Palmer JR, et al. Use of a Web-based ques-
tionnaire in the Black Women’s Health Study. Am J Epidemiol. 2010;
172:1286–1291.
23. Wolters FL, van Zeijl G, Sijbrandij J, et al. Internet-based data inclu-
sion in a population-based European collaborative follow-up study of
inflammatory bowel disease patients: description of methods used and
analysis of factors influencing response rates. World J Gastroenterol.
2005;11:7152–7158.
24. Blumenstein I, Herrmann E, Filmann N, et al. Female patients suffer-
ing from inflammatory bowel diseases are treated less frequently with
immunosuppressive medication and have a higher disease activity: a
subgroup analysis of a large multi-centre, prospective, Internet-based
study. J Crohns Colitis. 2011;5:203–210.
25. Muir AJ, Edwards LJ, Sanders LL, et al. A prospective evaluation of
health-related quality of life after ileal pouch anal anastomosis for ul-
cerative colitis. Am J Gastroenterol. 2001;96:1480–1485.
26. Waljee AK, Higgins PD, Waljee JF, et al. Perceived and actual quality
of life with ulcerative colitis: a comparison of medically and surgi-
cally treated patients. Am J Gastroenterol. 2011;106:794–799.
27. Dawber TR, Meadors GF, Moore FE Jr. Epidemiological approaches
to heart disease: the Framingham Study. Am J Public Health Nations
Health. 1951;41:279–281.
28. Willett WC, Stampfer MJ, Colditz GA, et al. Dietary fat and the risk
of breast cancer. N Engl J Med. 1987;316:22–28.
Inflamm Bowel Dis
Volume 18, Number 11, November 2012Long et al
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  • [Show abstract] [Hide abstract] ABSTRACT: The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. www.amjgastro.com, *2007 Journal Citation Report (Thomson Reuters, 2008)
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  • [Show abstract] [Hide abstract] ABSTRACT: The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. www.amjgastro.com, *2007 Journal Citation Report (Thomson Reuters, 2008)
    Full-text · Article · Jun 2012
  • [Show abstract] [Hide abstract] ABSTRACT: Adherence is a major factor in determining disease activity in ulcerative colitis (UC). There are limited data on long-term nationwide adherence levels among patients with UC. To evaluate the long-term adherence levels to oral mesalazine (mesalamine) in the Veterans Affairs (VA) healthcare system, to determine the impact of non-adherence on the risk of flares, and to evaluate the different pharmacy data-based adherence indicators. Nationwide data were obtained from the VA for the period 2001-2011. UC patients who started mesalazine maintenance during the inclusion period were included. Level of adherence was assessed using three different indicators: medication possession ratio (MPR), continuous single-interval medication availability (CSA) and continuous multiple-interval medication gaps (CMG). Cox regression modelling was used to predict disease flares and assess the predictive value of each adherence indicator. We included 13 062 patients into the analysis with median follow-up time of 6.1 years. Percentage of patients with high adherence was 47%, 43%, 31% as identified by CSA, MPR and CMG respectively. Low adherers had a significant increase in the risk of flares compared with high adherers (Hazard ratio: 2.8, 1.7 and 1.8, P < 0.001 for CSA, MPR and CMG, respectively). Compared with other adherence indicators, CSA offered the best trend in predicting disease flares. Long-term high-adherence level was lower than previously reported. Adherence was a significant factor in predicting disease flares. Pharmacy adherence indicators may be useful to healthcare providers in identifying patients at high risk of exacerbations.
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